Prevention of pancreatic fistula after cephalic duodenopancreatectomy]

A pancreatic fistula occurs in about 10% of cases after Whipple's procedure. This complication is associated with a mortality rate ranging from 7% to 30%. The main predisposing factor of pancreatic fistula is a soft pancreatic parenchyma. Several procedures have been proposed to decrease the rate of this complication. Occlusion of the residual stump is infrequently used and does not clearly reduce the rate of this complication. Pancreaticojejunostomy is the technique most frequently used. No alternative technique is clearly superior to pancreaticojejunostomy. Pancreaticogastrostomy and pancreaticojejunostomy have equivalent early results. Superiority of transient intubation of the Wirsung duct and mucosa-to-mucosa anastomosis is not demonstrated. Among the 7 controlled randomized studies which tested somatostatin or its analogs, many have methodological insufficiencies which prevent definite conclusions. Meanwhile, most studies suggest that these drugs decrease the rate of pancreatic fistula after pancreaticoduodenectomy. Further evaluation in high-risk patients (soft pancreatic parenchyma) is advisable.     

Resection of intrahepatic cholangiocarcinoma: a Western experience

We analyzed the results of an aggressive surgical approach to intrahepatic cholangiocarcinoma. Between 1990 and 1997, 30 of 42 patients with intrahepatic cholangiocarcinoma underwent resection with curative intent. Mean tumor size was 10 ± 5 cm, and the tumors were classified as TNM type III, IVa, and IVb in 63%, 34%, and 3% of the patients, respectively. All patients underwent hepaticoduodenal lymphadenectomy. Fifteen patients received adjuvant radio- and chemotherapy. The overall survival rates at 1, 2, and 3 years were 86%, 63%, and 22%, respectively, and the median survival time was 28 months. Tumor recurrence was the main cause of death. Three patients survived for more than 5 years, including 2 patients with no evidence of recurrence. Factors influencing survival were: presence of satellite nodules (P = 0.007) and lymph node invasion (P = 0.05). The width of the resection margin and the use of an adjuvant therapy had no impact on survival. Complete surgical resection may offer a chance for long-term survival in selected patients and may improve the quality of life of patients with more advanced disease.     

Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli (E. coli) using optical imaging. METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm³). Inflammation measuring myeloperoxidase (MPO) activity and reactive oxygen species production was monitored by a bioluminescent (BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitis-CEABAC10 DSS models, which mimicked Crohn’s disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume (P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group (P < 0.005). ELISA confirmed that MPO levels were significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 ng/mL P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model (CEABAC10/DSS). CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand host-pathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.     

Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma

BackgroundPrognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.Patients and methodsA total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.ResultsHigh CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002).ConclusionsCXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.     

Adenocarcinoma of the pancreas: Does prognosis depend on mode of lymph node invasion?

Background

Lymph node (LN) invasion in pancreatic ductal adenocarcinoma (PDAC) is the most important prognostic factor after surgical resection. The mechanisms of LN invasion include lymphatic spreading and/or direct extension from the main tumor. However, few studies have assessed the impact of these different patterns of invasion on prognosis.

Patients and methods

Pathologic reports of pancreatic resections for PDAC from 1997 to 2007 were retrospectively analyzed. The mode of LN invasion was defined as follows: standard lymphatic metastases (S), contiguous from the main tumor (C) and standard with extracapsular invasion (EI). Clinical outcomes were compared according to the mode of invasion and the number of invaded LN.

Results

306 patients were reviewed. Median age at resection was 61 years (range, 34–81). Eighty seven patients were N− (28.9%) and 214 were N+ (71.1%). Of the N+ patients, 195 (91.1%) were S+, 35 (16.3%) were C+, and 24 (12.3% of the S+ patients) were EI+. Median survival in N+ patients was lower than in N− patients (29 vs. 57 months, p < 0.001). In patients without standard involvement, C+ patients (n = 19) had worse survival than C− patients (n = 47) (34 vs. 57 months, p = 0.037). In S+ patients, C status was correlated with prognosis when the number of LN S+ was <2 (p = 0.07). EI status had no influence on prognosis. On multivariate analysis, only perineural invasion (p = 0.02) and LN ratio (p = 0.042) were independent prognostic factors.

Conclusion

Direct invasion of LN by the tumor is predictive of reduced survival, but has little impact compared to standard LN involvement and perineural invasion.     

Impact on survival of surgery after concomitant chemoradiotherapy for locally advanced cancers of the esophagus

BACKGROUND: To evaluate the results of chemoradiotherapy with or without surgery in locally-advanced esophageal carcinomas (T3 and/or nodal involvement). METHODS: One hundred twelve patients with locally-advanced carcinoma of the esophagus without histologically proven invasion of the tracheobronchial tree or distant visceral metastases were treated with concomitant chemoradiotherapy followed by re-evaluation; surgery was performed or chemoradiotherapy continued, based on tumor regression and the patient's general status. Chemoradiotherapy consisted of concomitant 5-fluorouracil (5FU)(1 g/m(2) day 1-3), cisplatinum (50 mg/m(2) day 1 and 2), and external beam irradiation up to a dose of 40 or 43.2 Gy. After a 4-week rest period, radical esophagectomy or a new cycle of chemoradiotherapy (up to a total dose of 65 Gy) was performed. RESULTS: A complete clinical response was obtained in 25.7% of the patients and a partial response in 45.9%. Fifty patients underwent surgery, but only 38 patients had an esophagectomy. Post-esophagectomy mortality was 5.3%. A complete histologic response rate of 23.7% was obtained. Two- and 5-year survival rates were, respectively, 41.5% and 28.6% for the whole population. According to multivariate analysis, prognostic factors for survival were Karnofsky index, esophagectomy, and response to chemoradiotherapy. Five-year survival for patients who experienced a partial response to radiation and chemotherapy was 49.1% for those who had surgery and 23.5% for those treated without surgery (p = 0.003). There was no obvious benefit for the small number of patients treated surgically after complete response to radiation and chemotherapy. Toxicity, essentially hematologic, was moderate. CONCLUSION: For locally-advanced esophageal carcinomas, esophagectomy, after concomitant chemoradiotherapy, could improve the survival rate, especially for patients who responded partially to the latter.     

Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer

Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APC^Min/+ mice colon. T-cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APC^min/+ mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T-cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor-infiltrating T lymphocytes (CD3⁺ T-cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3⁺ and CD8⁺ T-cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T-cells in the MLNs of CoPEC-infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD-1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T-cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti-PD-1 response in CRC.     

The value of antibiotic prophylaxis using cefotetan in high-risk abdominal hysterectomy. Apropos of a prospective randomized study of 71 patients

The advantage of antibiotic prophylaxis using a single dose of 2 g of cefotetan, administered during the induction of anesthesia, was studied in 71 patients undergoing an abdominal hysterectomy and presenting at least one of the following risk factors: obesity or procedure exceeding two hours. After random selection, 33 patients were treated, 38 were not and constitute the reference group. Comparison between the two groups shows a significant difference concerning the general morbidity, post-operative fever, urinary infection and abdominal wall abscess. Considering the excellent tolerance of the treatment and the fact that it is easy to use and inexpensive, antibiotic prophylaxis with cefotetan is quite interesting for this type of surgery.     

Adrenal gland pheochromocytomas. Apropos of 35 operated patients]

Thirty-five patients (20 female and 15 male, mean age = 47 years) operated on for an adrenal pheochromocytoma were reviewed. Catecholamine excessive production was symptomatic in 33 patients (94%). Urinary excretion of vanyl-mandelic acid, catecholamines and metanephrine was abnormal in 84%, 75% and 90% of cases, respectively. Tumor was presumed benign (no metastasis) in 31 cases. Sensitivity of CT scan (n = 35) and magnetic resonance imaging (n = 13) was 100%. Meta-iodo-benzylguanidine scan (n = 19) always recognized the main tumor, but did not visualize 1 second tumor in 1 patient and 1 metastasis in 1 other patient. An anterior intraperitoneal approach was performed in all cases. Operative mortality rate was 5.7%. In the last 15 patients, systematic preoperative treatment by prazosine did not lead to fall in rates of peroperative arrythmia and hemodynamic disorders. Twenty-two of 25 (88%) hypertensive patients remained normotensive without medication postoperatively. The risk of undiagnosed pheochromocytoma and problems in resection of large right-sided tumors are discussed.