Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series.

AIM: To describe the specific characteristics of duodenal/perivaterian carcinoids and to analyze the diagnostic/therapeutic approach. MATERIAL AND METHODS: Eight patients were included in our study. Symptoms on admission included dyspepsia, upper gastrointestinal (GI) bleeding and anemia. All patients underwent upper GI endoscopy and gastrointestinal peptides (gastrin) and neuroendocrine markers (Chromogranin-A, CgA) measurement. Imaging studies were performed in all patients, including OCTREOSCAN, while in patients with ACs MRCP or ERCP was also performed, when necessary. Definite diagnosis was confirmed by histopathologic examination. RESULTS: Polypoid masses (carcinoids) were revealed at duodenal bulb and ampulla of Vater, in 5 and 3 patients, respectively. Serum gastrin was moderately increased in 4 patients, while in one patient it was more than 1000 pg/ml. Serum CgA was moderately increased in one patient, in whom OCTREOSCAN detected a solitary hepatic metastasis. Two patients with DC, of less than 1 cm of diameter, were treated by endoscopic polypectomy, while all the other patients underwent surgery. The patient with hepatic metastasis and positive OCTREOSCAN received also Octreotide LAR, resulting in stabilization of disease. No recurrence or metastases were observed during follow-up (range : 1.5-9.6 years). CONCLUSIONS: In DC tumors <1 cm endoscopic excision with close follow-up is an adequate treatment, while in tumors >1 cm and in AC, surgical resection is the treatment of choice. In metastatic tumors, resection of the primary lesion with administration of somatostatin analogues may stabilize the disease and improve patient's quality of life.

Effect of Helicobacter pylori eradication and antisecretory maintenance therapy on peptic ulcer recurrence in cirrhotic patients: a prospective, cohort 2-year follow-up study.

BACKGROUND: The role of Helicobacter pylori eradication to cure peptic ulcer disease in patients with cirrhosis is not clear. AIM: To investigate the course of peptic ulcer disease in cirrhotics, first after healing with either H. pylori eradication or omeprazole therapy and second while on omeprazole maintenance therapy after recurrence. METHODS: Prospective cohort study in a tertiary-care hospital in Greece. Out of 365 consecutive cirrhotic patients who underwent endoscopy, 67 had peptic ulcer and 30 were enrolled. H. pylori positive patients received eradication therapy and H. pylori negative patients received omeprazole treatment. Follow-up endoscopies were performed at 12 and 24 months or when symptoms recurred. Patients with ulcer recurrence were treated with omeprazole maintenance therapy. The main outcome measurement of the study was peptic ulcer relapse rate during follow-up. RESULTS: Twenty-eight patients with healed ulcers were followed for up to 2 years. During follow-up, ulcer relapsed in 17 patients (8/18 H. pylori positive and 9/10 H. pylori negative at study entry, P=0.041), including 2 patients who died from ulcer bleeding. No further ulcer relapse was observed in the remaining 15 patients who received omeprazole maintenance therapy for the rest of follow-up. H. pylori negative status (P=0.002) and severity of cirrhosis (P=0.015) at study entry were independently related to shorter peptic ulcer relapse-free time. CONCLUSIONS: H. pylori eradication does not protect all cirrhotics from ulcer recurrence and the majority of ulcers recur in H. pylori negative patients. Therefore, omeprazole maintenance treatment is mandatory, irrespectively of H. pylori status.

Endoloop application as an alternative method for gastrotomy closure in experimental transgastric surgery.

BACKGROUND: Experimental studies investigating transgastric endoscopic surgery report closure of the gastric wall incision with clips. The author of this report describes endoloop placement as an alternative, equally efficient, faster method for gastrotomy closure. METHODS: Eight female pigs with a mean weight of 30 kg were used. Abdominal endoscopic exploration and transgastric operations including hepatic biopsies, bilateral tubal ligation, cholecystectomy, and closure of the gastrotomy were performed. The experiment was divided into two parts. The first part included five animals, which were killed immediately after the procedure. The second part included five animals, which were kept alive and killed 15 to 20 days later. RESULTS: The first part of the experiment, performed for technical skills acquisition, involved transgastric abdominal exploration, liver biopsies, and bilateral tubal ligation, which were successful for all five animals. The gastric wall incision was closed by applying clips in four animals and endoloops in one animal. During the autopsy at the end of the experiment, the sites of intervention were examined macroscopically. In the second part of the experiment, gastrotomy closure with endoloop application was performed in two animals and with clip application in one animal. All three animals survived, gained weight, and demonstrated no signs of infection. They were killed 15 to 20 days after the procedure, and no signs of intraabdominal infection were found. Cultures from the peritoneal cavity were negative. At necropsy, macroscopic and microscopic examination confirmed complete healing of the gastrotomy. CONCLUSIONS: Transgastric endoscopic surgery is technically feasible and effective. The application of endoloops for closure of the gastric opening is a fast, easy, and equally safe alternative to clip placement.

VIPomas: an update in diagnosis and management in a series of 11 patients.

BACKGROUND/AIMS: VIPoma is a rare pancreatic endocrine tumor (PET) which secretes excessive amounts of VIP (Vasoactive Intestinal Peptide) that causes a special clinical syndrome characterized by secretory diarrhea, hypokalemia and achlorhydria. Among a total number of 76 patients (pts) with PETs, we present in this study 11 pts with VIPoma syndrome focusing on our diagnostic and therapeutic approach, in parallel with a brief review of the literature. METHODOLOGY: Eleven pts (7 males and 4 females), aged from 2 to 83 years (mean age 53.1 years) were included. The diagnosis was based upon compatible clinical features and serum VIP values and was supported by the estimation of other peptides and neuroendocrine markers such as gastrin, pancreatic polypeptide and chromogranin-A (CgA). In 10/11 pts, diagnosis was confirmed histopathologically. The primary or metastatic lesions were located by conventional imaging methods or by OCTREOSCAN or Endoscopic Ultrasound (EUS). The follow-up period ranged from 2.5-13.5 years (mean 4.8 years). RESULTS: Chronic secretory diarrhea, which persisted despite fasting, was the main symptom in all pts of our study. VIP levels at the time of diagnosis were more than 3 or 10 times the upper normal limit in 7/11 (63.6%) or 4/11 (36.4%) pts, respectively. The primary lesion was detected by CT scan or MRI in 6/11 (54.5%), with EUS or abdominal angiography in 4/11 (36.4%). OCTREOSCAN revealed a solitary lesion in the right hepatic lobe, not detected by all the previous studies, while it detected, as a whole, the primary lesion in 10/11 (91%), and the metastases in 3/4 (75%) pts. In 7/11 (63.6%) the primary lesion was located in the pancreas, whereas in the rest it was in the duodenum or retroperitoneum. A surgical resection was possible in 7/11 (63.6%) pts, while pts with metastatic disease already or poorly differentiated tumors also received additional treatment with somatostatin analogues and chemotherapy. Liver metastases and poor differentiation of tumors seemed to be negative prognostic factors. CONCLUSIONS: Clinical suspicion, early diagnosis and precise management may affect survival and improve the quality of life of patients. Also, surgical treatment, as extensive as possible, in combination with somatostatin analogues or chemotherapy when necessary, may also result in prolonged survival, also in patients with advanced disease.

Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-A, somatostatin receptor scintigraphy and somatostatin analogues.

BACKGROUND/AIMS: Carcinoids are relatively rare tumors that arise from neuroendocrine cells and have proved to be slow growing malignancies which involve many organs and most frequently the gastrointestinal (GI) tract. Herein we present in this study 101 pts with carcinoid tumors that originated from the GI tract and pancreas. Also, we analyze the clinical and pathological features, pointing out the characteristics of this group of neoplasms and describing our diagnostic and therapeutical approach, in parallel with a brief review of the literature. METHODOLOGY: One hundred and one (66 females and 35 males, aged from 16 to 79 years) pts were included in our study. The primary tumors originated from the GI tract in 97/101 pts (appendix 34%, small intestine 31%, stomach 14%, duodenum 6%, colon 6%, rectum 3%) and from the pancreas in 4/101 (4%). The diagnosis was confirmed histologically in all cases, after surgical excision of the primary tumor or by biopsies taken during endoscopy. All pts were evaluated several times per year with clinical, biochemical and imaging assessments, including neuroendocrine markers [urinary 5-Hydroxyindoleacetic acid (5-HIAA), serum Chromogranin-A (CgA)] and Somatostatin Receptor Scintigraphy (OCTREOSCAN). The follow-up period ranged between 1.5 to 12.5 years (mean time: 5 years and 3 months) and it is still in progress. RESULTS: Patients were referred to us with gastrointestinal symptoms or symptoms of the "carcinoid syndrome" (flushing, and diarrhea), depending mainly on the location of the primary tumors and the existence or not of metastases. CgA and 5-HIAA levels were increased especially in metastatic tumors. Localization of the primary tumors to facilitate surgery was made by many imaging techniques (US, CT, MRI, Enteroclysis, OCTREOSCAN) and endoscopic procedures. OCTREOSCAN was positive in 94% pts with metastatic disease. Furthermore, it revealed the primary and the metastatic lesions in 16% and 33% of pts with carcinoids of the small intestine respectively, while other conventional imaging procedures (including MRI) were negative at the same time. Seventy-four percent of the pts underwent a surgical resection of the primary tumor, while in 21%, an endoscopic polypectomy was performed. All pts with metastatic tumors and positive OCTREOSCAN, were treated with Somatostatin analogues, which resulted in control of symptoms (75%), stabilization of tumor growth (71%) or tumor shrinkage (9%). A combined therapy with the addition of interferon-a was initiated in pts in whom, despite the increase of drug dosage and the shortening of administration intervals, a complete clinical and biochemical response was no more achieved with Somatostatin analogues alone. Pancreatic carcinoids and also those that originated from the proximal colon were found to have worst prognosis. CONCLUSIONS: a) Tumor size (especially in appendiceal and gastric carcinoids) and, also, the dispersion of disease, highly predict the evolution of the patients; b) serum Chromogranin-A seems to be a very useful tumor marker for the diagnosis and follow-up of pts with GI carcinoids; c) the introduction of new imaging techniques and especially OCTREOSCAN contributes to a better localization of the primary tumors and their metastases, as well as, to the right decision of the appropriate medical treatment; d) surgical excision is the treatment of choice in nonmetastatic tumors; and e) in pts with metastatic disease, the administration of Somatostatin analogues improves their quality of life.

Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: topical intrarectal versus subcutaneous application.

PURPOSE: To investigate the cytoprotective effect of subcutaneous vs. intrarectal administration of amifostine against acute radiation toxicity. METHODS AND MATERIALS: Patients were randomized to receive amifostine either intrarectally (Group A, n = 27) or a 500-mg flat dose subcutaneously (Group B, n = 26) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In Group A, 1,500 mg of amifostine was administered intrarectally as an aqueous solution in 40 mL of enema. Two different toxicity scales were used: the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (RTOG) rectal and urologic toxicity criteria and the Subjective-RectoSigmoid scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after radiotherapy completion. The area under the curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index. RESULTS: Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, Group A had superior results with a significantly lower incidence of Grades I-II rectal radiation morbidity (11% vs. 42%, p = 0.04) but inferior results concerning urinary toxicity (48% vs. 15%, p = 0.03). The mean rectal mucositis index and Subjective-RectoSigmoid score were significantly lower in Group A (0.44 vs. 2.45 [p = 0.015] and 3.9 vs. 6.0 [p = 0.01], respectively), and the mean urinary mucositis index was lower in Group B (2.39 vs. 0.34, p < 0.028). CONCLUSIONS: Intrarectal administration of amifostine (1,500 mg) seemed to have a cytoprotective efficacy in acute radiation rectal mucositis but was inferior to subcutaneous administration in terms of urinary toxicity. Additional randomized studies are needed for definitive decisions concerning the cytoprotection of pelvic irradiated areas.

Incidence of ulcerative colitis in Central Greece: a prospective study.

AIM: To study the incidence of ulcerative colitis UC in the prefecture of Trikala, Central Greece. METHODS: A prospective and population based epidemiological study of UC from 1990 to the end of 1994 was conducted. Trikala is a semirural prefecture of Central Greece with a population of 138 946 (census 1991). Three gastroenterologists (one hospital based, two private doctors) of the prefecture participated in this study. RESULTS: During the study period, 66 new histologically verified cases of UC were recorded. The mean annual incidence of the disease in 1990-1994 was 11.2 per 10(5) inhabitants (95%CI: 8.7-14.3). There was no difference between men and women (annual incidence: 10.5 and 12.0 per 10(5) inhabitants respectively), either among urban, semirural or rural populations (annual incidence: 11.7, 17.1 and 9.9 per 10(5) inhabitants respectively). The majority (56%) of the patients never smoked and a quarter were ex-smokers. About a half of all cases had proctitis. CONCLUSION: UC is common in Central Greece and its incidence is similar to that in North-Western European countries.

A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity.

PURPOSE: To investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity. PATIENTS AND METHODS: 67 patients with T1b-2 N0 M0 prostate cancer were randomized to receive amifostine intrarectally (group A, n = 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectally as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI). RESULTS: Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 +/- 0.1 in group A versus 2.2 +/- 0.4 in group B (p < 0.001), while S-RS score was 3.9 +/- 0.5 in group A versus 6.3 +/- 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups. CONCLUSION: Intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions.

Relationship of smoking and coffee and alcohol consumption with seroconversion to Helicobacter pylori: a longitudinal study in hospital workers.

BACKGROUND AND AIM: There are few data concerning the relationship between Helicobacter pylori seroconversion, and smoking habits and coffee and alcohol consumption. The aim of the present study was to investigate the relationship between smoking habits, coffee and alcohol consumption, and H. pylori seroconversion. METHODS: The data used were derived from a sample of 238 subjects (hospital employees) who were initially (on 1994) seronegative to H. pylori. These subjects were tested again 5 years later (1999). Information concerning smoking habits and coffee and alcohol consumption was collected by the use of a special questionnaire, which was completed by the same cohort of subjects in two different periods (1994 and 1999). Logistic regression was used to assess the relationship between H. pylori seroconversion and the aforementioned lifestyle factors. RESULTS: Neither smoking nor coffee consumption was significantly related to H. pylori seroconversion. Adjusted odds ratio for alcohol drinkers as compared with non-/occasional drinkers was 0.59 (95% confidence interval [CI]: 0.31-1.16, P = 0.13). However, the odds ratio was significantly lower (0.26, 95%CI: 0.07-0.95, P = 0.042) in subjects who reported moderate alcohol consumption at first (1994) examination, as compared with non-/occasional drinkers. Small and heavy drinking were not associated with H. pylori seroconversion. CONCLUSIONS: There is no significant relation between H. pylori seroconversion and smoking and coffee consumption. The present findings suggest that moderate alcohol consumption might be inversely associated with H. pylori seroconversion.

Impact on cytoprotective efficacy of intermediate interval between amifostine administration and radiotherapy: a retrospective analysis.

PURPOSE: To evaluate the cytoprotective impact of the interval between amifostine administration and radiotherapy (RT). METHODS AND MATERIALS: In a nonrandomized study, we reviewed the records of 177 patients with tumors localized in the pelvis (prostate, bladder, or gynecologic cancer), upper abdomen (pancreas, stomach, kidney), thorax (lung and breast cancer), head and neck (nasopharynx), soft tissue (sarcomas), and central nervous system. The patient records were stratified according to whether the patients had undergone RT either 25-40 min (Group 1, 96 subjects) or 10-15 min (Group 2, 81 subjects) after i.v. amifostine administration. The mean toxicity score was the mean value of recorded acute radiation toxicity. The mean interruption time was the mean value of the recorded interruption time due to radiation toxicity. RESULTS: A significantly reduced severity of symptoms related to oral (p = 0.023), esophageal (p = 0.05) and rectal (p = 0.015) mucosa was noted in Group 2. A statistically significant reduction in the mean toxicity score (p <0.001) and mean interruption time (p = 0.001) was observed in Group 2 vs. Group 1. In terms of the incidence of radiation-induced dermatitis and alopecia, multivariate logistic analysis revealed only the total dose (p = 0.018) and the amifostine-RT interval (p = 0.002) as independent factors. CONCLUSION: A significantly better cytoprotective effect of amifostine against radiation-induced mucositis, dermatitis, and alopecia was noted if RT was administered no later than 15 min after i.v. amifostine infusion. The results presented here need additional investigation with randomized prospective trials.

Adjuvant systemic therapy protocol for Dukes' B2 and C resectable colon carcinoma.

AIMS AND BACKGROUND: Trials of adjuvant systemic therapy in high risk patients with Dukes' B2 and C colon cancer utilizing 5-fluorouracil-based regimens have been ongoing since the 1960s. The aim of this study was to compare the combination of 5-FU and leucovorin with the combination of 5-FU and alfa-2b interferon (IFN) in patients who had undergone "curative" resection foronocarcinoma. STUDY DESIGN: A total of 322 patients with histologically proven adenocarcinoma of the colon, Dukes' stage B2 and C, were entered in the study. They were randomized to A) leucovorin 20 mg/m2 rapid intravenous injection and 5-FU 425 mg/m2 IV days 1-5 every 28 days for six cycles or B) 5-FU 600 mg/m2 24-hour infusion for five days, then 600 mg/m2 IV once a week and IFN 5 MU subcutaneously three times a week for six months. RESULTS: There was no statistically significant difference in either disease-free survival or overall survival. Toxicity was the same in the two groups with the exception of flu-like syndrome, which was universal in IFN-treated patients. CONCLUSIONS: There was no difference in disease-free survival or overall survival between the two combinations in any patient subset. Toxicity was greater with the 5-FU+IFN combination because of the flu-like syndrome. These data do not support the use of IFN in combination with 5-FU as systemic adjuvant therapy for patients with locally advanced colon carcinoma.