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

BACKGROUND: 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. METHODS: All patients undergoing APR between 2000 and 2009 were retrospectively reviewed. Perineal wound healing was compared between patients with PPC and those with perineal closure alone. RESULTS: APR was performed in 132 patients, including 31 with PPC and 101 with no PPC. Risk factors such as radiotherapy, smoking, diabetes mellitus, and obesity were not different between the two groups. The PPC group had significantly fewer cases of omentoplasty and adenocarcinoma histology. The overall perineal complication rate, perineal infection, or wound dehiscence was similar in the two groups, but the perineal healing rate at 6 and 12 weeks was significantly increased in the PPC group than in the non-PPC group (70.9% vs. 50%, P = 0.04, at 6 weeks; 90.3% vs. 73%, P = 0.04, at 12 weeks). CONCLUSIONS: PPC accelerates perineal wound healing after APR without decreasing the overall perineal complication rate.

Oncologic and functional results after abdominoperineal resection plus pseudocontinent perineal colostomy for epidermoid carcinoma of the anus.

PURPOSE: Surgical treatment for epidermoid carcinoma of the anus is reserved for patients after failure of primary chemoradiotherapy and consists of abdominoperineal resection with permanent iliac colostomy. The purpose of this study was to analyze the oncologic and the functional outcomes after abdominoperineal resection and pseudocontinent perineal colostomy for epidermoid carcinoma of the anus after external radiation at maximal doses (60 Gy). METHODS: Between 1990 and 2006, 95 patients underwent abdominoperineal resection for an epidermoid carcinoma of the anus. Eighteen (19 percent) underwent construction of a pseudocontinent perineal colostomy. Functional results were evaluated prospectively at regular intervals. RESULTS: Complete resection (R0) was obtained in 17 of 18 patients. After a median follow-up of 33 (range, 12-198) months, 15 of 18 patients were alive, and 11 were disease free. Five-year overall and disease-free survival rates were 67 and 53 percent, respectively. Functional outcomes were available for 16 patients. According to the Kirwan score, 15 were continent, and 13 did not require pad protection. Overall, 15 of 16 patients were satisfied. CONCLUSION: Pelvic reconstruction with a pseudocontinent perineal colostomy does not compromise the beneficial effect of salvage surgery, seems to be safe and feasible even after a high dose of radiotherapy, and provides a high degree of satisfaction.

Sentinel lymph nodes of colorectal carcinoma: reappraisal of 123 cases.

AIMS: Results concerning the usefulness of the sentinel lymph node (SLN) in colorectal carcinoma have been discordant. The SLN technique may be used to guide surgical resection (lymph mapping), restrict the lymph node analysis solely to the SLN (accuracy) and upgrade tumor staging when micrometastases are specifically detected in the SLN. METHODS: The blue dye injection technique was used. Serial sections of the SLNs were analyzed after hematoxylin-eosin (HES) staining. RESULTS: The SLN technique was tested in 123 patients, successfully in 112/118 (feasibility 95%) (five intraoperative exclusions). On average, twenty lymph nodes (range: 5-74) and two SLNs (range: 1-5) were identified. Lymph mapping was used in 11% of patients to guide surgical resection; the SLN was negative in 14 of 36 N+ patients (39% false-negatives); HES staining enabled detection of micrometastases in 8 of 84 initially N0 patients (10% secondary upgrading to N+). CONCLUSION: Limiting node analysis to the SLN cannot replace a complete pathology examination of all resected lymph nodes. Careful examination of serial sections of the SLN can however affect therapeutic decision making since staging may be upgraded in up to 10% of initially N0 patients.

Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Isolated hepatic metastases of colorectal cancer constitute a frequent and serious therapeutic problem that has led to the evaluation of hepatic arterial infusion (HAI) of different drugs. Oxaliplatin combined with fluorouracil (FU) and leucovorin is effective in the treatment of colorectal cancer. In this context, a phase II study was conducted to evaluate concomitant administration of oxaliplatin by HAI and intravenous (IV) FU plus leucovorin according to the LV5FU2 protocol (leucovorin 200 mg/m(2), FU 400 mg/m(2) IV bolus, FU 600 mg/m(2) 22-hour continuous infusion on days 1 and 2 every 2 weeks). PATIENTS AND METHODS: Patients had metastatic colorectal cancer that was restricted to the liver and inoperable. The patients were not to have previously received oxaliplatin. After surgical insertion of a catheter in the hepatic artery, patients were treated with oxaliplatin 100 mg/m(2) HAI combined with FU + leucovorin IV according to the LV5FU2 protocol. Treatment was continued until disease progression or toxicity. Response was evaluated every 2 months. RESULTS: Twenty-eight patients were included, and 26 patients were treated. Two hundred courses of therapy were administered, and the median number of courses received was eight courses (range, zero to 20 courses). The most frequent toxicity consisted of neutropenia. The main toxicity related to HAI was pain. The intent-to-treat objective response rate was 64% (95% CI, 44% to 81%; 18 of 28 patients). With a median follow-up of 23 months, the median overall and disease-free survival times were 27 and 27 months, respectively. CONCLUSION: The combination of oxaliplatin HAI and FU + leucovorin according to the LV5FU2 protocol is feasible and effective in patients presenting with isolated hepatic metastases of colorectal cancer.

Surgical treatment of peritoneal carcinomatosis from well-differentiated digestive endocrine carcinomas.

BACKGROUND: The presence of peritoneal carcinomatosis (PC) in association with endocrine carcinomas (EC) is generally considered to have no impact on life expectancy, contrary to liver metastases. This study was aimed at assessing the actual prognostic impact of PC and to evaluate a new treatment with respect to survival times. PATIENTS AND METHODS: Among 111 patients undergoing surgery for progressive, well-differentiated EC, 37 (33%) presented a histologically proven PC, with synchronous liver metastases in 36 of them. The origin was ileal or appendiceal (carcinoid tumors) in at least 81% of cases. The patients were divided into 2 groups. Patients in group 1 (n = 20) could not undergo complete resection of PC, while those in group 2 (n = 17) underwent complete cytoreductive surgery, followed by immediate intraperitoneal chemotherapy. Partial hepatectomy was performed in 65% of patients in group 2. The median follow-up was 6.9 years. RESULTS: There was no postoperative mortality, and the morbidity rate was 47%. In group 1, 15 of the 20 patients died (5-year survival rate, 40.9%). Deaths were caused either by liver failure (60% of patients) or bowel obstruction from PC (40%). In group 2, six of the 17 patients died (5-year survival rate, 66.2%; P = .007). These patients died of liver failure (n = 4, 23.5%), bowel obstruction (n = 1, 5.8%), and cerebral hemorrhage (n = 1, 5.8%). CONCLUSIONS: PC associated with EC is not a rare event; it is mainly caused by carcinoid tumors and is always associated with liver metastases. When present, PC is the direct cause of death in 40% of patients if no specific treatment is undertaken. Treatment of PC with maximal cytoreductive surgery and immediate intraperitoneal chemotherapy appears promising, even though it can only be considered as palliative.

Secondary implantation of an artificial sphincter after abdominoperineal resection and pseudocontinent perineal colostomy for rectal cancer.

INTRODUCTION: Fecal continence with a perineal colostomy performed after abdominoperineal resection (APR) is not always satisfactory despite retrograde colonic enemas. Functional improvement is currently examined using artificial sphincters. Preliminary results are disclosed. PATIENTS: In 3 female patients, 45, 59 and 68 years old, curative APR and perineal colostomy were performed after radiotherapy in 2, for T1-2N0 cancer of the lower rectum. Due to occasional leaks, need for strict diet and fear of incontinence, an Acticon Neosphincter (AMS) was implanted consecutively at a mean 4.5 years after APR. RESULTS: Device implantation was feasible and uneventful. In one case, a superficial hematoma was drained and healed by second intention. Devices were activated 3 months after implantation. At a mean 2.5 years follow-up, the 3 patients had an activated and functional artificial sphincter. Leaks and fecal urgency significantly decreased but colonic enemas were maintained. Dietary restrictions were less and quality of life improved. All 3 considered the device as a useful adjunct. CONCLUSION: In this limited experience, implantation of artificial sphincter around a perineal colostomy following APR for rectal cancer appeared feasible and safe even in case of previous radiotherapy. Mid-term tolerance was satisfactory. Continence and quality of life significantly improved.

Gene expression profile in human late radiation enteritis obtained by high-density cDNA array hybridization.

Late radiation enteritis is a sequela of radiation therapy to the abdomen. The pathogenic process is poorly understood at the molecular level. cDNA array analysis was used to provide new insights into the pathogenesis of this disorder. Gene profiles of six samples of fibrotic bowel tissue from patients with radiation enteritis and six healthy bowel tissue samples from patients without radiation enteritis were compared using membrane-based arrays containing 1314 cDNAs. Results were confirmed with real-time RT-PCR and Western blot analysis. Array analysis identified many differentially expressed genes involved in fibrosis, stress response, inflammation, cell adhesion, intracellular and nuclear signaling, and metabolic pathways. Increased expression of genes coding for proteins involved in the composition and remodeling of the extracellular matrix, along with altered expression of genes involved in cell- to-cell and cell-to-matrix interactions, were observed mainly in radiation enteritis samples. Stress, inflammatory responses, and antioxidant metabolism were altered in radiation enteritis as were genes coding for recruitment of lymphocytes and macrophages. The Rho/HSP27 (HSPB1)/zyxin pathway, involved in tissue contraction and myofibroblast transdifferentiation, was also altered in radiation enteritis, suggesting that this pathway could be related to the fibrogenic process. Our results provide a global and integrated view of the alteration of gene expression associated with radiation enteritis. They suggest that radiation enteritis is a dynamic process involving constant remodeling of each structural component of the intestinal tissue, i.e. the mucosa, the mesenchyme, and blood vessels. Functional studies will be necessary to validate the present results.

Preoperative selective portal vein embolization before hepatectomy for liver metastases: long-term results and impact on survival.

BACKGROUND: Some patients cannot undergo curative surgical procedures for liver metastases because of the risk of severe postoperative hepatic failure, which stems from a too-small future remaining liver (FRL). Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of the FRL, thus permitting safe hepatic resection. The aim of this retrospective study was to investigate the long-term results of this technique. METHODS: Sixty-eight patients underwent PVE. Of those, 60 (88%) subsequently underwent hepatic resection. Indication for PVE was an estimated FRL ratio (assessed by volumetric computed tomography) of less than 30%. However, if the patient had undergone multiple courses of chemotherapy, the threshold was 40%. The origin of the primary neoplasm was colorectal in 41 patients (68%); in the remaining 19 (32%), the primary neoplasms originated at other sites. RESULTS: Mean growth of the estimated FRL measured by computed tomography 1 month after PVE was 13%. Major complications after hepatectomy occurred in 27% of the patients, and the operative mortality rate was 3%. For the 60 patients who underwent PVE followed by hepatic resection, the 5-year overall survival rate and the disease-free survival rate were 34% and 24%, respectively. The 5-year overall survival rate and the disease-free survival rate of patients with colorectal metastases only were 37% and 21%, respectively. CONCLUSIONS: The long-term survival rate after PVE followed by resection is comparable with the survival rate obtained after resection without preoperative PVE. The 5-year survival rate of patients undergoing PVE followed by hepatectomy justifies the use of this technique. This technique thus increases the suitability of resection as a treatment choice for patients with liver metastases. PVE should number among the therapeutic options available to every hepatic surgeon.

Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study.

BACKGROUND: The timing and benefits of hepatectomy remain controversial for metastatic well-differentiated endocrine neoplasms, which are generally considered slow growth tumors. However, surveillance alone yields only a 22% 5-year survival when metastases occur. The aim of this study was to determine the results of hepatic and extra hepatic resections and to clarify the indications of surgery. METHODS: To define the role of hepatic resection, a database regrouping all patients (n = 47) who underwent hepatectomy with curative intent (R0 status) for well-differentiated endocrine neoplasms in the Gustave-Roussy Institute was constructed in 1984. New prognostic factors such as tumor growth and liver tumor mitotic index were studied. Median follow-up was 62 months. RESULTS: Hepatectomy was associated with extrahepatic tumor resection in 77% of the patients (primary tumor in 51%, lymph nodes in 21%, peritoneal carcinomatosis in 25%, and other in 6%). Resection was curative (R0) only in 53% of the patients, despite removing at least 97% of the tumor in each patient. Mortality was 5%, and morbidity was 45%. Median survival was 91 months, 5-year and 10-year overall survival rates were 71% and 35%, respectively. Liver recurrence rate was 75% at 10 years. No prognostic factor was correlated with overall survival in this population in which at least 97% of the tumor load was resected. The completeness of surgery, the presence of bilateral liver metastases, the number of liver metastases (>10) and a primary tumor from pancreatic origin were all significantly correlated with the disease-free survival. Preoperative tumor growth rate, mitotic index, and Ki67 expression were not predictive of prognosis. No significant prognostic factors could be found by the comparison of the patients who did and did not recur during the 3 years after hepatectomy. CONCLUSION: Hepatectomy for liver metastases from well-differentiated endocrine neoplasms is indicated when all visible intra- and extra hepatic lesions can be resected safely. The number, size, and localization of the tumor sites are less important than performing a complete (or near-complete) resection.

Surgical treatment of severe late radiation injury to the bowel: a retrospective analysis of 83 cases.

BACKGROUND/AIMS: The aim of this study was to determine the best surgical approach for the treatment of late radiation injury to the bowel. METHODOLOGY: Clinical and follow-up charts of 83 patients operated in our institution for late radiation injury to the bowel were retrospectively reviewed. The type of operation (resection-anastomosis or bypass) mortality, postoperative complications and reoperation rate were recorded. Seventy-six underwent resection with immediate anastomosis. A bypass or viscerolysis was performed in only 7 patients. RESULTS: Postoperative mortality was 2.4%, morbidity was 23. Twenty-seven patients underwent further surgery; early reoperation (within 1 month) was necessary in 12 (morbidity 41%). A late reoperation has been performed in 15 patients (no mortality, morbidity 53.5%). CONCLUSIONS: From the results of our study it can be concluded that resection with immediate anastomosis for late radiation injury to the bowel is safe and should be the first option for these patients.

[Surgery for rectal cancer: function rather than organ preservation surgery]. / Chirurgie du cancer du rectum: préserver la fonction plutôt que l'organe.

Rectal surgery continues to progress during the last ten years. This technical and treatment evolution give the possibility to increase survival, with local recurrence decrease, all associated with more digestive, urinary and sexual function preservation. These progressive and continues modifications make that today the surgeon was a major prognosis factor of success. Whatever the technical solution used, the function preservation that we reported here, was more and more associated with better oncological result, for the patient benefit. These improvements required mixed teams, medical and surgical, implicated in this specific cancer giving the possibility to use all the technical solutions described here.

[The sentinel lymph node in carcinomas of the digestive tract]. / Le ganglio sentinelle dans les cancers digestifs.

Localization of the sentinel lymph node (SLN) in digestive cancers was performed mainly for colorectal primaries and less frequently for oeso-gastric primaries. This technique is feasible in vivo or ex vivo, with a vital dye and/or with a radiolabeled marker. Technically, detection reliability is good, provided a few simple rules are respected. Such intra-operative mapping leads to the localization of unusual lymphatic spread in 5% of the cases and initial resection can be adapted accordingly. "Sophisticated" histological analysis of one SLN, considered negative after a standard pathological examination, leads to three types of additional analyses: scrutiny of multiple serial slices whose prognostic significance is unequivocal when positive, and immunohistochemistry or gene amplification (RT-PCR) to search for circulating cancer cells whose prognostic value is currently uncertain. In the future, the localization and analysis of one SLN could supplant the classic examination of all lymph nodes. If the SLN is proven disease free, only very limited and microinvasive resections would be required to treat some digestive cancers with a curative intent.

[Pseudomyxoma peritonei treated with complete resection and immediate intraperitoneal chemotherapy]. / Pseudomyxomes péritonéaux traités par exérèse complète et chimiothérapie intrapéritonéale immédiate.

AIM: Pseudomyxoma peritonei remains a fatal disease. This clinical pathological entity based on the presence of mucin includes different prognostic groups. Complete resection of macroscopic lesions, combined with immediate intraperitoneal chemotherapy to treat remnant infra-millimetric disease, might improve survival. The aim of this prospective study was to evaluate this treatment strategy. METHODS: Thirty-six patients with pseudomyxoma peritonei underwent resection of supra-millimetric lesions then were given either early postoperative intraperitoneal chemotherapy (5 days) (before January 1996) or intraoperative chemohyperthermia treatment (after January 1996). During this same period, only partial resection of the macroscopic lesion was possible in 15 patients; these patients were not given peritoneal chemotherapy. RESULTS: Postoperative mortality was 13.8% (n=5), including 2 deaths not specifically due to the procedure. Morbidity, including severe and non-severe complications was 44%. After a mean follow-up of 48 months, the overall 5-years survival rate was 66%, and disease-free survival rate was 55% (including the postoperative deaths). The main prognostic factor in this series was the pathological grading: 5-years survival was 74% for grade 1 tumors versus 54% for grades 2-3 (P=0.05). CONCLUSION: The main prognostic factor of the pseudomyxoma peritonei, after the completeness of the resection, is the pathological grading. The addition of an intraperitoneal chemohyperthermia improves long-term survival of grades 2-3 tumors and perhaps that of grade 1 (agreement of experts). This treatment is more easily performed, more well-tolerated, and more efficient when performed early.

Pancreatic metastases: a multicentric study of 22 patients.

AIMS OF THE STUDY: To evaluate the diagnosis, treatment and outcome of patients with pancreatic metastases. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with pancreatic metastasis managed in the Paris area between 1990 and 2000. RESULTS: The series analyzed included 22 patients, 10 men and 12 women, mean age 61 years (range: 35-76). The primary tumors were renal-cell carcinoma (N=10), colorectal cancer (N=4), lung cancer (N=4), breast cancer (N=2), cutaneous melanoma (N=1) and ileal carcinoid (N=1). The mean interval between primary treatment and presentation was 73.5 months (range: 2-151). Diagnosis was established because of clinical symptoms (N=15) or during surveillance (N=7). Computed tomography (N=19) and endoscopic ultrasound (EUS) (N=18) mainly showed solitary and hypodense/or hypoechoic masses. Histological diagnosis was obtained before surgery by EUS-guided fine needle aspiration (N=6), ultrasound-guided biopsy (N=3) or duodenoscopy (N=3). Among 10 patients with primary renal-cell carcinoma, 7 were treated by surgery. Median global survival was 33 months. Median survival was 61 months in the event of surgical treatment and 20 months in the other patients (ns). Mean survival depended on the type of primary tumor, 61 months for renal-cell carcinoma and 33 for colorectal cancer (P=0.06). CONCLUSIONS: Most pancreatic metastases develop from renal-cell carcinoma and can occur several years after nephrectomy. Histological diagnosis is often obtained before surgery. Surgical resection must be discussed as it can allow long-term survival.

[Locoregional therapy of neuroendocrine tumors]. / Traitements loco-régionaux des tumeurs neuro-endocrines.

In digestive neuroendocrine tumours, surgery is the cornerstone of the treatment of the primary tumour. The diameter of the lesion is the main prognostic indicator and consequently impacts the extent of the resection. Types of resection, regarding to tumours sizes and locations, are reported. In metastatic forms, an aggressive policy of multidisciplinary treatments is proposed. Arterial chemoembolization is very efficient in controlling clinical symptoms and liver tumours progression, and allows secondary radical resections in selected cases. Chemoembolization is actually considered as the first line treatment in well-differentiated forms, with rapid progression.

Real-time full field laser Doppler imaging.

We present a full field laser Doppler imaging instrument, which enables real-time in vivo assessment of blood flow in dermal tissue and skin. This instrument monitors the blood perfusion in an area of about 50 cm(2) with 480 × 480 pixels per frame at a rate of 12-14 frames per second. Smaller frames can be monitored at much higher frame rates. We recorded the microcirculation in healthy skin before, during and after arterial occlusion. In initial clinical case studies, we imaged the microcirculation in burned skin and monitored the recovery of blood flow in a skin flap during reconstructive surgery indicating the high potential of LDI for clinical applications. Small animal imaging in mouse ears clearly revealed the network of blood vessels and the corresponding blood perfusion.

Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.

PURPOSE: After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. PATIENTS AND METHODS: Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. RESULTS: Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. CONCLUSION: In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.