Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences.

Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.     

Acute motor sensory polyneuropathy (AMSAN) complicating active ulcerative colitis with a patchy distribution

We report a case of acute motor and sensory neuropathy during a flare of ulcerative colitis. A 28-year-old male presented with a flare of distal ulcerative colitis despite treatment with mesalamine enemas and suppositories simultaneously with rapidly deteriorating weakness and needle sensation in both legs. Neurological assessment showed axonal sensorimotor polyneuropathy affecting mainly the lower limbs and to a lesser extent the upper limbs. Colonoscopy revealed moderately to severe active ulcerative colitis with a patchy distribution involving the rectum and the right colon. Vitamin and folic acid levels were normal. Virological, immunological and other laboratory tests were negative except for positive anti-ganglioside antibodies (anti-GM1). Ulcerative colitis and polyneuropathy improved when patient was treated with immunosuppressive therapy (corticosteroids, immunoglobulin and azathioprine). Peripheral polyneuropathy is a rare extraintestinal manifestation of ulcerative colitis and it is probably associated with an autoimmune pathogenetic mechanism.     

The value of immunohistochemistry for collagen IV expression in colorectal carcinomas

The Dukes' classification has well-established prognostic value in colorectal cancer patients. Yet, in each Dukes' class, the survival of individual patients may vary considerably. Recent studies show prognostic significance of genetic alterations in colorectal carcinoma. However, the importance of tumor stromal components noted in the surrounding tissue may have been overlooked by the methods used. Therefore, in a longitudinal study of 154 patients with colorectal cancer operated on between 1967 and 1974, the authors determined the influence on prognosis of lymphocytic infiltration and expression of collagen type IV in tumor stroma. Also, age, sex, Dukes' classification, grade of tumor differentiation, vasoinvasion, and the number of positive lymph nodes were analyzed. Follow-up was at least 15 years. Lymphocytic infiltration and collagen IV expression were scored as mild, moderate, or severe. Survival was analyzed by a Cox proportional-hazards model. The density of lymphocytic invasion showed no significant influence on survival. Collagen IV expression analyzed as a single variable was significantly (P = 0.038) related to better prognosis in colorectal cancer patients. By multi-variate analysis collagen IV expression showed a trend toward better prognosis that was not statistically significant (P = 0.12). Dukes' classification (P less than 0.001), the presence of vasoinvasion (P = 0.009), and lymph node status (P = 0.04) significantly influenced survival. In conclusion immunohistochemistry for collagen IV is an important additional staining technique with prognostic value. In addition, collagen IV immunostaining facilitates recognition of vascular invasion by highlighting the basement membrane of vessels.     

Cholestatic hepatitis with severe systemic reactions induced by trimethoprim-sulfamethoxazole

Trimethoprim-Sulfomethoxazole (TMP-SMX) related hepatotoxicity and associated severe systemic reaction are not frequent and documented only in case reports. We report a case of a 30-year-old man, who underwent a 15-day therapy with TMP-SMX for urinary tract infection and two weeks later developed acute cholestatic hepatitis, fever and a skin rash followed by severe systemic reaction. He was admitted in Intensive Care unit and with supportive therapy and prednisolone administration, he showed subsequent improvement over a period of few days. He had fully recovered months later. All tests for other causes of liver disease were negative and his liver biopsy showed evidence of drug-induced hepatic injury.     

Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn's disease. A case report

We report the case of a 57-year old female patient with refractory to treatment pyoderma gangrenosum associated with clinically inactive Crohn's disease. Pyoderma gangrenosum was successfully treated with Infliximab, a chimeric monoclonal antibody that inhibits tumour necrosis factor alpha (TNF-alpha). Our case report suggests that Infliximab, a therapeutic agent for refractory and fistulizing Crohn's disease, may also be safe and effective in the treatment of Crohn's disease associated pyoderma gangrenosum, even though the inflammatory bowel disease is clinically inactive and repeated infusions may be required for successful treatment.     

Candida colitis in a middle-aged male receiving permanent haemodialysis.

Candida infections of the gastrointestinal tract are not rare, especially in immunocompromised patients. We present a case of candida colitis in a patient receiving permanent haemodialysis. Candida colitis can be a life-threatening condition and should be treated promptly, especially in immunocompromised patients.     

Evidence for the 'paradox' association between hypertensive lower esophageal sphincter and gastroesophageal reflux disease

There are several studies suggesting the paradoxical simultaneous presence of hypertensive lower oesophageal sphincter and gastroesophageal reflux disease. We present a case of a 22-year-old male patient who was examined in our outpatient clinic with oesophageal food bolus impaction during a meal, severe chest pain and drooling. Manometry revealed a hypertensive lower esophageal sphincter pressure (resting pressure 35 mmHg) and pHmetry revealed a DeMeester score > 14.72 (43.27). Six months after therapy with lansoprazole, manometry revealed a normal lower oesophageal sphincter (resting pressure 14 mmHg) and the DeMeester score was < 14.72 (5.89). The patient is now asymptomatic. This report is the only published case which exhibits the normalization of lower oesophageal pressure 6 months after gastroesophageal reflux disease management with lansoprazole, thus proving and establishing the above 'paradox'.     

Bax upregulation may provide a rationale for the low incidence of esophageal adenocarcinoma in a Greek cohort of patients with Barrett's esophagus

BACKGROUND/AIMS: Previously rare, esophageal adenocarcinoma (EA) is now the most common esophageal malignancy in Western countries whose incidence is increasing faster than any other cancer. However, mortality from esophageal cancer in Greece is among the lowest in the world and no clear-cut answer has emerged as to why the incidence of EA is so low in this country. Thus, the aim of the study was to provide an explanation for the low incidence of EA in Greece through molecular-based ethnic differentiations. METHODOLOGY: Out of 270 patients who underwent upper gastrointestinal endoscopic and histologic evaluation due to GERD symptoms, 31 patients (23 males, 8 females, mean age 47.10 +/- 11.88 years) with BE (typical salmon-pink lesions) and 21 GERD controls (12 males, 9 females, mean age 46.57 +/- 17.71 years) were ultimately included in the study. Esophageal mucosa biopsy specimens were evaluated immunohistochemically for Ki-67, Bax and Bcl-2 expressions. RESULTS: Increased expression of Ki-67 was observed in BE patients compared with GERD controls (p = 0.01); increased expression of Bax was noticed in the total BE patients compared with GERD controls (p < 0.001); Bcl-2 expression did not differ between the two groups. CONCLUSIONS: Our findings indicate a possible existence of a balance between cell proliferation (indicated by Ki-67 increased expression) and apoptosis (indicated by Bax protein overexpression), thereby providing an equilibrium between cell apoptosis and cell proliferation, and this may partly explain the low EA incidence in Greece.     

Methylene blue chromoendoscopy for the detection of Barrett's esophagus in a Greek cohort

BACKGROUND AND STUDY AIMS: Specialized columnar epithelium of Barrett's esophagus is a precursor of dysplasia and adenocarcinoma, and methylene blue selectively stains this type of epithelium. The present prospective study examined the detection of short-segment and long-segment Barrett's esophagus using methylene blue chromoendoscopy-directed biopsies, in comparison with biopsies directed using conventional endoscopic criteria. PATIENTS AND METHODS: Biopsies were obtained from macroscopically conspicous areas in the distal esophagus observed during conventional endoscopy in a total of 975 patients. Immediately after conventional biopsies, the distal esophagus was sprayed with methylene blue and directed biopsies were then obtained from the stained regions. All patients with a histologically established Barrett's esophagus underwent a second upper gastrointestinal endoscopy within 1 year in order to assess the reproducibility of the method. RESULTS: In a total of 3,900 conventional biopsy specimens (without staining), 54 specimens (1.4%) were found to show Barrett's esophagus and were confined to 16 of the 975 patients (1.6%). Of the total 130 directed biopsy specimens obtained during chromoendoscopy, 114 (87.7%) revealed Barrett's esophagus (P<0.00001) and were confined to 35 of the 975 patients (3.5%; P < or = 0.001). The findings were confirmed within 1 year in all dye-positive patients. CONCLUSIONS: Chromoendoscopy with methylene blue appears to be an accurate, simple, safe, inexpensive, and reproducible method of detecting specialized columnar epithelium in Barrett's esophagus.