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Chimeric antigen receptor (CAR) T-cell therapy has proven successful in the treatment of hematological malignancies, notably acute lymphoblastic leukemia and B-cell lymphoma. However, the efficacy of CAR T cells against solid tumors is poor, likely due to tumor-associated immunosuppression. Here, we demonstrated that antagonizing the “inhibitor of apoptosis proteins” with the clinical smac-mimetic, birinapant, significantly enhanced the antitumor activity of CAR T cells in a tumor necrosis factor (TNF)-dependent manner. Enhanced tumor cell death occurred independently of the perforin-mediated granule exocytosis pathway, underscoring the cytotoxic potential of CAR T-cell–derived TNF. Combining CAR T-cell therapy with birinapant significantly reduced established tumor growth in vivo, where either therapy alone was relatively ineffective. Using patient biopsy-derived tumoroids, we demonstrated the synergistic potential of combining CAR T-cell therapy with smac-mimetics. Taken together, we identified CAR T-cell–derived TNF as a potent antitumor effector, which can be further harnessed by smac-mimetics.

The prevalence of elderly patients with resectable colorectal peritoneal metastases (CRPM) is increasing. This study aimed to compare short and long-term outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPM in patients above and below 70 years of age.This was a retrospective, 10-year analysis of 90-day major morbidity and mortality, and long-term survival.Thirty-two (21.3%) of 150 consecutive patients who underwent CRS and HIPEC during the study period were aged 70 and older. PCI (P = 0.04), perioperative chemotherapy use (P 0.01) and organ resections (rectum P = 0.04, diaphragm P = 0.03) were less in the over 70 group. There was no significant differences in major morbidity (P = 0.19) and mortality (P = 0.32). There was also no difference in 5-year overall survival (OS) (≥70: 26% vs.70: 39%; P = 0.68) and disease-free survival (DFS) (≥70: 25% vs.70: 14%; P = 0.22). Age above 70 was not independently associated with worse OS (HR 1.55, P = 0.20) and DFS (HR 1.07, P = 0.81).The surgical management of CRPM appears safe and feasible in this elderly population. Appropriate selection of elderly patients for such radical intervention is reinforced by the comparable survival with those under 70.

Extended peritonoid drug sensitivity data

Patient characteristics & analyses.

Purpose:Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown.Experimental Design:CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing.Results:Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications.Conclusions:Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

Supplementary Methods

Introduction Peritoneal metastases confer the worst survival amongst all sites of metastatic colorectal cancer. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for patients with isolated colorectal peritoneal metastases (CRPM). The aim of this study was to evaluate the outcomes following CRS and HIPEC for CRPM from published high volume cohort studies and to highlight the latest controversies and future directions of CRPM treatment. Materials and methods A systematic review was performed on published studies on the treatment outcomes of CRS and HIPEC for colorectal peritoneal metastases. Results Twenty studies met the inclusion criteria for the systematic review. The median survival for all patients ranged from 14.6 to 60.1 months. The 5-year overall survival ranged from 23.4% to 52%. For patients with complete cytoreduction, the median survival was 25 to 49 months. Major morbidity and mortality ranged from 15.1% to 47.2% and 0% to 4.5%, respectively. Conclusion CRS and HIPEC for the treatment of CRPM is safe and current evidence suggests it improves both median and disease-free survival. However, the efficacy of intraperitoneal chemotherapy, in particular oxaliplatin, has recently come under scrutiny. Accordingly, higher quality evidence is urgently required to contribute to multidisciplinary and international consensus on CRPM treatment strategies.

Background Locally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates. Methods A systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded. Results Of the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%. Conclusion A validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.

Surgical site infections (SSI) are a significant cause of postoperative morbidity and mortality, contributing to a considerable financial burden on the healthcare system. Insufflation of the open surgical wound with warm, humidified carbon dioxide (COWe conducted a multi-site single-blinded randomized control trial on patients undergoing elective or emergency laparotomy at a single tertiary Colorectal Surgery service. The primary outcome measure was the incidence of SSI, with secondary outcomes including ICU length of stay (LOS), total LOS and mean core temperature.Patients who received HumiGard™ had a lower incidence of SSI, although this did not reach statistical significance (4.5% for treatment group versus 13.0% for control group; P = 0.092). There was no significant difference in ICU LOS or total LOS between cohorts. The HumiGard™ group had a higher mean core temperature than the control at the end of surgery (P 0.001).The present study could not confirm that utilization of warm, humidified CO2 with HumiGard™ reduces SSI in open colorectal surgery. Further research is indicated to validate and extend these findings.

Background Despite conflicting data regarding oncological outcomes, studies demonstrate that complete mesocolic excision (CME) and central vascular ligation (CVL) for right-sided colon cancer removes significantly more tissue and yields higher lymph node counts when compared to conventional resection. This study aims to report the safety profile of CME and CVL in patients undergoing robotic surgery for right-sided colon cancer during the introduction of this technique across two institutions. Methods Patients who underwent an elective robotic right colectomy with CME and CVL for right-sided colon cancer in a public quaternary and a private tertiary healthcare centre between November 2018 and April 2020 were included. Demographic, clinical, perioperative and histopathological variables were recorded and analysed. Results Twenty patients (13 females) with a median age of 69 (23-83) years and median body mass index of 27 (19-46) were included. All of them had a pre-operative diagnosis of right-sided colon adenocarcinoma. Median operative time and blood loss were 140 (130-300) min and 30 (20-100) mL, respectively. There were no conversions or intra-operative complications. There were two post-operative complications recorded (one ileus and one intra-abdominal collection treated with intravenous antibiotics) and no re-interventions. Median length of stay was 4 (2-8) days. All patients had an R0 resection, and the median lymph node yield was 36 (22-80) lymph nodes. Conclusion This series demonstrates a safe introduction of robotic CME and CVL in patients with right-sided colon cancer. The lymph node harvest obtained with CME and CVL in this setting was high.

Aim Robotic transanal minimally invasive surgery (R-TAMIS) is gaining traction around the globe as an alternative to laparoscopic conventional TAMIS for local excision of benign and early malignant rectal lesions. The aim was to analyse patient and oncological outcomes of R-TAMIS for consecutive cases in a single centre. Methods A prospective analysis of consecutive R-TAMIS procedures over a 12-month period was performed. Data were collated from hospital databases and theatre registers. Results Eleven patients (six men, five women), mean age 69.81 years (51-92 years), underwent R-TAMIS over 12 months utilizing a da Vinci Xi platform. The mean lesion size was 36 mm (20-60 mm) with a mean distance from the anal verge of 7.5 cm (3-14 cm). Five lesions were posterior in anatomical location, four anterior, one right lateral and one left lateral. All procedures were performed in the lithotomy position using a GelPOINT Path Platform. Mean operative time was 64 min (40-100 min). Complete resection was achieved in 10/11 patients with two patients being upgraded to a diagnosis of adenocarcinoma. Nine patients were diagnosed with dysplastic lesions. Four patients had a false positive diagnosis of an invasive tumour on MRI. Six patients required suturing for full-thickness resections. One patient had a postoperative bleed requiring repeat endoscopy and clipping. One patient (full-thickness resection of T3 tumour) proceeded to a formal resection without difficulty with no residual disease (T0N0, 0/22). One patient with a fully resected T2 tumour is undergoing a surveillance protocol. The mean length of stay was 1 day with two patients having a length of stay of 2 days and one patient of 4 days. Conclusion R-TAMIS could potentially represent a safe novel approach for local resection of rectal lesions.

Peritoneal metastases confer the worst survival among all sites in patients with metastatic colorectal cancer. They develop largely through transcoelomic spread, with a sequence of events that allow cells to first detach from primary tumours, survive in the peritoneal environment, attach to the peritoneal surface of organs and migrate into the submesothelial space to create a microenvironment conducive to metastatic growth. Diagnostic challenges have previously hindered early identification of peritoneal metastases. While advances in diagnostic modalities have improved our ability to identify peritoneal metastases, lesions under 0.5 cm remain challenging to detect. The advent of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with colorectal peritoneal metastases a favourable long-term survival. Recent trials, however, have cast doubts on the efficacy of HIPEC, with the recent PRODIGE 7 trial showing no benefit from oxaliplatin based HIPEC in addition to good quality cytoreductive surgery in resectable disease. While peritoneal recurrence can be reliably predicted from high-risk features in primary tumours such as a perforated cancer, ovarian metastases or T4a cancers, the use of prophylactic second look surgery with HIPEC or adjuvant HIPEC failed to demonstrate any survival benefit in high-risk cases in recent clinical trials, raising further questions about the efficacy of HIPEC. With high failure rates from systemic chemotherapy in unresectable disease, novel surgical techniques such as pressurized intraperitoneal aerolized chemotherapy are being investigated in clinical trials worldwide. Further collaborative research is needed to explore newer avenues of treatment for this poor prognostic cohort.

Aim Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. Method A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. Results Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. Conclusion This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.

Purpose The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB). Patients and Methods Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti–programmed cell death protein 1 [anti–PD-1] antibody) response was also assessed in a subset of patient specimens. Results Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423]; p < .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti–PD-1 antibody exposure. Conclusion Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.

Vaginal evisceration is a rare condition where abdominal contents herniate through a vaginal wall defect. The estimated incidence is 0.032–1.2% after hysterectomy, trachelectomy or upper vaginectomy. We present a 78-year-old lady who developed vaginal evisceration 2 years after radical cystectomy and hysterectomy for bladder cancer. It is rare surgical emergency that requires prompt recognition and damage control with bowel reduction and packing. We discuss the initial management and surgical options for definitive repair.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with colorectal peritoneal metastases (CRPM) a favorable long-term survival. While cytoreductive techniques are standardized, there remains great variability in HIPEC drugs with mitomycin C or oxaliplatin use based largely on institute preference. In this study, we compared outcomes based on mitomycin C or oxaliplatin use after complete cytoreduction. This is a retrospective analysis over a 7-year period of all patients undergoing complete cytoreduction with HIPEC. Seventy-eight patients underwent complete cytoreduction with HIPEC during this time. Forty-six patients received oxaliplatin as HIPEC, and 32 received mitomycin C. There was no difference in patient characteristics, resections, or major morbidity between the two groups. Superficial wound infections were higher in the mitomycin C group (37.5% v 15.2%, p = 0.02). Median overall and disease-free survival for the entire cohort was 40 and 14 months, respectively. There was no difference in overall survival or disease-free survival between the two HIPEC groups (HR 0.50, 95% CI 0.11–2.28). Complete cytoreduction and HIPEC can offer selected patients a favorable survival. The choice of mitomycin C or oxaliplatin for HIPEC had no influence on survival. Prospective studies are needed to explore this important issue.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the USA. Over 80% of CRC develop from adenomatous polyps. Hence, early treatment and prevention of adenomas would lead to a significant decrease of disease burden for CRC. MYB is a transcription factor that is overexpressed in both precancerous adenomatous polyps and colorectal cancer, and hence an ideal immunotherapeutic target. We have developed a cancer vaccine, TetMYB, that targets MYB and aim to evaluate its efficacy in the prophylactic and therapeutic management of adenomatous polyps. Six- to eight-week-old Apcmin/+ (Familial Adenomatous Polyposis model) and Apc580S (sporadic model) C57BL/6 mice were used. The Apcmin/+ mice are carried a germline mutation of one Apc allele whereas the Apc580S model has an inducible silencing of one Apc allele, when exposed to tamoxifen, via the Cre-Lox recombination enzyme system. In the prophylactic treatment group, Apcmin/+ and Apc580S C57BL/6 mice were vaccinated and surveyed for clinical signs of distress. Number of adenoma and survival were measured. In the therapeutic cohort, Apc580S C57BL/6 mice were given tamoxifen-laced food to activate Cre-Lox recombinase mediated silencing of one Apc allele and thus inducing adenoma development. Following adenoma detection, mice were vaccinated with TetMYB and treated with anti-PD-1 antibody and were analyzed for overall survival. In both the prophylactic and therapeutic setting, mice vaccinated with TetMYB had a significantly improved outcome, with the vaccinated Apcmin/+ mice having a median survival benefit of 70 days (p = 0.008) and the vaccinated Apc580S mice having a mean survival benefit of 134 days (p = 0.01) over the unvaccinated mice. In the prophylactic cohort, immunofluorescence confirmed a stronger cytotoxic CD8+ T cell infiltrate in the vaccinated group, implying an anti-tumor immune response. In the therapeutic cohort, vaccinated Apc580S mice showed significantly reduced adenoma progression rate compared to the unvaccinated mice (p = 0.0005). TetMYB vaccine has shown benefit in a prophylactic and therapeutic setting in the management of colonic adenoma in a murine model. This will form the basis for a future clinical trial to prevent and treat colonic adenomatous polyps.

Patients with locally advanced or metastatic colorectal cancer (CRC) display heterogeneous responses to standard-of-care therapy. Robust preclinical models of malignancy in the form of patient-derived tumor organoids (PDTOs) have recently come to the fore in tailoring patient care to a personalized medicine level. This study aimed to review the literature systematically regarding PTDOs and gauge their impact on precision medicine in the management of CRC. A PRISMA-compliant systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases was performed. The results were categorized based on the primary objective of the individual studies as follows: organoid use in predicting effective hyperthermic intraperitoneal chemotherapy (HIPEC), systemic chemotherapy in CRC, or neoadjuvant chemoradiotherapy in rectal cancer. The literature search found 200 publications, 16 of which met the inclusion criteria. Organoid models of primary and metastatic CRC have been increasingly used to assess clinical responses to standard therapy. Marked heterogeneity exists, matching the responses observed in clinical practice with ex vivo drug and radiation screening. Repeated correlation between organoid and patient sensitivity to forms of HIPEC, systemic chemotherapy, and chemoradiotherapy has been observed. Patient-derived tumor organoids are the latest tool in predictive translational research. Current organoid-based studies in precision medicine have shown their great potential for predicting the clinical response of patients to CRC therapy. Larger-scale, prospective data are required to fully support this exciting avenue in cancer care.

Penile cancer is an uncommon disease associated with significant psychological and physical morbidity. Penile cancer has an expectable pattern of spread in a stepwise fashion, from inguinal to pelvic lymph nodes (PLN) then distant spread. Patients with penile cancer have variable survival, with patients with a low burden of nodal metastatic disease having lasting survival with surgical management, however patients with a large amount of locoregional metastatic disease having a worse prognosis. The current management options for patients with metastatic lymph node disease in penile cancer aims to reduce the morbidity associated with radical inguinal lymph node (ILN) surgery with appropriate risk stratification to optimise oncological control of the disease. This article describes current challenges in managing the inguinal region in patients with penile squamous cell carcinoma (SCC).

BACKGROUND: The management of patients presenting with malignant small bowel obstruction is a challenging paradigm. The aim of this systematic review was to examine different management strategies in these complex patients. The primary outcomes evaluated were the type of intervention, 30-day morbidity and mortality and overall survival rates. METHODS: A systematic literature review of EMBase, Medline, PubMed and the Cochrane Library was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses for studies reporting on conservative and operative management of malignant small bowel obstruction. RESULTS: Fifteen studies (n = 882 patients) reporting on outcomes for malignant small bowel obstruction were analysed. Outcomes measured were primarily survival and relief of obstructive symptoms. The median age ranged from 52 to 66 years. The most common cause of malignant small bowel obstruction was gynaecological in nature (56%), followed by colorectal (19%). Four hundred and eighty-six patients underwent primary surgical management and the remaining 396 patients were assigned to non-surgical intervention. Median overall survival in the operative studies ranged from 2.5 to 7.4 months compared with 0.9 to 1.9 months (P

Purpose: Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Results: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. Conclusions: Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

BACKGROUND Soft tissue infections are a major health burden in the Top End of the Northern Territory of Australia. Necrotizing fasciitis (NF) is associated with mortality rates from 8 to 40%. Early recognition and aggressive surgical debridement are the cornerstones of successful treatment. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, developed by Wong et al., uses six routine biochemical variables to aid early diagnosis. We aim to assess the diagnostic efficacy of the LRINEC score in our population. METHODS A retrospective review of patients with NF between 2005 and 2013 was conducted. A time matched cohort of abscesses/cellulitis was selected. Admission bloods were used to calculate the LRINEC score. An intraoperative finding of NF was used as the gold standard definition for comparison. The diagnostic accuracy of the LRINEC score was assessed. RESULTS Ninety-eight patients with NF and 205 control patients were identified. The area under the receiver operator curve for the LRINEC score in detecting NF was 0.925 (0.890-0.959, P < 0.001). The sensitivity of the LRINEC ≥5 for NF was 76.3%, with a specificity of 93.1%. The positive and negative predictive values were 95.5 and 88.1%, respectively. The positive and negative likelihood ratios were 11 and 0.25. CONCLUSION The LRINEC score is a useful, robust, non-invasive and easily calculated scoring system that can be used as an adjunct to early diagnosis of NF. However, a high degree of clinical suspicion remains the most important factor in early diagnosis of NF.

Peritoneal metastasis (PM) occurs in approximately one in four colorectal cancer (CRC) patients. The pathophysiology of colorectal PM remains poorly characterized. Also, the efficacy of current treatment modalities, including surgery and intraperitoneal (IP) delivery of chemotherapy, is limited. Increasingly, therefore, efforts are being developed to unravel the PM cascade and at understanding the PM-associated tumor microenvironment (TME) and peritoneal ecosystem as potential therapeutic targets. Here, we review recent insights in the structure and components of the TME in colorectal PM, and discuss how these may translate into novel therapeutic approaches aimed at re-engineering the metastasis-promoting activity of the stroma.

BackgroundThere is great variability in the uptake of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of colorectal peritoneal metastases (CRPM) in Australia and New Zealand. This study aims to provide a snapshot of perceptions among colorectal surgeons in the management of CRPM.MethodsA structured ten-question online survey was sent to all colorectal surgeons, with three questions on clinical experience and demographics, one on health economics and six on hypothetical clinical scenarios. Scores were collated and reported based on Likert scales.ResultsEighty-one respondents (36.2%) completed the survey. Most surgeons (66.7%) strongly disagreed with offering CRS and HIPEC at all hospitals. The majority (87.7%) agreed that CRS and HIPEC offered a higher survival benefit than systemic chemotherapy in pseudomyxoma peritonei (PMP), and 69.1% in CRPM (comparators: 60.5% ovarian cancer, 14.8% gastric cancer). There were mixed strategies in managing low-volume, isolated peritoneal recurrences. The majority did not recommend second-look laparoscopy, but favoured operative management of Krukenberg tumours. In the presence of incidental peritoneal metastases, only 29.6% favoured biopsy only and referring the patient to a peritoneal disease centre.ConclusionsResponse rate was relatively low. In Australia and New Zealand, colorectal surgeons see a strong role for CRS and HIPEC in the management of PMP and CRPM. The role of “second look” surgery in high-risk cases is controversial and not supported. Krukenberg tumours are viewed as surgical disease. Regular updates and collaboration with peritoneal centres may help surgeons stay abreast with latest evidence in the field.

Background Colorectal cancer is the second leading cause of cancer-related mortality worldwide. Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer metastases. In recent years, the advent and acceptance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have greatly improved survival for selected patients with low-volume peritoneal metastases. Objective Here, we report the evolution of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases at a statewide tertiary referral center over an 8-year period. Design This is a retrospective study from 2009 to 2017. Setting The study was conducted at a single center over 8 years. Patients Patients with colorectal peritoneal metastases undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included. Main outcomes Main outcomes included evaluation of grade III/IV morbidity rate, mortality rate, overall and relapse-free survival, and prognostic factors influencing survival on a Cox multivariate analysis model. Results One hundred one cytoreductive surgeries were undertaken on 96 patients during this time for colorectal peritoneal metastases. The median patient age was 60 years with 55.2% being female. The median Peritoneal Carcinomatosis Index was 9, with complete cytoreduction achieved in 76 (75.2%) cases. Grade III or IV complications occurred in 26 cases (25.7%) with 2 (2%) perioperative mortalities. Median overall survival for the entire cohort was 32 months, with a 3-year survival of 38%. For patients who achieved a complete cytoreduction, median overall survival was 37 months, with a relapse-free survival of 13 months and a 3-year survival of 54%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival. Limitations The main limitation this study is its retrospective nature. Conclusion Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated low-volume colorectal peritoneal metastases is safe and effective, with low morbidity. It offers selected patients a highly favorable overall and relapse-free survival. See Video Abstract at http://links.lww.com/DCR/B2. EVOLUCION DE LA CIRUGIA CITORREDUCTIVA Y QUIMIOTERAPIA INTRAPERITONEAL HIPERTERMICA (HIPEC) PARA METASTASIS PERITONEALES COLORRECTALES: EXPERIENCIA INSTITUCIONAL DE 8 ANOS: El cancer colorrectal es la segunda causa de mortalidad relacionada con el cancer en todo el mundo. Las metastasis peritoneales tienen el peor pronostico entre todos los sitios de metastasis del cancer colorrectal. En los ultimos anos, el advenimiento y la aceptacion de la cirugia citorreductiva y la quimioterapia intraperitoneal hipertermica ha mejorado enormemente la supervivencia de pacientes seleccionados con metastasis peritoneales de bajo volumen. Objetivo Aqui, informamos sobre la evolucion de la cirugia citorreductiva y la quimioterapia intraperitoneal hipertermica para las metastasis peritoneales colorrectales en un centro de referencia terciario para todo el estado durante un periodo de ocho anos. DISENO:: Estudio retrospectivo del 2009 a 2017. CONFIGURACION:: Centro unico a lo largo de ocho anos. Pacientes Pacientes con metastasis peritoneales colorrectales sometidos a cirugia citorreductiva y quimioterapia intraperitoneal hipertermica. Resultados principales Los resultados principales incluyeron la evaluacion de la tasa de morbilidad de grado III / IV, la tasa de mortalidad, la supervivencia general y libre de recaida y los factores pronosticos que influyen en la supervivencia en el modelo de analisis multivariado Cox. Resultados Se realizaron el ciento uno cirugias citorreductivas en noventa y seis pacientes durante este tiempo por metastasis peritoneales colorrectales. La edad media de los pacientes fue de 60 anos, con un 55.2% de mujeres. El Indice de Carcinomatosis Peritoneal mediano fue de 9, con una citorreduccion completa lograda en 76 (75.2%) casos. Las complicaciones de grado III o IV ocurrieron en 26 casos (25.7%) con dos (2%) de mortalidad perioperatoria. La supervivencia mediana general para toda la cohorte fue de 32 meses, con una supervivencia de 3 anos del 38%. Para los pacientes que lograron una citorreduccion completa, la supervivencia global media fue de 37 meses, con una supervivencia sin recaida de 13 meses y una supervivencia de 3 anos del 54%. La citorreduccion completa y la histologia no mucinosa fueron factores clave asociados de forma independiente con una mejor supervivencia general. Limitaciones La principal limitacion es la naturaleza retrospectiva del estudio. CONCLUSION:: La cirugia citorreductiva y la quimioterapia intraperitoneal hipertermica para las metastasis peritoneales colorrectales aisladas de bajo volumen son seguras y eficaces, con baja morbilidad. Ofrece a los pacientes seleccionados una supervivencia global altamente favorable y libre de recaida. Vea el Resumen del video en http://links.lww.com/DCR/B2.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with colorectal peritoneal metastases (CRPM) a favorable long-term survival. While cytoreductive techniques are standardized, there remains great variability in HIPEC drugs with mitomycin C or oxaliplatin use based largely on institute preference. In this study, we compared outcomes based on mitomycin C or oxaliplatin use after complete cytoreduction.This is a retrospective analysis over a 7-year period of all patients undergoing complete cytoreduction with HIPEC.Seventy-eight patients underwent complete cytoreduction with HIPEC during this time. Forty-six patients received oxaliplatin as HIPEC, and 32 received mitomycin C. There was no difference in patient characteristics, resections, or major morbidity between the two groups. Superficial wound infections were higher in the mitomycin C group (37.5% v 15.2%, p = 0.02). Median overall and disease-free survival for the entire cohort was 40 and 14 months, respectively. There was no difference in overall survival or disease-free survival between the two HIPEC groups (HR 0.50, 95% CI 0.11-2.28).Complete cytoreduction and HIPEC can offer selected patients a favorable survival. The choice of mitomycin C or oxaliplatin for HIPEC had no influence on survival. Prospective studies are needed to explore this important issue.