Iatrogenic ureteral injury during colorectal surgery has a significant impact on patient outcomes: a French multicentric retrospective cohort study.

AIM: The long-term urological sequelae after iatrogenic ureteral injury (IUI) during colorectal surgery are not clearly known. The aims of this work were to report the incidence of IUI and to analyse the long-term consequences of urological late complications and their impact on oncological results of IUI occurring during colorectal surgery through a French multicentric experience (GRECCAR group). METHOD: All the patients who presented with IUI during colorectal surgery between 2010 and 2019 were retrospectively included. Patients with ureteral involvement needing en bloc resection, delayed ureteral stricture or noncolorectal surgery were not considered. RESULTS: A total of 202 patients (93 men, mean age 63 ± 14 years) were identified in 29 centres, corresponding to 0.32% of colorectal surgeries (n = 63 562). Index colorectal surgery was mainly oncological (n = 130, 64%). IUI was diagnosed postoperatively in 112 patients (55%) after a mean delay of 11 ± 9 days. Intraoperative diagnosis of IUI was significantly associated with shorter length of stay (21 ± 22 days vs. 34 ± 22 days, p < 0.0001), lower rates of postoperative hydronephrosis (2% vs. 10%, p = 0.04), anastomotic complication (7% vs. 22.5%, p = 0.002) and thromboembolic event (0% vs. 6%, p = 0.02) than postoperative diagnosis of IUI. Delayed chemotherapy because of IUI was reported in 27% of patients. At the end of the follow-up [3 ± 2.6 years (1 month-13 years)], 72 patients presented with urological sequalae (36%). Six patients (3%) required a nephrectomy. CONCLUSION: IUI during colorectal surgery has few consequences for the patients if recognized early. Long-term urological sequelae can occur in a third of patients. IUI may affect oncological outcomes in colorectal surgery by delaying adjuvant chemotherapy, especially when the ureteral injury is not diagnosed peroperatively.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

What Is the Optimal Elective Colectomy for Splenic Flexure Cancer: End of the Debate? A Multicenter Study From the GRECCAR Group With a Propensity Score Analysis.

BACKGROUND: The optimal elective colectomy in patients with splenic flexure tumor is debated. OBJECTIVE: This study aimed to compare splenic flexure colectomy, left hemicolectomy, and subtotal colectomy for perioperative, histological, and survival outcomes in this setting. DESIGN: This is a multicenter retrospective cohort study. SETTING: Patients diagnosed with nonmetastatic splenic flexure tumor who underwent elective colectomy were included. PATIENTS: Between 2006 and 2014, 313 consecutive patients were operated on in 15 French Research Group of Rectal Cancer Surgery centers. INTERVENTIONS: Propensity score weighting was performed to compare short- and long-term outcomes. MAIN OUTCOME MEASURES: The primary end point was disease-free survival. Secondary end points included overall survival, quality of surgical resection, overall postoperative morbidity, surgical postoperative morbidity, and rate of anastomotic leakage. RESULTS: The most performed surgery was splenic flexure colectomy (59%), followed by subtotal colectomy (23%) and left hemicolectomy (18%). Subtotal colectomy was more often performed by laparotomy compared with splenic flexure colectomy and left hemicolectomy (93% vs 61% vs 56%, p < 0.0001), and was associated with a longer operative time (260 minutes (120-460) vs 180 minutes (68-440) vs 217 minutes (149-480), p < 0.0001). Postoperative morbidity was similar between the 3 groups, but the median length of hospital stay was significantly longer after subtotal colectomy (13 days (5-56) vs 10 (4-175) vs 9 (4-55), p = 0.0007). The median number of harvested lymph nodes was significantly higher after subtotal colectomy compared with splenic flexure colectomy and left hemicolectomy (24 (8-90) vs 15 (1-81) vs 16 (3-52), p < 0.0001). The rate of stage III disease and the number of patients treated by adjuvant chemotherapy were similar between the 3 groups. There was no difference in terms of disease-free survival and overall survival between the 3 procedures. LIMITATIONS: The study was limited by its retrospective design. CONCLUSIONS: In the elective setting, splenic flexure colectomy is safe and oncologically adequate for patients with nonmetastatic splenic flexure tumor. However, given the oncological clearance after splenic flexure colectomy, it seems that the debate is not completely closed. See Video Abstract at http://links.lww.com/DCR/B703. CUL ES LA COLECTOMA ELECTIVA PTIMA PARA EL CNCER DE NGULO ESPLNICO FIN DEL DEBATE UN ESTUDIO MULTICNTRICO DEL GRUPO GRECCAR CON UN ANLISIS DE PUNTAJE DE PROPENSIN: ANTECEDENTES:La colectomía electiva óptima en pacientes con tumores del ángulo esplénico continua en debate.OBJETIVO:Comparar la colectomía de ángulo esplénico, hemicolectomía izquierda y colectomía subtotal para los resultados perioperatorios, histológicos y de supervivencia en este escenario.DISEÑO:Estudio de cohorte retrospectivo multicéntrico.ESCENARIO:Se incluyeron pacientes diagnosticados de tumores del ángulo esplénico no metastásicos que se sometieron a colectomía electiva.PACIENTES:Entre 2006 y 2014, 313 pacientes consecutivos fueron intervenidos en 15 centros GRECCAR.INTERVENCIONES:Se realizó una ponderación del puntaje de propensión para comparar los resultados a corto y largo plazo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la supervivencia libre de enfermedad. Los criterios de valoración secundarios incluyeron la supervivencia general, la calidad de la resección quirúrgica, la morbilidad posoperatoria general, la morbilidad posoperatoria quirúrgica y la tasa de fuga anastomótica.RESULTADOS:La cirugía más realizada fue la colectomía del ángulo esplénico (59%), seguida de la colectomía subtotal (23%) y la hemicolectomía izquierda (18%). La colectomía subtotal se realizó con mayor frecuencia mediante laparotomía en comparación con la colectomía de ángulo esplénico y la hemicolectomía izquierda (93% frente a 61% frente a 56%, p <0.0001), y se asoció con un tiempo quirúrgico más prolongado (260 min [120-460] frente a 180 min [68-440] frente a 217 min [149-480], p <0.0001). La morbilidad posoperatoria fue similar entre los tres grupos, pero la duración media de la estancia hospitalaria fue significativamente más prolongada después de la colectomía subtotal (13 días [5-56] frente a 10 [4-175] frente a 9 [4-55], p = 0.0007). La mediana del número de ganglios linfáticos extraídos fue significativamente mayor después de la colectomía subtotal en comparación con la colectomía del ángulo esplénico y la hemicolectomía izquierda (24 [8-90] frente a 15 [1-81] frente a 16 [3-52], p <0.0001). La tasa de enfermedad en estadio III y el número de pacientes tratados con quimioterapia adyuvante fueron similares entre los 3 grupos. No hubo diferencias en términos de supervivencia libre de enfermedad y supervivencia general entre los 3 procedimientos.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:En un escenario electivo, la colectomía del ángulo esplénico es segura y oncológicamente adecuada para pacientes con tumores del ángulo esplénico no metastásicos. Sin embargo, dado el aclaramiento oncológico tras la colectomía del ángulo esplénico, parece que el debate no está completamente cerrado. Consulte Video Resumen en http://links.lww.com/DCR/B703.

Circulating tumor DNA (ctDNA) in adjuvant therapy of early stage colon cancer: current status and future perspectives.

BACKGROUND: This article reviews the current knowledge on circulating tumor DNA (ctDNA) in early stage colon cancer and ongoing trials on ctDNA-guided treatment in the adjuvant setting. METHODS: A literature search of Pubmed was performed to identify studies on ctDNA in early stage colon cancer and neoadjuvant or adjuvant treatment. For ongoing trials, we searched clinicaltrials.gov and the Australian New Zealand Clinical Trials Registry (ANZCTR). RESULTS: Several studies show that ctDNA is a strong predictor for recurrence and survival after surgery and adjuvant chemotherapy. The specificity of this marker is extremely high, and the sensitivity is increasing with the development of technology. Recurrences can be detected very early and the analysis can potentially be used to guide neoadjuvant and adjuvant treatment. Ongoing and planned studies are now looking into escalation and de-escalation of therapy according to ctDNA-status after surgery. CONCLUSION: Serial measurement of ctDNA shows great promise as a marker for both prognosis and response to treatment in early colon cancer. Future studies will show whether we can use this analysis for tailoring treatment for patients in the adjuvant and neoadjuvant setting. With improved technology, ctDNA has the potential of becoming a 'game-changer' in the treatment of early stage colon cancers.

Acute Abdominal Complications in Deeply Neutropenic Onco-Hematology Patients: A Retrospective Series of 105 Cases.

BACKGROUND: Acute abdominal complications (AAC) in patients with deep neutropenia (DN) is challenging to manage because of the expected influence of AAC on oncological prognosis and higher surgical complication rate in a period of DN. In practice, these parameters are difficult to appreciate. This study reported our experience in managing these patients. METHODS: All consecutive patients treated in our tertiary care cancer center between 2010 and 2020 who developed AAC in the context of a DN were retrospectively analyzed. AAC was defined as an infection (intra-abdominal, perineal, or cutaneous), bowel obstruction, or intra-abdominal hemorrhage. FINDINGS: Among 105 patients, 18 (17%) required emergent surgery (group 1), 34 patients had a complication requiring surgical oversight (group 2), and 53 patients had a non-surgical etiology (group 3). Fifteen patients underwent surgery in the group 1, three in group 2, and one in group 3. Overall, 28 patients died during hospitalization. Mortality was statistically different between the groups (p = 0·01), with a higher rate in group 1 (n = 9/18, 50%) than in group 2 (n = 11/34, 32%) and group 3 (n = 8/53, 15%). All groups together had a median overall survival (OS) of 14 months and disease-free survival (DFS) of 10 months. OS was not comparable between the groups, and the median length of survival in group 1 was 6 months versus 8 months in group 2 and 23 months in group 3. In group 1, five patients (5/18, 28%) did not relapse at the end of the follow-up compared to 13 in group 2 (13/34, 38%) and 25 in group 3 (25/53, 47%). After discharge, OS and DFS were similar between the groups. INTERPRETATION: The advent of an AAC necessitating surgery in the context of DN is a deadly event associated with a 50% mortality; nonetheless, in case of unpostponable emergencies, surgery can provide long-term survival in selected patients.

Long-Term Results after Surgical Resection of Peritoneal Metastasis from Neuroendocrine Tumors.

INTRODUCTION: Peritoneal metastases from neuroendocrine tumors are associated with a bad prognosis. The objective of our study was to evaluate whether surgical resection could lead to prolonged survival in selected patients. This survival was compared to that of patients operated for liver metastasis. METHODS: From our prospectively maintained database we included 88 patients who underwent the complete resection of peritoneal and/or liver metastasis between January 1995 and December 2016 in Gustave-Roussy. Three resection groups were compared: peritoneal metastasis alone, liver metastasis alone, and the combined resection of liver and peritoneal metastases. RESULTS: The median peritoneal cancer index was 10 in the peritoneal group and 11 in the peritoneal + liver group. The 5-year overall survival was 81% (60-100) in the peritoneal group compared to 78% (65.2-92.8) in the liver group, and 72% (58.7-89.7) in the peritoneal + liver group (p = 0.71). The 3-year disease-free survival reached 26.9% (16.1-45.1) in the liver group, 12.5% (2.3-68.2) in the peritoneal group, and 32.4% (19.9-52.6) in the combined liver + peritoneal group (p = 0.45). In the univariate analysis, the prognosis factors for a longer survival were: small bowel primary tumor origin, low preoperative chromogranin A level, and tumor grade ≤1. CONCLUSION: Despite a high recurrence rate, long-term overall survival can be achieved after the resection of peritoneal metastasis in selected patients. This survival is comparable to that of patients operated for liver metastasis only. Surgery should stand as a standard treatment for peritoneal metastases in patients with resectable disease.

Strategies for Managing Intraoperative Discovery of Limited Colorectal Peritoneal Metastases.

BACKGROUND: Management of limited synchronous colorectal peritoneal metastases (CRPM) is critical to outcome. Resection of the primary tumor and CRPM can be performed concurrently, followed by hyperthermic intraperitoneal chemotherapy (HIPEC) either immediately, during the same procedure (one-stage), or during a systematic second-stage procedure (two-stage). OBJECTIVE: The aim of this study was to compare these two strategies for morbidity, mortality, and survival. METHODS: All patients presenting with limited (initial Peritoneal Cancer Index [PCI] ≤ 10) synchronous CRPM who had undergone complete cytoreductive surgery plus HIPEC between 2000 and 2016 were selected from a prospectively maintained institutional database. RESULTS: Overall, 74 patients were included-31 in the one-stage group and 43 in the two-stage group. During second-stage surgery, a peritoneal recurrence was diagnosed in 37 (86%) patients, 12 of whom had a PCI > 10 (28%) and 2 of whom had unresectable disease (5%). Among the one-stage group, peritoneal recurrence occurred in 29% of patients after a median delay of 23 months. Overall survival at 1, 3, and 5 years was similar between the two groups, i.e. 96%, 59%, and 51% for the one-stage group, and 98%, 77%, and 61% for the two-stage group. A PCI > 10 at the time of HIPEC, as well as liver metastases, were independent negative prognostic factors. CONCLUSIONS: For incidental limited CRPM diagnosed during primary tumor resection, one-stage curative treatment is preferable, avoiding a supplementary surgical procedure. Given the critical issues associated with completeness of resection, patients should be referred to centers specialized in peritoneal surgery.

Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial - PACHA-01 (NCT02494973).

BACKGROUND: After curative-intent surgery for colorectal liver metastases (CRLM), liver recurrence occurs in more than 60% of patients, despite the administration of perioperative or adjuvant chemotherapy. This risk is even higher after resection of more than three CRLM. As CRLM are mostly supplied by arterial blood flow, hepatic arterial infusion (HAI) of chemotherapeutic agents after resection of CRLM is an attractive approach. Oxaliplatin-based HAI chemotherapy, in association with systemic fluoropyrimidines, has been shown to be safe and highly active in patients with CRLM. In a retrospective series of 98 patients at high risk of hepatic recurrence (≥4 resected CRLM), adjuvant HAI oxaliplatin combined with systemic chemotherapy was feasible and significantly improved disease-free survival compared to adjuvant, 'modern' systemic chemotherapy alone. METHODS/DESIGN: This study is designed as a multicentre, randomized, phase II/III trial. The first step is a non-comparative randomized phase II trial (power, 95%; one-sided alpha risk, 10%). Patients will be randomly assigned in a 1:1 ratio to adjuvant systemic FOLFOX (control arm) or adjuvant HAI oxaliplatin plus systemic LV5FU2 (experimental arm). A total 114 patients will need to be included. The main objective of this trial is to evaluate the potential survival benefit of adjuvant HAI with oxaliplatin after resection of at least 4 CRLM (primary endpoint: 18-month hepatic recurrence-free survival rate). We also aim to assess the feasibility of delivering at least 4 cycles of HAI (or i.v.) oxaliplatin after surgical treatment of at least 4 CRLM, the toxicity (NCI-CTC v4.0) of adjuvant HAI plus systemic chemotherapy, including HAI catheter-related complications, compared to systemic chemotherapy alone, and the efficacy of adjuvant HAI on hepatic and extra-hepatic recurrence-free (survival and overall survival). DISCUSSION: If 18-month hepatic recurrence-free survival is greater than 50% in the experimental arm, the study will be pursued in phase III, for which the primary endpoint will be 3-year recurrence-free survival rate. Patients randomized in the phase II will be included in the phase III, with an additional number of 106 patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02494973 . Trial registration date: July 10, 2015.

Radiofrequency ablation for colorectal cancer liver metastases initially greater than 25 mm but downsized by neo-adjuvant chemotherapy is associated with increased rate of local tumor progression.

BACKGROUND: Radiofrequency ablation (RFA) is a valid treatment for liver metastases from colorectal cancer (CRLM) smaller than 25 mm and unsuitable for surgical resection. Tumor size is predictive for local tumor progression (LTP). The aim of this study was to evaluate whether RFA is indicated for lesions >25 mm at presentation but <25 mm after chemotherapy. METHOD: Patients who underwent RFA for CRLM after chemotherapy (January 2004-December 2012) were reviewed. Metastases were classified according to their size. Group 1: ≤25 mm before and after chemotherapy. Group 2A: >25 mm before but ≤25 mm after chemotherapy. Group 2B: >25 mm before and after chemotherapy. RESULTS: 133 CRLM were ablated in 83 patients (median follow-up 56 months). At 1-year, the LTP rate was higher in group 2A than in group 1 (32% vs. 16%, p ≤ 0.001). The highest rate of 1-year LTP was 64% in group 2B. Time to LTP (TLTP) was shorter in group 2A than in group 1 (HR: 2.89; 95% CI [1.04-8.01]; p = 0.004). Following multivariate analysis, the group type was the only predictive factor for TLTP (p < 0.001). CONCLUSIONS: RFA is not the optimal treatment for CRLM > 25 mm at presentation.

Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy.

BACKGROUND: This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM). METHODS: Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy. RESULTS: The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15-39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0-35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6-30). After a median follow-up period of 18 months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy. CONCLUSION: Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate.

Strategies to prevent peritoneal carcinomatosis arising from colorectal cancer.

In the last decades, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy became a curative option for peritoneal metastases in selected patients, otherwise considered for palliative therapy alone. Better knowledge of physiopathology of peritoneal spread and identification of predictive factors for peritoneal relapse prompted specialized centers to investigate the role of a 'proactive approach' in order to early detect peritoneal metastasis. These encouraging data could justify an active attitude in selected patients at high risk of peritoneal recurrence after curative resection of primary tumor. Selection criteria and the timing of complementary hyperthermic intraperitoneal chemotherapy remain important points of discussion. In this article, we will discuss treatment principles and future perspectives to early treat and, if possible, to prevent peritoneal dissemination after curative treatment of colorectal cancer.

Ninety percent of the adverse outcomes occur in 10% of patients: can we identify the populations at high risk of developing peritoneal metastases after curative surgery for colorectal cancer?

BACKGROUND: Peritoneal metastases (PM) occur in 3.4-6.3% after curative surgery for non-metastatic colorectal cancer. Systematic "2nd look" surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer. METHODS: A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate. RESULTS: Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified. CONCLUSIONS: Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype.

Linear Relationship of Peritoneal Cancer Index and Survival in Patients with Peritoneal Metastases from Colorectal Cancer.

BACKGROUND: The peritoneal cancer index (PCI) is the main prognostic factor for establishing potentially resectable peritoneal metastases from colorectal cancer. Attempts have been made to set a PCI cutoff on which to base indications of complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), but none have reached consensus. The aim of this study was to investigate the relation between the PCI and overall survival (OS). METHODS: We included all consecutive patients homogeneously treated with CCRS and HIPEC between 2003 and 2012. The PCI was calculated at the end of the surgical procedure. The correlation between the PCI and OS was studied using statistical modeling from the simplest to the most complex methods (including linear, quadratic, cubic, and spline cubic). These models were compared by Akaike's information criteria (AIC). RESULTS: For the 173 treated patients, 5-year OS reached 41 %. The mean PCI was 10.2 (±6.8). The linear model was the most appropriate to relate the PCI to OS as confirmed with the AIC scoring system. In multivariate analysis, the PCI was confirmed as being the most important prognostic factor (hazard ratio = 1.1 for each supplementary point, p < 0.0001). CONCLUSIONS: There is a perfect linear correlation between the PCI and OS, which precludes setting a unique PCI cutoff for CCRS + HIPEC. Overall, CCRS + HIPEC is generally indicated for PCI < 12 and contraindicated for PCI > 17. Between 12 and 17, other parameters have to be taken into account, such as the presence of extraperitoneal metastases, general performance status, and chemosensitivity.

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.

Laparoscopic Versus Open Surgery for Gastric Gastrointestinal Stromal Tumors: What Is the Impact on Postoperative Outcome and Oncologic Results?

OBJECTIVES: The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). BACKGROUND: The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown. METHODS: Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. RESULTS: In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively). CONCLUSIONS: Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Adjuvant chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence: a comparative study between hepatic arterial infusion of oxaliplatin and modern systemic chemotherapy.

INTRODUCTION: After curatively intended surgery for colorectal liver metastases, liver recurrences occur in more than 60% of patients, despite the administration of adjuvant systemic chemotherapy. The aim of this study was to assess the benefit of combined adjuvant hepatic arterial infusion (HAI) and intravenous (IV) 5-FU compared with standard modern adjuvant IV chemotherapy in patients at high risk of hepatic recurrence. PATIENTS AND METHODS: From January 2000 to December 2009, 98 patients, who had undergone curative resection of at least 4 colorectal liver metastases, were selected from a prospective database. Among them, 44 (45%) had received postoperative HAI combined with systemic 5-FU (HAI group) and 54 (55%) had received "modern" systemic chemotherapy (IV group). RESULTS: The 2 groups were similar in terms of age, sex, the stage of the primary, and the administration of preoperative chemotherapy. The median number of HAI cycles received per patient was 7 [range, 1-12]. Twenty-nine patients (66%) had received at least 6 cycles of HAI oxaliplatin, and 22 patients (50%) had received the full planned treatment. For the remaining 22 patients (50%), HAI chemotherapy had been discontinued because of toxicity (n = 8), HAI catheter dysfunction (n = 6), an early recurrence (n = 6), and patient's refusal (n = 2). After a median follow-up of 60 months (51-81 months), 3-year overall survival was slightly higher in the HAI group (75% vs 62%, P = 0.17). Three-year disease-free survival was significantly longer in patients in the HAI group than those in the IV group (33% vs 5%, P < 0.0001). In the multivariate analysis, adjuvant HAI chemotherapy and an R0 resection margin status were the only independent predictive factors for prolonged disease-free survival. CONCLUSIONS: Postoperative HAI oxaliplatin combined with systemic chemotherapy after curatively intended surgery of colorectal liver metastases is feasible and may significantly improve disease-free survival of patients at high risk of hepatic recurrence compared with adjuvant modern systemic chemotherapy alone. These results should be confirmed in a randomized study.

Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients.

BACKGROUND: Multiplex digital PCR (dPCR) enables noninvasive and sensitive detection of circulating tumor DNA with performance unachievable by current molecular-detection approaches. Furthermore, picodroplet dPCR facilitates simultaneous screening for multiple mutations from the same sample. METHODS: We investigated the utility of multiplex dPCR to screen for the 7 most common mutations in codons 12 and 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) oncogene from plasma samples of patients with metastatic colorectal cancer. Fifty plasma samples were tested from patients for whom the primary tumor biopsy tissue DNA had been characterized by quantitative PCR. RESULTS: Tumor characterization revealed that 19 patient tumors had KRAS mutations. Multiplex dPCR analysis of the plasma DNA prepared from these samples identified 14 samples that matched the mutation identified in the tumor, 1 sample contained a different KRAS mutation, and 4 samples had no detectable mutation. Among the tumor samples that were wild type for KRAS, 2 KRAS mutations were identified in the corresponding plasma samples. Duplex dPCR (i.e., wild-type and single-mutation assay) was also used to analyze plasma samples from patients with KRAS-mutated tumors and 5 samples expected to contain the BRAF (v-raf murine sarcoma viral oncogene homolog B) V600E mutation. The results for the duplex analysis matched those for the multiplex analysis for KRAS-mutated samples and, owing to its higher sensitivity, enabled detection of 2 additional samples with low levels of KRAS-mutated DNA. All 5 samples with BRAF mutations were detected. CONCLUSIONS: This work demonstrates the clinical utility of multiplex dPCR to screen for multiple mutations simultaneously with a sensitivity sufficient to detect mutations in circulating DNA obtained by noninvasive blood collection.

Ovarian metastasis is associated with retroperitoneal lymph node relapses in women treated for colorectal peritoneal carcinomatosis.

PURPOSE: To analyze the patterns of recurrence and the prognostic impact of ovarian metastases (OM) in a population of women with colorectal peritoneal carcinomatosis (CRPC) treated with curative intent. METHODS: Data from all consecutive women with CRPC who underwent curatively intended complete cytoreductive surgery (CRS) plus intraperitoneal chemotherapy at our institution were retrieved from a prospective database. A bilateral oophorectomy or a complementary unilateral oophorectomy was systematically performed during CRS. RESULTS: From 1994 to 2009, among 105 women who underwent CRS plus intraperitoneal chemotherapy for CRPC, 62 (60 %) had OM. Women with and without OM had comparable peritoneal cancer index (PCI) scores (10 vs. 12, respectively, p = 0.09). After a median follow-up of 60 (range 5-145) months, median overall survival of women with OM did not differ statistically from that of women without OM (respectively, 36 and 40 months; p = 0.75). Relapses occurred in 82 % of the patients, distributed similarly between the two groups except for retroperitoneal lymph node recurrence, which occurred in 19 patients (18 %), including 18 with OM. The only predictive factor for a retroperitoneal relapse was a history of OM (p = 0.0012). CONCLUSIONS: Retroperitoneal lymph node recurrence seems to be linked to OM originating from colorectal cancer and could worsen the prognosis. A systematic lymphadenectomy could be evaluated in women with isolated OM or very limited peritoneal carcinomatosis to analyze the incidence of invaded lymph nodes and study its potential benefit on survival.

The Position of Circulating Tumor DNA in the Clinical Management of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer type worldwide, with over 1.9 million new cases and 935,000 related deaths in 2020. Within the next decade, the incidence of CRC is estimated to increase by 60% and the mortality by 80%. One of the underlying causes of poor prognosis is late detection, with 60 to 70% of the diagnoses occurring at advanced stages. Circulating cell-free DNA (ccfDNA) is probably the most promising tool for screening, diagnosis, prediction of therapeutic response, and prognosis. More specifically, the analysis of the tumor fraction within the ccfDNA (circulating tumor DNA, ctDNA) has great potential to improve the management of CRC. The present review provides an up-to-date and comprehensive overview of the various aspects related to ctDNA detection in CRC.