Search

Background: Prehabilitation has been increasingly utilized to optimize perioperative outcomes. In this study, we aim to evaluate the impact of uni- and multimodal prehabilitation on functional capacity and postoperative outcomes among surgical oncology patients undergoing major abdominal surgery., Patients and Methods: Three electronic databases (PubMed, Embase, Cochrane) were systematically searched up until December 2023. We included randomized controlled trials comparing prehabilitation to standard of care in surgical oncology patients undergoing major abdominal surgery. Our primary outcome was functional capacity as measured by the 6-min walk distance (6MWD). Secondary outcomes include postoperative complications, emergency readmissions, and length of stay (LOS). We stratified our findings to determine the impact of uni- versus multimodal prehabilitation on outcomes., Results: We included 27 studies with 2532 surgical oncology patients. Overall, patients undergoing prehabilitation demonstrated a significant improvement in preoperative functional capacity compared to those without prehabilitation (mean difference in 6MWD 28.32 meters [m], 95% CI 15.26, 41.39, p < 0.01). Prehabilitation was also associated with significantly lower odds of postoperative complications (odds ratio [OR] 0.60, 95% CI 0.46, 0.78, p < 0.01). There was no difference in emergency readmission (OR 0.90, 95% CI 0.59, 1.38, p = 0.61) or LOS (mean difference -0.42 days, 95% CI -1.01, 0.16, p = 0.15). Comparing uni- versus multimodal prehabilitation, multimodal prehabilitation was associated with greater improvements in functional capacity (6MWD 37.35 m versus 13.38 m) and lower odds of postoperative complications (OR 0.61, 95% CI 0.45, 0.82, p < 0.01 versus OR 0.63, 95% CI 0.36, 1.11, p = 0.10) CONCLUSION: Prehabilitation improves functional capacity and reduces postoperative complications among surgical oncology patients undergoing major abdominal surgery., Competing Interests: Disclosure: The Authors declare that there is no conflict of interest. The above study was approved by SingHealth Centralized Institutional Review Board and informed consent obtained prior to enrolment. Deidentified data are available upon requests. Ethical approval: The above study was approved by SingHealth Centralized Institutional Review Board and informed consent obtained prior to enrolment., (© 2024. Society of Surgical Oncology.)

Introduction: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416)., Methods: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m 2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures., Results: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased., Conclusions: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent., (© 2024. The Author(s).)

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence., Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors., Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors., Discussion: Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity., 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 © 2024 Tan, Shannon, Lim, Teo, Yap, Lek, Tan, Tan, Hendrikson, Liu, Ng, Chong, Guo, Koh, Ng, Rajasegaran, Wong, Seo, Ong, Lim, Teh, Kon, Chia, Soo, Iyer and Ong.)

Introduction: Timely palliative care and surgical interventions improve symptoms, health-related quality of life (HRQoL), and reduce medical cost for seriously ill adults at end of life (EOL). However, there is still poor delivery and underutilization of these palliative services. We hypothesize that the sub-optimal delivery is due to limited understanding among healthcare providers., Methods: A nationwide cross-sectional online survey was conducted among primary and tertiary healthcare providers. The survey assessed challenges faced, palliative education, confidence in managing palliative patients, and knowledge on palliative surgery. Overall palliative care awareness and knowledge was assessed using a 6-point score. Likelihood of considering various palliative interventions at EOL was also determined using a threshold score (higher score = higher threshold)., Results: There were 145 healthcare providers who completed the survey (81.9% response rate); majority reported significant challenges in providing various aspects of palliative care: 57% ( n = 82) in the provision of emotional support. Sixty-nine percent ( n = 97) in managing social issues, and 71% ( n = 103) in managing family expectations. Most expressed inadequate palliative care training in both under-graduate and post-graduate training and lack confidence in managing EOL issues. Up to 57% had misconceptions regarding potential benefits, morbidity and mortality after palliative surgery. In general, most providers had high thresholds for Intensive Care Unit admissions and palliative surgery, and were more likely to recommend endoscopic or interventional radiology procedures at EOL., Conclusion: Healthcare providers in Singapore have poor knowledge and misconceptions about palliative care and surgery. Improving awareness and education among those caring for seriously ill adults is essential., 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 © 2024 Juan, Ng, Wong, Fong, Lee, Lie, Zhou, Cai, Ong, Seo, Chia and Wong.)

Background: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone., Methods: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years., Results: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months., Conclusion: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Seo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Palliative surgical oncology patients represent a unique group with complex needs who often require multidisciplinary input for the provision of timely and holistic care. The authors assembled a multi-disciplinary palliative intervention team and evaluated its association with the quality of discussions on goals of care (GOC) among advanced cancer patients undergoing palliative interventions., Methods: This prospective cohort study analyzed advanced cancer patients undergoing palliative interventions at a single urban academic center from October 2019 to March 2022. In January 2021, a multi-disciplinary palliative surgical intervention (MD-PALS) team was assembled. All palliative surgical oncology patients were discussed at multi-disciplinary meetings and managed by members of the MD-PALS team. An interrupted time series (ITS) model was built to evaluate the association of MD-PALS implementation and the quality of GOC discussions as measured by a consensus-derived four-point GOC discussion quality score., Results: The study recruited 126 palliative surgical oncology patients: 44 in the pre-MD-PALS group and 82 in the post-MD-PALS group. The two groups did not differ significantly in baseline demographics, treatment, or postoperative and survival outcomes. Compared with the pre-MD-PALS group, the post-MD-PALS group had a significantly higher mean GOC discussion quality score (1.34 vs 2.61; p < 0.001). Based on the ITS model, the average quarterly GOC discussion quality score increased significantly among patients after implementation of the MD-PALS team (change = 1.93; 95 % confidence interval, 0.96-2.90; P = 0.003)., Conclusion: The implementation of an MD-PALS team was associated with improvements in the quality of GOC discussions among palliative surgical oncology patients., (© 2023. The Author(s).)

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD)., Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence., Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported., Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results., Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The use of open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown improved oncological survival in terms of treating peritoneal surface malignancies (PSM). However, this procedure often comes with associated morbidity. The move towards use of laparoscopic surgery in this field is postulated to lead to a reduction in morbidity and earlier return to function, but literature on its use for CRS and HIPEC has been scarce. We performed a retrospective review of 6 patients with PSM who underwent laparoscopic CRS and HIPEC in our institution and analysed the patient characteristics, oncological history, perioperative and postoperative outcomes. Median peritoneal cancer index (PCI) score was 0 (IQR 0-1.25). All 6 patients had appendiceal primaries. Median operative time was 285 min (IQR 228.8-300); median length of stay was 7.5 days (IQR 5-8.8). All patients achieved complete cytoreduction, and there was no conversion to open surgery. One patient developed port site infection and another 2 patients subsequently developed adhesions. Median follow-up time was 35 (IQR 17.5-41) months. No patients had developed recurrence at the time of data collection. We conclude that in patients with limited PCI sore (< 2), laparoscopic CRS and HIPEC are safe and feasible. With increasing experience, a select group of patients with limited PSM may be treated via minimally invasive surgery, minimising the morbidity of a traditional laparotomy., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Peritoneal surface malignancies (PSM) present insidiously and often pose diagnostic challenges. There is a paucity of literature quantifying the frequency and extent of therapeutic delays in PSM and its impact on oncological outcomes., Methods: A review of a prospectively maintained registry of PSM patients undergoing Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (CRS-HIPEC) was conducted. Causes for treatment delays were identified. We evaluate the impact of delayed presentation and treatment delays on oncological outcomes using Cox proportional hazards models., Results: 319 patients underwent CRS-HIPEC over a 6-years duration. 58 patients were eventually included in this study. Mean duration between symptom onset and CRS-HIPEC was 186.0 ± 37.1 days (range 18-1494 days) and mean duration of between patient-reported symptom onset and initial presentation was 56.7 ± 16.8 days. Delayed presentation (> 60 days between symptom onset and presentation) was seen in 20.7% (n=12) of patients and 50.0% (n=29) experienced a significant treatment delay of > 90 days between 1 st presentation and CRS-HIPEC. Common causes for treatment delays were healthcare provider-related i.e. delayed or inappropriate referrals (43.1%) and delayed presentation to care (31.0%). Delayed presentation was a significantly associated with poorer disease free survival (DFS) (HR 4.67, 95% CI 1.11-19.69, p=0.036)., Conclusion: Delayed presentation and treatment delays are common and may have an impact on oncological outcomes. There is an urgent need to improve patient education and streamline healthcare delivery processes in the management of PSM., 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 © 2023 Tan, Wong, Seo, Lim, Zhu, Ong and Chia.)

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.)

To evaluate the trajectories and sustainability of health-related quality of life (HRQoL) outcomes after palliative gastrointestinal (GI) surgery and perioperative factors associated with HRQoL improvement postsurgery., Background: Palliative patients face a wide range of physical, emotional, social, and functional challenges. In evaluating the efficacy of palliative surgical interventions, a major pitfall of traditional surgical outcome measures is that they fall short of measuring outcomes that are meaningful to patients during end-of-life. HRQoL tools may provide a more comprehensive assessment of the true value and impact of palliative surgery., Methods: We prospectively recruit advanced cancer patients undergoing palliative GI surgery. The Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire was administered before and at regular intervals after surgery. HRQoL improvement was defined as ≥4-points increment in FACT-G total score over baseline. Duration of sustained HRQoL improvement above this threshold and factors associated with varying extents of HRQoL change were evaluated., Results: Of the 65 patients, intestinal obstruction was the most common indication for surgery (70.8%). The mean baseline FACT-G total score was 70.7 (95% CI: 66.3-75.1). Forty-six (70.8%) patients experienced HRQoL improvement after surgery. This HRQoL improvement was sustained over a median duration of 3.5 months and was driven mainly by improvements in patients' physical and emotional well-being. Albumin was significantly associated with the extent of HRQoL improvements ( P = 0.043)., Conclusion: A clinically significant and sustained improvement in HRQoL was observed after palliative GI surgery. Patients with higher preoperative albumin levels were more likely to experience HRQoL improvements., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Retroperitoneal liposarcomas (RPLPSs) are a rare tumor group for which current guidelines recommend aggressive en bloc resection to attain microscopically negative (R0) margins. To ensure R0 margins, resection of adherent or adjacent organs is often required. However, it is still unclear if R0 margins confer any additional benefit to patients over a grossly negative but microscopically positive (R1) margin. We performed a systematic search of PubMed and Embase databases for studies including patients receiving R0 or R1 resection for RPLPS. Nine retrospective cohort studies, one prospective cohort study, and 49 case reports/case series were included. A total of 552 patients with RPLPS were evaluated: 346 underwent R0 resection and 206 underwent R1 resection. In the R0 group, 5-year overall survival (OS) ranged from 58.3% to 85.7%; local recurrence (LR) ranged from 45.5% to 52.3%. In the R1 group, 5-year OS ranged from 35% to 55.3%; LR ranged from 66.7% to 91.7%. Among cohort studies, OS, disease-free survival (DFS), LR rate, and LR-free survival (LRFS) were significantly associated with R0 resections. Assessment of case series and reports suggested that the R0 margin led to a slightly higher morbidity than that of R1. In conclusion, this review found the R0 margin to be associated with reductions in LR rates and improved OS when compared with the R1 margins, though accompanied by slight increases in morbidity. The roles of tumor histotype and perioperative chemotherapy or radiotherapy were not well-elucidated in this review., 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 Paik, Seo, Tan, Juan, Soo, Ong, Chia and Wong.)

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.

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.)

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients., Content: A systematic review was performed on articles identified from Medline, EMBASE, PsycInfo, and Web of Sciences. A meta-analysis was conducted on further selected studies. ACROBAT-NRSI was attempted to assess the risk of bias (RoB)., Summary: Nine studies using the EORTC QLQ-C30 questionnaire to assess QoL after repeated PIPAC cycles were identified. Majority was found to be moderately biased and a great extent of heterogeneity was observed. Four studies on PM from either gastric cancer (GC) or epithelial ovarian cancer (EOC) were included for meta-analysis. In 31 GC patients and 104 EOC patients, QoL remained stable in 13/14 and 11/14 EORTC QLQ-C30 scales. PIPAC was inferior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in global QoL and functioning but superior in symptom reduction., Outlook: PIPAC is a well-tolerated option for most GC and EOC patients with irresectable PM. Future trials are warranted to confirm the findings., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Zhenyue Li 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.)

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) play an important role in the treatment of various peritoneal surface malignancies, but its efficacy in peritoneal sarcomatosis (PS) remains unknown. Hence, we performed a systematic review and meta-analysis to investigate outcomes of CRS-HIPEC in PS, in accordance with PRISMA guidelines. 16 studies with a total of 320 patients were included in the meta-analysis. Pooled mean length of hospital stay after CRS-HIPEC was 16.0 days (95% CI: 12.2-19.8) and rate of serious complications was 17.4% (95% CI: 9.8-26.3). The median DFS was 12.0 months (95% CI: 8.0-16.0) and the 5-year DFS was 21.8% (95% CI: 13.2-31.7). Overall pooled median OS was 29.3 months (95% CI: 23.8-34.8), with a 5-year OS of 35.3% (95% CI: 26.3-44.8). Subgroup analysis showed that patients with CC-0 cytoreduction had a higher median OS of 34.6 months (95% CI: 23.2-45.9). Median OS for patients with a primary tumour histology of leiomyosarcoma and liposarcoma was 33.5 months (95% CI: 15.9-51.1) and 39.1 months (95% CI: 20.8-57.5) respectively. The site of recurrence was locoregional in 57.3% (95% CI: 38.9-74.8), distant in 17.3% (95% CI: 3.9-35.6), and both in 17.4% (95% CI: 5.8-32.2). In conclusion, our results suggest that CRS-HIPEC may improve outcomes in a select group of PS patients., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Objective: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent a mainstay of treatment for peritoneal malignancies. There is evidence that HIPEC using high intra-abdominal pressure (IAP) results in increased tissue penetration, although its safety profile remains relatively unknown. We thus aim to evaluate differences in intra- and post-operative outcomes in patients undergoing CRS-HIPEC with different levels of IAP., Methods: This pilot prospective cohort study was conducted from January 2020 to February 2021 with patients undergoing CRS-HIPEC. Low IAP during HIPEC was defined as <18 mmHg and high IAP as ≥18 mmHg. Data was collected on patient and tumor characteristics, intra-operative clinical and biochemical parameters, and immediate post-operative outcomes., Results: 40 patients underwent CRS-HIPEC ( n low = 20, n high = 20). Median IAP in the low and high IAP groups were 12.0 and 19.0 mmHg respectively. During HIPEC, both groups experienced increase in heart rate, central venous pressure, end tidal CO2, temperature, and serum glucose, with decrease in mean arterial pressure and base excess. There were no significant differences in hemodynamics between the 2 groups. Mild electrolyte derangements and a decrease in hemoglobin were noted in the high IAP group but were of small magnitude. Post-operatively, high IAP did not result in increased rate of complications, time to full feeds, ICU or total hospital stay., Conclusions: High IAP in HIPEC is well tolerated and did not result in additional adverse events.

Background: Peritoneal metastasis (PM) is a late-stage manifestation of intra-abdominal malignancies. The current standard of care indicates that cure can only be achieved with cytoreductive surgery (CRS) which is often indicated with concurrent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). However, the utility of HIPEC within subsets of PM is not fully understood. We seek to compare the effectiveness of HIPEC in improving peritoneal recurrence rates in PM of different origins., Methods: We conducted a systematic review of trials on the PubMed, EMBASE, and Cochrane databases, last searched in August 2021. Biases were assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials as well as the Methodological Index for Non-Randomized Studies (MINORS) framework., Results: 7 gastric PM studies, 3 ovarian PM studies, and 3 colorectal PM studies were included. Recurrence-free survival was improved in the HIPEC + CRS cohort in 5 gastric trials but only 1 ovarian trial and none of colorectal origin., Discussion: Our findings indicate decent effectiveness of HIPEC in gastric PM, but limited utility in ovarian and colorectal PM. Limitations in the current literature are attributed to the paucity of data available, a lack of homogeneity and consideration of novel and personalised treatment regimens. We implore for further studies to be conducted with a focus on patient selection and stratification, and suggest a reframing of approach towards modern molecular and targeted therapeutic options in future studies of HIPEC., Systematic Review Registration: https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/60c1ffff0c1b78001e8efbe3/, identifier reviewregistry1166., 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 © 2021 Yap, Wong, Tan, Tan, Chia and Ong.)

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).)

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).)

Peritoneal carcinomatosis (PC) is often associated with malnutrition and an inability to tolerate enteral feeding. Although total parenteral nutrition (TPN) can be lifesaving for patients with no other means of nutritional support, its use in the management of PC patients remains controversial. Therefore, a systematic review and meta-analysis was performed to evaluate the benefit of TPN on the overall survival of PC patients, in accordance with PRISMA guidelines. A total of 187 articles were screened; 10 were included in this review and eight were included in the meta-analysis. The pooled median overall survival of patients who received TPN was significantly higher than patients who did not receive TPN ( p = 0.040). When only high-quality studies were included, a significant survival advantage was observed in PC patients receiving TPN ( p < 0.001). Subgroup analysis of patients receiving chemotherapy demonstrated a significant survival benefit ( p = 0.008) associated with the use of TPN. In conclusion, TPN may improve survival outcomes in PC patients. However, further studies are needed to conclude more definitively on the effect of TPN.

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.

We present an unprecedented case of torsion of a large ovarian cyst following colonoscopy. A 43-year-old female was found to have a 20 × 13 × 19 cm pelviabdominal mass possibly arising from the right ovary. Endoscopic evaluation was performed prior to planned resection of the ovarian mass. The patient experienced progressive lower abdominal pain after the procedure with a computed topography finding of torsion. She underwent exploratory laparotomy, right salpingo-oophorectomy with intra-operative frozen section and omentectomy. Final histology revealed features of benign serous cystadenoma with extensive haemorrhagic infarction in keeping with torsion. To our knowledge, this is the first reported case of torsion of a large ovarian cyst after colonoscopy. We propose a postulated mechanism of this patient's ovarian torsion and urge clinicians to be cognizant of acute ovarian torsion as a cause of severe abdominal pain following endoscopy., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2021.)

Acetaldehyde (AA) has been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC, WHO) and by the US Environmental Protection Agency due to its ability to cause tumours following inhalation or alcohol consumption in animals. Humans are constantly exposed to AA through inhalation from the environment through cigarette smoke, vehicle fumes and industrial emissions as well as by persistent alcohol ingestion. Individuals with deficiencies in the enzymes that are involved in the metabolism of AA are more susceptible to its toxicity and constitute a vulnerable human population. Studies have shown that AA induces DNA damage and cytogenetic abnormalities. A study was undertaken to elucidate the clastogenic effects induced by AA and any preceding DNA damage that occurs in normal human lung fibroblasts as this will further validate the detrimental effects of inhalation exposure to AA. AA exposure induced DNA damage, involving DNA double strand breaks, which could possibly occur at the telomeric regions as well, resulting in a clastogenic effect and subsequent genomic instability, which contributed to the cell cycle arrest. The clastogenic effect induced by AA in human lung fibroblasts was evidenced by micronuclei induction and chromosomal aberrations, including those at the telomeric regions. Co-localisation between the DNA double strand breaks and telomeric regions was observed, suggesting possible induction of DNA double strand breaks due to AA exposure at the telomeric regions as a new mechanism beyond the clastogenic effect of AA. From the cell cycle profile following AA exposure, a G2/M phase arrest and a decrease in cell viability were also detected. Therefore, these effects due to AA exposure via inhalation may have implications in the development of carcinogenesis in humans., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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: 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: 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.)