Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: The Efficiency of Mitomycin C.

BACKGROUND: Survival of patients affected by colorectal cancer peritoneal metastases (CRC-PM) can be improved with combined complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Two chemotherapeutic agents are mainly used: mitomycin C (MMC) and oxaliplatin. A recent prospective randomized clinical trial showed that oxaliplatin-based HIPEC does not improve survival compared with CCRS alone. The purpose of our study was to compare the survival effectiveness of MMC versus oxaliplatin-based HIPEC using a homogeneous surgical technique and drug protocol. METHODS: This retrospective monocentric study included all patients prospectively registered for having undergone CCRS and HIPEC using MMC or oxaliplatin for CRC-PM in Strasbourg University Hospital, France, from December 2004 until December 2019. MMC-based HIPEC and oxaliplatin-based HIPEC groups were compared with an inverse probability of treatment weighting. RESULTS: A total of 137 patients were included. Groups were comparable for all baseline characteristics except for peritoneal carcinomatosis index. In the weighted multivariate analysis, disease-free survival (DFS) and peritoneal disease-free survival (PDFS) were significantly higher in the MMC-based HIPEC group compared with the oxaliplatin-based HIPEC group with a hazard ratio of 0.74 (CI 95% 0.56-0.98), p = 0.035 and 0.59 (CI 95% 0.40-0.98), p = 0.0084, respectively. There was no difference in overall survival or postoperative morbidity between groups. CONCLUSIONS: These results favor a superiority of MMC for DFS and PDFS in comparison with oxaliplatin in HIPEC after CCRS in treatment with curative intent for CRC-PM.

Half of Postoperative Deaths After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Could be Preventable: A French Root Cause Analysis on 5562 Patients.

OBJECTIVE: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. BACKGROUND: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. METHODS: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. RESULTS: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). CONCLUSION: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.

Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study.

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.

How to Prevent Sarcopenia Occurrence during Neoadjuvant Chemotherapy for Oesogastric Adenocarcinoma?

The aim of this study was to evaluate the impact of a preoperative feeding jejunostomy (FJ) on the occurrence of sarcopenia before and after preoperative chemotherapy for patients with an oesogastric adenocarcinoma (OGA). Forty-six patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. Sarcopenia was evaluated by measuring muscle surfaces (psoas, paraspinal and abdominal wall muscles) on abdominal CT images at the level of the 3rd lumbar vertebra. A FJ was placed in 31 patients (67.4%) before the neoadjuvant treatment (FJ group), while 15 patients (32.6%) started neoadjuvant treatments without FJ (control group). After preoperative chemotherapy, there were significantly more sarcopenic patients in the control group, compared to the FJ group. In the FJ group, 13% of the patients (n = 4) were sarcopenic before treatment and 22.6% of them (n = 7) became sarcopenic after preoperative chemotherapy (p = 0.3). In the control group, if initially only 6.7% (n = 1) of patients were sarcopenic, the majority of the patients (60%, n = 9) became sarcopenic after chemotherapy (p = 0.012). The FJ was an independent risk factor of sarcopenia after neoadjuvant chemotherapy. FJ with enteral nutritional support during the preoperative management of OGA seemed to efficiently counteract sarcopenia occurrence during preoperative chemotherapy.

Multicystic peritoneal mesothelioma treated with cytoreductive surgery followed or not by hyperthermic intraperitoneal chemotherapy: results from a large multicentric cohort.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. METHODS: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. RESULTS: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). CONCLUSION: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

Is nonanatomic rectal resection a valid therapeutic option for rectal gastrointestinal stromal tumors? A proposed decision algorithm.

BACKGROUND AND OBJECTIVES: The best surgical approach to rectal gastrointestinal stromal tumors (GISTs) is still debated, and both nonanatomic rectal resection (NARR) and anatomic rectal resection (ARR) are applied. The aim of this study was to evaluate the feasibility and oncological outcomes of NARR and ARR for rectal GISTs (R-GISTs). METHODS: Through a large French multicentre retrospective study, 35 patients were treated for R-GIST between 2001 and 2013. Patients who underwent NARR and ARR were compared. RESULTS: There were 23 (65.7%) patients in group ARR and 12 (34.3%) in group NARR. Significantly more patients in the group with ARR had a neoadjuvant treatment (86%) with tyrosine kinase inhibitor (TKI) (imatinib) compared to those with NARR (25%) (p < .01). The median preoperative tumor size was significantly different between the groups without and with neoadjuvant TKI: 30 ± 23 mm versus 64 ± 44.4 mm, respectively (p < .001). Overall postoperative morbidity was 20% (n = 7) (26% for ARR vs. 8% for NARR; p = .4). After a median follow-up of 60.2 (3.2-164.3) months, the 5-year disease-free survival rates were 79.5% (confidence interval [CI] 95%: 54-100) for the NARR group and 68% (CI 95%: 46.4-89.7) for the ARR group (p = .697), respectively. CONCLUSION: The use of NARR for small R-GIST's does not seem to impair the oncological prognosis.

Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France.

BACKGROUND: Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. MATERIALS AND METHODS: Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. RESULTS: A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. CONCLUSION: Initial diagnostic management requires improvement, especially outside of specialized centers. IMPLICATIONS FOR PRACTICE: This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives.

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

BACKGROUND: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. OBJECTIVE: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. METHODS: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). RESULTS: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). CONCLUSION: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study.

BACKGROUND: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM). OBJECTIVE: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM. METHODS: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases. RESULTS: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype. CONCLUSIONS: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.

Could a Feeding Jejunostomy be Integrated into a Standardized Preoperative Management of Oeso-gastric Junction Adenocarcinoma?

PURPOSE: To evaluate the impact of a feeding jejunostomy (FJ) on the preoperative management of patients with an oesogastric adenocarcinoma (OGA). METHODS: From January 2007 to December 2014, patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. FJ was performed before starting perioperative treatments in patients presenting with dysphagia or with a nutritional risk index (NRI) <97.5. The patients who did not require a FJ served as a control group. RESULTS: Among the 114 patients with OGA consecutively admitted in our surgical department, 88 (77.2%) were enrolled for neoadjuvant treatment. A FJ was placed in 50 patients (56.8%) before the neoadjuvant treatment (FJ group), whereas 38 patients (43.2%) started neoadjuvant treatments without FJ (control group). Ninety-six percent of patients (n = 48) in the FJ group successfully completed the neoadjuvant treatment but only 81.6% of patients without FJ (n = 31; p = 0.004). The FJ group was divided between responders: 37 patients with a weight response (74%), and nonresponders: 13 patients without weight response (26%). In the FJ group, the nutritional response during preoperative chemotherapy was a significant predictive factor for the achievement of second stage oesogastric resection (p = 0.002). CONCLUSIONS: FJ with enteral nutritional support during the preoperative management of OGA is a safe and effective support for the completion of the preoperative chemotherapy. The weight response to the enteral support is a predictor factor for a completion of the preoperative chemotherapy and could identify a group of patients who would have a better chance of reaching radical surgery.

Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin.

BACKGROUND: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT. METHODS: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively). RESULTS: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis. CONCLUSION: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.

Can a Benefit be Expected from Surgical Debulking of Unresectable Pseudomyxoma Peritonei?

PURPOSE: This study evaluated the role of surgical debulking in improving pseudomyxoma peritonei (PMP)-related symptoms if complete cytoreductive surgery (CCRS) of huge PMP is unachievable. METHODS: This was a retrospective analysis of a prospective database of all patients in our tertiary care center treated for PMP between 1992 and 2014. All cases of surgical debulking in patients scheduled for CCRS that proved unachievable during the operation were selected for the present study. RESULTS: Among the 338 patients operated on for PMP, 39 (11.5 %) had undergone surgical debulking because CCRS was unachievable. All of these patients were symptomatic before surgery, and the median PCI was 32 (5-39). More than 80 % of the disease burden was resected in 23 patients (59 %). Mortality and major morbidity rates were 2.5 and 23 %, respectively. After debulking surgery, symptoms gradually subsided over a median time of 23 months and 50 % of the patients no longer experienced PMP-related symptoms after a median follow-up of 24.5 months. After a median follow-up of 46.4 months (range 3-120), median overall (OS) and progression-free (PFS) survival times were 55.5 and 20 months, respectively. Five-year OS and PFS rates were 46 and 11 %, respectively. CONCLUSIONS: Aggressive debulking surgery in case of unachievable CCRS for huge PMP can offer prolonged relief of PMP-related symptoms and long-term survival, in experienced centers that are able to be sufficiently aggressive to resect the major part of the disease, and conservative enough to achieve low mortality and good quality of life.

A case-control study of pre-operative levels of serum neutrophil gelatinase-associated lipocalin and other potential inflammatory markers in colorectal cancer.

BACKGROUND: Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP). METHODS: The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n=224) or for benign causes (n=252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured. RESULTS: Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p<0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR=2.44 (95% CI : 1.34-4.45, p=0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p=0.028) but this association was reduced after adjustment for CRP (p=0.11). CONCLUSION: Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.

Implementation of an enhanced recovery program for complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a referral center: a case control prospective study.

Objectives: Current recommendations regarding enhanced recovery programs (ERPs) after complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are based on a low level of evidence. The aim of this study is to evaluate the effect of implementing an adapted ERP for CCRS and HIPEC in a referral center. Methods: We conducted a study with a prospective group of 44 patients (post-ERP group) who underwent CCRS with HIPEC between July 2016 and June 2018, the period during which ERP was implemented. This group was compared to a second retrospective group of 21 patients who underwent CCRS with HIPEC between June 2015 and June 2016, during which ERP was not yet implemented (pre-ERP group). Results: The ERP compliance rate was 65% in the post-ERP group. The hospital length of stay (HLS) was shorter in the post-ERP group: 24.9 days (IQR 11-68, pre-ERP group) vs. 16.1 days (IQR 6-45, post-ERP group), as was the major morbidity rate (pre-ERP group=33.3% vs. post-ERP group=20.5%). The nasogastric tube, urinary catheter and abdominal drains were all retrieved faster in the post-ERP group. Conclusions: The implementation of an adapted ERP after CCRS with HIPEC procedures reduces morbidity and shortens the HLS.

Sarcopenia remaining after intensive nutritional feeding support could be a criterion for the selection of patients for surgery for oesogastric junction adenocarcinoma.

BACKGROUND: Sarcopenia is recognized as a negative prognostic factor in several cancers. The aim of this study was to investigate the impact of nutritional support with feeding jejunostomy (FJ) on the occurrence of sarcopenia and how it may affect postoperative short-term outcomes and long-term survival outcomes in patients undergoing esophagectomy for oesogastric junction adenocarcinoma (OJA). METHODS: Patients with OJA were included. The presence of sarcopenia was determined using cutoff values of the total cross-sectional muscle tissue measured on CT scan. We analyzed risk factors for sarcopenia occurrence and the impact of preoperative sarcopenia on postoperative results, overall survival and disease-free survival. RESULTS: A total of 124 patients were eligible for analysis. Ninety-one patients underwent surgery after chemotherapy, and 72 of them received preoperative FJ. Among the 91 patients, 21 patients (23.0%) were sarcopenic after preoperative chemotherapy. Multivariate analysis showed that FJ is a protective factor against sarcopenia occurrence. Overall survival was significantly different between sarcopenic and nonsarcopenic patients (median survival = 33.7 vs. 58.6 months, respectively, p = 0.04), and sarcopenia occurrence was an independent risk factor for overall survival in patients who underwent surgery (HR = 3.02; CI 95% 1.55-5.9; p < 0.005). Subgroup analyses showed no differences in overall survival between patients who presented sarcopenia despite nutritional prehabilitation with a FJ and patients excluded from surgery in palliative situations (median survival = 21.9 vs. 17.2 months, respectively, p = 0.46). CONCLUSION: The persistence of sarcopenia after preoperative chemotherapy despite renutrition with FJ could be a selection factor to propose curative surgery for OJA.

Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group.

PURPOSE: To evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS). METHODS: All consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS). RESULTS: A total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1-2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3-90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6-74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR. CONCLUSIONS: Unplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.

CDX2 controls genes involved in the metabolism of 5-fluorouracil and is associated with reduced efficacy of chemotherapy in colorectal cancer.

Most patients affected with colorectal cancers (CRC) are treated with 5-fluorouracil (5-FU)-based chemotherapy but its efficacy is often hampered by resistance mechanisms linked to tumor heterogeneity. A better understanding of the molecular determinants involved in chemoresistance is critical for precision medicine and therapeutic progress. Caudal type homeobox 2 (CDX2) is a master regulator of intestinal identity and acts as tumor suppressor in the colon. Here, using a translational approach, we examined the role of CDX2 in CRC chemoresistance. Unexpectedly, we discovered that the prognosis value of CDX2 for disease-free survival of patients affected with CRC is lost upon chemotherapy and that CDX2 expression enhances resistance of colon cancer cells towards 5-FU. At the molecular level, we found that CDX2 expression correlates with higher levels of genes regulating the bioavailability of 5-FU through efflux (ABCC11) and catabolism (DPYD) in patients affected with CRC and CRC cell lines. We further showed that CDX2 directly regulates the expression of ABCC11 and that the inhibition of ABCC11 improves 5-FU-sensitivity of CDX2-expressing colon cancer cells. Thus, this study illustrates how biological functions are hijacked in CRC cells and reveals the therapeutic interest of CDX2/ABCC11/DPYD to improve systemic chemotherapy in CRC.

Appendiceal tumors and pseudomyxoma peritonei: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (RENAPE, RENAPATH, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR).

INTRODUCTION: This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. RESULTS: AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. CONCLUSION: These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.