Single preoperative radiation therapy with delayed surgery for low-risk breast cancer: Oncologic outcome, toxicity and cosmesis of the SPORT-DS phase I trial.

BACKGROUND: A novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy. METHODS: Women of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results. RESULTS: Thirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0-10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients. CONCLUSIONS: Single-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498.

Predictive Value of C-Reactive Protein for Infectious Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Single-Center Prospective Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with significant morbidity and prolonged hospital stay. Postoperative infections account for a high burden of these complications. This study aimed to assess the predictive value of postoperative C-reactive protein (CRP) levels for overall infectious complications and anastomotic leaks. METHODS: This was a single-center prospective study of patients undergoing CRS and HIPEC for peritoneal metastases between 2018 and 2020 at Maisonneuve-Rosemont Hospital in Montreal, QC, Canada. CRP levels were measured daily for 10 days following surgery. A comparison was made between patients with infectious complications and those without. RESULTS: Ninety-nine patients were included. Thirty patients had infectious complications (30.3%) and four patients presented an anastomotic leak (4%). CRP levels were significantly higher in patients with infectious complications from postoperative days (PODs) 2-10. Daily cut-off values most accurately predicted infectious complications on day 8 (94.3 mg/L; area under the curve [AUC] 0.85, sensitivity [SE] 76.2%, specificity [SP] 94.7%, positive predictive value [PPV] 88.9%, negative predictive value [NPV] 87.8%; p < 0.0001) and day 9 (72.7 mg/L; AUC 0.89, SE 95.2%, SP 81.8%, PPV 76.9%, NPV 96.4%; p < 0.0001). Patients with infectious complications had longer operative time, higher peritoneal cancer index, and a higher number of intestinal anastomoses, while their baseline characteristics were comparable. CONCLUSION: Measurement of CRP helps predict infectious complications following CRS and HIPEC, particularly on PODs 8 and 9. Cut-off values are more accurate after the first postoperative week, especially in ruling out infectious complications.

Validation of the Return-to-Work Obstacles and Self-Efficacy Scale for Women on Sick Leave Due to Breast Cancer (ROSES-BC).

PURPOSE: Breast cancer (BC) is the most frequently diagnosed cancer among women. Approximately 40% of BC survivors are diagnosed during the peak years of their professional career. Women face numerous obstacles when returning to work (RTW) after BC. Their decision-making process and self-efficacy to overcome these barriers may undergo alterations. The objective of this study was to validate the Return-to-work Obstacles and Self-Efficacy Scale (ROSES) for BC survivors, with a focus on three psychometric properties: construct validity, test-retest reliability, and predictive validity. METHODS: This prospective study consists of three phases: Phase 1 (baseline, during sick leave) was conducted to evaluate construct validity, Phase 2 (2 weeks later) assessed test-retest reliability, and Phase 3 (6-month follow-up, RTW or not) aimed to evaluate predictive validity. A total of 153 BC survivors participated in Phase 1 of the study, where they completed the 10 dimensions of the ROSES (e.g., fear of relapse, cognitive difficulties). Confirmatory factor analyses (CFA), Pearson correlations, and Cox regressions were performed, with respect to each phase. RESULTS: The mean duration for RTW with the same employer was 62.7 weeks. CFAs confirmed the ROSES structure, which had previously been established for other health conditions, showing satisfactory coefficients. Significant Pearson correlation coefficients were observed between the ROSES dimensions from Phase 1 to Phase 2, ranging from 0.66 to 0.88. When considering various confounding variables, chemotherapy treatment and cognitive difficulties (ROSES dimension) emerged as the only significant predictors of RTW. CONCLUSION: These findings support the utilization of the ROSES in clinical and research settings for BC survivors to improve their successful RTW. After an initial screening using the ROSES, occupational health professionals can further conduct a focused and thorough evaluation of specific dimensions, such as cognitive difficulties. Additional research and information are required to assist BC survivors in dealing with cognitive impairments induced by chemotherapy when they return to work.

Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Combined Interval Cytoreductive Surgery and Carboplatin-Based Hyperthermic Intraperitoneal Chemotherapy in Advanced Primary High-Grade Serous Ovarian Cancer.

Combining interval cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in advanced epithelial ovarian carcinoma (EOC). Although limited, growing evidence regarding carboplatin-based HIPEC highlights its potential. This retrospective study included all patients with advanced primary high-grade serous ovarian cancer who underwent interval CRS combined with carboplatin-based HIPEC at our Canadian tertiary care center between 2014 and 2020. We identified 40 patients with a median age of 61 years. The median peritoneal cancer index was 13 and complete cytoreduction was achieved in 38 patients (95%). Median hospital stay was 13 days and there were four admissions to the intensive care unit (10%) and six readmissions (15%). Severe adverse events occurred in eight patients (20%) and there was no perioperative death. Recurrence was seen in 33 patients (82%) with a median DFS of 18.0 months and a median overall survival of 36.4 months. Multivariate analyses showed that age, peritoneal cancer index, completeness of cytoreduction, occurrence of severe complications, and bowel resection did not significantly impact DFS or OS in our cohort. Interval CRS combined with carboplatin-based HIPEC for advanced primary EOC is associated with acceptable morbidity and oncological outcomes. Larger studies are required to determine the long-term outcomes.

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes.

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.

A prediction model to refine the timing of an early second-look laparoscopic exploration in patients with colon cancer at high risk of early peritoneal metastasis recurrence.

BACKGROUND: In patients at high risk of peritoneal metastasis (PM) recurrence following surgical treatment of colon cancer (CC), second-look laparoscopic exploration (SLLE) is mandatory; however, the best timing is unknown. We created a tool to refine the timing of early SLLE in patients at high risk of PM recurrence. METHODS: This international cohort study included patients who underwent CC surgery between 2009 and 2020. All patients had PM recurrence. Factors associated with PM-free survival (PMFS) were assessed using Cox regression. The primary endpoint was early PM recurrence defined as a PMFS of <6 months. A model (logistic regression) was fitted and corrected using bootstrap. RESULTS: In total, 235 patients were included. The median PMFS was 13 (IQR, 8-22) months, and 15.7% of the patients experienced an early PM recurrence. Synchronous limited PM and/or ovarian metastasis (hazard ratio [HR]: 2.50; 95% confidence interval [CI]: [1.66-3.78]; p < 0.001) were associated with a very high-risk status requiring SLLE. T4 (HR: 1.47; 95% CI: [1.03-2.11]; p = 0.036), transverse tumor localization (HR: 0.35; 95% CI: [0.17-0.69]; p = 0.002), emergency surgery (HR: 2.06; 95% CI: [1.36-3.13]; p < 0.001), mucinous subtype (HR: 0.50; 95% CI [0.30, 0.82]; p = 0.006), microsatellite instability (HR: 2.29; 95% CI [1.06, 4.93]; p = 0.036), KRAS mutation (HR: 1.78; 95% CI: [1.24-2.55]; p = 0.002), and complete protocol of adjuvant chemotherapy (HR: 0.93; 95% CI: [0.89-0.96]; p < 0.001) were also prognostic factors for PMFS. Thus, a model was fitted (area under the curve: 0.87; 95% CI: [0.82-0.92]) for prediction, and a cutoff of 150 points was identified to classify patients at high risk of early PM recurrence. CONCLUSION: Using a nomogram, eight prognostic factors were identified to select patients at high risk for early PM recurrence objectively. Patients reaching 150 points could benefit from an early SLLE.

A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.

Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients' responses to regorafenib treatment.

The Impact of Computed Tomography Measurements of Sarcopenia on Postoperative and Oncologic Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal metastases (PM) but is associated with significant postoperative morbidity. The aim of this study was to determine the prognostic value of computed tomographic (CT)-measured sarcopenia on postoperative outcomes and survival in patients undergoing CRS-HIPEC for PM from various origins. A retrospective cohort study was conducted between 2012 and 2020. Three-hundred and twelve patients (mean age 57.6 ± 10.3, 34.3% male) were included, of which 88 (28.2%) were sarcopenic. PM from a colorectal origin was the most common in both groups. The proportion of major postoperative complications (Clavien-Dindo ≥ III) was not higher in the sarcopenic group (15.9% in sarcopenic patients vs. 23.2% in nonsarcopenic patients, p = 0.17). The mean Comprehensive Complication Index scores, HIPEC-related toxicities, length of hospital stay, and duration of parenteral nutrition were comparable regardless of sarcopenia status. In the multivariate logistic regression analysis of severe complications, only peritoneal carcinomatosis index reached statistical significance (OR, 1.05; 95% CI, 1.01 to 1.08, p = 0.007). Sarcopenia did not impact origin-specific overall survival on Cox regression analysis. Sarcopenia was not associated with worse rates of postoperative severe complications or worse survival rates. Future prospective studies are required before considering sarcopenia as part of preoperative risk assessment.

Tumor bed extending to margins in breast cancer specimens after neoadjuvant chemotherapy: Incidence and clinical significance.

BACKGROUND: Pathologic examination of post-neoadjuvant chemotherapy (NAC) breast surgical specimens includes assessment of margins. It has been recommended that tumor bed (TB) changes extending to margins should be documented; however, its' incidence and clinical significance have not yet been established. The aim of our study was to gather prognostic data on this histological finding. DESIGN: We retrospectively identified all cases where TB was reported at margin. Cases where margins were also positive for invasive carcinoma or DCIS were excluded. RESULTS: From 2016 to 2019, 115 cases of NAC treated breast cancers were identified with 21 having at least one margin positive for TB after initial surgery (incidence of 18.3 %). Five cases were estrogen receptor (ER)-/HER2-, 9 were HER2+ and 7 were ER+/HER2-. Nineteen patients underwent partial mastectomy and 2 underwent total mastectomy. Nine patients had a pathological complete response (pCR).Ten cases had more than one positive margin for TB. None of the 21 patients underwent a second surgery for margin re-excision. Twenty patients received adjuvant therapy. With an average follow-up of 28.1 months, there has been one local recurrence. Four other patients developed metastatic disease, one of which died of the disease. The rates of locoregional and distant recurrence and mortality were statistically similar to those from patients whose margins were negative for TB. CONCLUSIONS: Our results suggest low risk of local recurrence when a positive margin for TB is not re-excised. Further data and follow-up will be needed to confirm the adequacy of conservative management in this setting.

Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.

BACKGROUND: Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first-line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome. METHODS: Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression-free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes. RESULTS: We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first-line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR-adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post-treatment resistant lesions but not in responder lesions (two-tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors. CONCLUSION: This investigation of genomic-phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.

Morbidity associated with the use of oxaliplatin versus mitomycin C in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal or appendiceal origin: a multi-institutional comparative study.

Background: The raw costs of mitomycin C (MMC) and oxaliplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) differ substantially. We sought to compare the morbidity and toxicity profiles associated with the use of oxaliplatin and MMC in patients undergoing cytoreductive surgery (CRS) and HIPEC for peritoneal carcinomatosis (PC) of colorectal or appendiceal origin, to evaluate whether the costeffectiveness of these 2 agents should dictate drug choice. Methods: We conducted a retrospective multi-institutional study of all patients with PC of colorectal or appendiceal origin treated with CRS-HIPEC using MMC or oxaliplatin from 2010 to 2015. Demographic, perioperative, morbidity, toxicity and cost data were compared between the 2 treatment groups and between cancer-origin subgroups. Results: Forty-two patients treated with MMC and 76 treated with oxaliplatin were included in the study. Baseline demographic and tumour characteristics were comparable in the 2 groups, except that the patients treated with MMC had higher Charlson Comorbidity Index scores. The MMC group had a higher rate of cancer of colorectal origin (76.2% v. 57.9%, p = 0.047) and longer operative times (553 v. 320 min, p < 0.001). In the subgroup of patients whose cancer was of colorectal origin, patients treated with MMC had a higher transfusion rate (50.0% v. 28.6%, p = 0.023) and lower postoperative baseline hemoglobin level (100 v. 119 g/L, p = 0.002) than those treated with oxaliplatin. There was no difference in hematologic toxicity scores after controlling for postoperative anemia. There was no difference in the rates of major complications and 90-day mortality. However, MMC was less costly than oxaliplatin ($724 v. $8928). Conclusion: MMC and oxaliplatin are both suitable agents for HIPEC and are associated with comparable morbidity and toxicity profiles, regardless of cancer origin. Thus, we propose that cost-effectiveness should ultimately dictate drug selection.

Contexte: Les coûts bruts de la mitomycine C (MMC) et de l'oxaliplatine pour la chimiothérapie hyperthermique intrapéritonéale (CHIP) sont très différents. Nous avons voulu comparer la morbidité et la toxicité associées à l'oxaliplatine et à la MMC chez les patients subissant une chirurgie de réduction tumorale (CRT) et une CHIP pour une carcinomatose péritonéale (CP) d'origine colorectale ou appendiculaire afin d'évaluer si le choix des professionnels de la santé devrait reposer sur le rapport coût­efficacité de ces médicaments. Méthodes: Nous avons mené une étude multicentrique rétrospective sur tous les patients qui, entre 2010 et 2015, présentaient une CP d'origine colorectale ou appendiculaire et ont subi une CRT ainsi qu'une CHIP à la MMC ou à l'oxaliplatine. Les données relatives aux caractéristiques démographiques, aux résultats périopératoires, à la morbidité, à la toxicité et aux coûts ont été comparées entre les 2 groupes de traitement et entre les sous-groupes formés en fonction de l'origine du cancer. Résultats: Au total, 42 patients traités à la MMC et 76 patients traités à l'oxaliplatine ont été inclus dans l'étude. Les caractéristiques démographiques et tumorales des 2 groupes avant le traitement étaient semblables, à l'exception de l'indice de comorbidité de Charlson, qui était plus élevé dans le groupe MMC. Le groupe MMC présentait un taux plus important de cancer d'origine colorectale (76,2 % c. 57,9 %; p = 0,047), de même qu'un temps opératoire plus long (553 min c. 320 min; p < 0,001). En ce qui concerne le sous-groupe de patients atteints d'un cancer d'origine colorectale, les personnes traitées à la MMC affichaient un taux de transfusion plus élevé (50,0 % c. 28,6 %; p = 0,023) et un taux d'hémoglobine postopératoire de référence plus bas (100 g/L c. 119 g/L; p = 0,002) que celles traitées à l'oxaliplatine. Une fois l'anémie postopératoire prise en compte, aucune différence n'a été observée quant à la toxicité hématologique. Les taux de complications majeures et de mortalité à 90 jours étaient aussi comparables. La MMC coûtait toutefois moins cher que l'oxaliplatine (724 $ c. 8928 $). Conclusion: La MMC et l'oxaliplatine conviennent à la CHIP, et la morbidité et la toxicité qui y sont associées sont comparables, quelle que soit l'origine du cancer. Nous proposons donc que le choix du médicament à utiliser repose sur le rapport coût­efficacité.

Self-directed learning by video as a means to improve technical skills in surgery residents: a randomized controlled trial.

BACKGROUND: With their demanding schedules, surgical residents have limited time to practice techniques. The aim is to evaluate the pedagogic model of self-directed learning using video in surgery residents. METHODS: Informed consent was obtained from all the participants. A randomized controlled trial was conducted in 2018 at Hôpital Maisonneuve-Rosemont (University of Montreal). Participants were general surgery residents. There were 27 eligible residents; 22 completed the study. They were filmed performing an intestinal anastomosis on cadaveric pig bowel. The self-directed learning by video (SDL-V) group was given an expert video, which demonstrated the technique performed by an experienced surgeon. The control group continued with their regular duties. Three weeks later, participants performed a second filmed anastomosis. Two attending surgeons evaluated the residents' filmed anastomosis using the Objective Structured Assessment of Technical Skills scale. After their second anastomosis, all participants had access to the expert video and completed a survey. RESULTS: Score did not differ significantly between groups during the first (control: 23.6 (4.5) vs. SDL-V: 23.9 (4.5), p = 0.99, presented as mean (SD)) or second filmed anastomosis procedure (control: 27.1 (3.9) vs. SDL-V: 29.6 (3.4) p = 0.28). Both groups improved significantly from pre- to post-intervention (mean difference between the two anastomosis procedure with 95% CI for control: 3.5, [1.1; 5.9] and for SDL-V: 5.8, [3.4: 8.2]). Correlation between the evaluators for score was moderate (r = 0.6, 95% CI: [0.3: 0.8]). The pass/fail global evaluation exhibited poor inter-rater reliability (Kappa: 0.105, 95% CI: [- 0.2:0.4]). On the survey, all participants wanted more expert-made videos of specific surgical techniques. CONCLUSIONS: Despite a higher final OSATS score for the intervention group, self-directed learning by video failed to produce a statistically significant difference on the overall OSATS scores between the two groups in this small cohort.

Rectal anastomosis and hyperthermic intraperitoneal chemotherapy: Should we avoid diverting loop ileostomy?

INTRODUCTION: Literature on rectal anastomosis and diverting ileostomy in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) is limited. This study assesses the safety of rectal anastomoses during cytoreductive surgery (CRS) and HIPEC, with and without fecal diversion, and its morbidity when performed. MATERIALS AND METHODS: From January 2012 to January 2020, patients with peritoneal metastases who underwent CRS and HIPEC that required a rectal anastomosis were included in this single-hospital retrospective chart review. RESULTS: 84 patients were included, of which 29 had a diverting loop ileostomy. The rectal anastomotic leak (AL) rate for the series was 8.3%. Factors associated with AL were male gender (p = 0.031) and increased BMI (p < 0.0005). Diverting loop ileostomy was associated with a significant decrease of clinically significant rectal AL (0% vs 12.7%, p = 0.045). However, the 90-day readmission rate was higher in this group (37.9% vs 10.9%, p = 0.003). Stoma reversal surgery was performed for all patients, but 3 patients experienced AL (10.7%). CONCLUSIONS: This study suggests that creation of a diverting loop ileostomy may be an effective strategy to prevent symptomatic rectal AL following CRS with HIPEC. However, it is also associated with an increased readmission rate and increased risk of AL following reversal surgery.

Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index.

BACKGROUND: Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI. METHODS: All consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected. RESULTS: Eight patients underwent the two-step approach. The median PCI was 33 (29-39) and the median time between the two procedures was 111 days (90-212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3-73 months). CONCLUSION: A two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.

The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23-24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.

Carboplatin Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Stage IVB Endometrial Cancer.

BACKGROUND: Endometrial cancer presenting with peritoneal metastases carries a poor prognosis. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to the surgical management of these patients has been studied in recent years, but only with cisplatin. CASES: This is a series of 3 patients presenting with endometrial cancer and synchronous peritoneal metastases who underwent cytoreductive surgery and carboplatin HIPEC as primary treatment. Complete cytoreductive surgery was achieved for each patient. No grade 3-5 complications were observed. Two patients died at 12 and 18 months, respectively, and 1 patient was alive with disease at 29 months. CONCLUSION: This case series suggests that the addition of carboplatin HIPEC to the surgical management of peritoneal metastases from endometrial cancer is safe as primary treatment. However, long-term survival remains poor.