Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Predictive factors for cancer-associated thrombosis in a large retrospective single-center study.

BACKGROUND: The relationship between cancer and thrombosis has been studied for years, but reliable guidelines for thromboprophylaxis in that situation are still unclear. METHODS: We retrospectively reviewed the files of 3159 consecutive patients with newly diagnosed solid tumors at Jules Bordet Institute from January 2008 to December 2011. Among them, 99 developed a symptomatic thromboembolic episode and were matched with 2 controls (nested case control). The aim was to identify risk factors of thromboembolic events and to validate in our setting the Khorana score. RESULTS: In the cohort study, nodal status ≥ 2, presence of metastases, and primary tumor site were found to be the most significant predictive factors of a thromboembolic event (n = 99; 3.1%) in the multivariate analysis. In the nested study (n = 265), hemoglobin < 13 g/dL or treatment with a red cell growth factor, CRP ≥ 31.6 mg/L, creatinine level > 0.96 mg/dL, chronic inflammatory disease, and personal or familial history of thromboembolic events were found to be the most significant predictive factors of a thromboembolic event in the multivariate analysis. In our population, the sensitivity, specificity, positive predictive value, and negative predictive value of the Khorana score were respectively 29%, 93%, 15%, and 96%. CONCLUSION: We confirm the value of the risk factors identified in the literature with the additional presence of nodal involvement, elevated CRP, and creatinine levels, which may be helpful for patient risk stratification and should be considered in future clinical trials. Our results also suggest that the Khorana score might help to identify patients who can safely be spared of thromboprophylaxis.

Serial FDG-PET/CT for early outcome prediction in patients with metastatic colorectal cancer undergoing chemotherapy.

BACKGROUND: The study purpose was to assess the predictive value of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computerized tomography (CT) metabolic response after a single course of chemotherapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: FDG-PET/CT scans were carried out at baseline and on day 14 in 41 patients with unresectable mCRC treated with a biweekly regimen of chemotherapy. Metabolic nonresponse was defined by <15% decrease in FDG uptake in the dominant proportion of the patient's lesions or if a lesion was found metabolically progressive. The PET-based response was correlated with radiological response (primary end point) and patient's outcome (secondary end points). RESULTS: RECIST response rate in metabolically responding patients was 43% (10 of 23) compared with 0% (0 of 17) in nonresponding patients (P=0.002). The metabolic assessment's predictive performance for RECIST response was sensitivity 100% [95% confidence interval (CI) 69% to 100%], specificity 57% (95% CI 37% to 75%), positive predictive value 43% (95% CI 23% to 66%), and negative predictive value 100% (95% CI 80% to 100%). Comparing metabolically responding versus nonresponding patients, the hazard ratio (HR) was 0.28 (95% CI 0.10-0.76) for overall survival and 0.57 (95% CI 0.27-1.21) for progression-free survival. CONCLUSION: The metabolic response measured by FDG-PET/CT after a single course of chemotherapy in mCRC is able to identify patients who will not benefit from the treatment.

Pneumocystis carinii as a cause of pneumonia in HIV-infected patients in Lusaka, Zambia.

PIP: 4 cases of Pneumocystis carinii pneumonia in HIV-infected patients studied at the University of Zambia Medical School, Lusaka, were verified by bronchoalveolar lavage. Pneumocystis is common in North American AIDS patients, but has been considered rare in Africa. One reason may be that facilities for diagnosis, bronchoscopy with bronchoalveolar lavage, are not usually available. 44 consecutive HIV seropositive patients who were unresponsive to a 10-day course of antibiotics, and whose sputum was negative for acid fast bacteria, underwent bronchoalveolar lavage from February 1990 to December 1990. HIV status was assayed with Welcozyme ELISA kits, and P. carinii was detected with toluidine blue O stain. The 1st case of confirmed P. carinii pneumonia was a 35-year old man who had a productive cough for 4 weeks, fever, and dyspnea. He was treated with co-trimoxazole and was symptom-free in 3 weeks, but developed severe Stevens-Johnson reaction. His cultures were positive for M. tuberculosis at week 8. He was lost to follow-up. The 2nd case was a 26-year old man with a 6-month history of cough and white sputum, treated without effect with antituberculous medication. He improved over 3 weeks with co-trimoxazole, but died of respiratory failure 2 months later. The 3rd case was a 30-year old woman being treated for pulmonary tuberculosis, who became progressively dyspneic 7 months later. She developed a generalized maculo-papular rash after taking co-trimoxazole, so was given dapsone 100 mg/day, prednisone 1 mg/kg/day, and trimethoprim 15 mg/kg for 1 week. She improve in 3 weeks. The 4th case was a 30-year old man with a 4-week history of dry cough and dyspnea and recent high fever. He was given co-trimoxazole, but developed generalized purpura after 5 days. His treatment was changed to Dapsone 100 mg/day, prednisone 1 mg/kg/day, and antituberculous medication. He improved after 3 weeks, and is being maintained on Fansidar 1 tablet/week. These cases are remarkable because 2 of them also had pulmonary tuberculosis, which is often the presumed diagnosis of pneumonia in African AIDS patients. Furthermore, 3 developed serious drug reactions to co-trimoxazole, also considered an uncommon occurrence.^ieng