Amine Souadka

The impact of perioperative chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: a multicenter comparative study.

Objective:The aim of this retrospective study was to evaluate the survival impact of perioperative chemotherapy (PCT) in patients with gastric signet ring cell (SRC) adenocarcinoma. Background:PCT is a standard treatment for advanced resectable gastric adenocarcinoma (GA). SRC has a worse prognosis compared to non-SRC and the chemosensitivity of SRC is uncertain. Methods:Among 3010 patients registered in 19 French centers between January 1997 and January 2010, 1050 (34.9%) were diagnosed with SRC. Of those treated with curative intent (n = 924), 171 (18.5%) received PCT with surgery (PCT group), whereas 753 (81.5%) were treated with primary surgery (S group). PCT was based mainly on a fluorouracil-platinum doublet or triplet regimen. Results:The groups were comparable regarding age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, tumor location and cTNM stage. 60 patients did not undergo resection because of tumor progression (10) or metastases (50) found at operation. The R0 resection rates were 65.9% and 62.3% in the S and PCT groups, respectively (P = 0.308). Fewer patients received adjuvant chemotherapy in the S group than in the PCT group (35.2% vs. 66.5%, P < 0.001). At a median follow-up of 31.5 months, the median survival was shorter in the PCT group (12.8 vs. 14.0 months, P = 0.043). On multivariate analysis, PCT was found to be an independent predictor of poor survival (HR = 1.4, 95% CI 1.1–1.9, P = 0.042). Conclusions:PCT provides no survival benefit in patients with gastric SRC. Clinical Trial.gov record: ADCI001, Clinical Trial.gov identifier NCT01249859.

Definition of Patients Presenting a High Risk of Developing Peritoneal Carcinomatosis After Curative Surgery for Colorectal Cancer: A Systematic Review

BackgroundIn colorectal cancer, complete cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy achieves encouraging results in early peritoneal carcinomatosis (PC), but this early detection can only be accurately accomplished during a systematic second-look surgery. This costly and invasive approach can only be proposed to selected patients. The objective of this study was to identify risk factors predictive of developing PC after curative surgery for colorectal cancer.MethodsAfter a systematic review of the literature published between 1940 and 2011, all clinical studies reporting the incidence of PC after curative surgery for colorectal cancer were searched for factors associated with the primary tumor that were likely to influence the incidence of recurrent PC.ResultsSixteen clinical studies were considered informative, all nonrandomized, three prospective and 13 retrospective, including 4–395 patients. Overall, the methodological quality of the reported studies was low. Data were available for the following factors: synchronous PC, synchronous ovarian metastases, perforated primary tumor, serosal and/or adjacent organ invasion, histological subtype, and positive peritoneal cytology with reported incidences of recurrent PC between 8 and 75xa0%. No study was found that mentioned an impact of lymph node invasion, tumor location, laparoscopy, occlusive tumors, or bleeding tumor on recurrent PC.ConclusionsEvidence regarding the incidence of recurrent PC after curative surgery for colorectal cancer is poor. Emerging data indicate three situations that could result in a real higher risk of recurrent PC: synchronous PC, synchronous isolated ovarian metastases, and a perforated primary tumor.

Extent of Colorectal Peritoneal Carcinomatosis: Attempt to Define a Threshold Above Which HIPEC Does Not Offer Survival Benefit: A Comparative Study

BackgroundThe main prognostic factors after complete cytoreductive surgery (CCRS) of colorectal peritoneal carcinomatosis (PC) followed by intraperitoneal chemotherapy (IPC) are completeness of the resection and extent of the disease. This study aimed to determine a threshold value above which CCRS plus IPC may not offer survival benefit compared with systemic chemotherapy.MethodsBetween March 2000 and May 2010, 180 patients underwent surgery for PC from colorectal cancer with intended performance of CCRS plus IPC.ResultsAmong the 180 patients, CCRS plus IPC could be performed for 139 patients (curative group, 77xa0%), whereas it could not be performed for 41 patients (palliative group, 23xa0%). The two groups were comparable in terms of age, gender, primary tumor characteristics, and pre- and postoperative systemic chemotherapy. The mean peritoneal cancer index (PCI) was lower in the curative group (11xa0±xa07) than in the palliative group (23xa0±xa07) (pxa0<xa00.0001). After a median follow-up period of 60xa0months (range 47–74xa0months), the 3-year overall survival (OS) rate was 52xa0% [95xa0% confidence interval (CI) 43–61xa0%] in the curative group compared with 7xa0% (95xa0% CI 2–25xa0%) in the palliative group. Comparison of the survivals for each PCI (ranging from 5 to 36) shows that OS did not differ significantly between the two groups of patients when the PCI was higher than 17 (hazard ratio 0.64; range 0.38–1.09).ConclusionThis study confirmed the major prognostic impact of PC extent. When the PCI exceeds 17 in PC of colorectal origin, CCRS plus IPC does not seem to offer any survival benefit.

Patients operated on for initially unresectable colorectal liver metastases with missing metastases experience a favorable long-term outcome.

Background:After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with “missing CRLMs.” Patients:Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. Results:After a median follow-up of 55 months (24–137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. Conclusion:Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.

Variation in the peritoneal cancer index scores between surgeons and according to when they are determined (before or after cytoreductive surgery)

INTRODUCTIONnThe prognosis of peritoneal carcinomatosis (PC) is highly dependent on the extent of the PC. This extent is calculated by the peritoneal cancer index (PCI). In the future, the indications for complete cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) should be partially based on the PCI. This raises the question of the concordance between the PCI scores calculated by different surgeons, and a possible variation before and after CRS.nnnOBJECTIVEnTo analyze variations in the PCI score between surgeons and according to when it is determined (before and after surgery).nnnPATIENTS AND METHODSnProspective recording of the PCI score independently calculated by senior and junior surgeons, before CRS (when the surgeon decided to perform this procedure), and after CRS, in 75 consecutive patients. A concordance analysis was conducted.nnnRESULTSnThe origins of the PC were colorectal (n = 38), pseudomyxoma (n = 22), mesothelioma (n = 8) and miscellaneous lesions (n = 7). Concordance between the PCI score was very high (close to 90%) among the senior surgeons and junior surgeons before and after CRS. After CRS, the mean PCI score increased by 1.75 (IC-95%: 2.09-1.41). This high concordance was similar whatever the level of the PCI score and whatever the origin of the tumor.nnnCONCLUSIONnThe PCI is a reliable tool for measuring the extent of PC. It is easy to use and inter-surgeon concordance is high. It increases by approximately 2 before and after CRS.

Risk factors of peritoneal recurrence in eso-gastric signet ring cell adenocarcinoma: Results of a multicentre retrospective study

INTRODUCTIONnThe poor prognosis of signet ring cell (SRC) eso-gastric adenocarcinoma (EGA) might be explained by its great affinity for the peritoneum. The aim of this study was to identify predictors of peritoneal carcinomatosis recurrence (PCR) after curative surgery and hence identify high risk patients.nnnMETHODSnA retrospective national survey was conducted over 19 French surgical centers between 1997 and 2010. Patients with non-metastatic disease who benefited from curative surgery without postoperative death were included. Event-free patients who did not reach the time point of 24 months were excluded.nnnRESULTSnIn a cohort of 3010 patients, 1050 were SRC EGA and 424 patients met the selection criteria. The tumor location was mainly gastric (68.9%) and a total gastrectomy was performed in 218 patients (51.4%). Chemoradiotherapy or chemotherapy alone was given preoperatively to 71 (16.7%) and postoperatively to 150 (35.4%) patients. After a median follow-up of 54 months, recurrence was diagnosed in 214 patients (50.5%) within a mean delay of 17 ± 10.7 months. PCR was diagnosed in 81 patients (19.1%). In multivariable analysis, four factors were identified as predictors of PCR: linitis plastica (p < 0.001; OR = 4.83), tumor invasion of/or through the peritoneal serosa (p = 0.022; OR = 1.58), lymph node involvement (p = 0.005; OR = 1.7) and tumors of gastric origin (p = 0.026; OR = 2.36), with PCR rates of 55%, 26%, 23% and 22%, respectively.nnnCONCLUSIONnIdentification of strong predictors for PCR among this large series of SRC EGA patients helps to identify subgroups of patients that may benefit from specific therapeutic strategies such as prophylactic hyperthermic intraperitoneal chemotherapy.

HIPEC for Peritoneal Carcinomatosis: Does an Associated Urologic Procedure Increase Morbidity?

PurposeTo report the incidence of urinary tract procedures performed during complete cytoreductive surgery (CCRS) plus intraperitoneal chemotherapy, and to report the types of procedure, specific morbidity, risk factors, and treatment.MethodsData were extracted from a prospective database of patients with malignant peritoneal disease treated with CCRS plus intraperitoneal chemotherapy who had undergone a resection or suture of the bladder, ureter, or kidney. Patients were eligible whatever the tumor origin.ResultsBetween 1994 and 2010, among the 598 patients treated with CCRS plus intraperitoneal chemotherapy, 48 (8%) had undergone a resection or suture in the urinary tract. Procedures included 4 nephrectomies, 19 partial cystectomies, 8 surgically repaired bladder injuries, and 18 ureteral resections. Postoperative mortality was 4% and morbidity was 41%. Specific complications included 6 urinary fistulas (12%), two among the 27 bladder sutures (7%) and four among the 18 ureteral sutures (22%) (Pxa0=xa0NS). In the multivariate analysis, the risk factors for urinary fistula were severe preoperative malnutrition (Pxa0=xa00.05, relative risk [RR]xa0=xa07.3) and extensive peritoneal disease (peritoneal cancer index ≥20, Pxa0=xa00.05, RRxa0=xa08.3). Urinary fistulas had been treated nonsurgically in most of the cases.ConclusionsAssociated urinary tract procedures had occurred in 8% of the cases but did not greatly increase morbidity. Therefore, urinary tract involvement or injury are not contraindications to performing CCRS plus intraperitoneal chemotherapy. Fistulas had complicated only 12% of urinary sutures, mainly in cases of malnutrition or extensive peritoneal disease.

Impact of perineal pseudocontinent colostomy on perineal wound healing after abdominoperineal resection

Abdominoperineal resections (APR) for anorectal tumors are associated with a high rate of perineal wound complications. The aim of this study was to evaluate the impact of pseudocontinent perineal colostomy (PPC) following APR on perineal wound healing.

Radiation induced rectal cancer: a case report with review of the literature

Cervical cancer is the second most common cancer and the third cause of cancer death in women. Radiotherapy occupies a prominent place in the therapeutic arsenal of cervical cancer in localized stages. Radiation induced secondary cancer is an entity that has been well described in the literature. We report a case of a rectal adenocarcinoma occurring in a woman previously treated by radiotherapy and brachytherapy for a squamous cell carcinoma of the cervix.

Can we rely on the adequate mesorectum excision and the complete pathological response in case of rectal signet-ring cell carcinoma?

Lino-Silva et al. reported an interesting study describing the relationship between the quality of total mesorectal excision (TME) and survival of patients [1]. They found that patients with adequate TME had lower recurrence rates and better survival compared to inadequate TME. We do agree with the authors that the quality of TME in rectal tumors significantly impacts patients’ oncological outcomes. Other important prognostic factors for rectal cancer include response to neoadjuvant chemotherapy and tumor histologic features [2].We would like to focus specifically on the prognosis of patients with rectal signet ring cell carcinoma (SRCC) who achieved an adequate TME after complete pathological response (pCR) to neoadjuvant chemoradiotherapy. Patients achieving a pCR have better outcomes compared to those who do not achieve a pCR in rectal adenocarcinoma, with low rates of local recurrences (0–2.6%) [3,4] On the contrary, SRCC tumors are known to be aggressive, associated with poor survival and higher rates of local recurrences [5]. Is pCR and TME in the case of SRCC rectal adenocarcinoma associated with better prognosis? Our experience of two cases of local recurrence after pCR and adequate TME in patients with rectal SRCC has led us to reevaluate this question. The patientswere a 46-year old female and a 50-year oldmale, both had a cT3N1 low rectal SRCC. There were no distant metastases on computed tomography. Both patients received neoadjuvant chemoradiotherapy (CRT) to the whole pelvis (50.4Gy) with Capecitabine, followed 6 and 8 weeks later by curative surgical resections (abdominoperineal resection and anterior resection, respectively). The pathology reports showed a pCR. In both cases, the mesorectal excision was adequate and the distal and lateralmarginswere negative. Five negative lymph nodeswere retrieved in the two cases. The female patient was readmitted eight months later for a pelvic mass involving the vagina, the bladder, and the two ureters, compatible with a local recurrence. The male patient was readmitted 16 months later for pelvic recurrence and generalized carcinomatosis. Both of these cases of rectal SRCC were associated with poor prognosis despite a pCR after neoadjuvant therapy and good quality surgery. Pathologists were asked to review the surgical specimens twice to ensure the absence of residual tumor cells. Therefore, the occurrence of early local recurrences is more probably related to the histologic type of the tumors. It would be interesting if Lino-Silva et al. could report specifically the outcomes of their patients with rectal SRCC who achieved an adequate mesorectal excision with pCR, compared to those who did not achieve a pCR. Based on these two cases, we hypothesize that in case of SRCC, although a pCR may be achieved after neoadjuvant CRT with good quality TME, it would not necessarily be associated with better prognosis. A large study analyzing the prognosis of this subgroup of patients may be necessary to clarify this question. In the meantime, we suggest that physicians should be careful in predicting the prognosis in such cases and in the information given to their patients.