Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer.

BACKGROUND: The optimal timing of surgery following preoperative chemoradiotherapy (CRT) is controversial. This trial aimed to compare pathological complete response (pCR) rates obtained after an interval of 8 weeks or less versus more than 8 weeks. METHODS: Patients with locally advanced rectal adenocarcinoma situated within 12 cm of the anal verge (T3-4 or N+ disease) were randomized to undergo total mesorectal excision (TME) within 8 weeks (classical interval, CI group) or after 8 weeks (long interval, LI group) following CRT. RESULTS: Among the 327 included patients (CI 160, LI 167), the pCR rate was significantly higher in the LI group than in the CI group (10·0 versus 18·6 per cent; P = 0·027). The highest pCR rate (29 per cent) was observed between 10 and 11 weeks. There was statistically significant disease regression in the LI group, with better stage (P = 0·004) and T category (P = 0·001) than in the CI group. There was no significant difference in surgical quality (rates of tumour-positive margins, TME quality, anastomotic leakage and intraoperative perforation) between the groups. The overall morbidity rate was 22·5 per cent in the CI group and 19·8 per cent in the LI group (P = 0·307). Regression analysis including sex, age, clinical stage, tumour location, tumour differentiation, TME quality, concomitant chemotherapy and interval to surgery revealed no statistically significant predictors of pCR. CONCLUSION: Disease regression and pCR rate are increased with an interval between CRT and surgery exceeding 8 weeks. Registration number: NCT03287843 (http://www.clinicaltrials.gov).

Infliximab in experimental alkali burns of the oesophagus in the rat.

BACKGROUND: We aimed to investigate the efficacy of infliximab, a chimeric TNF-alpha antibody, in the prevention of fibrosis in an experimental alkaline burn of the oesophagus in the rat. METHODS: Thirty-two Wistar albino rats divided into four experimental groups. Caustic oesophageal burn was induced by applying 37.5% NaOH to the distal oesophagus. Infliximab was given at a dose of 5 mg/kg via the intraperitoneal route. Group A (sham) animals were uninjured, group B had untreated oesophageal burns, group C had oesophageal burns treated with a single dose of infliximab on the first day, and Group D had oesophageal burns treated with infliximab on the first and 14th days. Efficacy of the treatment was assessed on the 28th-day by measuring stenosis index of the oesophagus and histopathological damage score, and biochemically by determining tissue hydroxyproline content. RESULTS: There was no significant difference between the Group B and the infliximab treated Groups C and D in means of tissue hydroxyproline content and histopathological damage scores. Stenosis index was not significantly different between the Group B, Group C, and Group D. CONCLUSION: Anti-TNF-alpha treatment with infliximab does not ameliorate the degree of fibrosis in alkali burns of the oesophagus in the rat. Further evaluation of inflammatory and immunological events leading to stricture in alkaline oesophageal burns may provide new perspectives for the treatment of alkaline oesophageal burns.

Severe colitis after administration of UFT chemotherapy for temporal bone carcinoma.

UFT (Uftoral), a blend of uracil and Tegafur, is an antitumour agent for oral administration that is presumed to maintain the concentration of 5-fluorouracil (5-FU) in tumour tissue. As a result of increased use of high-dose 5-FU-based chemotherapy for various solid tumours, complicated drug-induced colitis is more frequently observed. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU and its deficiency is responsible for the severe toxicities encountered in cancer patients receiving 5-FU. The authors present the case of a patient with locally advanced temporal bone carcinoma who developed haematochezia during a course of chemotherapy with UFT. Colonoscopy of the patient showed bleeding petechia-like lesions and superficial inflammatory exudate, whilst histology revealed non-specific inflammatory changes of the colon mucosa. As the haematochezia improved with supportive treatment, neutropenia complicated the clinical picture. This patient developed life-threatening UFT toxicity without an exon-14 DPD gene mutation.

Autoimmune haemolysis as an unusual cause of anaemia in von Recklinghausen's disease.

Von Recklinghausen's disease, now classified as neurofibromatosis type 1 (NF-1), is a relatively frequent autosomal dominant disorder and has clinical manifestations, such as cafe-au-lait spots, freckling, generalised cutaneus neurofibroma, Lisch nodules, short stature, optic glioma and central nervous system tumours. In adults, anaemia in the course of NF-1 is usually due to gastrointestinal tumour bleeding. Association of NF-1 and autoimmune haemolytic anaemia is unusual. Here, we report a 48-year-old woman with NF-1 presenting as autoimmune haemolytic anaemia. We also reviewed the literature about the association of NF-1 and autoimmune diseases.

An experimental model of hemolysis-induced acute pancreatitis.

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

An experimental model of hemolysis-induced acute pancreatitis

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20 percent. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20 percent (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20 percent ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70 percent) of 50 rats, moderate hemolysis in seven (14 percent), and no hemolysis in eight (16 percent). Thirty-three of 35 (94.2 percent) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8 percent) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80 percent of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines