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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.

Background Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). Method The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon–colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). Findings A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. Interpretation These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.

Up to a few years ago peritoneal carcinomatosis was considered as an "incurable" disease. The aim of this paper is to review the surgical approach with curative intent to carcinomatosis: it consists of complete resection of macroscopic disease (R1), associated with hyperthermic intraperitoneal chemotherapy (HIPEC) to treat residual microscopic disease, and to evaluate its indications. Overall 5-year survival of patients with peritoneal carcinomatosis treated by HIPEC is similar to that of patients with hepatic metastases treated with curative intent. Those patients should no longer be considered as patients with a terminal disease but as patients with a potentially treatable localized disease.

This study was designed to compare the impact of a permanent colostomy and sociodemographic characteristics on the quality of life of patients operated on for low rectal cancer. A cross-sectional study was performed by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires. Patients came to the hospital to fill out the self-administered questionnaire or were sent the questionnaire by mail, followed by a live or telephone interview. All patients had undergone one of four operations: low anterior resection with colorectal or coloanal anastomosis (non-stoma group), or abdominoperineal resection with pseudocontinent perineal colostomy (nonstoma group) or left lower quadrant colostomy (stoma group). A total of 132 patients were included for analysis and there were no missing data. For the majority of quality of life scores (26/29), there was no significant difference between stoma and nonstoma patients. However, stoma patients complained of diminished body image (P = 0.0022), and this was especially true for married (P = 0.0073) and less educated (P = 0.0014) patients at subgroup analysis. Stoma patients experienced greater financial worries (P = 0.0029), whereas nonstoma patients had greater gastrointestinal concerns (P = 0.0098). Although most quality of life scores between stoma and nonstoma patients were similar, significant differences regarding body image, finance, and gastrointestinal symptoms, especially for married and less educated patients, were noticed. These factors should be taken into account, along with oncologic criteria, to better tailor treatments to patients.

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/m2, FU 400 mg/m2 IV bolus, FU 600 mg/m2 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/m2 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.

Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative peritoneal hypertermic chemotherapy (IPHC) are used in addition with cytoreductive surgery to treat with curative intent peritoneal carcinomatosis arising from colorectal adenocarcinomas. Three patients with such a disease were treated with perioperative intraperitoneal chemotherapy in addition to cytoreductive surgery and presented isolated local recurrence located in the inguinal canal (round ligament in two and spermatic cord in one). All these patients were treated by local surgical excision. No patient showed evidence of intra-abdominal recurrence at the last follow-up, but one developed pulmonary metastasis. When communicating with the peritoneal cavity, the inguinal canal may act as a sanctuary site for peritoneal carcinomatosis, since it is not totally soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus possible. New clinical presentations such as this one have first to be described in order to improve patient follow-up.

Objective: To assess the efficacy of 5-fluorouracil (5-FU) and either platinum compounds or irinotecan in patients with advanced small bowel adenocarcinoma (SBA), for whom data on the efficacy of chemotherapy are scarce. Methods: We reviewed data on all patients with advanced SBA who received chemotherapy over a 9-year period at our institution. Results: Twenty patients with advanced SBA received a median of 6 cycles (range 2–15) of chemotherapy with 5-FU and either cisplatin (n = 15), carboplatin (n = 2), or oxaliplatin (n = 3). The overall response rate was 21%, and median progression-free and overall survival 8 and 14 months, respectively. Toxicity was moderate. Second-line chemotherapy with 5-FU and irinotecan resulted in disease stabilization in 4 (50%) of 8 patients (median progression-free survival: 5 months), and in a biological complete response in another patient with nonmeasurable peritoneal carcinomatosis, allowing surgical cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. No tumor response or disease stabilization was seen among the patients who received protracted venous infusion of 5-FU (n = 4) or infusional 5-FU and cisplatin (n = 1) as second-line chemotherapy. Conclusion: Chemotherapy with 5-FU and platinum compounds seems effective and well-tolerated in patients with advanced SBA. 5-FU-irinotecan combination chemotherapy deserves further investigation in the first-line setting.

Surgical treatment of peritoneal carcinomatosis with curative intent involves the resection of all macroscopic malignant tissue and the treatment of microscopic residual tissue with local chemotherapy. Intraperitoneal chemotherapy is efficient only when associated with hyperthermia. This article details the technical aspect of intraperitoneal chemohyperthermia. These techniques involve specific and important features. At these conditions, peritoneal carcinomatosis can be cured in two-thirds of cases.

Surgical treatment of peritoneal carcinomatosis with curative intent involves the resection of all macroscopic malignant tissue and the treatment of microscopic residual tissue with local chemotherapy. Surgical procedures for peritoneal carcinomatosis involve specific features and should be performed at the condition that all supramillimetric deposit could be removed with an acceptable postoperative quality of life. This article details the technical aspect of peritonectomy.

The aim of our prospective study was to assess the MR imaging characteristics of hepatic metastases of neuroendocrine tumors and to determine the optimal MR sequence for their detection.Thirty-seven consecutive patients with liver metastases from neuroendocrine tumors underwent 1.5-T MR imaging of the liver comprising T2-weighted fast spin-echo with respiratory monitoring, breath-hold T2-weighted single-shot fast spin-echo, and T1-weighted gradient-recalled echo sequences before and after the injection of gadoterate dimeglumine. Images were reviewed independently by three observers for the number, location, and pattern of signal and enhancement of metastases.A total of 359 metastases were detected, 279 on T2-weighed fast spin-echo, 231 on T2-weighed single-shot fast spin-echo, 272 on unenhanced T1-weighted, 322 on hepatic arterial phase, and 228 on portal venous phase images. Hepatic arterial phase images revealed the greatest number of metastases in 70% of patients, including 35 metastases seen only on this sequence, and was significantly superior to the unenhanced T1-weighted and portal venous phase sequences (p0.01). The lesion-to-liver contrast was significantly greatest with T2-weighed fast spin-echo sequences. The enhancement patterns of metastases were predominantly hypervascular, hypovascular, peripheral with progressive fill-in, and delayed in, respectively, 27, four, four, and two patients. Most metastases with peripheral enhancement and progressive fill-in were heterogeneous on T2-weighted images and were without globular peripheral enhancement.Hepatic metastases of neuroendocrine tumors had a typical hypervascular pattern in 73% of patients. Hepatic arterial phase and fast spin-echo T2-weighed sequences are the most sensitive.

Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment.

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. (Surgery 2002;131:294-9.)

How to select patients likely to benefit from reoperation? When a neoadjuvant treatment is still feasible, is it useful to perform preoperative radiation or chemoradiation? What can be expected after resection of local recurrences in terms of survival and quality of life? Does surveillance of patients operated for rectal carcinoma influence resectability of local recurrences and results? These are the main questions concerning the management of local recurrences after resection of a rectal carcinoma.

Resume L’exerese locale, realisee de preference par voie endo-anale s’adresse seulement a des tumeurs rectales de petite taille, peu infiltrantes et bien differenciees et donne environ 90 % de survie a cinq ans. La contact-therapie a les memes indications et donne des resultats equivalents mais ne peut etre effectuee que par des equipes entrainees. Le principal risque de ces traitements locaux est la recidive tumorale, d’ou la necessite d’une selection rigoureuse des patients et d’une surveillance rigoureuse dans les suites.

Screening was performed in 130 consecutive patients with apparently sporadic neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) and hormonal production. Screening for MEN1 included measurement of serum calcium and PTH[ PTH-(1–84)], gastrin, PRL, and insulin-like growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in patients with two components of the MEN1 syndrome. Screening for hormonal production included measurement of serum neuron-specific enolase (NSE), calcitonin (CT), glycoprotein α-subunit (GPα), hCG β-subunit (free hCGβ), and somatostatin levels. Twenty-four-hour urinary free cortisol (UFC) and 5-hydroxyindolacetic acid (5-HIAA) determinations were also performed. Four patients had hyperparathyroidism, none of whom had pituitary or familial disease. Hyperprolactinemia was compatible with a pituitary disease in one patient. No acromegalic feature or any increase in IGF-I was found. Hypergastrinemia, compatible with an associated ...

Background and Objectives It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear. Methods From 1984 to 1996, 196 patients underwent curative hepatectomy for liver metastases and were studied prospectively. Surgery was to be curative (or a complete R0 resection) and mortality was to be avoided. Of these 196 patients, 136 had surgical margins of less than 10 mm. Sixty-eight percent had multiple liver metastases and 15% had extrahepatic metastatic lesions. Clinical and pathological factors were studied specifically and a multivariate analysis was carried out. Results Overall 5-year survival rate of these 136 patients (taking into account postoperative mortality which attained 1.5%) was 27.8% and the disease-free survival was 22.9%. The surgical margin was 0 mm in 30 cases. The sole prognostic factor was the discovery of unsuspected (resectable) extrahepatic lesions at laparotomy (P < 0.001); the width of the free margin had no significant effect. However, in the multivariate analysis of prognostic factors for the entire series (269 hepatectomies), three powerful parameters were identified : (1) the curative nature of resection (P = 0.0007), (2) less than 20% of liver involvement (P = 0.002), and (3) a free margin exceeding 9 mm (P = 0.02). A correlation was found between narrow margins and extensive disease (high number of metastases, bilateral sites, and extended hepatectomy). There was also a greater likelihood of microscopic satellite lesions within 10 mm around the metastases. Conclusions The prognostic impact of the width of the surgical margin should not be overestimated. Hepatectomy for liver metastases can procure long-term survival, even in patients with supposedly poor prognostic factors. Resection is justified as long as it is complete and the risks are minimal. J. Surg. Oncol. 1998;69:88–93. © 1998 Wiley-Liss, Inc.

Purpose : A series of patients with rectal carcinoma irradiated by a sandwich technique combined with surgery is retrospectively analyzed. Methods and Materials : From 1978 to 1991, 155 patients with low or mid rectal carcinoma received abdominoperineal resection combined with a preoperative irradiation regimen of 35 Gy delivered in 14 fractions of 2.5 Gy each over a period of 3.5 weeks. The dose was increased to 45 Gy in the case of tumor fixation. According to histopathological findings, this irradiation was complemented in 87 cases by a postoperative dose of 25 Gy delivered in 10 fractions, for a total dose of 60 Gy delivered in the posterior pelvis. Results : Five-year survival was 66.8% for the entire population. The 5-year actuarial local control rate was 77.6%. Carcinologic results and toxicity were analyzed according to the pathological findings and the modalities of radiation therapy. Conclusions : The postoperative boost after a preoperative moderate dose of irradiation seems to have no utility. Thus, this sandwich technique is not recommended.

Intra-arterial hepatic (i.a.h.) administration of the doxorubicin analogue pirarubicin was evaluated in a phase I trial, based on preclinical studies that showed an advantage of pirarubicin over doxorubicin after locoregional hepatic administration. Pirarubicin was given to 9 patients with metastatic liver disease with intrapatient dose escalation. Of the 58 cycles evaluable for tolerance, no hepatobiliary or vascular toxicity was observed. The doselimiting toxicity was granulocytopenia: the maximum administered doses ranged from 50 to 120 mg/m 2 , suggesting variable rates of pirarubicin hepatic extraction between patients. Pharmacokinetic data obtained in 7 patients, in which a direct comparison of intravenous (i.v.) and i.a.h. administration was possible, indicated a median i.v./i.a.h. ratio of 7.4 for the maximal plasma concentration, and a median ratio of 4 for the area under the plasma concentrations versus time curves, suggesting a high pirarubicin hepatic extraction. An unexpectedly high response rate was observed: two complete (colorectal carcinoma) and two partial responses. These data demonstrate that i.a.h. pirarubicin not only produced high locoregional concentrations and reduced systemic exposure, but can also achieve responses in metastatic liver disease of colorectal origin.

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/m2) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m2/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.

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. J. Surg. Oncol. 2012; 105:628–631. © 2011 Wiley Periodicals, Inc.

Repeat hepatectomy, when feasible, is the standard treatment for isolated liver recurrences after hepatectomy for malignancies. But percutaneous radiofrequency (RF) thermoablation is less invasive than and almost as safe as repeat hepatectomy. The percutaneous approach may be contraindicated when the liver recurrence is too high, too large, too close to major vessels, or isoechogenic. Repeat laparotomy is generally performed in these situations, for hepatectomy or mixed hepatectomy and RF thermoablation, or RF thermoablation alone. We describe a very simple curative treatment of a large liver tumor recurrence after a difficult primary hepatectomy, based on RF thermoablation by a transpleuro-diaphragmatic approach.

International audience; BACKGROUND: Transfusion of red blood cells (RBCs) has been associated with immunomodulatory effects. Persistence of donor cells in the recipient may be contributive. STUDY DESIGN AND METHODS: A randomized single-center trial was conducted to compare microchimerism and immune responses in 35 patients undergoing cancer surgery and transfused perioperatively with either unmodified RBCs (UN-RBCs, n = 18) or leukoreduced RBCs (LR-RBCs, n = 17). Biologic parameters included microchimerism assessment peripheral blood mononuclear cell (PBMNC) phenotyping, cytokine production by stimulated PBMNCs, FoxP3 gene expression, and T-cell repertoire (TCR) analysis. RESULTS: Microchimerism was documented in 8 of 18 patients after UN-RBC transfusion while absent after LR-RBC transfusion (0/17; p = 0.001). After UN-RBC transfusion, microchimerism was associated with increased interleukin (IL)-10 production (p = 0.02), reduced TCR alteration (p = 0.04), and reduced CD56+ cell counts (p = 0.02) when compared to recipients without evidence for microchimerism. FoxP3 gene expression did not differ significantly between both treatment groups nor with the presence or absence of microchimerism in the UN-RBC group. Finally, after an initial early decrease after surgery and transfusion, IL-12 production increased and more significantly so after UN-RBC transfusion versus LR-RBC transfusion (p = 0.05). CONCLUSION: UN-RBC-induced microchimerism is associated with specific immunomodulatory effects in cancer patients who received transfusions during surgery.

Summary 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.

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7–38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0–3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.

Summary Background Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer. This study aimed to investigate whether regional chemotherapy (given by intraperitoneal or intraportal methods) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II–III colorectal cancer. The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole. Methods During surgery, 753 patients with stage II–III colorectal cancer were randomly assigned to systemic chemotherapy alone (379 with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole), and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid (n=368) or with fluorouracil and levamisole (n=380). Regional chemotherapy was given intraperitoneally (n=415) or intraportally (n=235) according to institution. The primary endpoint was 5-year overall survival. Secondary endpoints were 5-year disease-free survival and toxic effects. Analyses were by intention to treat. Findings Median follow-up was 6·8 years (range 0·0–10·1). 5-year overall survival was 72·3% (95% CI 69·0–75·6) for patients assigned regional and systemic chemotherapy, compared with 72·0% (68·7–75·3) for those assigned systemic chemotherapy alone (hazard ratio [HR] 0·97 [0·81–1·15], p=0·69). 5-year overall survival for all patients assigned fluorouracil and levamisole was 72·0% (68·7–75·2) compared with 72·3% (69·0–75·6) for all those assigned fluorouracil and folinic acid (HR 0·98 [0·82–1·17], p=0·81). The hazard ratios for 5-year disease-free survival were 0·94 (0·80–1·10) for regional versus non-regional treatment, and 0·92 (0·79–1·08) for all fluorouracil and levamisole versus fluorouracil and folinic acid. Grade 3–4 toxic effects were low in all groups. Interpretation Fluorouracil-based regional chemotherapy adds no further benefit to that obtained with systemic chemotherapy alone in patients with advanced colorectal cancer.

Summary 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 Neosphincterr (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.

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.

Background Results and indications of intra-operative radiofrequency (RF) ablation of liver metastases (LM) are not well defined in the literature. Aim To appreciate the survival rate of patients with strictly unresectable LM (defined on technical but not oncological criteria) when undergoing liver resection plus RF, along with optimal systemic chemotherapy. Patients and Methods Sixty three patients with technically unresectable LM (either >5, or bilateral with no sparing of at least one sector of the liver, or with tumor proximity to central major vascular structures) were treated. Extrahepatic metastases were also resected in 27% of patients. All patients received perioperative chemotherapy. The median follow-up was 27.6 months (range: 15–74). Results There was no postoperative mortality and the morbidity rate was 27%. The 2-year overall survival rate of the 63 patients was 67% with a median survival of 36 months. The local recurrence rates were similar for the three types of local treatments: 7.1% for the 154 RF ablations, 7.2% for the 55 wedge resections, and 9% for the 44 segmental anatomic resections (P = 0.216). Hepatic recurrences occurred in 71% of patients. Conclusion The combination of anatomic segmental and wedge resections, RF ablation, and optimal chemotherapy in patients with technically unresectable LM results in a median survival of 36 months. J. Surg. Oncol. 2005;90:36–42. © 2005 Wiley-Liss, Inc.

The presence of extrahepatic disease (EHD) is considered a contraindication to hepatectomy in patients with colorectal liver metastases. After resection, the prognosis is based more on the total number of resected metastases (located inside and outside the liver) than on the site of these metastases (only inside the liver or not). A total of 308 patients with colorectal cancer underwent hepatectomy, and 84 (27%) also underwent resection of miscellaneous EHD. The study was a prospective data registration and retrospective analysis. When considering the total number of resected metastases, each liver metastasis and each EHD location was counted as one lesion. Univariate and multivariate analyses were performed. The median follow-up was 99 months. The overall 5-year survival rate was 32%. In the multivariate analysis, the total number of metastases (inside or outside the liver) had a greater prognostic value than the criterion “presence or absence of EHD.” Considering the total number of resected metastases (whatever their site), 5-year survival rates were 38% (SD: 4%) in the group with one to three metastases, 29% (SD: 5%) in patients with four to six metastases, and 18% (SD: 5%) in patients with more than six metastases (P = .002). A very simple prognostic score based on sex and the total number of metastases is proposed. EHD, when resectable, is no longer a contraindication to hepatectomy. More importantly, the total number of the metastases, whatever their location, has a stronger prognostic effect than the site of these metastases.

The standard treatment of epidermoid carcinoma of the anal canal consists of radiotherapy or chemoradiotherapy. The recommended salvage treatment for local failures relies on abdominoperineal resection and permits a 5-year overall survival rate around 50%. However, the morbidity associated with this surgery is important with regard to delayed perineal wound healing. New techniques for perineal reconstruction offer interesting solutions to limit this morbidity. Musculocutaneous flaps permit to fill the perineal wound left after the resection and in some cases to reconstruct the posterior vaginal wall. Although less popular, the construction of a pseudocontinent perineal colostomy enables some patients to avoid a permanent iliac colostomy. The surgical excision of metastatic inguinal nodes, followed by radiotherapy, is an alternative to radiotherapy alone. Surgery can also be performed after failure of radiotherapy, at the cost of an increased morbidity.

Summary 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.

Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC).Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely.Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%-far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival.This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.

The indications and results of intraoperative radiofrequency ablation (RFA) of liver metastases (LMs) are not well defined in the literature and have never been compared with those of hepatectomy. The aim of the study was to appreciate the local recurrence rate of RFA in comparison with anatomic and wedge resection.Eighty-eight patients with technically unresectable LMs were treated with curative intent. The LMs were treated by anatomic resection (40 patients, 213 LMs) when large, by wedge resection (64 patients, 99 LMs) when peripheral and small, and by RFA (88 patients, 227 LMs) when central and small. The median follow-up was 27.6 months (range, 15-74 months), and a total of 539 LMs were treated (median of 5 per patient).The local recurrence rates were 5.7% for the 227 RFAs, 7.1% for the 99 wedge resections, and 12.5% for the 40 anatomic resections (P =.216). Local recurrence rates after RFA were correlated with LMs larger than 30 mm (P.001) and with LMs in direct contact with large vessels (P.001).RFA is as efficient and safe as wedge or anatomic resections in terms of local control.

Extrahepatic malignant disease has always been considered an absolute contraindication to hepatectomy for colorectal liver metastases. This study reports the long-term outcome and prognostic factors of patients undergoing extrahepatic disease resection simultaneously with hepatectomy for liver metastases.From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal liver metastases. They were inscribed in a registry and then prospectively followed up. They represented 25% of the 294 patients who underwent an R0 hepatectomy for colorectal liver metastases during the same period.The mortality rate was 2.7%, and morbidity was 25%. After a median follow-up of 4.9 years (range, 1.7-13.4 years), the overall 3- and 5-year survival rates were 45% and 28%, respectively. By using a Cox model, there was a significant difference in survival between patients with single versus multiple sites of extrahepatic disease. Also, the presence of more than five liver metastases was a significant parameter.Extrahepatic disease in colorectal cancer patients with liver metastases should no longer be considered as a contraindication to hepatectomy. However, this intended R0 resection cannot be performed in 50% of laparotomized patients, and negative prognostic factors for surgery include the presence of multiple extrahepatic disease sites or more than five liver metastases.

Purpose: The purpose of this work was to describe the computed tomography (CT) features of peritoneal carcinomatosis after surgery combined with intraperitoneal chemohyperthermia (IPCH). Method: Between 1999 and 2001, 51 consecutive patients (33 women and 18 men, with a mean age 45 years) were treated in our institution with IPCH for peritoneal carcinomatosis. Patients that were symptomatic (33 patients) underwent contrast enhanced helical CT of the abdomen and the pelvis during the first 15 postoperative days. The CT scans were reviewed retrospectively by two blinded observers. Computed tomography abnormalities were compared with surgical, biochemical, and clinical findings. Results: None of the CT scans were completely normal. Most postsurgical CT findings, including bowel and peritoneal thickening (14 and 13 cases, respectively), increased intraperitoneal fat density (13 cases), and compartmentalized ascites (8 cases), resulted from an inflammatory mesenteric reaction or inflammation of the small bowel or the peritoneum and did not require specific treatment. Major complications requiring appropriate treatment were intra-abdominal abscesses (5 cases), hemoperitoneum (5 cases), urinary fistula (2 cases), acute pancreatitis (1 case) and abdominal wall abscesses (2 cases). Conclusion: Knowledge of early CT findings after therapy with surgery combined with IPCH for peritoneal carcinomatosis is useful for accurate posttreatment management of these patients.

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.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.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).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.

To compare, over a 48-hr follow-up period, the analgesia and side-effects of patient controlled iv analgesia (PCA) with morphine alone vs combined intrathecal and PCA morphine (IT+PCA) in patients undergoing major abdominal surgery.Sixty adult patients undergoing abdominal surgery for cancer were randomly allocated to receive preoperative IT (0.3 or 0.4 mg) plus postoperative PCA morphine or postoperative PCA morphine alone. Postoperative analgesia was tested at rest and while coughing on a visual analogue pain scale and morphine consumption was recorded. Patients' satisfaction, arterial oxygen saturation, respiratory rate, episodes of nausea, vomiting and pruritus were also noted.Analgesia at rest and while coughing was significantly better in the IT+PCA morphine group (rest: P = 0.01; coughing: P = 0.005) on the first postoperative day only. IT+PCA morphine constantly provided adequate analgesia during this period. Morphine consumption was lower in the IT+PCA morphine group during this period also (IT+PCA: 9 (17) vs PCA: 40 (26); mg of morphine, mean (SD), P = 0.0001). No difference was found in pain relief and morphine consumption between the groups on the second postoperative day. Nausea and vomiting were more frequent with IT+PCA morphine on the first postoperative day. No respiratory depression occurred in either group. Satisfaction was high in both groups.IT+PCA morphine improves patient comfort constantly during the first postoperative day after major abdominal surgery. However, after the first postoperative day, IT+PCA morphine provides no additional benefit.

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 aim of this study was to determine the best surgical approach for the treatment of late radiation injury to the bowel.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.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%).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.

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.

The objective of our study was to evaluate the efficacy and safety of radiofrequency ablation of hepatic metastases performed either percutaneously for treatment of hepatic metastases in patients deemed ineligible for surgery or intraoperatively during partial hepatectomy to destroy unresectable metastases.Sixty-eight patients with 121 hepatic metastases (5 metastases per patient) that were mainly colorectal in origin underwent 76 sessions of radiofrequency ablation with cooled-needle electrodes under sonographic guidance. Twenty-one patients with 33 metastases of 5-20 mm in diameter (mean +/- SD,13 +/- 7 mm) underwent intraoperative radiofrequency ablation. Forty-seven patients with 88 metastases of 10 to 42 mm in diameter (mean +/- SD, 26 +/- 9 mm) were treated with percutaneous radiofrequency ablation. Procedure efficacy was evaluated with dynamic enhanced CT and MR imaging performed 2, 4, and 6 months after treatment and then every 3 months.Radiofrequency ablation allowed eradication of 91% of the 100 treated metastases that were followed up for 4-23 months (mean, 13.7 months). Tumor control was equivalent for percutaneous radiofrequency ablation (90%) and for intraoperative radiofrequency ablation (94%). Failure to achieve tumor control occurred mostly with the largest tumor nodules. One bilioperitoneum and two abscesses were the major complications encountered after treatment of 121 metastases with a follow-up of more than 2 months.Radiofrequency ablation appears to be a promising therapeutic modality capable of extending the possibilities of partial hepatectomy and of efficiently treating small metastases percutaneously.