Impact of neoadjuvant chemotherapy cycles prior to interval surgery in patients with advanced epithelial ovarian cancer.

OBJECTIVES: Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients. METHODS: Data from EOC patients (stages IIIC-IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (<4=group B1; >4=group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed. RESULTS: 367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p<0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p<0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p<0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p<0.001)) with an independent impact from disease stage and WHO performance status. CONCLUSIONS: Patients with advanced EOC receiving complete IDS after more than 4cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.

[Impact of surgery in the management of pancreatic metastases of renal cell cancer]. / Place de la chirurgie dans la prise en charge des métastases pancréatiques des cancers du rein.

INTRODUCTION: Incidence of renal cell carcinoma (RCC) is increasing over the 25 last years. Pancreatic metastases of RCC are rare. The aim of this work was to study overall survival of patients operated for pancreatic metastases of RCC in Montpellier cancer institute. PATIENTS AND METHODS: Between 2000 and 2012, a retrospective monocentric study was performed at Montpellier cancer institute. We evaluated the outcomes of curative pancreatic metastases from renal primary and the impact of targeted therapies. RESULTS: Thirty-eight patients were treated in our center for pancreatic metastases of RCC. Twelve patients had a curative surgery of metachronous pancreatic metastases. Four patients were without recurrence after pancreatic resection (33.3%). None had adjuvant therapy. Six patients were treated by targeted therapies, because of metastatic progression. Five of 6 died, the sixth evolved with targeted therapies by thyrosine kinase inhibitor. Average deadline between appearance of metastases and death was 89.9 months for operated patients. Average deadline between appearance of c metastases and death was 33.1 months for the others (P=0.004). CONCLUSION: Surgical treatment of pancreatic metastases should increase life expectancy of patients. Others studies are necessary to prove the impact of targeted therapies in metastatics patients in this indication. LEVEL OF EVIDENCE: 5.

Total laparoscopic radical hysterectomy for locally advanced cervical carcinoma (stages IIB, IIA and bulky stages IB) after concurrent chemoradiation therapy: surgical morbidity and oncological results.

OBJECTIVES: To evaluate the surgical outcome and the oncologic results of total laparoscopic radical hysterectomy (TLRH) after neoadjuvant chemoradiation therapy (CRT) for locally advanced cervical carcinoma. METHODS: All patients who underwent TLRH after CRT for stages IIB-IIA and bulky IB diseases were reviewed. The control group for this analysis was a cohort of patients treated with abdominal radical hysterectomy (ARH) after CRT for the same stage cancers. RESULTS: We reviewed 102 patients operated on between 2000 and 2008 (46 TLRH and 56 ARH). Mean age at diagnosis was 44 years, and mean B.M.I was 22.1. There was no difference in tumor characteristics between the two groups. Seven patients in the laparoscopic group required conversion to laparotomy (15%). Mean estimated blood loss (200 vs. 400 mL, p<0.01) and the median duration of hospital stay (5 vs. 8 days, p<0.01) were significantly lower in the laparoscopic group. Morbidity rates and urinary complications were reduced in the laparoscopic group (p=0.04). Local recurrence rates, disease-free and overall survival were comparable in the two groups. Best survival was observed for patients with pathological complete response or microscopic residual disease compared to patients with macroscopic residues (p<0.01). CONCLUSIONS: Radical hysterectomy after CRT is known to be difficult with significant morbidity rates and remains controversial in comparison to exclusive CRT. TLRH after preoperative CRT is feasible for patients with locally advanced cervical cancer in 85% of the cases. For these patients, TLRH compared with ARH was associated with favorable surgical outcome with comparable oncological results.

The value of endoscopic rectal ultrasound in predicting the lateral clearance and outcome in patients with lower-third rectal adenocarcinoma.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether preoperative endorectal ultrasound (ERUS) is able to predict histological infiltration of the external anal sphincter or the levator ani muscle in patients with a lower-third rectal neoplasm and so the possibility of treatment by sphincter-saving surgery. PATIENTS AND METHODS: Between May 1996 and May 2003, 66 patients with a lower-third rectal neoplasm that was staged as uT2 or greater were entered into a prospective evaluation of ERUS. All patients underwent neoadjuvant treatment before surgery. RESULTS: The first ERUS (ERUS 1) was performed before neoadjuvant treatment; the second ERUS (ERUS 2) was performed between the end of the radiotherapy and the surgery. An abdominoperineal resection was performed mainly when the lower extent of the tumor was within 3.5 cm from the anal verge (P = 0.011), but no correlation was observed between the lateral clearance determined by ERUS 1 and the histological clearance (P = 0.091). After neoadjuvant treatment, the ERUS 2 lateral clearance was significantly correlated with the type of surgery (P = 0.003) and the histological clearance (P < 0.001). With regard to the performance of ERUS 2 for predicting histological infiltration of the external anal sphincter or the levator ani muscle, the sensitivity was 100%, the negative predictive value was 100%, the specificity was 87%, and the positive predictive value was 53%. In a multivariate analysis, the histological clearance and tumor T stage were statistically correlated with disease-free survival (P = 0.035 and P = 0.05, respectively). CONCLUSIONS: ERUS could help oncologists and surgeons in the management of patients with lower rectal carcinomas. Moreover, ERUS is able to predict lateral histological clearance after neoadjuvant treatment.

Intraoperative immunophotodetection for radical resection of cancers: evaluation in an experimental model.

The aim of our study was to assess the technique of immunophotodetection (IPD) in intraoperative situations in an experimental model and to determine its capacity to detect very small tumor masses. IPD is a recent technology involving fluorescent dye-labeled monoclonal antibodies (MAbs) directed against tumor-associated antigens. Up to now, no intraoperative device for IPD has been developed, and limits of detection of the technique are unknown. MAb-dye conjugates were prepared using the anti-carcinoembryonic antigen MAb 35A7 labeled with indocyanine and (125)I. Time-dependent (6, 12, 24, 48, and 96 h post i.v. injection) and dose-dependent (10, 40, and 100 microg of conjugate) biodistribution studies were performed in nude mice bearing an LS174T peritoneal carcinomatosis demonstrating high tumor uptake (up to 21% of the injected dose/g of tumor 48 h postinjection). Intraoperative IPD was studied, using a newly developed device, in 16 mice 48 h after i.v. injection of 40 microg of the (125)I-MAb 35A7-indocyanine conjugate. The fluorescent status of 333 biopsies was compared with their histological analysis. Sensitivity was 90.7%, specificity was 97.2%, the positive predictive value was 94.7%, and the negative predictive value was 94.9%. Detection of very small nodules (<1 mg in weight or <1 mm in diameter) was possible. However, we observed a decrease in sensitivity as a function of tumor mass: 100% for nodules >10 mg versus 78% for nodules < or =1 mg. These experiments demonstrate that intraoperative IPD is easy to use and associated with high sensitivity and specificity, even for low tumor masses. On the basis of these encouraging results, intraoperative IPD should be assessed in a clinical study.

A phase II study of 5-fluorouracil, leucovorin and cisplatin (FLP) for metastatic gastric cancer.

The modulation of 5-fluorouracil (5-FU) with folinic acid (leucovorin, LV) is more efficacious than 5-FU alone in the treatment of metastatic colorectal cancer, and the combination of 5-FU with cisplatin is currently one of the most active regimens in advanced gastric cancer. A phase II study was therefore conducted to test the efficacy and toxicity of the combination of 5-FU, LV and cisplatin (FLP) in metastatic gastric cancer. 28 patients entered the study. Metastatic sites were observed in the liver (in 21 patients), the peritoneum (in 8), the lymph nodes (in 7) or the bones (in 1) and a local recurrence was noted in 4 cases. The performance status (using World Health Organisation criteria) was 0 for 13 patients and 1 or 2 for the others. Cycles of treatment were administered every 28 days and consisted of LV 200 mg/m2/day for 5 days followed by 5-FU 400 mg/m2/day for 5 days with cisplatin 100 mg/m2 on day 2. The response rate for the 27 evaluable patients was 51.8% (95% confidence interval (CI), 33-70.6%). There were four complete responses (14.8%) and 10 partial responses (37%). Median survival was 11 months and 4 patients were alive at 2 years. Both response rate and survival were better for patients with a good performance status. The overall toxicity was very low, except for 1 patient who died of dehydration and cardiac failure. In conclusion, the FLP protocol was effective and well tolerated in patients with metastatic gastric cancer.

Intra-operative radiotherapy in soft tissue sarcomas.

We treated 31 soft tissue sarcoma bearing patients with intraoperative radiation therapy (IORT) with ages ranging from 26 to 71: first curative intent treatment, 16 patients; and recurrent tumors, 15 patients. The tumor site was the pelvis and the retroperitoneal spaces in 13 patients and the limbs or the trunk in 18 patients. The histological type was: malignant histiocytofibroma, 14 patients; liposarcomas, 10 patients; malignant schwanoma, 1 patient; leiomyosarcoma, 2 patients; hemangiopericytoma, 1 patient; embryonic rhabdomyosarcoma, 2 patients; and synovialosarcoma, 1 patient. All the patients were diagnosed without any distant metastatic evolution at the moment of the treatment. All the patients except one underwent a complete surgical excision without any gross residual disease and received an intraoperative radiation single dose of 10 Gy in one case, 12.5 Gy in one case, 13 Gy in one case, 15 Gy in 17 cases, 18 Gy in three cases, 20 Gy in seven cases and 25 Gy in one case. Thereafter the treatment was completed by a postoperative X-ray dose of 45-50 Gy in 4.5-5 weeks for 16 patients. Local control (LC) was obtained in 27 out of 31 patients (87%), with a minimal follow-up duration of 2 years. Eleven out of 31 patients died: seven with local control (one from an intercurrent disease, six from distant metastasis) and four with local failure inside the IORT fields. Twenty patients are alive with no evolutive disease in 19 cases and with a distant metastasis in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of cytochrome P-450p (P450IIIA1) gene expression during liver regeneration from two-thirds hepatectomy in the rat.

Regenerating liver from partial hepatectomy (HPX) is known to exhibit a strong and transient deficiency in both spectrally detectable microsomal cytochrome P-450 (P-450) and related monooxygenase activities. Male Wistar rats (250-300 g) were HPX or sham operated and liver was excised at different times after operation. The time course of accumulation of five different forms of P-450 (including P-450b/e, P-450c, P-450d, P-450p and P-450UT-A) was determined in the regenerating liver, by Western blots developed with specific antibodies. With the exception of P-450c, whose level was not affected, the accumulation of other forms strongly decreased during the first 24 hr after HPX. For P-450b/e and P-450d, 80% of initial level was restored at 96 hr, whereas for P-450p and P-450UT-A, two major forms in control rat liver, the accumulation was only 20-25% of the initial, 1 week after HPX. No significant decrease was observed in sham operated animals. Plasmid pDex 12 containing a cDNA insert coding for P-450p was used to further investigate the effects of HPX on P-450p mRNA level and gene transcription. Northern blot analysis of RNA from regenerating liver (cDNA insert of pDex 12 being used as a probe) demonstrated that P-450p mRNA level decreased strongly to a minimum 12 hr after operation. This was correlated with a strong and transient decrease in P-450p gene transcription determined from nuclear run on experiments, the time course of which, however, did not account for the early decrease in mRNA level. We conclude that P-450p deficiency in the regenerating liver results from a combination of transient inhibition of gene transcription and early increase of mRNA degradation. Time course and amplitude of the decrease in P-450 UT-A accumulation suggest an inhibition of gene transcription as observed with P-450p.

Repeated hepatic resections for liver metastases from colon carcinoma. Montpellier Cancer Institute experience.

The main cause of death after hepatic resection for colorectal liver metastases is tumor recurrence. An improvement in survival may be achieved by resection of recurrent hepatic metastases as previously reported. In this paper we report our experience with 13 repeated liver resections in 11 patients. The post-operative mortality was 8% and the morbidity was 23% with two biliary tract fistulas and one recurrent pleural effusion. The median survival time from the first hepatic resection was 23 months, but differed according to the length of the disease-free interval (more than 1 year and less than 1 year: 49 and 17 months, respectively (P < 0.05). Our results suggest that repeated hepatic resection is technically a safe procedure and may be beneficial to selected patients. All candidates should be carefully evaluated pre-operatively for extrahepatic disease.

Single photon emission computerized tomography (SPECT) for monitoring regeneration of the human liver after partial hepatectomy for secondary tumours.

In 18 patients, the liver volume during regeneration after partial hepatectomy for secondary tumours was estimated by single photon emission computerized tomography (SPECT). Hepatic weight index (HWI) was subsequently calculated to follow evolution of the regeneration as a function of postoperative complications over a 30-day period. In patients with postoperative complications the HWI curves initially rose progressively and either reached a plateau or declined thereafter. The same pattern of HWI evolution was observed in patients with tumour recurrence, which was diagnosed later. On the other hand, in patients without postoperative complications the HWI curves rose continuously. These findings showed that a regenerative response was not the same in patients with or without postoperative complications; whereas in patients with tumour recurrence it could additionally provide prognostic information.

Plasma and jejunal glutamine levels after extensive small bowel resection in dogs.

Recent studies have demonstrated that glutamine may be required for mucosal growth and that it is widely utilised by the intestinal tract after surgery. This study has evaluated the effect of massive small bowel resection on plasma and jejunal glutamine and related amino-acids level evolution after surgery. Transection was performed in 6 dogs (control group) and enterectomy in 10 dogs leaving 25cm of jejunum, associated with colectomy (group 1). Plasma glutamine levels decreased on D2 (p = 0.03) in the resected group while a significant decrease of plasma alanine levels was observed on D2 (p = 0.002), D4, D6 and D8 (p < 0.001). Intestinal mucosa glutamic acid content was increased on D8 in this group (p < 0.001). No changes were observed in the control group. These results suggest that glutamine is a required substrate after massive small bowel resection which could improve the intestinal adaptation encountered after enterectomy.

Mediation by an androgen receptor of the stimulatory effect of testosterone on the growth of a fibrosarcoma in the rat.

We studied the effect of testosterone on the growth of a 20- methylcholanthrene-induced transplanted fibrosarcoma and assayed androgen receptors in this tumor. The effect of an antiandrogen in male rats and the comparative tumor growth in females confirmed the androgen sensitivity. A synthetic androgen that strongly binds to the androgen receptor was used to characterize the binding activity in nuclear extracts of tumor. Scatchard analysis showed that the dissociation constant of the hormone receptor complexes (Kd) was 26 +/- 2 nmol/l and the number of binding sites was about 95 +/- 12 fmol/mg of protein. The hormone-receptor complexes sedimented in the region of 3.7 S.

Influence of N-acetylglutamine or glutamine infusion on plasma amino acid concentrations during the early phase of small-bowel adaptation in the dog.

Glutamine is a nonessential neutral amino acid that is widely consumed by the intestinal tract in catabolic states. We have followed up the plasma amino acid profile after extensive small-bowel resection in dogs receiving total parenteral nutrition (TPN) with or without glutamine (GLN) or N-acetylglutamine (aGLN) supplementation. Animals were divided into four groups according to the type of surgery (enterectomy or transection) and nutrition (TPN, TPN with aGLN, or TPN with GLN). Plasma GLN levels decreased in group I (enterectomy and TPN) on day 2 (p = .03) and significantly increased on postoperative days in groups III (enterectomy and TPN with aGLN) and IV (enterectomy and TPN with GLN). A significant increase of plasma GLN was observed in groups III and IV compared with group I on days 6 and 8 (p = .03 and p = .01). Plasma alanine decreased in groups with bowel resection, whereas no change was observed in the control group (transection) and the decrease of plasma alanine was significantly less pronounced in groups III and IV compared with group I. The increase of crypt depth and villous height was more pronounced in groups III and IV. These results suggest that GLN is a required substrate for mucosal growth and function, which could improve the intestinal adaptation encountered after enterectomy.

Ambulatory home total parenteral nutrition.

Ambulatory total parenteral nutrition (TPN) at home was used in 85 patients within a 6-yr period. Indications include severe malabsorption, fistulas, anorexia nervosa, and malignancies. The median duration of home TPN (HPN) was 67 days (range: 30-4,155 days). HPN duration for patients with benign diseases was longer [357.12 days (range: 30-4,155 days)] than for cancer patients [93.54 days (range: 30-421 days)]. Under HPN, patients gained a good nutritional status with an increase of total protein (p less than 0.001) and serum albumin levels (p less than 0.001). Weight gain was also significant (p less than 0.001). The rehospitalization rate was low (7.8%), but it was higher when HPN lasted for more than 3 months (10.87% +/- 1.58%) compared with short-term HPN (5.69% +/- 1.25%). Metabolic complications were unusual, and rehospitalization was related to the oncological treatment and/or infectious complications. Therefore, ambulatory HPN is a nutritional support that can significantly improve the life of patients with alimentary failure. Moreover, HPN allows significant cost savings compared to the alternative of prolonged hospitalization.

Home enteral nutrition system: one patient, one daily ration of an "all-in-one" sterile and modular formula in a single container.

A home enteral nutrition (HEN) system was introduced to deliver a day's ration of an "all-in-one" sterile and modular formula from a large container. The nutrient formula consisted of carbohydrate, protein, and lipid modules sterilized separately, in an autoclave at 120 degrees C, then mixed and supplemented with minerals and trace elements. Vitamins were given the patients through a feeding tube before connecting the nutrient container. The system was used to feed 12 malnourished patients (10 men and two women) with cancer (carcinoma of esophagus or tongue) or without cancer (esophageal perforation). All patients had normal gastrointestinal function but could not take in more than 500 kcal/day orally, because of their primary disease or the treatment for it (surgery in four patients; and radiotherapy, associated in some cases with chemotherapy, in eight). HEN duration ranged from 30 to 435 days at a daily cost of approximately US $15 to $20. Statistical analysis (Student's t-test for paired data) showed significant body weight gain (p less than 0.05) and significant increases in serum levels of albumin, transthyretin (p less than 0.05, respectively), and transferrin (p less than 0.01). Increases of serum total protein level were not statistically significant (p less than 0.09). The nutrient formula was well tolerated and there were no HEN-related rehospitalizations. Seventy-five % (nine of the patients) considered that HEN had improved their quality of life. The daily savings per patient, compared to the cost of treatment in a hospital, was about $260/day.(ABSTRACT TRUNCATED AT 250 WORDS)

[Possible role of sexual and gastrointestinal hormones on cancer of the digestive system]. / Rôle possible des hormones sexuelles et gastro-intestinales sur les cancers digestifs.

This is a review of the most interesting studies on the possible role of sex and gut hormones in gastrointestinal (GI) carcinomas. Many experimental and some human studies suggest that sex and gut peptides may have a growth effect on normal or neoplastic gut cells. It may be possible in the future to develop strategies for patients with GI cancers that will be based upon hormonal manipulation in a manner similar to current strategies that are at present employed in the treatment of patients with breast cancer.

[Computed gamma-tomographic estimation of a hepatic weight index during liver regeneration]. / Mise au point par gammatomographie computérisée d'un index pondéral hépatique au cours de la régénération du foie.

Single photon emission computed tomography was used to evaluate the total functioning liver mass and the regeneration process after partial hepatectomy. Serial tomographic sections were performed after infusion of 99m Technetium. In studies on dogs and in human beings, computed gammatomography enabled to calculate the liver mass with less than 10 p. 100 error. Hepatic regeneration was studied in 10 patients following resection of 46 to 84 p. 100 of the initial liver mass. The remaining liver mass increased rapidly postoperatively and doubled within 13 to 18 days. The regeneration process followed an exponential curve. Assessment of liver regeneration by this non-invasive technique should be of great help following partial hepatectomy.

[Contribution of endorectal ultrasonography in preoperative evaluation for very low rectal cancer]. / Apport de l'échographie endorectale dans le bilan préopératoire des cancers du très bas rectum.

UNLABELLED: Abdominoperineal resection is the standard treatment of very low rectal carcinoma. Pretherapeutic evaluation of locoregional extension relies mainly on digital rectal examination. The interest of endorectal ultrasonography to assess lateral and inferior margins is still to be determined. AIM OF THE STUDY: To assess the ability of endorectal ultrasonography to evaluate the possibility of conservative anal sphincter surgery. PATIENTS AND METHODS: Between April 1996 and June 1998, 34 patients (20 men, 14 women, mean age: 61 years, range: 43-80) have been treated for rectal adenocarcinoma. Endorectal ultrasonography was made with a linear probe (EUP-U33). Before treatment, the mean distance between the lower pole of the tumor and the anal verge was 3.9 cm (range: 2-5), and between the lower pole and the puborectalis sling 2.3 mm (range: 0-7). A uTN classification was made. Preoperative treatment was radiotherapy (40 Gy in 4 patients, 60 Gy in 24 patients), or radiochemotherapy (6 patients). Pre- and post-radiotherapy endorectal ultrasonography results were compared to the patholocical analysis of operative specimen. RESULTS: Wall infiltration was correctly evaluated in 57% of patients after radiotherapy. In 26/34 cases, a safe plane existed before and after radiotherapy, and correlation of endorectal ultrasonography with histology was 96%. For patients without safe plane, correlation with histology was 75%. CONCLUSION: For very low rectal tumors, with an aggressive sphincter conservation approach, endorectal ultrasonography allows to assess sphincter invasion with 96% fiability when safe plane exists.

[Secondary debulking surgery and intraperitoneal chemotherapy in advanced or recurrent epithelial ovarian cancer]. / Chirurgie de fermeture et chimiothérapie intra-péritonéale dans les cancers de l'ovaire de stade avancé ou en récidive.

OBJECTIVE: The aim of this study was to evaluate the indications and the results of secondary cytoreduction surgery with intraperitoneal (i.p.) paclitaxel chemotherapy in advanced or recurrent epithelial ovarian cancer. PATIENTS AND METHODS: In a retrospective study, records were reviewed for 13 patients who received i.p. paclitaxel therapy (175 mg/m2) during secondary cytoreductive surgery or surgery for recurrent disease. All these patients were initially treated with optimal debulking surgery (macroscopic persistent residual disease) and systemic chemotherapy. RESULTS: Nine patients were operated for secondary cytoreductive surgery (group I) and four patients operated for recurrent disease (group II). Postoperative residual disease was absent or microscopic in 69% (n = 9). Median hospital stay was 16 days. Hematologic toxicity grade III-IV was reported by 12 patients (92%). Operative mortality was 7.7% (n = 1). Median follow-up was 22.7 months. The median overall survival was 25.5 months. The median disease-free survival was 8.5 months. The median disease-free survival for group I and II were respectively 11.7 months and 4.2 months (P = 0.3). Progression of disease after completion of treatment was documented in 62% (n = 8): six patients for group I and two patients for group II. DISCUSSION AND CONCLUSION: Secondary cytoreduction surgery associated with intraperitoneal chemotherapy is feasible after adjuvant systemic chemotherapy for patients with recurrent or suboptimally resected ovarian cancer. Results on loco-regional control for recurrent disease are poor. Intraperitoneal chemotherapy should be discussed during a two-step surgical strategy, as secondary cytoreductive surgery.

[Proctectomy and colo-anal anastomosis after high-dose irradiation of cancers of the lower third of the rectum. Functional and oncological results]. / Proctectomie et anastomose colo-anale après irradiation à hautes doses des cancers du tiers inférieur du rectum. Résultats fonctionnels et carcinologiques.

This prospective study was designed to evaluate morbidity and functional and oncological outcomes in patients with carcinoma of the distal third of the rectum treated by high-dose radiation therapy followed by conservative surgery. Twenty-two patients with adenocarcinoma of the distal third of the rectum treated after June 1990 were included in the study. Mean distances separating the tumor from the upper edge of the levator ani muscle and from the anal verge were 17 mm and 47 mm, respectively. None of the tumors were fixed; preoperative stage, established by endoscopic ultrasound, was T2 in 12 patients and T3 in 10. Patients received induction radiation therapy in two series delivered three weeks apart (40 Gy on the pelvis, then 20 Gy on the tumor only) followed by surgical resection (proctectomy with colo-anal anastomosis in 17 cases and amputation in five). After radiation, two tumors were negative for malignant cells, 12 were Astler-Coller B1, two were B2, and six were C2. Mean safety margin after colo-anal anastomosis was 16.8 mm; all the resection margins were negative. Mortality and morbidity were not increased by the high-dose radiation protocol. Conservation of the sphincter was possible in 80% of patients. All the patients were continent. Functional outcome was rated good in 77% of cases, fair in 9% and poor in 4%. During the mean follow-up of 24 months, there were three disease-related deaths, including one due to a strictly regional recurrence; metastatic dissemination to the lungs occurred in two patients and the remaining 17 patients (80%) were disease-free. These data suggest that high-dose radiation therapy followed by conservative surgery ensures satisfactory functional outcomes in patients with carcinomas of the distal rectum. Evaluation of oncological outcomes will require a longer follow-up.