Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities.

PURPOSE: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. METHODS AND MATERIALS: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2[4h]) and 24 hours (SF2[24h]) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. RESULTS: The SF2(4h) was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio(30min) (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio(4h)/γH2AX-ratio(30min)) showed a significant direct association with high toxicity grade (P=.01). CONCLUSIONS: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance.

Evaluating the importance of the tentorial angle in the paramedian supracerebellar-transtentorial approach for selective amygdalohippocampectomy.

OBJECTIVE: A challenging step of the paramedian supracerebellar-transtentorial approach is to expose the anterior portion of the mediobasal-temporal region (MTR), a step that seems most affected by the steepness of the tentorium. The objective of this study was to define magnetic resonance imaging measurements that can predict the level of challenge in exposing the anterior portion of the MTR. METHODS: Cranial magnetic resonance imaging studies of 100 healthy individuals were examined. The tentorial and occipital angles were measured, and the amount of brain tissue that remained hidden on the microscopic view in front of the petrous apex was indirectly estimated. These measurements were statistically compared with the cephalic index of each person. RESULTS: The mean values for the tentorial and occipital angles were 42° (range 25°-53°) and 98° (range 69°-122°), respectively. The results proved that the higher the tentorial angle, the higher the occipital angle and the greater the amount of hidden brain tissue. Of 100 persons, 3 (3%) were found to be dolichocephalic, 23 (23%) were mesocephalic, and 74 (74%) were brachycephalic. Statistical analysis proved that individuals with a dolichocephalic cranial shape have lower tentorial and occipital angles. CONCLUSIONS: The results provide strong evidence proving that the lesser the tentorial and occipital angles, the easier the exposure of the anterior portion of the MTR during the paramedian supracerebellar-transtentorial approach. The tendency of the cranial shape toward dolichocephaly seems to have the same practical value in choosing the approach. It is easier to expose the anterior portion of the MTR in these individuals.

Alexandre Yersin's explorations (1892-1894) in French Indochina before the discovery of the plague bacillus.

Alexandre Yersin, the great French discoverer of yersinia pestis, was a keen explorer of unknown lands. At the age of 30, a member of the French Colonial Health service, he set off to fulfil his intimate dream and explore other continents. For almost two years and three long expeditions, he journeyed through widely unknown regions in the province of the French Indochina, in southeast Asia, territories of Vietnam, Cambodia and Laos. This article presents vignettes from his explorations. During his difficult travels, he carefully planned and noted his itineraries; designed new routes, but also observed and recorded sociodemographic and environmental data and unidentified diseases. The immature science of late 19th century geography had the strength to allure such an influential medical figure and place him among the early medical geographers. His journeys, observations and recordings brought to Yersin great experience, and he made his most important scientific contributions after he had concluded his explorations.

A 20-year-old man with large gastric lipoma--imaging, clinical symptoms, pathological findings and surgical treatment.

A broad search of the available literature yielded no other report of gastric lipoma of that size (13.5 x 6.5 x 4.5 cm) at this early age. The patient (a 20-year-old man with giant lipoma in the anterior gastric wall) presented with haematemesis and melena after excessive alcohol consumption. Gastric resection was performed. At 5-year follow up the patient is healthy and doing well. Epidemiology of gastric lipoma, the differential diagnosis, means of diagnosis and treatment are discussed.

Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer.

BACKGROUND AND AIMS: D2 gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. PATIENTS AND METHODS: Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. RESULTS: The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50+/-8 and 62+/-10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). CONCLUSION: Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.