[Subjective grading of Barrett's neoplasia by pathologists: correlation with objective histomorphometric variables]. / Subjektive Graduierung von Barrett-Neoplasien durch den Pathologen: Korrelation mit objektiven histomorphometrischen Variablen.

Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia.

A novel device to improve colon cleanliness during colonoscopy.

BACKGROUND AND STUDY AIM: Effective colonoscopy depends on adequate visualization of the intestine, which might be ensured by intraprocedural use of a cleansing device. We investigated the performance of a novel endoscopic device with regard to cleanliness, safety, and tolerability during colonoscopy, compared with standard cleansing. PATIENTS AND METHODS: At a single center, colonoscopy patients in whom the cecum was accessed and at least one bowel segment was inadequately cleansed were assigned to either use of a disposable catheter cleansing device (JetPrep), used through the endoscope working channel, or standard manual cleansing using a 50-ml syringe. The cleansing quality, for each segment and before and after irrigation, was recorded using a 4-point scale ranging from excellent (grade 1, no more than small bits of adherent feces) to poor (grade 4, large amount of fecal residue). RESULTS: 38 patients were included, 19 in each group. Reasons for referral included colorectal cancer screening (52 %), or blood loss (31 %). Each segment showed improvement after cleansing with JetPrep. Overall cleansing grade improved by a mean of 0.74 points (standard deviation [SD] 0.82) in the investigation group compared with 0.19 (0.40) in the control group (P < 0.0001), and right colon cleansing improved by 1.59 points (0.71) versus 0.31 (0.48) in the controls (P < 0.0001). There was no significant difference in procedure time between the groups. No adverse events or side effects were encountered. CONCLUSIONS: The JetPrep disposable catheter device is safe and efficient for intraprocedural cleansing of a suboptimally prepared colon, allowing higher quality colonoscopy.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

Outcome and early complications of ERCP: a prospective single center study.

BACKGROUND/AIMS: ERCP has been used since 1968 both as a diagnostic and as a therapeutic procedure. In the last ten years several less invasive imaging methods have developed which allow visualization of bile ducts and pancreatic ducts; therefore ERCP has become mainly a therapeutic tool. The aim of the study was to prospectively evaluate the early outcome of ERCP when used essentially as a therapeutic tool. METHODOLOGY: All patients referred to our unit between April 1 1998 and March 31 2000 were included in the study. The indication for the procedure, number of cannulations, duration of procedure, performance of endoscopic sphinterotomy or pre-cut, insertion of stent and the final outcome were recorded. All patients were visited (in-patients) or contacted by phone (outpatients) 24 hours and one week after the procedure. If a complication occurred the patient was followed until it was resolved. RESULTS: 722 ERCP procedures were performed on 534 patients (59% females), mean age 63.4 years (range 3 to 98 years). The procedure was performed with a therapeutic intention in 95% of cases because of suspicion of: cholelithiasis (58%), tumor of pancreas/bile ducts (30%), post-cholecystectomy bile leak or bile duct stenosis (6%) or treatment of chronic pancreatitis (1%). The overall success rate of selective duct cannulation was 92%. Endoscopic sphincterotomy was performed in 375 procedures (52%), pre-cut in 152 (21%) and stent inserted in 180 (25%). Among the 701 procedures with complete information 76 complications occurred in 73 patients (10.8%): pancreatitis 4.3%, perforation 1.3%, sepsis 3.7%, bleeding 1.4%. Most of the complications (63/701, 9%) were mild to moderate. Procedure-related mortality was 0.6% due to perforation (1 patient), and sepsis (3 patients). The main factors influencing the complication rate were the difficulty of the examination, performance of an invasive procedure or the operator. CONCLUSIONS: In the era of therapeutic ERCP, the risk of severe complication from the procedure is low--1.8% (including a mortality rate of 0.6%) when using the appropriate technique in experienced and skilled hands.

Severe pulmonary disease in association with Crohn's disease in a 13-year-old girl.

Pulmonary manifestations of Crohn's disease are infrequent in adults and even less common in children. Our literature search found only a few cases of Crohn's disease causing pulmonary manifestations in children. We report on the case of a 13-year-old girl in whom severe pulmonary disease was found four years after the onset of Crohn's disease. Open lung biopsy uncovered bronchiolitis obliterans and granulomatous lung disease. Aggressive treatment has yielded gradual improvement. This case emphasizes the importance of recognizing the association, the differential diagnosis, and treatment implications.

Right heart failure as the sole presentation of carcinoid syndrome.

We report the case of a woman with symptomatic right heart failure. Despite lack of the characteristic features of the carcinoid syndrome, echocardiographic and histologic investigations confirmed the diagnosis of carcinoid disease with cardiac involvement.

Intracardiac mass as the initial manifestation of metastatic germ cell tumor.

Cardiac metastases as initial presentation of disseminated germ cell tumors have rarely been reported. The hematogenous route is believed to be the most common pattern of dissemination by germ cell tumour, mainly to the lung, central nervous system and liver. We report a 33-year-old patient with embryonal cell carcinoma who presented with an intraatrial metastatic mass as the initial manifestation of metastatic disease.

Colon cancer bearing rats produce a lymphokine which induces macrophage migration inhibition (MIF) in vitro.

We studied a series of 40 rats at various stages of colorectal carcinoma, as induced by N-methyl-N-nitro-Nitrosoguanidine. Lymphokine containing supernatants were obtained simultaneously from splenic and peripheral lymphocytes, after exposure to rat colon cancer antigen in vitro. The lymphokine was found capable of performing Macrophage Migration Inhibition (MIF) when obtained from rats with: carcinoma through serosa, carcinoma of submucosa, carcinoma of the mucosa and carcinoma in situ. All control rats were free of cancer and were MIF negative. The MIF response in this study was evaluated as a marker of chemically induced colorectal carcinoma in rats in order to better understand the lymphocyte response to tumor progression from atypia to adenocarcinoma of the colon.

Neutropenic colitis predominantly involving the transverse colon: CT aspect of an unusual presentation.

A 62-year-old woman developed fulminant neuteopenic colitis following aggressive chemotherapy for limited-stage small cell lung cancer. An urgently performed computerized tomographic [CT] study demonstrated the predominant involvement of the transverse colon. We present a brief description of the CT features of neutropenic colitis in this unusual presentation.

Radiation therapy in epidemic, AIDS-related Kaposi's sarcoma in southern Africa.

AIMS AND BACKGROUND: Acquired Immunodeficiency Syndrome (AIDS) associated Kaposi's Sarcoma (EKS) is widely spread in the Southern African Region. No large studies concerning the role of radiation therapy in the Southern African variant of EKS have been reported to date. METHODS: Over a 10 year period (1982-1992) 25 patients with EKS (disseminated skin involvement) were treated primarily with radiation therapy at the Johannesburg General Hospital. Radiation fields were individually tailored to the extent of the disease. Total administered doses ranged between 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks. RESULTS: Overall response and symptomatic relief rates were 72% and 80%, respectively. Toxicity was mild and manageable. CONCLUSIONS: Our retrospective analysis supports the use of radiation therapy for the Southern African type of EKS.

PIP: Data suggest that 10-20% of African HIV-infected persons have Kaposi's Sarcoma (KS). African epidemic, AIDS-related KS (EKS) is widespread in the southern African region, with patients often needing treatment because of the disfiguring and stigmatic nature of the disease. Cytotoxic chemotherapy has shown antitumor activity, but it may further compromise the underlying immune deficiency. EKS is, however, very radiosensitive and radiation therapy is considered to be the treatment of choice for palliation, despite the absence of large studies concerning the role of radiation therapy in the southern African variant of EKS reported to date. The authors report findings from a 1982-92 study of radiation therapy among 25 patients with EKS at the Johannesburg General Hospital. Radiation fields were individually tailored to the extent of the disease. Total administered doses ranged 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks to yield 72% and 80% overall response and symptomatic relief rates, respectively. Toxicity was mild and manageable. This retrospective analysis therefore supports the use of radiation therapy for the southern African type of EKS.

[Undiagnosed celiac disease in adults unmasked by endoscopy].

BACKGROUND: Celiac disease may be present in many patterns other than the classical manifestations of diarrhea and malabsorption. The prevalence of celiac disease is greater than usually reported as mild cases are often undiagnosed. Diagnosing celiac disease may have major health significance. AIMS: The aim of our study was to determine the prevalence of celiac disease in adults appearing for endoscopy with abdominal pain, in an open access setting. METHODS: Two hundred and seventy consecutive, non-selected adult patients undergoing upper endoscopy for abdominal pain were included in the study. Three biopsies were routinely taken from the second part of the duodenum. In those cases with flattened villi on histology, antiendomysial antibody (AEA) was tested. RESULTS: The prevalence of celiac disease among Israeli patients undergoing endoscopy for abdominal pain was high (1:23), greater than its highest reported prevalence in general populations (1:200-300). CONCLUSIONS: Routine small bowel biopsies should be considered in patients undergoing upper endoscopy for otherwise unexplained pain.

Outcome and complications of colonoscopy: a prospective multicenter study in northern Israel.

Background. Colonoscopy for screening the population at an average risk of colorectal cancer (CRC) is recommended by many leading gastrointestinal associations. Objectives. The objective was to assess the quality, complications and acceptance rate of colonoscopy by patients. Methods. We prospectively gathered data from colonoscopies which were performed between October 2003 and September 2006. Patients were asked to return a follow-up form seven days after the procedure. Those who failed to do so were contacted by phone. Results. 6584 patients were included (50.4% males). The average age of subjects was 57.73 (SD 15.22). CRC screening was the main indication in 12.8%. Cecal intubation was achieved in 92% of patients and bowel preparation was good to excellent in 76.2%. The immediate outcome after colonoscopy was good in 99.4%. Perforations occurred in 3 cases-1 in every 2200 colonoscopies. Significant bleeding occurred in 3 cases (treated conservatively). 94.2% of patients agreed to undergo repeat colonoscopy in the future if indicated. Conclusions. The good quality of examinations, coupled with the low risk for complications and the good acceptance by the patients, encourages us to recommend colonoscopy as a primary screening test for CRC in Israel.

Evaluation of the PillCam Colon capsule in the detection of colonic pathology: results of the first multicenter, prospective, comparative study.

BACKGROUND AND STUDY AIMS: Population-based screening for colorectal cancer is widely recommended, with conventional colonoscopy considered to be the preferred diagnostic modality. However, compliance with screening colonoscopy is low and manpower capacity is limited. Capsule endoscopy might therefore represent a desirable alternative strategy. PATIENTS AND METHODS: The PillCam Colon capsule endoscope was prospectively tested in a multicenter setting. The indications for endoscopy in the enrolled patients included colorectal cancer screening (43 %), postpolypectomy surveillance (26 %), and lower gastrointestinal signs and symptoms (31 %). Study subjects underwent colon preparation and then ingested the capsule on the morning of the examination, with conventional colonoscopy being performed the same day. The PillCam Colon capsule findings were reviewed by three experts in capsule endoscopy who were blinded to the conventional colonoscopy findings. RESULTS: A total of 91 subjects were enrolled in three Israeli centers (55 men, 36 women; mean age 57), and the results were evaluable in 84 cases. The capsule was excreted within 10 hours in 74 % of the patients and reached the rectosigmoid colon in the other 16 %. Of the 84 evaluable patients, 20 (24 %) had significant findings, defined as at least one polyp of 6 mm or more in size or three or more polyps of any size: 14/20 (70 %) were identified with the capsule and 16/20 (80 %) were identified by conventional colonoscopy. Polyps of any size were found in 45 patients, 34/45 (76 %) found by the capsule and 36/45 (80 %) by conventional colonoscopy. In comparison with conventional colonoscopy, false-positive findings on PillCam Colon capsule examination were recorded in 15/45 cases (33 %). There were no adverse events related to the capsule endoscopy. CONCLUSIONS: PillCam Colon capsule endoscopy appears to be a promising new modality for colonic evaluation. Further improvements in the procedure will probably increase capsule examination completion and polyp detection rates. Additional studies are needed to evaluate the accuracy of PillCam Colon endoscopy in other patient populations with different prevalence levels of colonic disease.