Search

Background: Immunonutrition has been shown to reduce hospital stay and postoperative morbidity in patients undergoing gastrointestinal, and head and neck surgery. However, its use has not been demonstrated in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aims to determine the effectiveness of perioperative immunonutrition on patients undergoing CRS-HIPEC in reducing length of hospitalization and postoperative complications., Patients and Methods: From April 2017 to December 2018, patients undergoing CRS-HIPEC for peritoneal metastases in a single center were enrolled in a randomized controlled trial. Patients with evidence of intestinal obstruction or with diabetes mellitus were excluded. Patients were randomly assigned in a 1:1 fashion to receive perioperative oral immunonutrition or standard nutritional feeds. Length of hospital stay and rates of wound infection and complications were recorded and compared between the two groups in an intention-to-treat manner., Results: A total of 62 patients were recruited and randomized into two groups. Compliance to nutritional feeds in the preoperative period was significantly higher in the standard nutrition group (95.2% versus 75.4%, p = 0.004). There was no difference in postoperative compliance rates. Length of hospital stay and rates of wound infection and postoperative complications were higher in the standard nutrition group when compared with patients on immunonutrition (15.5 versus 11.1 days, p = 0.186; 19% versus 9.7%, p = 0.473; 16% versus 9.7%, p = 0.653; respectively)., Conclusions: Patients undergoing CRS-HIPEC who received perioperative immunonutrition had shorter hospitalization and less wound infections and postoperative complications, although the differences with the standard nutrition group were not statistically significant. Potential benefits of perioperative immunonutrition need to be further evaluated in larger studies., (© 2022. Society of Surgical Oncology.)

Background: The performance of MRI versus CT in the detection and evaluation of peritoneal surface malignancies (PSM) remains unclear in the current literature. Our study is the first prospective study in an Asian center comparing the two imaging modalities, validated against intra-operative findings. Methods: A total of 36 patients with PSM eligible for CRS-HIPEC underwent both MRI and CT scans up to 6 weeks before the operation. The scans were assessed for the presence and distribution of PSM and scored using the peritoneal cancer index (PCI), which were compared against PCI determined at surgery. Results: Both MRI and CT were 100% sensitive and specific in detecting the overall presence of PSM. Across all peritoneal regions, the sensitivity and specificity for PSM detection was 49.1% and 93.0% for MRI, compared to 47.8% and 95.1% for CT (p = 0.76). MRI was more sensitive than CT for small bowel disease, although the difference did not reach statistical significance. Comparing PCI on imaging with intra-operative PCI, the mean difference was found to be −3.4 ± 5.4 (p < 0.01) for MRI, and −3.9 ± 4.1 (p < 0.01) for CT. The correlation between imaging and intra-operative PCI was poor, with a concordance coefficient of 0.76 and 0.79 for MRI and CT, respectively. Within individual peritoneal regions, there was also poor agreement between imaging and intra-operative PCI for both modalities, other than in regions 1 and 3. Conclusion: MRI and CT are comparable in the detection and evaluation of PSM. While sensitive in the overall detection of PSM, they are likely to underestimate the true disease burden.

Introduction: There is paucity of data on the occurrence of cardiovascular events (CVEs) in critically ill patients with sepsis. We aimed to describe the incidence, risk factors and impact on mortality of CVEs in these patients., Methods: This was a retrospective cohort study of critically ill patients admitted to the medical intensive care unit (ICU) between July 2015 and October 2016. The primary outcome was intra-hospital CVEs, while the secondary outcomes were in-hospital mortality, ICU and hospital length of stay., Results: Patients with sepsis (n=662) had significantly more CVEs compared to those without (52.9% versus 23.0%, P <0.001). Among sepsis patients, 350 (52.9%) had 1 or more CVEs: 59 (8.9%) acute coronary syndrome; 198 (29.9%) type 2 myocardial infarction; 124 (18.7%) incident atrial fibrillation; 76 (11.5%) new or worsening heart failure; 32 (4.8%) cerebrovascular accident; and 33 (5.0%) cardiovascular death. Factors associated with an increased risk of CVEs (adjusted relative risk [95% confidence interval]) included age (1.013 [1.007-1.019]); ethnicity-Malay (1.214 [1.005-1.465]) and Indian (1.240 [1.030-1.494]) when compared to Chinese; and comorbidity of ischaemic heart disease (1.317 [1.137-1.527]). There were 278 patients (79.4%) who developed CVEs within the first week of hospitalisation. Sepsis patients with CVEs had a longer median (interquartile range [IQR]) length of stay in the ICU (6 [3-12] vs 4 [2-9] days, P <0.001), and hospital (21 [10-42] vs 15 [7-30] days, P <0.001) compared to sepsis patients without CVEs. There was no difference in in-hospital mortality between the 2 groups (46.9% vs 45.8%, P =0.792)., Conclusion: CVEs complicate half of the critically ill patients with sepsis, with 79.4% of patients developing CVEs within the first week of hospitalisation, resulting in longer ICU and hospital length of stay.

Objectives: Peritoneal cancer index (PCI) score is a common prognostication tool in peritoneal metastases (PM). We hypothesize that the distribution of PCI score and involvement of specific regions affects survival and morbidity outcomes., Methods: Data was collected from a prospective database of patients who underwent CRS and HIPEC for PM at the National Cancer Centre Singapore. We evaluate the relationship between PCI, PCI distribution, and survival and morbidity outcomes., Results: One hundred and fifty-two patients underwent CRS and HIPEC with a median PCI score of nine (range 0-31). Median overall survival (OS) and progression free survival (PFS) were 43 and 17 months, respectively. Region six (pelvis) was most commonly involved and had the highest frequency of heavy disease burden. Presence of PM in the lower abdomen, flanks, and small bowel were associated with poorer OS (p=0.01, 0.03, <0.001) and PFS (p=0.04, 0.02, <0.001). Involvement of porta hepatitis predicted poorer OS but not PFS (p=0.03). Involvement of the gastric antrum resulted in higher rates of postoperative complications., Conclusions: The pattern of PCI distribution may be associated with varying survival and morbidity outcomes., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Jolene Si Min Wong et al., published by De Gruyter, Berlin/Boston.)

Objectives: Various studies have shown that good quality of life (QoL) can be achieved after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is prognostic value of baseline QoL in post-operative outcome in Western setting. Our prospective study aims to validate these observations and elucidate clinical factors that predict poorer QoL in Asian peritoneal carcinomatosis patients., Methods: European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was administered to patients before CRS and HIPEC and thereafter at 3, 6 and 12 months., Results: A total of 151 patients underwent 155 surgeries. Four hundred and seventy two questionnaires were completed. Median disease-free survival (DFS) was 16.5 months. Three year DFS and overall survival (OS) were 24.0% and 73.0% respectively. Post-operative global health status significantly increased at 3, 6 and 12 months. The decreases in functional scales recovered to baseline by 1-year post-surgery. Peritoneal carcinomatosis index (PCI), presence of stoma, peritonectomy duration, death within one year, post-operative complication and length of SICU stay negatively influenced QoL. Complication rates were higher in patients with lower global health status, physical and role functioning scores and higher symptom summary scores at baseline. Lower social functioning score, and higher pain, dyspnoea and symptom summary scores at baseline were significantly associated with poorer OS., Conclusions: Various clinical factors can help us predict a patient's QoL after surgery. Several baseline factors were also able to predict morbidity and survival. Going forward, we can use these factors to help us better select patients who will have a greater benefit from CRS and HIPEC., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Claramae Shulyn Chia et al., published by De Gruyter, Berlin/Boston.)

Peritoneal carcinomatosis (PC) present a ubiquitous clinical conundrum in all intra-abdominal malignancies. Via functional and transcriptomic experiments of ascites-treated PC cells, we identify STAT3 as a key signaling pathway. Integrative analysis of publicly available databases and correlation with clinical cohorts (n = 7,359) reveal putative clinically significant activating ligands of STAT3 signaling. We further validate a 3-biomarker prognostic panel in ascites independent of clinical covariates in a prospective study (n = 149). Via single-cell sequencing experiments, we uncover that PAI-1, a key component of the prognostic biomarker panel, is largely secreted by fibroblasts and mesothelial cells. Molecular stratification of ascites using PAI-1 levels and STAT3 activation in ascites-treated cells highlight a therapeutic opportunity based on a phenomenon of paracrine addiction. These results are recapitulated in patient-derived ascites-dependent xenografts. Here, we demonstrate therapeutic proof of concept of direct ligand inhibition of a prognostic target within an enclosed biological space., Competing Interests: C.-A.J.O., J.H., Y.L., W.H.N., J.W.S.T., Q.X.T., G.H.C.T., C.S.C., and M.C.C.T. report a Patent Cooperation Treaty (PCT) filed by Singapore Health Services for PAI-1 as a biomarker with therapeutic implications for peritoneal carcinomatosis (PCT/SG2020/050177). All of the other authors declare no competing interests., (© 2022 The Author(s).)

Background: Palliative gastrointestinal (GI) surgery potentially relieves distressing symptoms arising from intestinal obstruction (IO) in patients with advanced peritoneal carcinomatosis (PC). As surgery is associated with significant morbidity risks in advanced cancer patients, it is important for surgeons to select patients who can benefit the most from this approach. Hence, we aim to determine predictors of morbidity and mortality after palliative surgery in patients with PC. In addition, we evaluate the utility of the UC Davis Cancer Care nomogram (UCDCCn) and develop a simplified model to predict short-term surgical mortality in these patients., Methods: A retrospective review of patients with IO secondary to PC undergoing palliative GI surgery was performed. Logistic regression was used to determine independent predictors of 30-day morbidity and mortality after surgery. UCDCCn was evaluated using the area under the curve (AUC) for discriminatory power and the Hosmer-Lemeshow test for calibration. Our simplified model was developed using logistic regression and evaluated using cross-validation., Results: A total of 254 palliative GI surgeries were performed over a 10-year duration. The 30-day morbidity and mortality were 43% (n = 110) and 21% (n = 53), respectively. Preoperative albumin, age, and emergency nature of surgery were significant independent predictors for 30-day morbidity. A simplified model using preoperative Eastern Cooperative Oncology Group (ECOG) status and albumin (AUC = 0.71) achieved better predictive power than UCDCCn (AUC = 0.66) for 30-day mortality., Conclusion: Good ECOG status and high preoperative albumin levels were independently associated with good short-term outcomes after palliative GI surgery. Our simplified model may be used to conveniently and efficiently select patients who stand to benefit the most from surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wong, Lek, Lim, Chia, Tan, Ong and Teo.)

Background: Postoperative readmissions not only burden the healthcare system but may also affect clinical outcomes of cancer patients. Despite this, little is known about readmissions after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), or their impact on survival outcomes., Patients and Methods: A single-institution retrospective cohort study of CRS-HIPEC procedures from April 2001 and September 2019 was performed. Early readmission (ERA) was defined as hospitalization within 30 days of discharge post-CRS/HIPEC, while late readmission (LRA) was defined as hospitalization between day 31 and 90 after discharge. Patient demographic, oncological, and perioperative factors were analyzed to identify predictors of readmission, and comparison of survival outcomes was performed., Results: Overall, 342 patients who underwent CRS-HIPEC were included in the study. The incidence of ERA and LRA was 18.5% and 7.4%, respectively. High-grade postoperative complication was the only independent predictor of ERA (HR 3.64, 95% CI 1.47-9.02), while comorbid hypertension (HR 2.71, 95% CI 1.17-6.28) and stoma creation (HR 2.83, 95% CI 1.23-6.50) were independent predictors for LRA. Patients with readmission had significantly worse disease-free survival than patients who had no readmission (NRA) (LRA 1.1 years, ERA 1.2 years, NRA 1.8 years, p = 0.002), and patients with LRA had worse median overall survival (2.1 years) than ERA patients (3.3 years) or patients without readmission (4.4 years) (p < 0.001)., Conclusions: Readmission following CRS-HIPEC is associated with adverse survival outcomes. In particular, LRA may portend worse prognosis than ERA., (© 2021. The Author(s).)

Background: The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative inflammatory marker trend in peritoneal carcinomatosis (PC), with a focus on colorectal PC (CPC), and to propose optimal surveillance periods and cutoffs., Methods: Data were collected from a prospectively maintained database of PC patients treated at the authors' institution from April 2001 to March 2019. The platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR), and the lymphocyte-monocyte ratio (LMR) were collected preoperatively and on postoperative days 0, 1 to 3, 4 to 7, 8 to 21, 22 to 56, and 57 to 90 as averages. Optimal surveillance periods and cutoffs for each marker were determined by maximally selected rank statistics. The Kaplan-Meier method and Cox proportional hazard regression models were used to investigate the association of inflammatory markers with 1-year overall survival (OS) and recurrence-free survival (RFS) using clinicopathologic parameters., Results: The postoperative inflammatory marker trend and levels did not differ between the patients with and those without hyperthermic intraperitoneal chemotherapy (HIPEC). Low postoperative LMR (days 4-7), high postoperative NLR (days 8-21), and high postoperative PLR (days 22-56) were optimal for prognosticating poor 1-year OS, whereas high postoperative PLR and NLR (days 57-90) and low postoperative LMR (days 8-21) were associated with poor 1-year RFS. A composite score of these three markers was prognostic for OS in CPC., Conclusions: The reported cutoffs should be validated in a larger population of CPC patients. Future studies should account for the inflammatory response profile when selecting appropriate surveillance periods., (© 2021. The Author(s).)

Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity. A signature predicting cisplatin sensitivity was generated using the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, and ERI1) were identified and optimized for immunohistochemistry (IHC). Validation was performed on a cohort of patients (n = 50) treated with surgical resection followed by adjuvant carboplatin. Predictive models were established to predict chemosensitivity. The four biomarkers were also assessed for their ability to prognosticate overall survival in three ovarian cancer microarray expression datasets from The Gene Expression Omnibus. The extreme gradient boosting (XGBoost) algorithm was selected for the final model to validate the accuracy in an independent validation dataset (n = 10). CYTH3 and S100A14, followed by nodal stage, were the features with the greatest importance. The four gene signature had comparable prognostication as clinical information for two-year survival. Assessment of tumour biology by means of gene expression can serve as an adjunct for prediction of chemosensitivity and prognostication. Potentially, the assessment of molecular markers alongside clinical information offers a chance to further optimise therapeutic decision making., (© 2021. The Author(s).)

Up to 10% of well-differentiated liposarcoma (WDLS) progress to dedifferentiated liposarcoma (DDLS). We aimed to identify gene expression changes associated with dedifferentiation and whether these were informative of tumour biology of DDLS. We analysed datasets from the Gene Expression Omnibus (GEO, ID = GSE30929) database to identify differentially expressed genes between WDLS ( n = 52) and DDLS ( n = 39). We validated the signature on whole and laser-capture microdissected samples from patients with tumours consisting of mixed WDLS and DDLS components. A subset of this signature was applied to an independent dataset from The Cancer Genome Atlas (TCGA, n = 58 DDLS) database to segregate samples based on gene expression and compared for recurrence and overall survival (OS). A 15-gene signature consisting of genes with increased expression in DDLS compared to WDLS was generated. This signature segregated WDLS and DDLS samples from patients with mixed component tumours and across multiple recurrences. A further subset of this signature, consisting of five genes (AQP7, ACACB, FZD4, GPD1, LEP), segregated DDLS in a TCGA cohort with a significant difference in OS ( p = 0.019) and recurrence-free survival (RFS) ( p = 0.061). The five-gene model stratified DDLS into prognostic groups and outperformed clinical factors in existing models in retroperitoneal DDLS.

Background: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs., Methods: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared., Results: Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group., Conclusions: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.

Background: This study aimed to determine pre- and peri-operative parameters with significant predictive value for post-operative outcomes in patients with recurrent colorectal cancer presenting as peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and to develop a novel prognostic scoring system for prediction of survival outcomes., Methods: A single-institution review of prospectively collected data from all patients who underwent CRS-HIPEC between October 2005 and October 2017 was conducted. Univariate and multivariate analyses were used to identify significant parameters for prediction of post-CRS-HIPEC disease-free survival and overall survival (OS)., Results: A total of 278 patients underwent CRS-HIPEC, of whom 72 were for peritoneal carcinomatosis from recurrent colorectal cancer. Disease-free interval (DFI; P = 0.006), peritoneal cancer index (PCI; P = 0.001) and left upper quadrant disease (P = 0.023) were significant independent predictors of 3-year OS. DFI (0.007), PCI (P < 0.001) and intraoperative blood loss (BL; P = 0.001) were significant independent predictors of 5-year OS. PCI and BL were significant independent predictors of both 3-year (P = 0.026, PCI; P = 0.009, BL) and 5-year (P = 0.002, PCI; P = 0.011, BL) disease-free survival. Predictive models were developed for risk stratification of OS., Conclusion: PCI, DFI, left upper quadrant disease and BL have significant predictive value for post-CRS-HIPEC outcomes. Risk stratification models allow for more prudent patient selection and ultimately more accurate prognostication of post-operative outcomes., (© 2020 Royal Australasian College of Surgeons.)

Background: Retroperitoneal sarcoma represents 15% of sarcomas. The mainstay of treatment is surgery where a majority of patients require multi-visceral resections that may significantly impact their quality of life (QOL) following surgery. Studies in other cancers have shown that QOL may not be significantly impacted after radical or extensive surgery. However, there are limited studies examining the QOL specifically in patients with retroperitoneal sarcoma. In this pilot study, we retrospectively evaluated the QOL of patients with retroperitoneal sarcoma., Methods: 32 out of 90 patients who underwent surgical intervention for retroperitoneal sarcoma in National Cancer Centre Singapore from January 1999 to August 2018 who were alive and on follow-up were included in this study. EORTC-QLQ-C30 was administered to the patients., Results: The median age of our patients was 59 years (range, 35-84), and median time from surgery to the implementation of questionnaire was 2.5 years (range, 0.05-9.6). Younger patients had significantly better differences in global health, physical and role functioning scores as compared to older individuals. Female patients reported higher global health, physical, emotional and social functioning scores than males. Patients who were more than 2 years post-surgery exhibited better QOL scores as compared to those who had more recent surgery. Our patients had comparable global health and functioning scores compared to a reference group of outpatient cancer patients at our institution., Conclusions: Our pilot study investigating the QOL of patients with retroperitoneal sarcoma has shown that patients need to be followed up for at least 2 years following surgery to evaluate their QOL. In general, they achieved better functioning scores when compared with other cancer patients. These findings support the need for larger-scale prospective studies to further evaluate the QOL of these patients.

Background: Lateral pelvic lymph node (LLN) metastasis (LLNM) occur in up to 28% of patients with low rectal tumours. While prophylactic lateral pelvic lymph node dissection (LLND) has been abandoned by most western institutions in the era of neoadjuvant chemoradiation therapy (CRT), the role of selective LLND in patients with enlarged LLN on pre-CRT imaging remains unclear. Some studies have shown improved survival and recurrence outcomes when LLNs show "response" to CRT. However, no management algorithm exists to differentiate treatment for "responders" vs "non-responders"., Aim: To determine if selective LLND in patients with enlarged LLNs results in improved survival and recurrence outcomes., Methods: A systemic search of PubMed and Embase databases for studies reporting on patients with synchronous radiologically suspicious LLNM (s-LLNM) in rectal cancer receiving preoperative-CRT was performed., Results: Fifteen retrospective, single-centre studies were included. 793 patients with s-LLNM were evaluated: 456 underwent TME while 337 underwent TME with LLND post-CRT. In the TME group, local recurrence (LR) rates range from 12.5% to 36%. Five-year disease free survival (DFS) was 42% to 75%. In the TME with LLND group, LR rates were 0% to 6%. Five years DFS was 41.2% to 100%. Radiological response was seen in 58%. Pathologically positive LLN was found in up to 94% of non-responders vs 0% to 20% in responders. Young age, low tumour location and radiological non-response were associated with final positive LLNM and lowered DFS., Conclusion: LLND is associated with local control in patients with s-LLNM. It can be performed in radiological non-responders given a large majority represent true LLNM. Its role in radiological responders should be considered in selected high risk patients., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution., Methods: A review of our institution's database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression., Results: 225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14-77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (p < 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15-0.81, p < 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31-8.30, p = 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003-1.002, p = 0.007; and OR 1.002, 95% CI 1.001-1.002, p < 0.001, for low and high grade, respectively)., Conclusion: Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors., Methods: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm 3 ), neutropenia (absolute neutrophils < 2000/mm 3 ), and thrombocytopenia (platelets < 140 000/mm 3 )., Results: Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression., Conclusion: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC., (© 2019 John Wiley & Sons Australia, Ltd.)

Angiosarcomas of the breast (ASB) are rare, making up to less than 8% of all angiosarcomas. The surgical management for this disease continues to vary throughout centres worldwide due to the current limited evidence. We aim to examine the necessity of axillary lymph node dissection in this pathology through a retrospective study of axillary metastasis and recurrence patterns in patients treated at our institution. A retrospective review of a prospectively-maintained database was performed. All adult patients with a histologically confirmed diagnosis of ASB seen at the National Cancer Centre Singapore between 2006 and 2019 were identified. Axillary lymph node status, treatment, survival, and recurrence data were collated. Thirteen patients were identified with a confirmed diagnosis of ASB, of which there were 11 primary and 2 secondary angiosarcoma cases. Eight patients had some form of axillary lymph node dissection and 5 did not. No positive nodes were found in any examined axillary nodes despite high median number of nodes harvested (13, range 8-24). 5/13 patients had disease progression, of whom none had locoregional recurrence to the axilla. ASB continues to be rare and recurrent and presents as a challenge to treat. Axillary lymph node involvement is most likely not present in a majority of patients. Prophylactic removal is unwarranted in patients presenting without lymph node involvement due to the lack of axillary metastasis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Sharanniyan Ragavan et al.)

Generation of large amounts of genomic data is now feasible and cost-effective with improvements in next generation sequencing (NGS) technology. Ribonucleic acid sequencing (RNA-Seq) is becoming the preferred method for comprehensively characterising global transcriptome activity. Unique to cytoreductive surgery (CRS), multiple spatially discrete tumour specimens could be systematically harvested for genomic analysis. To facilitate such downstream analyses, laser capture microdissection (LCM) could be utilized to obtain pure cell populations. The aim of this protocol study was to develop a methodology to obtain high-quality expression data from matched primary tumours and metastases by utilizing LCM to isolate pure cellular populations. We demonstrate an optimized LCM protocol which reproducibly delivered intact RNA used for RNA sequencing and quantitative polymerase chain reaction (qPCR). After pathologic annotation of normal epithelial, tumour and stromal components, LCM coupled with cDNA library generation provided for successful RNA sequencing. To illustrate our framework's potential to identify targets that would otherwise be missed with conventional bulk tumour sequencing, we performed qPCR and immunohistochemical technical validation to show that the genes identified were truly expressed only in certain sub-components. This study suggests that the combination of matched tissue specimens with tissue microdissection and NGS provides a viable platform to unmask hidden biomarkers and provides insight into tumour biology at a higher resolution.

Background: Colorectal peritoneal metastases (CPM) occur in up to 13% of patients with colorectal cancer, presenting either synchronously or metachronously. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) have been increasingly utilised for selected CPM patients with favourable outcomes, though its benefits may differ for synchronous (s-CPM) and metachronous CPM (m-CPM)., Methods: A retrospective analysis of CPM patients treated with CRS and HIPEC at the National Cancer Centre Singapore over 15 years was performed. In the s-CPM group, CPM was diagnosed at primary presentation with CRS and HIPEC performed at the time of or within 6 months from primary surgery. In the m-CPM group, patients developed CPM > 6 months after primary curative surgery., Results: One hundred two patients with CPM were treated with CRS and HIPEC. Twenty (19.6%) patients had s-CPM and 82 (80.4%) had m-CPM. Recurrences occurred in 45% of s-CPM and in 54% of m-CPM (p = 0.619). Median overall survival was significantly prolonged in patients with m-CPM (45.2 versus 26.9 months, p = 0.025). In a subset of m-CPM patients with limited PCI in whom ICU stay was not required, a survival advantage was seen (p = 0.031)., Conclusion: A survival advantage was seen a subset of m-CPM patients, possibly representing differences in disease biology.

Background: Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria-Peritoneal Surface Disease Severity Score (PSDSS), Verwaal's Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability., Methods: Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (p < 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity., Results: PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity., Conclusions: PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity and mortality. We aim to generate and validate a biomarker set predicting sensitivity to Mitomycin-C to refine selection of patients with colorectal peritoneal metastasis (CPM) for this treatment. A signature predicting Mitomycin-C sensitivity was generated using data from Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas. Validation was performed on CPM patients who underwent CRS-HIPEC (n = 62) using immunohistochemistry (IHC). We determined predictive significance of our set using overall survival as a surrogate endpoint via a logistic regression model. Three potential biomarkers were identified and optimized for IHC. Patients exhibiting lower expression of PAXIP1 and SSBP2 had poorer survival than those with higher expression (p = 0.045 and 0.140, respectively). No difference was observed in patients with differing DTYMK expression (p = 0.715). Combining PAXIP1 and SSBP2 in a set, patients with two dysregulated protein markers had significantly poorer survival than one or no dysregulated marker (p = 0.016). This set independently predicted survival in a Cox regression model (HR 5.097; 95% CI 1.731-15.007; p = 0.003). We generated and validated an IHC prognostic set which could potentially identify patients who are likely to benefit from HIPEC using Mitomycin-C.

Background: Metastatic gastric cancer has a poor prognosis. We aim to study how clinical features and prognosis differs between different metastatic sites, and to identify prognostic factors for overall survival., Methods: We retrospectively reviewed patients with metastatic gastric adenocarcinoma managed at a tertiary referral cancer center over a 5-year period. We divided our cohort into three groups based on the site(s) of metastasis at presentation-peritoneal metastasis only (P), distant metastasis only (D), and peritoneal and distant metastases (PD)., Results: We studied 470 patients with 175 (37.2%), 193 (41.1%) and 102 (21.7%) patients in the P, D and PD groups, respectively. Patients with peritoneal disease (both P and PD) had higher proportions of patients experiencing chemotherapy disruption due to unplanned hospitalizations, which were also of a longer average duration. The P group had the longest overall median survival of 8.9 months compared to the PD and D groups with 7.4 and 5.5 months, respectively (P < 0.001). On multivariate Cox regression analysis, the presence of ≥1 metastatic site (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.23-2.28; P  =  0.001) was significantly associated with increased overall mortality, whereas palliative systemic chemotherapy (HR 0.29; 95% CI, 0.22-0.37; P < 0.001) and palliative gastrectomy (HR 0.24; 95% CI, 0.15-0.39; P < 0.001) were significantly associated with decreased overall mortality., Conclusion: Metastatic gastric cancer represents a heterogeneous disease, with specific disease complications and treatment outcomes unique to different metastatic sites. We can consider novel multimodality therapies for patient subgroups with isolated metastatic disease and good prognostic factors in a bid to improve long-term survival., (© 2018 John Wiley & Sons Australia, Ltd.)

Introduction: Dedifferentiated liposarcoma is rare and tends to present with discrete tumors in the retroperitoneum, limbs and trunk. Majority of cases arise de-novo as primary tumors, while a minority occur as recurrences of well-differentiated liposarcomas. There has been no previous report of dedifferentiated liposarcoma presenting as disseminated intraperitoneal sarcomatosis., Presentation of Case: This report describes a young Asian female with disseminated intraperitoneal sarcomatosis arising from de-novo dedifferentiated liposarcoma, and discusses the diagnostic challenges faced in this highly unusual disease presentation. Initial biopsy was unconclusive, and considerations included sclerosing mesenteritis or an inflammatory myofibroblastic tumor. Fluorescence in situ hybridization was subsequently performed and showed amplification of the MDM2 gene. A diagnosis of dedifferentiated liposarcoma was then made., Discussion: This was an extremely unusual presentation of advanced dedifferentiated liposarcoma that was eventually diagnosed using fluorescence in situ hybridization. Prognosis is poor and the only viable treatment options was palliative chemotherapy., Conclusion: The diagnosis of dedifferentiated liposarcoma should be considered early and surgery carried out when still feasible., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The evaluation of lymph nodes and the role of groin dissection for groin sarcomas has been controversial where there have not been previous studies or guidelines published. In this study, we aim to first formulate a clinical approach in the evaluation of regional lymph nodal metastases. Second, we aim to also evaluate the role of regional lymphadenectomy in the setting of pathologically involved regional lymph nodes for groin sarcomas., Materials and Methods: In total, 43 consecutive patients with groin sarcomas underwent treatment at the National Cancer Centre Singapore between 2002 and 2015. Univariate comparisons were performed using the log-rank test. A Cox multivariate analysis was performed for disease-specific survival to identify independent prognostic factors., Results: The median disease-free survival was 18 months (range, 1 to 180 mo). The median overall survival (OS) was 28 months (range, 3 to 180 mo). In total, 28 patients underwent a groin dissection. Of the 28 patients who underwent groin dissections, 15 had negative lymph node involvement, 7 had positive lymph node involvement and 6 had lymphovascular invasion.On univariate analysis, grade (P=0.047) and clinical and/or radiological involvement (P=0.039) were significant for regional lymph nodal metastases.The 5-year OS for patients with positive lymph nodes was 31%., Conclusions: Our study suggests that the evaluation of lymph nodes via groin dissections in groin sarcomas in the Asian population should be based primarily on clinical and radiologic evidence. Regional lymph node dissection seems to confer OS benefit in patients with these high-risk tumors and can improve local control of disease.

Background: Primary mucosal melanomas (MM) are rare neoplasms arising from melanocytes in mucosal membranes. Delayed diagnosis and aggressive disease biology contribute to a poorer prognosis. The clinical patterns of MMs treated in a large tertiary centre, and the differences between MMs in the head and neck versus other anatomical sites are described., Methods: A retrospective review of 43 patients diagnosed with MM in the head and neck, urogenital, esophageal and anorectal sites from 1993 to 2015 was conducted., Results: Distribution of head and neck, urogenital and gastrointestinal MM were 42, 30 and 28% respectively. Disease extent was local in 44%, regional in 40% and distal in 12% at diagnosis. Head and neck MMs were more likely to be diagnosed at an earlier stage as compared to other sites (P = 0.04). Surgery was performed with curative intent in 72%, while 2% had palliative surgery for symptom control. Of the remaining patients who did not undergo surgery, four had palliative chemotherapy and/or radiotherapy. Median disease-free survival was 13 months (1-179 months). There was a significantly longer time to locoregional recurrence in head and neck MM (16 months) compared to other sites (11 months) (P = 0.03). The 2-year overall survival was also significantly higher in head and neck MM (P = 0.003)., Conclusion: MM of the head and neck is diagnosed at an earlier stage and associated with a longer time to locoregional recurrence. Surgical resection is the mainstay of treatment and may offer long-term survival benefit in selected patients., (© 2018 Royal Australasian College of Surgeons.)

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used for selected patients with peritoneal metastasis, but can be associated with high complication rates, prolonged hospital stay, and mortality. Our objective was to determine the learning curve of CRS/HIPEC in our institution, representing the largest Asian cohort to date., Methods: A total of 200 consecutive patients with peritoneal metastasis treated with CRS/HIPEC between 2001 and 2016 were grouped into four cohorts of 50 patients and studied. Primary outcomes were severe morbidity (Clavien-Dindo III-V), procedure-related mortality, and duration of ICU and hospital stays. Secondary outcome was duration of surgery., Results: Median age was 53 years (10-75). There was no significant age, sex, or histology difference across cohorts. Rates of severe morbidity (23 %), and 60 day inpatient mortality (0.5 %) were comparable to previously reported data. Decreases in rates of serious morbidity, (34 %, 30 %, 12 %, 14 %, p<0.01) and duration of total hospital stay (14, 16, 13, 12 days, p=0.041) were seen across consecutive cohorts. Operation time decreased significantly after the first cohort (10, 7.8, 7.8, 7.2 h, p<0.01), despite increase in average PCI score after the first cohort (8, 14, 12, 13, p=0.063)., Conclusions: Whilst 50 cases were adequate for procedural familiarity and decreased average operation time, significant improvement in rate of serious morbidity was observed after 100 operations. We demonstrate a novel biphasic nature to the learning curve, reflecting initial training in which technical competence is achieved, followed by a subsequent period characterized by increasingly complex cases (higher PCI score) and finally refinement of patient selection., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are used in the management of selected peritoneal malignancies. While most patients achieve long-term disease-free survival, there remains a group with early recurrence (ER). We aim to investigate the clinical factors associated with ER., Methods: A retrospective review of a prospectively maintained database of CRS-HIPEC patients treated between April 2001 and Feb 2016 was performed. ER was defined as recurrence within 12 months of CRS-HIPEC. Patients were stratified according to time to recurrence and only patients with at least 12-month follow-up were included. Perioperative factors were investigated, and subgroup analyses of colorectal, ovarian and appendiceal groups were performed., Results: Of the 144 patients included, 30.6% were colorectal, 36.8% ovarian and primary peritoneal, 24.3% appendiceal, 2.1% mesothelioma and 6.3% were of other origins. Thirty-nine patients (27%) suffered ER. Univariable and multivariable analyses revealed that primary tumour type (p = 0.02) and post-CRS adjuvant treatment (p = 0.04) were associated with ER. Appendiceal patients had a lower odds of ER compared to colorectal patients [OR = 0.15 (0.043-0.502) p < 0.002]. Patients who received post-CRS adjuvant treatment had a lower odds of ER than patients without adjuvant treatment [OR = 0.32; (0.128-0.818) p = 0.02]., Conclusion: There remains a 27% risk of ER after CRS-HIPEC. Better patient selection and the administration of adjuvant chemotherapy may help to reduce ER.

Introduction: Currently, factors such as size, mitotic rate, and degree of necrosis have been shown to influence survival in patients with solitary fibrous tumors (SFTs); however, there remains no consensus regarding the associations between tumor characteristics and the malignant nature of these tumors. The aim of this article was to identify factors that would help in prognosticating SFTs and to validate the MD Anderson Cancer Center (MDACC) SFT nomogram in the largest known series of SFTs treated in an Asian population., Methods: A retrospective review of all patients with a diagnosis of SFT treated surgically in our institution between 2005 and 2015 was carried out. Basic demographics, clinicopathological, and surgical factors were analyzed for association with clinical outcomes. Factors that predicted for distant recurrence (DR) and poor survival were identified as high-risk features. The MDACC nomogram was validated by assessing the extent of discrimination, quantified using Harrell's concordance index (C-index)., Results: Fifty-nine patients were included in analysis. Significant univariate associations for DR were found for mitotic rate ( P = .05) and presence of necrosis ( P = .04). Significant univariate associations for overall survival were found for presence of recurrence ( P = .035), presence of necrosis ( P = .072), and mitotic rate ( P = .033). The C-index associated with the nomogram was 0.75., Conclusion: There is a negative association for DR and overall survival, with the mitotic rate and presence of necrosis. We propose that SFTs with these features should be regarded as high risk. The MDACC nomogram generally predicts well for patients in an Asian population.

Introduction: CRS and HIPEC confer survival benefit in selected patients with peritoneal metatases (PM). Accurate preoperative assessment of disease burden and exclusion of distant metastases are crucial in selecting the appropriate patient. We evaluate the utility of PET-CT scans in comparison with CT and MRI scans in patients considered for CRS and HIPEC., Methods: Data were retrospectively collected from patients who had been discussed for CRS and HIPEC between January 2011 and December 2015, at our institutional multidisciplinary tumour board. Patients who underwent PET-CT scan were included. Results of PET-CT were compared against traditional imaging. Patient and tumour factors were analysed to identify those who were most likely to benefit from PET imaging., Results: Four hundred and seven patients were considered for CRS and HIPEC. PET-CT was performed for 128(31.4%) patients: being the only imaging modality in 37 and used as an adjunct in 91. In the latter group, it was not beneficial in 58 patients as it provided no additional information (n = 33) or showed lesions of minimal FDG uptake (n = 25). In 33 patients, PET-CT provided definitive answers for indeterminate lesions seen on CT and MRI, confirmed the diagnosis of peritoneal disease in 10 patients (30.3%), identified extra-peritoneal disease and/or nodal metastases in 15 (45.5%) and excluded peritoneal disease in 8 (24.2%). The usefulness of PET-CT was predicted by tumour histology (p = .009), with non-mucinous tumours benefitting the most., Conclusion: Our results suggest that PET-CT can be used as an adjunct to CT and/or MRI scans, when lesions on the CT/MRI scans are indeterminate, and that it is most useful in patients with non-mucinous tumours.

Aim: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay., Methods: Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n = 19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien-Dindo grades III-V). Secondary outcomes were durations of ICU and hospital stays., Results: Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p < 0.01), and duration of ICU (2 vs. 1 days, p < 0.01) and total hospital stays (16 vs. 14 days, p = 0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p = 0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480 min) in which operative duration remained independently prognostic (p < 0.01)., Conclusions: After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC., Methods: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared., Results: Out of 214 CRS-HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I-II), and 49 patients (23%) suffered high-grade complications (grade III-V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens., Conclusions: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.

Objective: This study seeks to evaluate pre and post-operative CA-125 in patients undergoing complete cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and understand the time frame before values normalise allowing use as a surveillance tool to resume., Methods: A retrospective review was carried out of 94 patients undergoing CRS-HIPEC to compare pre-operative CA-125 values, measured within one week prior to surgery to post-operative readings within the first 30 d. Raised CA-125 was defined using as a value >35 U/ml., Results: Of 63 (67%) patients with normal pre-operative CA-125, 22 (35%) had raised post-operative CA-125, and consisted of patients with colorectal (n = 8), appendiceal (n = 6), ovarian (n = 4) or other (n = 4) cancers. The average peak CA-125 was 80 U/ml occurring on median 10th post-operative day (POD) (range 7-30). The median day of normalisation for patients with normal pre-operative and raised post-operative CA-125 was 57 (range 28-115). The median day of normalisation for patients with raised pre-operative CA-125 was POD 41 (range 1-114). Notably 10 patients had initial normalisation (median POD 1, range 1-6), followed by subsequent raised value (median POD 10, range 5-40) and re-normalisation (median POD 47, range 19-104)., Discussion: For patients with raised pre-operative CA-125 an immediate post-operative CA-125 within 3 d may be useful to assess normalisation following surgery. Aside from immediate measurement CA-125 is misleading and should not be measured post-operatively within the first 3 months after surgery following which its use as a surveillance marker can resume.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival in selected patients with peritoneal metastases. However, only some patients who are potentially eligible for the procedure are considered and referred to the appropriate surgical department. By studying the trends of patients being considered for CRS and HIPEC in our centre, we hope to better understand the demographics of our patient cohort and the attitudes of physicians involved towards CRS and HIPEC., Methods: Patients who were presented and discussed at our institution's multidisciplinary tumour board (MDTB) for consideration of CRS and HIPEC, between 5 January 2011 and 16 December 2015, were identified from the institutional database and included in the study. Patient demographics and clinico-pathological data were retrospectively collected from electronic records and clinical charts., Results: A total of 407 patients were presented at the MDTB for consideration of CRS and HIPEC. Referrals were most commonly from oncology-related departments (65.8%, n = 268). This was followed by referrals from other hospitals (15.0%, n = 61), overseas self-referrals (12.0%, n = 49) and non-oncologic departments within the same institution (7.1%, n = 29). Referrals made by oncology-related departments and overseas self-referrals showed an increasing trend over the years. Of the patients discussed, 197 patients (48.4%) were recommended for CRS and HIPEC, and 134 (68.0%) successfully underwent the procedure., Conclusions: There is growing acceptance of CRS and HIPEC in patients and oncologic-related departments. However, consideration of this procedure as a treatment option remains low in non-oncologic departments. Dissemination of information and well-defined clinical recommendations may help physicians identify and select potentially eligible patients for consideration of CRS and HIPEC.

Objective: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are increasingly being used to treat peritoneal malignancies. Urological resections and reconstruction (URR) are occasionally performed during the surgery. We aim to evaluate the impact of these procedures on peri-operative outcomes of CRS and HIPEC patients., Methods: A retrospective review of a prospectively maintained database of all patients who underwent CRS-HIPEC from April 2001 to February 2016 was performed. Outcomes between patients who had surgery involving, and not involving URR were compared. Primary outcomes were the rate of major complications and the duration of stay in the intensive care unit (ICU) and hospital. Secondary outcomes were that of overall survival (OS) and prognostic factors that would indicate a need for URR., Results: A total of 214 CRS-HIPEC were performed, 21 of which involved a URR. Baseline clinical characteristics did not vary between the groups (URR vs. No URR). Urological resections comprised of 52% bladder resections, 24% ureteric resections, and 24% involving both bladder and ureteric resections. All bladder defects were closed primarily while ureteric reconstructions consisted of two end-to-end anastomoses, one ureto-uretostomy, five direct implantations into the bladder and three boari flaps. URR were more frequently required in patients with colorectal peritoneal disease ( p  = 0.029), but was not associated with previous pelvic surgery (76% vs. 54%, p  = 0.065). Patients with URR did not suffer more serious complications (14% vs. 24%, p  = 0.42). ICU (2.2 days vs. 1.4 days, p  = 0.51) and hospital stays (18 days vs. 25 days, p  = 0.094) were not significantly affected. Undergoing a URR did not affect OS ( p  = 0.99), but was associated with increased operation time (570 min vs . 490 min, p  = 0.046)., Conclusion: While concomitant URR were associated with an increase in operation time, there were no significant differences in postoperative complications or OS. Patients with colorectal peritoneal metastases are more likely to require a URR compared to other primary tumours, and needs to be considered during pre-operative planning.

Introduction: Radiological imaging often underestimates the extent of low volume peritoneal disease. The benefit of laparoscopy in assessing peritoneal metastases from colorectal and gastric cancer is accepted, but is inconclusive for appendiceal malignancy. We report our experience of diagnostic (DL) and therapeutic laparoscopy (TL) in patients with appendiceal tumours to determine indications and role in assessment and management., Methods: A retrospective review of a National Peritoneal Malignancy Centre's prospectively maintained database was performed. All patients with appendiceal neoplasms who underwent DL or TL between September 2011 and January 2016 were included. The indications and outcomes of the laparoscopy, complications and interval to laparotomy were evaluated., Results: Six hundred and eighty-five patients underwent surgery for appendiceal neoplasms during the study period, of which 73 (10.6%) underwent laparoscopy (50 DL, 23 TL). The main indications for DL were to clarify imaging and stage patients with high-risk histology. Indications for TL were an abnormal appendix without gross pseudomyxoma peritonei (PMP) or with low volume PMP, and concerns for fertility in the presence of PMP. DL resulted in 16 patients (32%) avoiding laparotomy because of extensive disease or no tumour found. Overall, 28 patients were assessed to have resectable disease and at laparotomy, 25/28 had complete cytoreduction with three patients unresectable. In the TL group, appendicectomy and peritoneal lavage was achieved in all four women with fertility concerns, allowing them to conceive thereafter. There were no complications., Conclusions: Patients with high-risk appendiceal neoplasm may benefit from DL, and potentially avoid unnecessary laparotomy. TL is useful in patients with low volume PMP and may aid fertility in selected patients.

Aim: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is known to improve survival in selected patients with peritoneal metastasis. However, there is limited data supporting the role of CRS and HIPEC in elderly patients (≥65 years old)., Methods: A retrospective review of a prospectively maintained database of patients who underwent CRS-HIPEC between April 2001 and July 2015 from a single institution was performed. Patients were divided into two groups non-elderly (<65 years old), and elderly (≥65 years old). Clinico- pathological parameters, morbidity and overall (OS) and disease-free survival (DFS) of the patients were compared., Results: A total of 177 patients (median age 52, range 9-74) underwent CRS-HIPEC with curative intent. There were 159 non-elderly patients and 18 elderly patients. Median PCI scores were 12 (0-39) for the non- elderly patients and 11 (1-29) for the elderly patients (p=0.77). High-grade complications occurred in 39 non-elderly patients (24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non-elderly patients (38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day (p=0.69). There was no difference in the 30-day mortality between the two groups (0% vs. 0%, p=1). After a median follow-up of 16 months for all patients, there was no difference in 5-years OS (51.0% vs. 59.6%, p=0.88) and 5-years DFS (23.3% vs. 53.3%, p=0.60) between non-elderly and elderly patients., Conclusions: Surgical outcomes after CRS-HIPEC do not differ significantly between non-elderly and elderly patients. Hence, age should not be a contraindication in selecting patients for CRS and HIPEC., (© 2017 John Wiley & Sons Australia, Ltd.)

Aim: To determine the clinical characteristics of patients undergoing palliative surgery for Krukenberg tumors, including disease presentation, outcomes, and prognostic factors., Methods: This was a retrospective clinical study of all patients who underwent palliative surgery for Krukenberg tumors between January 2004 and December 2015. Patient information was obtained from inpatient and outpatient case notes as well as the hospital electronic records. Patients who underwent potentially curative resection, and patients with Krukenberg tumors who did not undergo surgery were also excluded from the study. Palliative surgery was defined as those performed for either alleviation of symptoms or for asymptomatic patients for whom surgical removal of the tumors were deemed necessary following a multidisciplinary consensus. Tumors were diagnosed pre-operatively by computed tomography scans and all had histologic confirmation of the surgical specimens., Results: Over the study duration, 38 female patients underwent palliative surgery for Krukenberg tumors at our institution. Mean age was 54.2 ± 11.7 years. The colon was the most frequent primary source of metastases ( n = 21) followed by the stomach ( n = 4). Prophylactic palliative surgery was performed for eight (21.1%) asymptomatic patients. Median post-operative length of stay was 8 d (IQR 6-12 d). Five patients (13.2%) experienced post-operative complications, although high grade morbidity was only seen in one patient (2.6%). Median overall survival from surgery was 17 mo (95%CI: 12.1-21.9) at a median follow-up duration of 12 mo (IQR 8-17 mo). The median survival was shorter for patients who underwent emergency surgery, younger patients, those with a colorectal primary, larger tumors, or synchronous peritoneal or hepatic metastases., Conclusion: Palliative surgery for Krukenberg tumors can be performed safely with acceptable complication rates. Bilateral oophorectomy should be performed to prevent the risk of symptomatic contralateral tumors., Competing Interests: Conflict-of-interest statement: All authors declare no conflict-of-interest.

Ovarian cancer often presents at an advanced stage with widespread peritoneal and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of treatment for disease confined to peritoneum. But in patients with distant metastases, the role and rationale is less obvious. One of the the most common sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this paper, we described the management of a patient with International Federation of Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent complete cytoreduction including excision of enlarged CPLN, following neoadjuvant chemotherapy. We examined the literature to determine the prognostic value of enlarged CPLN and their relevance in managing patients with advanced ovarian cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision of CPLN is feasible without major complications. But as its correlation with overall or progression-free survival is not yet evident, large-scale prospective studies are warranted., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS)., Methods: A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed., Results: The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003-0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients., Conclusions: OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases from ovarian cancer have been shown to have a role in recurrent ovarian cancer, but are still not considered standard therapy., Methods: From March 2005 to July 2013, 41 patients who underwent 44 CRS and HIPEC for peritoneal metastases in recurrent ovarian cancer were included in this study. Details were obtained from a prospectively maintained database. Our aim was to report our 5-year overall and disease-free survivals, as well as prognostic factors for survival., Results: Median age was 50 years old (range 23-73). Median duration of surgery was 510 min (range 230-840) and median peritoneal carcinomatosis index (PCI) score was 9.5 (range 0-31). About 92.7% of the patients had completeness of cytoreduction (CC) scores of 0 or 1. Median follow-up was 43.9 months (range 0.7-108.9). There were no mortalities and the high-grade morbidity rate was 31.8%. Median overall survival was 42.8 months (range 28.6-99.9) 5-year overall and disease-free survivals were 49.3% and 7.5% respectively. On multivariate analysis, histology and CC score were significantly associated with overall survival while histology and disease-free interval were associated with disease-free survival. The odds of developing a high-grade complication more than doubled for each additional surgical procedure performed (p=0.01)., Conclusions: CRS and HIPEC can attain prolonged survival in selected patients with peritoneal metastasis in recurrent ovarian cancer., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Cervical myomas are rare and account for <1% of uterine leiomyomas. Clinical complications include bulk-related symptoms of pelvic pain, abnormal bleeding and infertility. While hysterectomies may be readily performed for postmenopausal women; the management of women with cervical myomas of childbearing age remains a challenge.Traditionally described fertility-preserving procedures such as myomectomy, endometrial ablation or myolysis may only be applied to leiomyomas within the uterine corpus. Little is known about the surgical management of its cervical counterpart.Radical abdominal trachelectomy has been described as a potential fertility-preserving procedure in the management of women with early cervical cancer. As such, we present a case of a giant cervical myoma that was treated with an abdominal trachelectomy in an attempt to preserve fertility., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To review our experience in the management of retroperitoneal sarcomas (RPSs) in a single institution, with a predominantly Asian population, and identify associated prognostic factors for overall survival (OS), disease-free survival (DFS) and local recurrence., Materials and Methods: All RPSs diagnosed and managed at our center between January 2000 and March 2014 were included. Exclusion criteria included patients whose medical records were untraceable and patients who underwent biopsy but did not undergo resection. The variables studied were age, gender, histological subtype, tumor size, tumor grade, surgical margins, type of presentation of tumor (primary or recurrent) and presence of contiguous organ resection. The primary outcome measured was OS., Results: Eighty-five patients underwent resection of RPS with curative intent. Eight patients underwent adjuvant chemotherapy and 15 patients underwent radiotherapy. The median DFS was 21 months (range: 0-146) and median OS was 45 months (range: 1-233). On univariate analysis, resection margin (P = 0.04), tumor grade (P = 0.011) and type of presentation of tumor (P = 0.007) were found to significantly affect OS. Patients with tumor adherent to contiguous organs had a greater OS as compared to patients with tumor invasive into the contiguous organs (P = 0.02)., Conclusion: An aggressive surgical approach in primary and recurrent RPS is associated with good OS. Complete resection, with contiguous organ resection if necessary should be performed to achieve microscopically negative surgical margins to allow for long-term survival. However, tumor biology remains the main determinant for OS., (© 2017 John Wiley & Sons Australia, Ltd.)

Aim: A nomogram for prediction of 12-year sarcoma-specific survival has been developed based on patients with soft tissue sarcomas treated in Memorial Sloan Kettering Cancer Centre (MSKCC). We aim to evaluate the predictive accuracy of the MSKCC sarcoma nomogram in a cohort of patients treated at an Asian institution. This has not been validated in an Asian population and thus its universal applicability remains unproven., Materials and Methods: Between 1990 and 2013, 840 adult patients underwent treatment for primary soft tissue sarcoma (STS) at the National Cancer Centre Singapore. Patients who presented with locally recurrent or metastatic disease were excluded from the analysis. The variables included in the MSKCC nomogram included age at diagnosis, tumor size, histologic grade, histologic subtype, depth and site. A total of 399 patients were left for analysis. The nomogram was validated by assessing its extent of discrimination and level of calibration., Results: All patients had deep tumors. Disease occurred most commonly in the lower extremity (n = 149 [37.3%]), the most common histologic subtype was "Others" (angiosarcoma, ewing's sarcoma, endometrial stromal sarcoma, sarcoma NOS [not otherwise specified] and rhabdomyosarcoma). Sixty-four percent of all patients had high-grade tumors while 36% had low-grade tumors. The median patient age at diagnosis was 54 years (range: 17-88 years). The median follow up time for all patients and surviving patients were 29 (range: 1-174) and 33 (range: 1-157) months, respectively. The observed 5- and 10-year sarcoma-specific survival were 55% and 33%, respectively. The concordance index was 0.71. For level of calibration, the observed correspondence between predicted and actual outcomes suggest that the MSKCC nomogram generally predicts well for patients with higher survival probability, but consistently overpredicts survival for the other groups, in our cohort of patients., Conclusion: The MSKCC sarcoma nomogram was found to be accurate in terms of extent of discrimination. In terms of level of calibration, it generally predicts well for patients with higher survival probability, but consistently overpredicts survival for the other groups in our population., (© 2016 John Wiley & Sons Australia, Ltd.)

Background: Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC) prolongs survival in patients with metastatic peritoneal disease. We look at the incidence of acute kidney injury (AKI) in patients who have received cisplatin during CRS-HIPEC in the treatment of peritoneal carcinomatosis from an ovarian primary, and identify possible peri-operative risk factors., Methods: Between 2005 and 2013, we performed CRS-HIPEC on 47 patients with ovarian primaries and peritoneal metastasis. Retrospective data were collected on the patient's demographics, treatment details and outcomes. Renal impairment was graded according to the NCI-CTCAE 3.0 criteria., Results: There were 47 patients, with a median age of 50 (24-74) years. The median baseline creatinine was 53 μmol/L (23-102) and median baseline albumin of 39 g/L (13-45). All underwent pre-operative chemotherapy for a median of six cycles (0-22) with a median of 15 days between chemotherapy and surgery. They received intra-operative cisplatin at a temperature of 40 °C for 60 min at a median dose of 90 mg/kg. 19 (40.4%) experienced post-operative AKI, of which 5 (8.5%) developed grade 3 and 4 impairment. Two (4.3%) required long-term dialysis. Univariate analysis showed that risk factors for AKI included age, baseline creatinine, baseline estimated glomerular filtration rate, pre-operative albumin, number of cycles of pre-operative carboplatin, time interval between pre-operative chemotherapy and CRS-HIPEC and volume of blood transfusions., Conclusions: Identification of risk factors for AKI post-CRS-HIPEC helps improve pre-operative patient selection and optimisation, facilitate tailoring of chemotherapy, and foster closer peri-operative monitoring and fluid management in at-risk patients.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed treatment for selected patients with peritoneal metastases (PM) arising from appendiceal, colorectal, epithelial ovarian, primary peritoneal and gastric cancers. However, the results of CRS with HIPEC remain unclear in PM from other tumor histologies., Methods: We report a series of 10 patients who underwent CRS and HIPEC between 2006 and 2015, for PM arising from uncommon tumor origins., Results: Ten patients with PM from uncommon tumor origins underwent CRS and HIPEC. Median age was 46.5 years. Two patients had ovarian Sertoli-Leydig cell tumors (SLCT) and two had small bowel adenocarcinomas. The other histologies included: ovarian transitional cell carcinoma, ovarian granulosa cell tumor, endometroid adenocarcinoma, endocervical adenocarcinoma, synovial sarcoma, and ovarian leiomyosarcoma. Median peritoneal cancer index was 9 (2-18) and complete cytoreduction was achieved for all patients. Median follow-up was 14 months (2-100), and median time to recurrence from CRS and HIPEC was 16.0 months by Kaplan-Meier estimate. Four patients remain alive and disease-free, five are alive with disease, and one had died with disease. Median survival was not reached., Conclusions: Eight of ten patients with peritoneal metastases in the above rare indications survived 10 months or more after CRS and HIPEC. These encouraging results are a rationale for prospective clinical trials in these tumor histologies., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Background: Gastrointestinal stromal tumours (GISTs) represent the most common mesenchymal tumour of the gastrointestinal tract. Although the efficacy of targeted therapy cannot be over-emphasized, surgery remains the only curative primary treatment for patients with localized disease. The median size of GIST at diagnosis is approximately 5-7 cm; however, it is not uncommon for tumours to be as large as 30-40 cm and involving multiple viscera., Methods: Data were retrospectively collected from patients with GISTs treated at the Singapore General Hospital and the National Cancer Centre Singapore over a 15-year period. Standard resection of GIST without any additional organ removal was termed as a single organ resection (SOR). If the tumour was adjacent to another organ, necessitating the removal of more than one organ, the procedure was defined as a multivisceral resection (MVR). We aim to evaluate the role of MVR in the management of large GISTs., Results: A total of 187 patients underwent curative surgery for GIST between January 2000 and January 2014. Of the 187 patients, 40 (21%) underwent MVR whereas 147 (79%) had SOR. Patients in the MVR group had significantly larger tumour sizes (P < 0.001) yet R0 and R1 resection was achieved in all patients, and no intra-peritoneal rupture was reported. On comparison of MVR versus SOR groups, there was no significant difference in in-hospital morbidity and mortality., Conclusion: MVR may be required to achieve negative margins in patients with large GISTs, and can be performed with acceptable morbidity and mortality., (© 2016 Royal Australasian College of Surgeons.)