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Background: To distinguish large (LFN) and small fiber neuropathies (SFN) in Sjögren's syndrome (SS) requires electroneuromyography (EMG) first, but this is time-consuming and has sometimes a limited accessibility, which can lead to a diagnostic delay. We aimed to identify clinical features that could distinguish SFN from sensitive LFN in SS., Methods: The study included patients with SS who were monitored in the internal medicine and neurology departments at Angers University Hospital between 2010 and 2016, and who were tested for suspected peripheral neuropathy. Patients with clinical motor involvement were excluded. LFN diagnosis was based on EMG. SFN diagnosis was based on intraepidermal nerve fiber density on skin biopsies in patients with no abnormality on EMG., Results: LFN and SFN were diagnosed respectively in 22 (6.9%) and 17 (5.4%) patients among 317 patients with SS. Prevalence of anti-SSA antibodies was lower in the SFN group compared to the LFN group (p=0.002). The types of paresthesia did not differ between the 2 groups. After adjustment for age and sex, SFN was associated with dysautonomia (p=0.01, OR 8.4 [CI 95%: 1.7-42.4]) and without length-dependent topography (p=0.03, OR 0.2 [0.04-0.8] in comparison with the LFN group., Conclusions: An association of non-length-dependent pattern and dysautonomia seems to predict the absence of LFN in SS and encourages the search for SFN. In contrary, patients with length-dependent involvement and without dysautonomia should be prioritized for EMG., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia., Methods: All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951-2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days., Results: Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01-7.70; p = 0.04)., Conclusions: This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate. Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment. We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.

Objectives: Esophageal cancer outcome greatly depends on the pathological stage. Our objectives were to assess prognosis on the basis of the initial fluorodeoxyglucose (FDG)-PET scan, focusing on the correlation between overall survival and FDG uptake in the primary, as well as the presence of FDG-positive lymph nodes or distant metastases., Methods: Fifty-two esophageal cancer patients undergoing FDG-PET as part of initial routine staging procedure before treatment were included. The maximum standardized uptake value (SUV max) was determined in each primary lesion and the number of abnormalities including primary, lymph nodes, or distant metastases was recorded. Correlation with overall survival was performed using Kaplan-Meier method and Cox regression analysis was used to assess the prognostic value of PET parameters., Results: Half of the patients were planned for initial curative surgery (52%). Using univariate survival analysis, either surgery, SUV max >9, two or more PET abnormalities or the presence of FDG-positive nodes were significant overall survival prognostic predictors. After multivariate analysis, only SUV max >9 and FDG-positive lymph nodes were found as independent predictors of poor outcome., Conclusion: In this prospective study, FDG-PET was found to provide prognostic information supporting a new indication for initial FDG-PET examination in esophageal cancer.

We reviewed two cases of adenocarcinoma of the gastric tube used for reconstruction after esophagectomy for cancer. The first case gastric cancer was detected during follow-up by endoscopic examination. Total resection of the gastric tube and reconstruction by Roux-en-Y was performed each time. The patient was alive and disease-free 1 year after surgery. In the second case the tumor was revealed via thoracic pain. Chemotherapy, using carboplatin-5-fluorouracil, was performed because of lung metastasis but the patient died 1 year later. The incidence of gastric tube cancer after esophagectomy has recently increased in conjunction with the lengthening of survival of esophageal cancer patients. The clinical symptoms related to tumors are associated with short-term survival, whereas the cancers detected by routine endoscopy screening have occasional long-term survival. Gastrectomy is proposed for surgical treatment but the operating procedure is complex with a high morbidity rate. Lesions detected at an early stage could be treated by minimally invasive surgery such as endoscopic mucosal resection.

Background: Resection for adenocarcinoma of the gastroesophageal junction (AGEJ) is associated with severe mortality and morbidity. This retrospective study aimed to evaluate mortality and morbidity after resection for AGEJ and to determine their predictive factors., Study Design: Data from 1,192 patients (mean age 65 +/- 11 years) who underwent resection for AGEJ by members of French Association of Surgery from 1985 to 2000 were collected. A stepwise logistic regression model was built to identify by multivariate analysis the variables independently associated with mortality, morbidity, anastomotic leakage, and major pulmonary complications., Results: Distribution of Siewert's type was: I = 480 (40%), II = 500 (42%), and III = 212 (18%). Most type I and II tumors were treated by esophagectomy and proximal gastrectomy (93% and 58%, respectively), using an approach including a thoracotomy (82% and 64%, respectively); type III tumors were treated mainly by total gastrectomy and distal esophagectomy (83%), through an exclusive transabdominal approach (69%). Seventy-six (6%) patients died postoperatively. Only American Society of Anesthesiologists (ASA) scores III and IV (p < 0.001) and period of study (p = 0.025) were predictive of mortality. Predictive factors of overall morbidity (overall rate = 35%) were high ASA score (p < 0.001), age more than 60 years (p = 0.020), male gender (p = 0.039), and cervical anastomosis (p = 0.001). Factors predictive of anastomotic leakage (overall rate = 9%) were high ASA score (p = 0.006) and manual anastomosis (p = 0.010). Factors predictive of major pulmonary complications (overall rate = 23%) were high ASA score (p = 0.015), age more than 60 years (p < 0.001), anastomotic leakage (p < 0.001), and abdominal complications (p = 0.003)., Conclusions: ASA score is a reliable predictive factor of operative mortality and morbidity after resection of AGEJ.

Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad prognosis. Specific therapies are now developed against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study was aimed at assessing their expression in a large series of SCCO, as well as their potential therapeutic interest in this pathology. Immunohistochemical expression of these factors was assessed retrospectively in 107 cases of SCCO with primary surgery, as well as their relationships to recurrence, metastasis and overall survival on a long-term follow-up. Human epidermal growth factor receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases, and VEGF in 38.3%. Epidermal growth factor receptor overexpression was significantly related to vascular invasion (P=0.023). Its diffuse positivity was significantly related in multivariate analysis to higher local recurrence (P=0.006) and lower overall survival (P=0.003), in a subgroup of patients of poor outcome who had received postoperative adjuvant treatment. These results highlight the great potential prognostic and therapeutic interest of evaluating EGFR diffuse positivity in locally advanced SCCO.

Presentation of a multicentric retrospective french study concerning 4,655 cases of gastric cancer operated between 1980 and 1996. The mean age was 67.4 years old with a male predominance of 63.1%. Pains was the predominant presenting symptom (60%) followed by alteration of the general condition (44%) and anaemia (20%). 35.5% of tumors were of distal, 18.8% of middle and 18.6% of proximal localisation. As regard cancer stages, 40% were of stage I,-II and 60% of stages III,-IV. Subtotal gastrectomy was realised in 44%, total radical gastrectomy in 42.1% and other surgical procedures in 14% of cases (proximal gastric resection or atypical resection). D1 lymphadenectomy was associated in 58.4% and D2 in 41.6%. Morbidity was of 23% and mortality of 11.9% which passed from 19% during the first (1980,-85) to 8% in the last interval of time (1990,-96). The 5 years survival was 41% in case of gastric resection. In univariate analysis the 5 years relative survival was better in female patients (44% at 5 years), in patients younger than 50 years old (46%), when pain was the only clinical symptom (52.7%), in middle and distal third localisation (47%), in case of subtotal distal resection (47%) and in less advanced stages (79% at 5 years for stage I cancer). In multivariate analysis the 5 years survival was essentially correlated to the stage of the tumor and no real prognosis improvement was shown during the period of the study.

Loss of heterozygosity (LOH) on chromosome 9 and p16 (MTS1/CDKN2) gene mutations have been reported in various human cancers. The present study aimed to determine the prevalence of LOH in 100 oesophageal squamous cell carcinomas (OSCCs) by typing microsatellite loci and mutations of the p16 gene. The methods used included denaturing gradient gel electrophoresis (DGGE) and DNA sequencing of exon 2. LOH was found in 14.7% of the OSCC cases. Six gene alterations were identified in exon 2. They consisted of three deletions and the same polymorphism in three samples. The relatively low rate of p16 mutation compared with the frequency of LOH suggests the possible involvement of another tumour suppressor gene located on chromosome 9 in oesophageal carcinogenesis.

From April 1989 to October 1995, 184 patients with squamous cell carcinomas of the esophagus were treated either with surgery alone (112 patients) or with preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in 5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4 more courses of chemotherapy alone for good responders. Twenty-seven of these last 72 patients showed histological complete response at surgery (37.5%). There was no statistically significant difference in overall survival between the 2 groups although there were much more T1 patients (small tumors < or = 5 cm in the previous TNM classifications) and less T3 patients (evidence of spread beyond the esophagus) in the surgery alone group, and nevertheless, median survival was better in the combined treatment group (33.6 months versus 21.8 months). However, considering tumor size, there was a statistically significant difference in median survival in favor of the combined treatment group for all T2 patients (> 5 cm without evidence of spread beyond the esophagus in the previous TNM classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1 patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For the few T3 patients (evidence of spread beyond the esophagus in the previous TNM classification), there was no statistically significant difference between the 2 groups, but the survival curves seemed to show some advantage in favor of the combined treatment group for T3N1 patients. The sex of the patients and the third of the esophagus involved by the tumor did not seem to be of any influence on survival. On the other hand, patients 70-year-old and older showed a poorer survival than other patients. Finally, significantly less patients died with loco-regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%) than in the group treated by surgery alone.

75 patients with an epidermoid carcinoma of the esophagus were studied. They all were stage T3 with or without lymph node involvement but without distant metastasis (T3 N0 M0 or T3 N+, M0). All the patients had a curative esophagectomy according to the Ivor Lewis procedure without any adjuvant treatment. In hospital mortality was 4%. There is a 28% 5 year actuarial survival in this group of patients where 60% had lymph node involvement. None of the 13 prognostic factors showed a significant relevance with respect to survival after an univariate analysis. Meanwhile surgical treatment ensured good digestive comfort and good quality of life at home.

The complications of colostomies may constitute a handicap for patients: their prevalence severity and methods of treatment remain poorly known. 500 colostomy patients, with a mean age of 66 +/- 14 years, were retrospectively reviewed. The mean follow-up of the study was 6 +/- 5 years. Colorectal cancers represented 65% of the initial diseases. 59.5% of colostomies were terminal. They were performed for resection of the colon and or rectum in 56.5% of cases. 30.5% of patients (n = 152) presented complications (n = 235). The early complications (n = 147) observed in 29.5% of patients were mostly benign (20 required emergency operations). The late complications (n = 88), observed in 22.5% of 391 patients with a follow-up of more than one year required another operation in 1/3 of cases (11 cases of stenosis, 9 incisional hernias and 8 prolapses). Complications of colostomies remain frequent (one out of every 4 stomies ends in a complication) and the reoperation rate is situated between 13 and 33%. The therapeutic success rate of late reoperation is between 63 and 74%. When a reoperation is necessary, it should be ideally radical via a midline incision. The transposition technique gives better results than the repositioning technique via a local approach.

The TP53 gene is the most frequently mutated gene in human cancers. Barrett's esophagus provides an excellent model by which to understand the genetic events that lead from dysplasia to cancer. We screened for mutations in the TP53 gene by a combination of denaturing gradient gel electrophoresis and DNA sequencing in ten cases of adenocarcinoma arising in Barrett's mucosa. We have identified missense mutations in five of the ten samples, three transitions (R282W, G245S, R248W) and two transversions (E286Q and C176F). In one case we have analyzed biopsy specimens taken from the same site, one year before the patient developed an intra mucosal carcinoma. The mutation that was identified in this high grade dysplastic area was identical to that detected in the cancer. This would suggest TP53 mutations occur as an early genetic event in the development of Barrett's adenocarcinoma.

Fistulas of the anastomosis is the most severe complication after the Lewis-Santy operation. Over the last 10 years, we have performed 227 such operations for cancer of the oesophagus and have observed 16 fistulizations (7%). The aim of this study was to analyze the clinical manifestations and laboratory findings in these cases of fistulization as a function of the site of the plasty, the treatment and the results. We attempted to determine factors which could lead to means of preventing this complication. The fistula occurred at the oeso-gastric anastomosis in 11 cases (4.8%), at the apex of the gastric tube in 2 and on the line of gastric tubulization in 3. A comparison between patients with fistulas (group 1) and those without (group 2) showed that 19% of the patients in group 1 were over 70 years of age versus 9% in group 2 (NS). Three of the 16 patients (19%) with fistula had cirrhosis due to ethylism versus 2 of the 211 patients in group 2 (p < 0.001). Six patients among the 58 with palliative with a fistula (6%) (NS). Thoracic drainage was sufficient in 11 patients and surgical treatment was not required. In 5 reoperation (thoracotomy 4, cervicotomy 1) was necessary due to an intrapleural abscess. After 227 Lewis-Santy operations, 11 patients died during hospitalization (4.8%, 4 of which were complicated with fistula (1.7% of the operated patients and 25% of the patients with fistulas). The frequency of fistulizations after Lewis-Santy operation has decreasing (8%) and the gravity has improved (3 out of 4 were cured).(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal squamous cell carcinoma is a form of cancer occurring most commonly in males, particularly those living in some areas of Asia, Africa, and western Europe. In some of these tumors, a sequence alteration has been identified in the coding region of the TP53 gene which is known to inactivate the tumor suppressor function of its product. Using a GC clamp (i.e., a GC rich domain) denaturing gradient gel electrophoresis assay we have been able to identify sequence modifications in 27 of the 32 tumor samples analyzed (84%). Most of the mutations occur in exon 6, a region of the gene which has not previously been reported as being a hot spot for the mutations of other cancers. Twelve of the mutations reported here have not been described in other types of tumors and these consist mostly of frameshift or splice mutations. The distribution of mutations [transitions (45%), transversions (34%), and frameshift (21%)] suggests that the etiological contribution of genotoxic factors might be complex and might associate different exogenous and endogenous mutagen exposures.

Hepatic microsomal cytochromes P-450 CYP1A2, and CYP2E1 contents and catalytic activities have been simultaneously investigated in 42 patients undergoing diagnostic liver biopsy. CYP1A2 contents, measured by Western blotting, were correlated with methoxyresorufin-O-demethylation and ethoxyresorufin-O-deethylation (r = 0.65 and r = 0.66, p < 0.001, respectively). CYP2E1 contents were correlated with 1-butanol oxidation and 6-hydroxylation of chlorzoxazone (r = 0.75 for both, p < 0.001). CYP1A2 catalytic activities varied by 30- to 40-fold, whereas CYP2E1 activities varied by 6- to 20-fold. In our study, these variations were not related to liver diseases or cancer of the digestive tract nor to alcohol drinking or smoking habits, because patients were alcohol- and tobacco-free for 1 month before the study. Other environmental factors, diet habits, and/or genetic factors could explain the large interindividual variations observed.

168 Ivor Lewis operations for squamous carcinoma of the lower esophagus are reviewed. 155 men and 13 women with a mean age of 59 years were operated on. 46 tumors were stage I and II, and 122 were stage III. Operations were considered to be curative for 120 patients and only palliative for 48. An esophagectomy associated with lymphadenectomy was performed through laparotomy and right thoracotomy. Feeding jejunostomy and pyloroplasty were routine. EEA or ILS 25 staplers were used to perform esophagogastric anastomosis and the gastroplasty tube was fashioned by TA 90 stapler. In every case an extended esophagectomy was performed with anastomosis between 3 ans 7 cm below the pharyngo-esophageal junction. Postoperative mortality was 4.7%. There were 10 leaks (6%) and 28 pulmonary complications. Median actuarial survival is 17 months. Actuarial survival at 2 years is significantly greater for stages I and II (68.4%) than for stage III (23.2%) (p < 0.01). Ivor Lewis esophagectomy is a reliable procedure to treat squamous carcinoma of the lower two thirds of the esophagus ensuring a good quality of life.