hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients.

Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A unique disease-causing mutation has been identified in seven out of nine (78%) families. The types of mutations identified are nonsense (five out of seven) (hMLH1: E557X, R226X; hMSH2: Q158X, R359X and R711X), a 2 bp deletion (hMSH2 1704_1705delAG) and a 2.2 kb Alu-mediated deletion encompassing exon 3 of the hMSH2 gene. The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.

Staging of ampullary and pancreatic carcinoma: comparison between endosonography and surgery.

BACKGROUND: The aim of the study was to update our previously published data on the clinical TNM staging of ampullary and pancreatic carcinoma by endosonography. METHODS: Endosonography was performed in 70 patients with pancreatic cancer and in 32 patients with ampullary carcinoma. TNM staging was carried out before surgery and compared with findings of histology and/or surgery. RESULTS: Endosonography was accurate in staging the depth of tumor invasion. Early-stage carcinomas could be distinguished from advanced cancers. Nonresectability was accurately assessed on the basis of vascular involvement using real-time ultrasound. Tumor compression due to peritumoral pancreatitis and direct tumor invasion into the base of the mesocolon could not be diagnosed by endosonography. The overall accuracy in tumor staging for pancreatic and ampullary carcinomas was 83.6% and 84.4%, respectively. Endosonography was accurate in diagnosing regional lymph node metastases but not accurate in defining nonmetastatic lymphadenopathy and distant metastases. CONCLUSION: Endosonography was accurate in staging tumor stage and lymph node metastases. Minimally invasive methods of resection for superficial ampullary cancers should be based on endosonography staging.

Prognosis of esophageal cancers preoperatively staged to be locally invasive (T4) by endoscopic ultrasound (EUS): a multicenter retrospective cohort study.

BACKGROUND: Endosonography is a significant advance in the preoperative staging (TNM classification) of esophageal cancer. Its accuracy for evaluating depth of tumor invasion is over 80%. METHODS: A multicenter retrospective cohort study of patients with esophageal carcinomas defined to be invasive (T4) by endosonography was performed to compare the survival of surgically and nonsurgically treated patients. Median survival time, overall mortality, and Kaplan-Meier survival curves were compared by treatment group. Univariate and Cox regression analysis were used to evaluate the effects of various prognostic factors and treatment on the risk of death. RESULTS: A total of 79 patients were studied. The surgical group (Group I, n = 42) was significantly younger and had more distal tumors (adenocarcinomas) than the nonsurgical group (Group II, n = 37). Endosonography was significantly more accurate than CT scanning in identifying tumor invasion (87.5% versus 43.8%, respectively, p = .0002). Overall mortality rate was not significantly different between treatment groups; 59.5% of the surgical group and 64.9% of the nonsurgical group were dead at follow-up (p = 0.65). Similarly, the median survival times of Group I and Group II patients were similar (5.2 and 7.0 months, respectively, p = 0.50). Survival curves for the two groups were almost overlapping (log rank test, p = 0.84). Even after adjusting for age, histologic diagnosis, tumor location, and regional lymph node status, surgical treatment did not significantly influence survival (p = 0.24). CONCLUSIONS: Endosonography accurately identifies patients with invasive T4 tumors who have a poor prognosis. This prognosis is independent of mode of therapy.

Functional evidence for the presence of nitric oxide synthase in the dorsal motor nucleus of the vagus.

BACKGROUND & AIMS: Histochemical studies indicate that reduced nicotinamide adenine dinucleotide phosphate diaphorase, the nitric oxide synthase-related enzyme, is present in the dorsal motor nucleus of the vagus of the cat. We have previously shown in vitro that NO synthase is present in this nucleus in the rat and that the excitatory effect of N-methyl-D-aspartate on these neurons is in part caused by NO formation. The aim of this study was to obtain functional evidence for the presence of NO synthase in the cat dorsal motor nucleus of the vagus. METHODS: L-Glutamate, L-arginine, D-arginine, the NO donor S-nitroso-N-acetyl-penicillamine, and the NO synthase inhibitor NG-nitro-L-arginine-methyl ester were unilaterally microinjected into the rostral dorsal motor nucleus of anesthetized cats, and antral and pyloric motility were monitored using extraluminal force transducers. RESULTS: Microinjection of L-arginine increased gastric motility, whereas D-arginine had no effect. Vagotomy eliminated the L-arginine-induced increases. Microinjection of S-nitroso-N-acetyl-penicillamine increased antral motility. NG-Nitro-L-arginine-methyl ester prevented L-arginine from exerting an effect on gastric motility. CONCLUSIONS: Motility increases obtained after microinjection of L-arginine into the dorsal motor nucleus and prevention of these motility increases with microinjection of a NO synthase inhibitor provide functional evidence for the presence of NO synthase in the dorsal motor nucleus of the vagus in the cat.

Endoscopic ultrasound for staging esophageal cancer, with or without dilation, is clinically important and safe.

BACKGROUND: To fully evaluate patients with esophageal cancer by endoscopic ultrasonography (EUS), the transducer must pass through the entire tumor to the cardia to scan the celiac axis. Dilation may be necessary. Published information suggests that dilation with EUS carries a sizeable risk. METHODS: In order to assess the complication rate associated with dilation prior to EUS in patients with esophageal cancer and the clinical significance of dilation for complete EUS staging, we reviewed the records of all patients who had undergone EUS for esophageal cancer. RESULTS: Sixty-three patients underwent EUS staging of esophageal cancer. Thirty-nine (62%) had lesions through which the EUS scope was passable (Group I). Ten (16%) patients (Group II) had lesions through which an EUS scope (diameter 13 mm) was unable to pass even after dilation. Fourteen patients (22%) had lesions that were dilated to allow passage of the EUS scope (Group III). All patients in Groups II and III had confirmation of EUS staging by CT and/or surgery. In Group II, five patients had tumors defined as T4 (50%) and five as T3 (50%). In Group III, nine (64%) had T4 tumors, four (29%) had T3, and one (7.7%) had T2. No complications were encountered in any group. CONCLUSION: EUS, either alone or after dilation, is a safe procedure and the complete EUS examination with celiac node visualization adds prognostically significant information.

Endoscopic ultrasonography of perigastrointestinal lymph nodes.

The introduction of endoscopic ultrasonography (EUS) has opened a window in the diagnosis of the perigastrointestinal lymph nodes. Initial euphoria has been sobered by the fact that false-positive and false-negative diagnoses may occur. We review here the use of EUS to stage gastrointestinal cancer, and particularly to predict the presence or absence of lymph-node metastases. The role of EUS-guided fine-needle aspiration using a radial scanner or a curved array echoendoscope is mentioned.

Endoscopic ultrasonography of perianorectal fistulas and abscesses.

In this article we describe the history, instrument, indications, and results of endoscopic ultrasonography (EUS) in the evaluation of perianorectal fistulas and abscesses. EUS has been reported to be helpful in the management of patients with Crohn's disease or colitis associated with fistulas and abscesses, due to its clear imaging of the leasion and valuable topographic anatomical information. Recent studies point out the relationship between EUS and electromyography. We believe EUS will become a standard procedure in the management of these complex disease processes.

The role of endoscopic ultrasonography in diagnosis of benign lesions of the upper GI tract.

The contribution of endoscopic ultrasonography (EUS) in the diagnosis of benign lesions of the upper gastrointestinal (UGI) tract was studied in 46 patients with polypoid lesions which were not thought to have invaded adjacent tissues or organs. Precise visualization of the five layers of the UGI tract was possible with EUS. The site of origin of the tumour was also determined. The diameter of the hypochoic lesions ranged between 1-4 cm, with well-defined margins, and were demarcated precisely from adjacent tissues. Lesions included: (1) leiomyoma of the esophagus, stomach, duodenum (n = 7); (2) ectopic pancreatic tissues (n = 3); (3) polyp of the esophagus, stomach or duodenum (n = 12); (4) hypertrophic gastric folds (n = 19); (5) extra gastric compression (n = 5). Patients from groups 1, 2 and 3 had the diagnosis confirmed and staged surgically. It was possible to differentiate between polypoid lesions of the UGI tract and extra gastric compression. The sensitivity of EUS in the diagnosis of benign tumours was 92%.

Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study

Cincuenta y cuatro pacientes, 41 varones y 13 mujeres, entre 26 y 76 años, afectados de úlcera duodenal y curados entre 4 y 8 semanas con subcitrato de bismuto coloidal, 360 mg dos veces por día, fueron estudiados. A todos los pacientes se les practicó endoscopia gastroduodenal antes del tratamiento, 4 a 8 semanas luego del mismo y 6 meses después. Se tomaron biopsias gástricas endoscopicas para determinar la presencia de campilobacter pilori por medio del test de la ureasa. Todos los pacientes eran C.P. positivos incialmente. Las bacterias fueron erradicadas en 36/54 pacientes (67%) al final de la terapéutica. La curación ulcerosa fue obtenida después de 8 semanas en 45/54 pacientes. Ventisiete (66%) fueron entonces C.P. negativo y 14 fueron C.P. positivo. Se observó recurrencia ulcerosa en 15/41 pacientes (37%), cuyas úlceras habían curado previamente. Todos los pacientes con recidiva fueron C.P. positivos. se observó una correlación estadisticamente significativa entre la persistencia de C.P. y el grado de recidiva ulcerosa (p , 0,001). Se concluye que: a) La erradicación de C.P. en los pacientes ulcerosos duodenales no tuvo influencia en la curación de la úlcera. b) La recidiva de la úlcera duodenal estuvo correlacionada con la persistencia de C.P

Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study

Cincuenta y cuatro pacientes, 41 varones y 13 mujeres, entre 26 y 76 años, afectados de úlcera duodenal y curados entre 4 y 8 semanas con subcitrato de bismuto coloidal, 360 mg dos veces por día, fueron estudiados. A todos los pacientes se les practicó endoscopia gastroduodenal antes del tratamiento, 4 a 8 semanas luego del mismo y 6 meses después. Se tomaron biopsias gástricas endoscopicas para determinar la presencia de campilobacter pilori por medio del test de la ureasa. Todos los pacientes eran C.P. positivos incialmente. Las bacterias fueron erradicadas en 36/54 pacientes (67%) al final de la terapéutica. La curación ulcerosa fue obtenida después de 8 semanas en 45/54 pacientes. Ventisiete (66%) fueron entonces C.P. negativo y 14 fueron C.P. positivo. Se observó recurrencia ulcerosa en 15/41 pacientes (37%), cuyas úlceras habían curado previamente. Todos los pacientes con recidiva fueron C.P. positivos. se observó una correlación estadisticamente significativa entre la persistencia de C.P. y el grado de recidiva ulcerosa (p , 0,001). Se concluye que: a) La erradicación de C.P. en los pacientes ulcerosos duodenales no tuvo influencia en la curación de la úlcera. b) La recidiva de la úlcera duodenal estuvo correlacionada con la persistencia de C.P (AU)

Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study.

Fifty-four patients were studied, 41 men and 13 woman, aged 26-76 years, suffering from duodenal ulcer that healed 4-8 weeks after colloidal bismuth subcitrate therapy (360 mgr twice a day). All patients underwent endoscopy before treatment, 4-8 weeks and 6 months later. Biopsy was taken for campylobacter pylori (C.P.) detection by urease test. All patients were C.P. positive initially. The organisms were eradicated in 36/54 patients (67%) at the end of therapy. Ulcer healing was obtained after 8 weeks in 45/54 patients (83%). They were re-examined 6 months later or sooner if symptoms had recurred. Twenty seven (66%) were then C.P. negative and 14 were C.P. positive. Ulcer recurrence was observed in 15/41 patients (37%) whose ulcer had previously cured. All patients with recurrence were C.P. positive. There was a statistically significant positive correlation between persistence of C.P. and ulcer recurrence rate (p less than 0.001). It is concluded: a) that eradication of C.P. in duodenal ulcer patients has no influence on ulcer healing. b) Duodenal ulcer recurrence is correlated with persistence of C.P.

Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study.

Fifty-four patients were studied, 41 men and 13 woman, aged 26-76 years, suffering from duodenal ulcer that healed 4-8 weeks after colloidal bismuth subcitrate therapy (360 mgr twice a day). All patients underwent endoscopy before treatment, 4-8 weeks and 6 months later. Biopsy was taken for campylobacter pylori (C.P.) detection by urease test. All patients were C.P. positive initially. The organisms were eradicated in 36/54 patients (67

) at the end of therapy. Ulcer healing was obtained after 8 weeks in 45/54 patients (83

). They were re-examined 6 months later or sooner if symptoms had recurred. Twenty seven (66

) were then C.P. negative and 14 were C.P. positive. Ulcer recurrence was observed in 15/41 patients (37

) whose ulcer had previously cured. All patients with recurrence were C.P. positive. There was a statistically significant positive correlation between persistence of C.P. and ulcer recurrence rate (p less than 0.001). It is concluded: a) that eradication of C.P. in duodenal ulcer patients has no influence on ulcer healing. b) Duodenal ulcer recurrence is correlated with persistence of C.P.