Transient loss of Polycomb components induces an epigenetic cancer fate.

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2, substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6, suggesting that genetic mechanisms might not be the only drivers of malignant transformation7. However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila. This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK-STAT signalling pathway and zfh1, the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates.

Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors.

BACKGROUND: Multiple myeloma (MM) is still a fatal plasma cell cancer. Novel compounds are currently clinically tested as a single agent in relapsing patients, but in best cases with partial response of a fraction of patients, emphasising the need to design tools predicting drug efficacy. Histone deacetylase inhibitors (HDACi) are anticancer agents targeting epigenetic regulation of gene expression and are in clinical development in MM. METHODS: To create a score predicting HDACi efficacy, five MM cell lines were treated with trichostatin A (TSA) and gene expression profiles were determined. RESULTS: The expression of 95 genes was found to be upregulated by TSA, using paired supervised analysis with Significance Analysis of Microarrays software. Thirty-seven of these 95 genes had prognostic value for overall survival in a cohort of 206 newly diagnosed MM patients and their prognostic information was summed up in a histone acetylation score (HA Score); patients with the highest HA Score had the shorter overall survival. It is worth noting that MM cell lines or patients' primary MM cells with a high HA Score had a significant higher sensitivity to TSA, valproic acid, panobinostat or vorinostat. CONCLUSION: In conclusion, the HA Score allows identification of MM patients with poor survival, who could benefit from HDACi treatment.

3-O sulfation of syndecan-1 mediated by the sulfotransferase HS3ST3a1 enhances myeloma aggressiveness.

Multiple myeloma is a hematological neoplasm derived from plasma cells invariably developing in the bone marrow (BM). The persisting clinical challenge in MM resides in its high ability to resist drugs as shown by the frequent relapses observed in patients regardless of the treatment applied. In a mouse model of MM, we identified a subpopulation of cells harboring increased resistance to current MM drugs. These cells bound a proliferation inducing ligand (APRIL), a key MM promoting/survival factor. APRIL binding involved the heparan sulfate (HS) chain present on syndecan-1 (SDC-1), and correlated with reactivity to the anti-HS antibody 10e4. 10e4+cells had a high proliferation activity, and were able to form colonies in 3-D cultures. 10e4+ cells were the only cells able to develop in BM after intravenous injection. They also resisted drugs in vivo, since their number increased after treatment in BM. Notably, 10e4+ cells differentiated into 10e4- cells upon in vitro and in vivo expansion. Expression of one sulfotransferase, HS3ST3a1, allowed modification of syndecan-1 to confer reactivity to 10e4 and binding to APRIL. HS3ST3a1 deletion inhibited tumorigenesis in BM. Notably, the two populations coexisted at a variable frequency in the BM of MM patients at diagnosis. In total, our results indicate that 3-O-sulfation on SDC-1 carried out by HS3ST3a1 defines aggressive MM cells, and that targeting of this enzyme could possibly be used to better control drug resistance.

Atacicept in relapsed/refractory multiple myeloma or active Waldenström's macroglobulinemia: a phase I study.

BACKGROUND: Advanced multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are incurable B-cell malignancies. This is the first full clinical report of atacicept, a fusion protein that binds to and neutralises the B-cell survival factors, B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), in MM and WM. METHODS: In this open-label phase-I study, 16 patients with advanced disease (12 MM, 4 WM) received one cycle of five once-weekly subcutaneous injections of atacicept (2, 4, 7 or 10 mg kg(-1)). Patients with stable disease after cycle 1 entered an extension study (either two additional cycles (2, 4 and 7 mg kg(-1) cohorts) or 15 consecutive weekly injections of atacicept 10 mg kg(-1)). RESULTS: Atacicept was well tolerated, systemically and locally; the maximum tolerated dose was not identified. Of 11 patients with MM who completed initial treatment, five patients were progression-free after cycle 1 and four patients were progression-free after extended therapy. Of four patients with WM, three patients were progression-free after cycle 1. Consistent with atacicept's mechanism of action, polyclonal immunoglobulin isotypes and total B cells were reduced. Bone-marrow density, myeloma cell numbers and plasma concentrations of soluble CD138 also decreased. CONCLUSION: Atacicept is well tolerated in patients with MM and WM, and shows clinical and biological activity consistent with its mechanism of action.

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma.

The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-alpha were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) - neuregulin-1, amphiregulin, HB-EGF - promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10(5) molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients. Interestingly, RECQ1 knockdown inhibits cells growth and induces apoptosis in MMCs. Moreover, RECQ1 depletion promotes the development of DNA double-strand breaks, as evidenced by the formation of 53BP1 foci and the phosphorylation of ataxia-telangiectasia mutated (ATM) and histone variant H2A.X (H2AX). In contrast, RECQ1 overexpression protects MMCs from melphalan and bortezomib cytotoxicity. RECQ1 interacts with PARP1 in MMCs exposed to treatment and RECQ1 depletion sensitizes MMCs to poly(ADP-ribose) polymerase (PARP) inhibitor. DNMT inhibitor treatment results in RECQ1 downregulation through miR-203 deregulation in MMC. Altogether, these data suggest that association of DNA damaging agents and/or PARP inhibitors with DNMT inhibitors may represent a therapeutic approach in patients with high RECQ1 expression associated with a poor prognosis.

[Does consumption of tobacco, alcohol, and cannabis in adolescents and young adults with cancer affect the use of analgesics during hospitalizations?]. / La consommation de tabac, alcool et cannabis chez les adolescents et jeunes adultes atteints de cancer a-t-elle un impact sur l'utilisation hospitalière des traitements antalgiques pendant la période de traitement ?

INTRODUCTION: The specificities of adolescents and young adults (AYAs) aged 15-25 years with cancer are now well recognized. Dedicated care was initiated in 2012 in France under the leadership of the INCa (National Cancer Institute). Research on supportive care and particularly pain management are still rare. This study aimed to evaluate the consumption of toxic substances (tobacco, cannabis, alcohol) in AYAs with cancer as well as its progression during the month following the diagnosis and to analyze its influence on opioid analgesic prescriptions during treatment. METHODS: This is a prospective study including all new patients aged 15-25 years in two centers between January and June 2013. Data on consumption of psychoactive substances were obtained during an individual interview with a questionnaire. National surveys were used to compare this cohort with the general population. Data on opioid treatments were collected from the computerized prescription software and computerized patient record. RESULTS: Thirty-seven AYAs were eligible and 30 were included; 67% of them were male and the median age was 18.7 years. The questionnaire on tobacco, alcohol, and cannabis consumption at diagnosis was well accepted. Consumption profiles were comparable to the general population. Changes in behavior were observed during the 1st month after diagnosis, with a decrease or cessation of consumption, particularly among young people. This study showed differences in the use and requirements for opioid analgesics during hospitalization according to these consumption data. CONCLUSION: Prevention and support for AYAs who are regular consumers of toxic substances must be organized during initial care in oncology.

Lymphocytes of dogs immunised with purified excreted-secreted antigens of Leishmania infantum co-incubated with Leishmania infected macrophages produce IFN gamma resulting in nitric oxide-mediated amastigote apoptosis.

The role of nitric oxide (NO) in the anti-leishmanial activity has been confirmed both in vitro and in vivo. Recently, we demonstrated that NO-mediated apoptosis-like amastigote death pathway is an important and highly regulated mechanism used for the clearance of Leishmania within infected murine macrophages stimulated to produce NO endogenously. To further characterize these important effector mechanisms in dog, a natural host-reservoir of L. infantum/L. chagasi, we have developed an ex vivo infection model of canine macrophages. Exposure of L. infantum-infected macrophages to autologous peripheral lymphocytes derived from dogs immunised with purified excreted-secreted antigens of L. infantum promastigotes (LiESAp) formulated with muramyl dipeptide (MDP) as adjuvant resulted in a significant leishmanicidal effect due to interferon (IFN)-gamma dependent macrophage activation. Concomitant accumulation of NO(3)(-)/NO(2)(-) in supernatants of co-cultured cells and in situ staining of parasites with terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) and YOPRO-1 showed that NO-mediated apoptosis of intracellular L. infantum amastigotes is occurring in canine macrophages as previously observed in mouse models. Monitoring these parameters in dogs after immunisation and before experimental challenge can represent a useful and easy way to rapidly evaluate vaccine candidates against canine visceral leishmaniasis.

Traditional surgical management of common bile duct stones: a prospective study during a 20-year experience.

PURPOSE: To analyze the operative findings and evaluate the hospital morbidity and mortality. This experience is documented in order to provide a basis for comparison with therapeutic alternatives. PATIENTS AND METHODS: Prospective data were collected on 579 patients who underwent elective (n = 443) or emergent (n = 136) operations between 1970 and 1990. Their mean age was 60.1 years. Prior biliary symptoms were present in 96% and suggestive of choledocholithiasis in 69%. Acute pancreatitis was associated in 3%. RESULTS: Cholecystectomy was performed with intraoperative cholangiography in 85% of cases. Stones were extracted via the cystic duct in 18%, through a choledochotomy in 79%, and through an additional sphincterotomy in 3%. Cholangioscopy has been routinely used since 1977. The incidence of extraction of the stones via the cystic duct increased and the incidence of biliary-enteric bypass decreased significantly during the second decade. Complications occurred in 24.5% of the patients. General complications were significantly fewer in the second decade than in the first (6% versus 15%). The main biliary complications were related to biliary tubes (5%) and retained stones (5%). Ten patients (2%) required early reoperation. The overall mortality rate was 0.3%. Mortality was 1.4% after emergency operations and zero after elective operations and in patients under 60 years of age. The mean stay was 16.6 +/- 7.2 days, decreasing with time. CONCLUSION: Traditional open surgery is an effective and safe option for the management of cholelithiasis with choledocholithiasis. The choice between open surgery, laparoscopic surgery, and endoscopic sphincterotomy should be made for each patient according to the local availability and efficacy of these methods.

Obliteration of the pelvic space with pedicled omentum after excision of the rectum for cancer.

From 1979 through 1982, removal of the rectum for cancer in 67 patients (50 of whom underwent preoperative radiotherapy) was completed by obliteration of the resulting dead space with pedicled omentum. No complication could be related to the method. After abdominoperineal resection (54 patients), primary healing of the perineal wound was achieved in 77 percent of the patients (85 percent during the last 2 years), and the mean postoperative hospital stay was 22 days. Minor perineal suppuration occurred in 10 patients with a 40 day average time of healing, and major suppuration occurred in 1 patient only with a 3 month time of healing. After the extended Hartmann operation (12 patients), no pelvic abscess was observed and the median hospitalization stay was 19 days. Pelvic filling in the management of patients undergoing rectal excision is an adjunctive procedure that is mainly intended to provide a better postoperative course. It might also facilitate postoperative radiotherapy.

Gastric adenocarcinoma in the gastric stump after partial gastrectomy.

Carcinomas of the gastric stump are divided into two types. In the main group of patients (n = 18), carcinoma developed after resection for benign ulcer disease, and in the second group (n = 4) after resection for early gastric carcinoma. In the first group, the mean age of the patients was 63, and the male-to-female ratio of 17:1. The mean interval between the primary operation and the diagnosis of cancer was 27 years. Biopsies were positive in 16 out of 18 patients. The resectability rate was 72%, resection being performed with curative intent in 50%. Total gastrectomy was performed in 50% of the cases. There were no postoperative deaths. The 5-year survival rate was 33% for all patients and 50% after tumoral resection. Early detection was achieved by means of an endoscopic survey of the gastric stump. A comparison between gastric stump carcinomas and other gastric carcinomas in our series fails to reveal any major differences. Gastric stump carcinoma is not specific. In the second group, the mean age of the patients was 72.5 and the sex ratio 1:1. The mean interval between the two operations was 5 years. The resectability rate was 100%, and all the patients survived with follow-up ranging from 2 to 10 years. The second lesion could be considered a metachronous cancer, but it may have been present and overlooked at the time of the initial gastrectomy. Differentiating between synchronous and metachronous lesions is quite difficult.

[Remote results of surgical treatment in chronic pancreatitis. Study of a series of 107 patients]. / Les résultats lointains du traitement chirurgical dans les pancréatites chroniques. Etude d'une série de 107 malades.

The aim of the present study was to report the follow-up results of 107 consecutive patients (among whom there were 105 males and 90 p. 100 chronic alcoholics) who have been operated from 1963 to 1976, for chronic calcifying pancreatitis. Pancreatic resection was performed in 66 patients and one or several palliative procedures in 41 patients. There was one post-operative death, after pancreatico-duodenectomy; 13 patients were lost to follow-up, 43 were dead and 50 were reviewed with a 5- to 18-year (mean: 10 years) follow-up. Secondary deaths mainly occurred during the five years following pancreatic resection. For a mean follow-up of ten years, the mortality rate was 49 p. 100 for patients who underwent pancreatic resections and 41 p. 100 for those who underwent palliative procedures. Besides pancreatitis, other complications of chronic alcohol consumption associated with smoking-related diseases were the main causes of death (carcinoma of upper respiratory tract in 6 of the 27 cases for whom the cause of death was known). Clinical results were judged as excellent or good in 70 p. 100 of the 30 patients followed after pancreatic resection, and in 65 p. 100 of the 20 patients followed after palliative surgery. Persistent alcoholism (50 p. 100 of dead patients, 10 p. 100 in living patients) appeared as a decisive factor, influencing long-term survival and determining surgical indications. In conclusion, the present study shows that: (a) in patients with chronic calcifying pancreatitis who have not stopped alcohol consumption, surgery seems indicated only in the event of complications; the surgical procedure should be limited to palliative treatment of the complication, without pancreatic resection; (b) in patients who have freed themselves from alcoholism, surgery is indicated in the event of persistent pain or complications; the choice between a partial pancreatic resection and a palliative procedure should be based on clinical symptoms and operative findings.

[Multiple cancers of the colon and rectum. Incidence and results of surgical treatment]. / Les cancers multiples du côlon et du rectum. Fréquence et résultats du traitement chirurgical.

Out of 1,528 patients operated upon for cancer of the colon or rectum between 1964 and 1984, synchronous carcinomas were observed in 63 patients, metachronous carcinomas in 36 patients and both synchronous and metachronous carcinomas, in 3 patients. Synchronous carcinomas were double in 59 patients and triple in 4 patients. In 80 p. 100 of the cases, the lesions were confined to the same surgical segment or to an adjacent segment. Rectal locations were less frequent (18 p. 100). Preoperative diagnosis was made in only 40 p. 100 of cases. Ninety-three p. 100 had resection, 81 p. 100 with a curative intent. Associated benign polyps were found on the resected specimen in 58 p. 100 of the cases. The resectability rate (93 p. 100) and 5-year survival rate (55 p. 100 of all operated patients and 67 p. 100 of those who underwent curative resection) were similar to those observed in our personal series of single carcinomas of the colon. A second cancer of the colon or rectum occurred in 36 patients. The time interval between the first and second carcinomas ranged from 1 to 24 years and the mean interval time was 6.3 years. Three of the 36 patients developed a third metachronous lesion. The distribution of the sites of successive carcinomas was similar to that of synchronous carcinomas; the second carcinoma was located in the rectum in 8 p. 100 of cases. Diagnosis of the second carcinoma was made through routine periodic colonoscopy in one third of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Limy bile. A surgical experience in 16 patients.

OBJECTIVES: This study is a retrospective analysis of clinical symptoms and operative findings in 16 patients with limy bile (mean age: 47.3 years, M/F ratio: 1/7) operated on over a 25-year period. METHODS: The patients were separated into two groups: patients with limy bile limited to the gallbladder and those with limy bile extending to the common bile duct. RESULTS: In the group of patients with limy bile in the gallbladder (n = 11), previous attacks of biliary pain were present in 9 and the gallbladder was entirely inactive in 9; an elective cholecystectomy was performed; an impacted stone was found in the neck of the gallbladder (n = 5) or in the cystic duct (n = 6), and the intraoperative cholangiogram was normal. The material deposited in the gallbladder was characteristically creamy or dense, white or yellow-brown, and consisted of calcium carbonate. The patients with limy bile extending to the common duct (n = 5) were admitted with acute pain and jaundice, and operated on a few days later. In the common bile duct, limy bile was associated with small stones (n = 4). CONCLUSION: Abdominal radiographs are sufficient to identify limy bile. The presence of this condition in the gallbladder is always associated with biliary lithiasis and the obstruction of the cystic duct. The presence of limy bile in the common bile duct is due to the migration of impacted stone and calcareous material deposited in from the gallbladder. Surgical treatment is only necessary in patients with specific biliary symptoms.

[Results of the surgical treatment of pancreatic cancer. Study of a series of 96 surgically treated patients]. / Les résultats du traitement chirurgical du cancer du pancréas. Etude d'une série de 96 opérés.

From 1970 to 1980, 96 patients were operated on for pancreatic adenocarcinoma. Histological confirmation was obtained in all but 12 cases. The tumour was located in the right portion of the pancreas in 80 cases and in the left portion in 16 cases. Metastases were present in 39 patients, hepatic in 28 cases and peritoneal in 23 cases. Among the cases without metastasis, lymph node involvement was found in 12 patients out of 25. A partial pancreatectomy was carried out in 12 patients, by-pass operations in 50 patients and laparotomy only in 34 patients. The 30-day postoperative mortality rate was 12 p. 100 in the by-pass group; there was no postoperative death in the resected group. By 1982, all the patients were dead. The mean length of survival after Whipple resection was 15.6 months, after by-pass operations 8 months, after laparotomy 3.4 months, operative mortality excluded. When lymph nodes were involved (stage III), the mean duration of survival after resection (n = 4) was the same (i.e. 7,5 months) as that after by-pass operations. The period of survival after by-pass procedures only exceeded one year in 8 cases. After pancreatic resection, only one patient survived five years. These results show that the resectability rate of pancreatic carcinoma is very low. Pancreatic resection seems to be justified mainly in stage I and II tumors. However, prognosis of pancreatic carcinoma remains very poor and the 5-year survival rate after resection does not exceed 10 p. 100.

[Extracorporeal lithotripsy in experimental vesicular lithiasis in pigs]. / Lithotritie extracorporelle de la lithiase vésiculaire expérimentale chez le porc.

Experimental extracorporeal shock wave lithotripsy of gallstones was performed with the EDAP LT 01 piezoelectric lithotripter. Fragmentation of biliary stones was evaluated after implantation of human stones inside the gallbladder in 10 pigs. Lithotripsy was performed with a firing frequency of 2.5 shots per second during a mean time of 50 min. Zero to 18 days after lithotripsy, complete fragment clearance was seen in 6 cases, fragments less than 2 mm were found in 2 cases and fragments larger than 2 mm with only 1 non fragmented stone in 2 cases. There were no stone fragments in the cystic and common ducts. Damage to gallbladder and adjacent organs was appreciated after lithotripsy to the empty gallbladder of pigs with firing frequencies from 40 to 1.25 shots per second. Perforation of the gallbladder was observed in both pigs treated with a firing frequency of 40 shots per second and in 1 pig out of 3 treated with a firing frequency of 20 shots per second. With 10 shots per second and lower firing frequencies, mild histological changes of the gallbladder walls were only observed in 3 cases reoperated on the 2nd day after lithotripsy. The gallbladder wall was normal in the 5 cases reoperated on the 15th day and there were no hepatic, duodenal and pancreatic lesions. These experimental results are consistent with utilization of this machine in the treatment of gallstones in man; low firing frequencies are effective for fragmentation of gallstones without any adverse effects.

[Carcinoid tumors and neuroendocrine carcinomas of the stomach. Prognosis and therapeutic management. Study of 6 cases]. / Les tumeurs carcinoïdes et carcinomes neuro-endocrines de l'estomac. Pronostic et conduite thérapeutique. Etude de six observations.

UNLABELLED: The six reported cases were separated into 2 groups: 1) the tumors of sporadic type, carcinoids (n = 2) and neuro-endocrine carcinomas (n = 2); 2) the gastrin-promoted tumors (n = 2). The purpose of this retrospective study was to review for each group of tumors, the clinicopathologic characteristics, prognosis factors and optimal management. In the first group, patients with a small and well differentiated tumor revealed by digestive bleeding, were treated by wedge excision and are alive and well 24 and 22 years later; the patients with large, invasive and poorly differentiated tumors were treated by subtotal (n = 1) and total (n = 1) gastrectomy, and died 1 year and 3 years later with metastases. In the second group, one patient with a small asymptomatic carcinoid tumor revealing chronic atrophic gastritis, was treated by endoscopic resection, without recurrence 3 years later; another patient with asymptomatic multifocal carcinoid tumors (about 100) associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1, was treated by total gastrectomy and is alive and well 7 years later. No patient had carcinoid syndrome. Synaptophysin was the most sensitive marker and secretion of serotonine was detected in 2 tumors. CONCLUSION: Sporadic carcinoids serotonin and neuro-endocrine carcinomas are life-threatening tumors and need aggressive surgical therapy: their prognosis depends on tumors size, histological differentiation and mostly on tumor extension. In contrast, gastrin-promoted carcinoids do not result in disseminated disease and death, and a rather conservative approach seems appropriate.

[Cancer of the gallbladder. A surgical experience]. / Le cancer de la vésicule biliaire. Une expérience chirurgicale.

Between 1965 and 1987, carcinoma of the gallbladder was found in 65 patients, 59 of whom were operated upon. Seventy-seven per cent of these patients were women. Mean age was 68 years. Cholelithiasis was present in 77 per cent of the patients. Since 1977, the preoperative diagnosis was made by ultrasonography in 43 per cent of the cases. The overall actuarial 1-year, 5-year and 10-year survival rates were 30, 13 and 13 per cent respectively. For patients whose tumour was limited to the gallbladder wall (Tis, T1, T2), the actuarial 5-year survival rate was 73 per cent. For patients with T3 and T4 tumour, the 2-year survival rate was nil. The resection rate with "curative aim" was 25 per cent, but recurrences occurred in 3 patients (2 T2, 1 T3) out of 11 after cholecystectomy and in 4 patients (1 T2, 3 T3) out of 5 after cholecystectomy and wedge resection of the liver at gallbladder fossa level with regional lymph node dissection. No major hepatic resection was performed. The prognosis mainly depended on the tumoral extension in depth. For the early stages, the survival rate could be higher with a more aggressive surgical procedure. For the usually observed tumours which extend beyond the gallbladder wall, the prognosis has not been improved.

[Colonic cancers. Results of surgical treatment and prognosis. 579 cases]. / Les cancers coliques. Résultats du traitement chirurgical et pronostic. Cinq cent soixante-dix-neuf observations.

Between 1964 and 1981, 579 patients were operated upon for carcinoma of the colon. Hepatic and/or peritoneal metastases were present in 17.3%. Excision was performed in 530 cases (91.5%). Carcinomas of the left colon were usually treated by segmental resection. The peritoneum and lymph nodes were involved in 21.7% and 31% respectively of the patients who underwent resection. There were 6 post-operative deaths: 2 after exploratory or derivative surgery and 4 after excision of the tumour. All but 8 of the 395 patients operated upon before 1978 were followed up; 229 survived for more than 5 years, 58% of all operated patients and 63.6% of those who had their tumour excised. The 5-year survival rate was 6% after palliative excision and 73.6% after curative excision (caecum and ascending colon: 81%; transverse colon: 83%; descending colon: 65%; sigmoid flexure: 70.7%). Tumoral invasion in depth and lymph node involvement had a significant influence on prognosis. Based on Dukes' classification, the 5-year survival rates for stages A, B, C and D tumours were 89%, 75.4%, 54% and 6% respectively. The time elapsed between the first symptoms and the operation did not alter the prognosis which was slightly better in women and in young patients.

[Radiotherapy before amputation of the rectum for cancer. 100 cases]. / La radiothérapie avant amputation du rectum pour cancer. 100 observations.

Between 1977 and 1982, 100 patients were treated with pelvic irradiation of 3000 rads given over a 3-week period for a carcinoma located in the lower third (51 cases) or the middle third (49 cases) of the rectum. The irradiation was well tolerated by all patients. The tumour disappeared in 4 patients who were not operated upon and survived for more than 5 years. Among the remaining 96 patients, 18 of whom had fixed lesions, rectal excision was performed in 87 (90.6 per cent) and was considered curative in 75 (78 per cent). Pathological examination of the surgical specimens revealed the absence of tumour in 4 cases. There were 2 post-operative deaths. After curative excision, the 5-year survival rate was 70 per cent and the locoregional recurrence rate was 8 per cent, with perineal recurrence in only one case. Patients treated with pre-operative irradiation have been compared with a historical series of patients who had abdominoperineal excision without irradiation. In the present series of irradiated patients, thromboembolic complications were more severe, and the problems encountered with healing of the perineum were solved by changing the surgical technique in order to close the perineal wound. The rectal tumours were smaller, with a smaller proportion of tumours of more than 5 cm in diameter (P less than 0.001), but there was no significant change in Duke's stage distribution. The 5-year survival rate was higher (70 per cent versus 55.3 per cent; P less than 0.05), and the 5-year locoregional recurrence rate was lower (8 per cent versus 18.4 per cent; P less than 0.05).