Israel Medical Association Journal

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.

Objective: To investigate hemodynamic variables, including small and large artery compliance, in cirrhotic patients during total paracentesis.

Methods: The study included 15 cirrhotic patients admitted for an episode of tense diuretic-resistant ascites. Hemodynamic variables including vascular compliance were measured using an HDI pulse wave cardiovascular profiling instrument CR-2000. The variables were measured in these patients before, immediately after and 24 hours following large volume (mean 5.6 L) paracentesis.

Results: Cardiac output increased immediately after paracentesis due to increment in stroke volume, with no change in heart rate. However, 24 hours later the cardiac output decreased to below the basal level. The fluctuation was statistically significant (P < 0.05). There was no change in large artery compliance, but small artery compliance increased after paracentesis (P < 0.05) and partially returned to the basal level after 24 hours. Systemic vascular resistance measurement showed the same pattern of change: vasodilatation occurred during paracentesis and was attenuated 24 hours later.

Conclusions: Large volume paracentesis with albumin replacement caused an accentuation of the vasodilatation (small but not large artery) already present in these patients. This may be the first sign of enhanced vasodilatation due to large volume paracentesis before the clinical expression of impaired hemodynamics and deterioration of renal function.

Background: During ingestible capsule endoscopy, video images are recorded throughout the device's natural propulsion through the digestive system. Shortening the transit time of the wireless video capsule through the stomach and small bowel could reduce the time needed to read and analyze the resultant images, utilize more effectively the short life of the capsule battery (7 ± 1 hours) and make it possible to image the entire small bowel.

Objective: To measure gastric and small bowel transit times, with and without preparation, using capsule endoscopy.

Methods: Capsule transit times through the stomach, small bowel and colon were evaluated by analysis of the videos generated during the capsule's passage. The study group included 62 patients with small and large bowel pathologies (e.g., iron deficiency anemia, Crohn's disease). The patients were divided into three groups: prepared with polyethylene glycol (Group A, n = 9), prepared with sodium phosphate (Group B, n = 13), and with no preparation (Group C, n = 40).

Results: The gastric emptying times were 20.4 ± 15.2 minutes in group A, 55.7 ± 45.1 in group B, and 48.3 ± 28.7 in group C (P = 0.01). The capsule produced views of the cecum in only 49 of the 62 patients. The mean small bowel transit time for these 49 patients was 238.8 ± 82.1 minutes, making the mean times for the groups (A,B,C) 148.9 ± 32.6, 289.4 ± 77.2 and 249.3 ± 73.9 minutes respectively (P = 0.0001).

Conclusion: Compared to both SP[1] and no preparation, preparation of the colon with PEG[2] significantly shortened the transit time of the capsule through the stomach and small bowel.

Background: Chronic nicotine administration has a dual effect on inflammatory bowel disease: augmentation of jejunitis and amelioration of colitis. We previously showed that chronic nicotine administration has divergent regional effects on small bowel and colonic mucosal mediators and blood flow.

Objective: To examine the effects of nicotine administration on cytokine levels in normal rat small bowel mucosa, colonic mucosa, and blood.

Methods: Male Sprague-Dawley rats weighing 200–250 g were given nicotine (12.5 μg/ml) that was dissolved in tap water. Rats were sacrificed on days 1, 2, 7 and 14 after nicotine initiation; blood was withdrawn, and small bowel and colon were resected, washed and weighed. Mucosal scrapings were extracted in 2 ml Krebs-Hemselest buffer for determination of interleukins-2, 6 and 10 using the Biosource International Immunoassay Kit.

Results: Nicotine decreased IL-10[1] and increased IL-6 levels in small bowel mucosa (from 3.5 ±  0.5 to 0.4 ± 0.1 pg/ml and from 1.9±0.4 to 13.6±0.4 pg/ml respectively; P < 0.05). Nicotine decreased IL-2 levels in the colon (from 15.8±3.0 to 7.9±1.0 pg/ml; P < 0.05), having no effect on IL-10 or IL-6 levels. Rats treated with nicotine had lower IL-6 and IL-2 blood levels compared to control rats.

Conclusions: Nicotine has different regional effects on small bowel and colonic cytokine mucosal levels, which might explain some of its opposite effects on small bowel and colonic inflammation.