Does enhanced recovery improve the survival rates of patients 3 years after undergoing surgery to remove a tumor in the colon?

PURPOSE: The advantages of enhanced recovery programs (ERP) after colorectal surgery for morbidity and length of stay are well known. On a longer term, evidence is much more limited. The aim of this study is to determine the impact of ERP on survival after 3 years of follow-up, following colorectal cancer surgery. METHODS: All the patients undergoing resection for colorectal cancer between the years 2010 and 2014 were included. Patients were classified according to their compliance with the ERP (< 70 or ≥ 70%). RESULTS: Among the 206 patients included during the period, 129 were male (62.6%). The 3-year overall survival rate was 70.4% (145 patients) and relapse-free survival was 59.2% (122 patients). The survival after 3 years was influenced by the initial metastatic status (p < 0.0001), operative morbidity (p < 0.001), and the presence of peritumoral emboli (p = 0.006). However, the compliance with the ERP ≥ 70% did not influence overall survival (p = 0.63), nor relapse-free survival (p = 0.93). The same observations were found among the "at-risk" population (synchronous metastasis and postoperative complication). CONCLUSION: The ERP does not seem to influence the 3-year relapse-free survival after colorectal resection for cancer.

Human papillomavirus does not play a role in the Barrett esophagus: a French cohort.

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).

Radiation-induced cholangitis with hepatocellular carcinoma.

There are no reports of hepatocellular carcinoma complicating postradiotherapy cholangitis. We report the case of a 45-year-old patient who had undergone upper abdominal radiotherapy for Hodgkin's disease, 21 years before, which was complicated years later by cholangitis with stricture of the common bile duct. Biliodigestive anastomosic surgery was scheduled due to recurrent angiocholitis, and hepatocellular carcinoma was discovered. The patient died from carcinoma some months later.

Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402).

The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P=.68), respectively. Multivariate analysis identified four independent prognostic factors for survival: alpha-fetoprotein (AFP)>400ng/mL (P=.008), abdominal pain (P=.011), hepatomegaly (P=.023) and Child-Pugh score (P=.032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P=.70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P=.58). In this subgroup, two prognostic factors were statistically significant for survival: AFP>400ng/mL (P=.004) and Spitzer Index (P=.013) as shown by multivariable analysis. In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.

The combination of everolimus and zoledronic acid increase the efficacy of gemcitabine in a mouse model of pancreatic adenocarcinoma.

BACKGROUND: Gemcitabine is a standard treatment for pancreatic adenocarcinoma. Many mechanisms are involved in gemcitabine resistance, such as reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) membrane transporter, deoxycytidine kinase deficiency, and changes in the signal transmission of mitogen-activity protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K) pathways. AIM: To evaluate the anti-tumor efficiency of blocking signaling pathways using combined action of gemcitabine, everolimus and zoledronic acid versus gemcitabine alone in a mouse subcutaneous xenograft. METHODS: Implantations of two human pancreatic adenocarcinoma cells lines (PANC1, K-ras mutated and gemcitabine-resistant; and BxPc3, wild-type K-ras and gemcitabine-sensitive) were performed on male athymic nude mice. The mice received different treatments: gemcitabine, gemcitabine plus everolimus, everolimus, gemcitabine plus zoledronic acid, everolimus plus zoledronic acid, or gemcitabine plus everolimus and zoledronic acid, for 28 days. We measured the tumor volume and researched the expression of the biomarkers involved in the signaling pathways or in gemcitabine resistance. RESULTS: In wild-type K-ras tumors, the combinations of gemcitabine plus everolimus; zoledronic acid plus everolimus; and gemcitabine plus zoledronic acid and everolimus slowed tumor growth, probably due to caspase-3 overexpression and reduced Annexin II expression. In mutated K-ras tumors, gemcitabine plus everolimus and zoledronic acid, and the combination of zoledronic acid and everolimus, decreased tumor volume as compared to gemcitabine alone, inhibiting the ERK feedback loop induced by everolimus. CONCLUSION: The combination of zoledronic acid and everolimus has an antitumor effect and could increase gemcitabine efficacy.

A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU)+leucovorin and bi-weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon digestive carcinomas.

In patients with non-colon digestive carcinomas, various schedules and doses of 5-fluorouracil (5-FU) and leucovorin combined with cisplatin (CDDP) have been used extensively. The present study explored the toxicity and activity of a weekly 24-h infusion of high dose 5-FU modulated by high dose leucovorin with bi-weekly CDDP. 59 patients with measurable disease were treated with a weekly infusion of high dose 5-FU (2 or 2.6 g/m2)+leucovorin 500 mg/m2 for 6 weeks and a bi-weekly dose of CDDP (50 mg/m2). All patients had metastatic or locoregionally advanced disease and had a performance status < or =3. All patients were evaluable for toxicity and 58 for response. Toxicity was different according to the schedule of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2.6 g/m2 with a high incidence of grade 3/4 neutropenia (16%) and febrile neutropenia (13%), and led to dose reductions in both CDDP and 5-FU in 13 patients (34%). For patients who started 5-FU at a dose of 2 g/m2, no reduction in 5-FU was required, and only 4 patients required a dose reduction of CDDP (19%). Grade 3/4 neutropenia was seen in 10% of patients of this group and only 1 patient required hospitalisation for febrile neutropenia. Other grade 3/4 toxicities were rare in both groups. Renal toxicity was infrequent and mild and did not require dose adjustments. The overall response rate was 33%; 19 patients achieved a partial responses (PR). No patient had a complete response (CR). The median duration of response was 5.7 months (range 2-24 months) and the median survival was 7.9 months ( range: 1-30, 95% confidence interval (CI): 7-9). The combination of weekly 24-h infusion of high dose 5-FU with leucovorin and bi-weekly cisplatin seems a well-tolerated and active treatment in non-colon digestive carcinomas. A dose of 2 g/m2 of 5-FU seems to be recommended.

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer.

PURPOSE: The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m(2) every 3 weeks were investigated as first-line treatment for advanced colorectal cancer (CRC). PATIENTS AND METHODS: Patients were enrolled into the study to receive a first cycle of therapy with irinotecan at a dose of 350 mg/m(2) every 3 weeks, which could be escalated to 500 mg/m(2) for the second and subsequent cycles depending on toxicity. Efficacy, safety and pharmacokinetics were determined in the intent to treat (ITT) population and the high-dose population (i.e. patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m(2)). RESULTS: Of 49 patients enrolled into the study (ITT population), 31 (63%) received at least three cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m(2) (the high-dose population). The response rates (RR) for the ITT and high-dose populations were 24.5% and 35.5%, respectively. The main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively. The pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2. Irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1 to identify patients for dose increase in subsequent cycles. The exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m(2). CONCLUSION: These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle.

The natural history of hereditary chronic pancreatitis: a study of 12 cases compared to chronic alcoholic pancreatitis.

The aim of this study was to document the natural history of chronic hereditary pancreatitis and to compare its evolution to that of chronic alcoholic pancreatitis. Twelve subjects with chronic hereditary pancreatitis were followed up for a mean duration of 15.8 years (range, 1-23) and compared to subjects with chronic alcoholic pancreatitis who were followed up from 1972 to 1980. The subjects with chronic hereditary pancreatitis, when compared to those with chronic alcoholic pancreatitis, were found to have an earlier onset of symptoms (10.5 vs. 46.0 years, p < 0.05); a significant delay in diagnosis (14.3 vs. 3 years); a similar prevalence of pancreatic calcification (58 vs. 57%); a similar amount of pancreatic insufficiency; both endocrine (50 vs. 70%) and exocrine 42 vs. 38%); and a higher prevalence of pseudocysts (33 vs. 10%, p < 0.05). Only one pancreatic adenocarcinoma was diagnosed in a patient with chronic alcoholic pancreatitis. Apart from the earlier onset and the delay in diagnosis, chronic hereditary pancreatitis has a natural history similar to that of chronic alcoholic pancreatitis. The disease is progressive with a high incidence of complications, but all subjects were alive after follow-up.

Survival and quality of life after palliative surgery for neoplastic gastrointestinal obstruction.

OBJECTIVE: The aim was to identify the prognostic factors which relate to the results, in terms of survival and quality of life, of palliative surgery in cancer patients presenting with an occlusion. METHODS: The files of 109 patients with a neoplasm who were operated on for occlusion between 1990 and 2000 have been re-examined. The prognostic factors studied were age, sex, the location of the primary tumour, the extension of the cancer at the time of the operation, and the surgical procedure carried out. The impact on the quality of life was assessed by the resumption of transit and the return home. RESULTS: The median survival was 64 days and the peroperative mortality was 21%. The quality of life of patients has been improved in 65% of cases. The only factors clearly correlating to survival and the success of the operation are the aetiological diagnosis of the occlusion (local recurrence better than carcinomatosis) and the type of procedure it was possible to carry out (resection better than bypass). CONCLUSION: Palliative surgery can, in a certain number of cases, improve the quality of life of patients, but it has not been possible for us to demonstrate prognostic factors which would allow the selection of patients who could benefit the most from such surgery.

Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients.

The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg x kg(-1) x day(-1)) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45% of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated gamma-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability.

Extensive aetiological investigations in acute pancreatitis: results of a 1-year prospective study.

BACKGROUND: Epidemiological data on acute pancreatitis are poorly defined. AIMS: To prospectively evaluate the aetiology of acute pancreatitis and to assess the benefits of intensive investigations. METHODS: In a prospective, 1-year study all cases of acute pancreatitis in the Nice catchment area were enrolled. Subjects underwent routine (serum calcium, phosphate and triglycerides; abdominal ultrasonography and CT scan) and additional, delayed intensive investigations (ERCP with bile sampling and/or endoscopy ultrasonography). RESULTS: One hundred and twenty-one cases were included. After routine investigations, a biliary, alcoholic, miscellaneous or unknown origin was diagnosed in 43%, 31.4%, 9.9% and 15.7%, respectively. In subjects with biliary pancreatitis, 43% had no previous history of biliary disease. In the alcohol-related subgroup, pancreatitis recurred in 18.5% during 114.5 days mean follow-up. In subjects with a first episode of alcoholic pancreatitis, delayed supplemental investigations revealed underlying chronic pancreatitis in 92.8%. After routine investigations, a diagnosis of pancreatitis of unknown origin was made in 15.7% (n = 19) of subjects. Additional investigations revealed an underlying cause in 57.8% of these patients (n = 11), including malignancy (n = 3) and biliary disease (n = 4), reducing the overall rate of pancreatitis with no apparent cause to 6.6%. CONCLUSIONS: Investigative techniques, particularly ERCP, will reveal the underlying aetiology of pancreatitis in the majority of patients presenting with 'idiopathic' pancreatitis and should be considered when routine tests are negative.

[Multifocal MALT lymphoma and acute cytomegalovirus gastritis revealing CD4 lymphopenia without HIV infection]. / Lymphome du MALT multifocal et gastrite aiguë à cytomégalovirus révélant une lymphopénie CD4 sans infection VIH.

We report the case of a 63 year-old female who presented with a seven-year history of epigastric pain and a sudden overall deterioration. Gastroscopy demonstrated inflammatory aspect and ulceration in the antrum and fundus. Histology showed a lymphocytic infiltrate consistent with low grade mucosa-associated lymphoid tissue lymphoma and cytomegalovirus gastritis. There was no evidence of Helicobacter pylori infection. Other investigations demonstrated two pulmonary foci consistent with lymphomatous infiltration and a reduced CD4 + T-lymphocyte count (85/mm3). Other screening tests including HIV serology were negative. This case of idiopathic CD4 lymphopenia, in conjunction with the other rare cases in the literature, allows us to reevaluate this condition and its unusual clinical presentation with two opportunistic pathologies.

[Cholecystocolic fistula: from symptoms to diagnosis]. / Fistules cholécysto-coliques: du symptôme au diagnostic.

We report 2 patients with a cholecystocolic fistula in whom diametrically opposite symptoms (isolated steator-rhea, jaundice and fever) were responsible for important clinical difficulties. These fistulae are far less common than cholecysto-duodenal fistulae. Endoscopic retrograde cholangiography was performed because of abnormal liver tests and led to diagnosis in both cases. Classical aerobilia was absent in both of our cases. Barium enema was disappointing (case n. 1), whereas technetium 99m scintiscan visualized the fistula (case n. 2). Two therapeutic approaches are possible in the case of cholecystocolic fistula. Surgery, usually combining cholecystectomy and extraction of common bile duct stones with the treatment of the fistula, may be performed systematically or in case of failure of sphincterotomy (case n. 1). On the other hand, endoscopical sphincteromy during endoscopic retrograde cholangiography, which, by reducing increased biliary pressure, may be sufficient to achieve spontaneous closure of the fistula in an elderly or high risk patient (case n. 2).

[Contact litholysis of common bile duct calculi. Study of 44 patients]. / Litholyse de contact des calculs de la voie biliaire principale. Etude chez 44 malades.

OBJECTIVES: Endoscopic sphincterotomy has become a generally accepted method for extracting common bile duct stones in high risk or cholecystectomized patients. However, stone extraction is impossible by the usual methods in 5 to 10% of cases. The purpose of this study was to evaluate the effect of a recently developed solvent system in patients with large bile duct stones. METHODS: Forty four patients (15 men and 29 women, median age of years) underwent contact dissolution after unsuccessful Dormia extraction. Solvents were administered via a nasobiliary catheter in 41 patients following papillotomy and through a T-tube in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution; and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused continuously and alternatively for 2 hours. RESULTS: Bile duct stones disappeared in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in stone volume occurred, allowing complete endoscopic extraction of the fragments. In 4 patients, the size of the stone did not change. Only mild and transient side-effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea and sleepiness (50%) were observed. CONCLUSION: Direct dissolution therapy could be an effective method for the non-surgical management of large bile duct stones in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.

[Palliative endoscopic treatment of malignant duodenal stenosis by metal prosthesis]. / Traitement endoscopique palliatif des sténoses malignes duodénales par prothèse métallique.

PURPOSE: To evaluate the efficacy of through-the-scope metal stents for palliation of malignant duodenal stenosis. MATERIAL AND METHODS: Fourty two patients with malignant primary or secondary duodenal stenoses who were treated with a through-the-scope metal stent were analysed. When obstructive jaundice occurred either before, during, or after the initial episode of gastrointestinal luminal obstruction, a biliary stent was inserted. RESULTS: Duodenal metal stents were deployed in 40 patients. Endoprosthesis insertion led to restoration of oral intake in 39 patients. The procedure was not associated with morbidity or mortality. During a mean follow-up of 9.7 weeks, adequate oral intake was maintained in 38/39 cases. Tumour in-growth led to stent occlusion in 4 cases and re-cannulation was obtained by placement of another stent within the original stent. Obstructive jaundice occurred during the course of the illness in 32 patients and was successfully treated with a biliary metal stent in all cases. CONCLUSIONS: Endoscopically placed metal stents offer an effective, well-tolerated alternative to surgical palliation in case of incurable malignant obstruction to gastric outflow.

[Hemorrhagic pancreatic cystadenocarcinoma with colonic fistula. An unusual mode of manifestation]. / Cystadénocarcinome pancréatique hémorragique fistulisé dans le côlon. Un mode de révélation exceptionnel.

We report a case of a cystadenocarcinoma of the pancreatic tail, in a 85-year-old man. This tumor was successively revealed by a wirsungorrhagia and a hemorrhagic pancreatico-colic fistula. To our knowledge, it's an exceptional revelation of a pancreatic cystadenocarcinoma and the first case reported in the literature.

[Acute inoperable cholecystitis treated by endoscopic naso-vesicular drainage. Study of 15 patients]. / Cholécystite aiguë inopérable traitée par drainage nasovésiculaire endoscopique. Etude chez 15 malades.

OBJECTIVES: Cystic duct cannulation during endoscopic retrograde cholangiography is now possible, due to advances in endoscopic equipment and methodology. The aim of this study was to assess the role of endoscopic transpapillary cholecystostomy in inoperable patients with acute cholecystitis. METHODS: Between October 1993 and February 1996, cystic duct cannulation was performed in 15 patients with acute cholecystitis (9 men and 6 women; mean age 74.8 years. Acute calculous cholecystitis was associated with cholangitis in 4 cases, with pancreatitis in 2 cases, and with perforation of the gallbladder in 1 case. RESULTS: Cystic duct cannulation was successful in 13 patients (86.6%), and resulted in remission of cholecystitis by nasovesicular drainage associated with antibiotherapy in all cases. No morbidity and mortality due to this method was observed at one month. No recurrence was observed after a mean follow-up of 8 months (range: 6 weeks-14 months). CONCLUSION: This study suggests that endoscopic nasovesicular drainage is a good alternative treatment to percutaneous cholecystostomy in inoperable patients.

[Intestinal obstruction in cancer patients: results of palliative surgery]. / Occlusions intestinales chez le patient cancéreux: résultats de la chirurgie palliative.

OBJECTIVE: The study aim was to investigate predictive factors related to the results, in terms of survival and quality of life, of palliative surgery in cancer patients presenting with intestinal obstruction. METHODS: A total of 109 patients already treated for a neoplasm were operated on for intestinal obstruction between 1990 and 2000. The investigated prognostic factors were age, sex, location of the primary tumour, extension of the cancer at the time of the operation and the surgical procedure carried out. The impact on the quality of life was assessed by the resumption of intestinal transit and the return home. RESULTS: The median survival rate was 64 days and the postoperative mortality rate 21%. The quality of life was improved in 65% of the patients. The only factors clearly correlated with survival and the success of the operation were the aetiological diagnosis of the intestinal obstruction and the type of procedure which was possible to carry out. CONCLUSION: Palliative surgery may improve the quality of life of a certain number of patients, but it was not possible to demonstrate predictive factors for the selection of patients who could have the larger benefits of such surgery.