Expanding the spectrum of germline variants in cancer.

Our ability to identify germline variants in hereditary cancer cases remains challenged by the incomplete cataloging of relevant genes and lack of consensus on who should be tested. We designed a panel [hereditary oncogenesis predisposition evaluation (HOPE)] that encompasses most of the genes known to be associated with cancer development and tested its yield on more than 1300 samples of cancer patients. Pathogenic or likely pathogenic variants in high and intermediate risk genes were identified in 16, 23.9, 9.7 and 2.7%, respectively, of peripheral blood or normal tissue samples taken from patients with breast, ovarian, colorectal and thyroid cancer. To confirm specificity of these findings, we tested an ethnically matched cohort of 816 individuals and only identified pathogenic or likely pathogenic variants in 1.59% (0.98% in high risk and 0.61% in intermediate risk). Remarkably, pathogenic or likely pathogenic alleles in DNA repair/genomic instability genes (other than BRCA2, ATM and PALB2) accounted for at least 16.8, 11.1, 50 and 45.5% of mutation-positive breast, ovarian, thyroid and colorectal cancer patients, respectively. Family history was noticeably lacking in a substantial fraction of mutation-positive cases (63.7, 81.5, 42.4 and 87.5% in breast, ovarian, colorectal and thyroid, respectively). Our results show high contribution of germline mutations to cancer predisposition that extends beyond "classical" hereditary cancer genes. Family history was lacking in 63.5% mutation-positive cases, shows that hereditary cancer need not appear familial and suggests that relaxed selection of cancer patients for hereditary cancer panels should be considered.

Disseminated (miliary) abdominal tuberculosis after laparoscopic gastric bypass surgery.

The development of disseminated (miliary) abdominal tuberculosis (TB) in patients following operations which affect their immunity, such as laparoscopic gastric bypass, is rare. The authors report the case of middle aged woman, who a few months after undergoing laparoscopic gastric bypass surgery for morbid obesity (body mass index 49), presented with generalised fatigability and abnormal liver function. A CT scan of the abdomen was suggestive of miliary TB. The patient developed acute abdomen pain. Intraoperative findings included perforated stomal ulcers at the gastrojejunostomy, diffuse micronodular involvement of the liver and spleen and thickened omentum. The perforation was closed and liver and omental biopsies were taken. Histology results from the liver and omentum revealed necrotising granulomatous inflammation suggestive of TB. Abdominal TB is a relatively rare manifestation of extrapulmonary TB. However, this diagnosis should be considered in patients immunocompromised due to immunosuppressive medication or operations affecting their nutrition. Early diagnosis and effective treatment of abdominal TB may decrease morbidity and mortality in such patients.

Laparoscopic vs. open adrenalectomy: experience at King Faisal Specialist Hospital and Research Centre, Riyadh.

BACKGROUND: The laparoscopic approach for adrenalectomy is now widely accepted and preferred over the conventional open approach. We describe our experience of adreanalectomy and compare the results of open and laparoscopic approach. PATIENTS AND METHODS: From March 1999 to March 2002, we performed 23 adrenalectomies. An anterior transabdominal approach was used for the open procedure, and a lateral transperitoneal approach for the laparoscopic procedure. Data from both groups were analyzed and compared. RESULTS: There was no difference in tumor size or pathology between two groups. The tumor size was smaller, operative time was longer and estimated blood loss was less in the laparoscopic procedure group, however these differences were statistically insignificant. The mean length of hospital stay was shorter (5.1 vs. 9.2 days, P<0.01), the mean use of postoperative narcotic analgesia was less (4.2 vs. 8.1 injections, P<0.05), and the mean time for resumption of oral intake was faster (1.17 vs. 2 days, P<0.01) in the laparoscopic procedure group compared to the open adrenalectomy group. CONCLUSION: Laparoscopic adrenalectomy is a safe procedure that can be performed for most adrenal pathology. It is associated with faster recovery, less postoperative pain, and shorter hospital stay.