The Analysis of Surgical Outcomes in Operable Gastric Cancer Patients Presenting With or Without Sarcopenia.

We aimed to identify the patients with increased risk of post-operative complications using pre-operative sarcopenia as an indicator of adverse outcome in gastric cancer patients undergoing resection. This study was a prospective observational cohort study including patients with adenocarcinoma of stomach, undergoing gastric resection with curative intent. All the patient underwent pre-operative evaluation of sarcopenia including skeletal muscle index (SMI) measurements and hand grip strength (HGS) analysis. The post-operative parameters assessed were the time to initiate enteral feeding, the time to pass first flatus, post-operative complications, post-operative hospital stay, and histopathological staging of the resected specimen. All these parameters were compared between the sarcopenia and non-sarcopenia arms to obtain the final results. The total number of patients enrolled was 72 (46 male, 26 female). The mean SMI of the study cohort was 47.1 cm2/m2 and the mean HGS was 29.35 kg. Thirty-six patients (24 male, 12 female) were sarcopenic pre-operatively. Sixty-two patients underwent subtotal gastrectomy with D2 lymphadenectomy, and 10 patients underwent total gastrectomy with D2 lymphadenectomy. The median time to pass flatus was 4 days, the median time to initiation of enteral feeding was 4 days, and the median post-operative hospital stay was 12 days. Majority of the study patients had a pT3N1-2 disease. Sarcopenia was significantly associated with worsening ECOG performance status (p = 0.001), delay in passage of first flatus post-operatively (p = 0.017), higher post-operative complications (p = 0.012), higher T stage (p = 0.040), and higher N stage (p = 0.001). But there was no significant association between sarcopenia and time to initiation of enteral feeding and post-operative hospital stay. Sarcopenia is an independent prognostic factor for adverse short-term post-operative outcomes in patients undergoing curative intent resection of gastric cancer.

Evaluation of cytotoxic potential of newly synthesized antiviral aminopyrazoloquinoline derivatives.

In the present study, we screened newly synthesized antiviral aminopyrazoloquinoline derivatives for cytotoxic potential in human normal and breast cancer cell lines using apoptosis as biomarker. These derivatives and the well known antiviral drug, acyclovir, were incubated with the normal (MCF-10A, MCF-12A) and cancer (MCF-7, MDA-MB-231) cell lines at 10, 50 and 100 µM for 72 h at 37°C. Both the parent compounds and their sugar derivatives were found to be differentially cytotoxic in various cell lines. MCF-7 cells were more or less completely resistant to all these compounds while MDA-MB-231 cells were significantly killed by apoptosis. The methoxy derivative of aminopyrazoloquinoline (compound 3) was found to be the most cytotoxic in the normal breast epithelial cell lines (MCF-10A and MCF-12A) and MDA-MB-231 cell lines at 100 µM killing over 90% of the cells with up to 80% apoptosis. Interestingly MCF-7 cells showed only up to 50% killing at 100 µM dose with less than 20% apoptosis. Acyclovir did not cause any cytotoxicity, apoptosis or cell cycle arrest in any of the cells lines at the doses tested. Our results suggest that the newly synthesized antiviral compounds have an associated risk of being cytotoxic compared to the acyclovir.

Defective repair of UV-induced DNA damage in cultured primary skin fibroblasts from Saudi thyroid cancer patients.

This study was conducted to examine the sensitivity of primary skin fibroblasts from Saudi thyroid cancer (TC) patients to ultraviolet (UV) irradiation. Cell survival was studied by a colony forming assay and DNA repair defects with a host cell reactivation (HCR) assay using UV-irradiated Herpes Simplex Virus (HSV). In addition, p53 gene expression was examined in the same TC cells exhibiting enhanced radiosensitivity. Skin fibroblasts from TC patients (n=4) showed significantly enhanced sensitivity to UV radiation. The average UV dose to reduce survival to 37% of the initial survival (D(37)) value (in Jm(-2)) for fibroblasts from TC patients was 4.6 (3.7-5.6) compared to 7.3 (6.3-8.3) for healthy individuals (n=3). UV-sensitive xeroderma pigmentosum (XP) cells, which were used as positive control, were found to be extremely sensitive with a D(37) value of 0.6 Jm(-2). In a host cell reactivation assay, UV-irradiated HSV was tested for its plaque-forming ability (PFA), by plating infected fibroblasts from TC patients (used as host cells) on African Green Monkey (Vero) kidney cells to form plaques. A significant reduction in the PFA of the UV-irradiated virus (about three fold) on TC cells compared to fibroblasts from the healthy subjects was seen, suggesting a DNA-repair deficiency in the primary fibroblasts of the TC patients. Furthermore, no significant accumulation in radiation-induced p53 expression was observed in cells from the TC patients. Our results, based on a relatively small group of subjects, indicate that Saudi TC patients primary fibroblasts (non-cancerous in nature) may be carriers of cancer-susceptible gene(s) arising from defective DNA repair/processing. These results warrant a larger study to investigate the role of UV-induced bulky DNA damage in thyroid cancer susceptibility.

Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the ATM gene.

Ataxia-telangiectasia (A-T), is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. A-T cells exhibit a greatly decreased survival and a reduction in DNA synthesis inhibition as well as p53 induction in response to ionizing radiation. Occasionally, some strains of A-T cells have been reported to manifest a slightly enhanced sensitivity with no consistent observations of a deficiency in either cell cycle control or the repair of DNA damage after treatment with ultraviolet (UV) light. In the present study it is shown that skin fibroblasts from four A-T patients, compared with the control, display enhanced sensitivity to the killing effect of UV-light, moderate radioresistant DNA synthesis, and a reduction in viral recovery in the host cell reactivation (HCR) assay. PCR based analysis indicated that three of these UV-sensitive A-T cell strains bear a large deletion in the ATM gene, and no ATM polypeptide was detected in their cell free extracts. Moreover, it is shown that, in non-replicative conditions, these A-T cells are less efficient than normal cells in repairing the T4 endonuclease V sensitive sites. These results constitute the first clear evidence showing the deficiency of A-T cells in the repair of UV-induced DNA damage, and provide further information on the relationship between cell cycle control and DNA repair in human cells.

Rare case of iatrogenic pan hypopituitarism.

Excess glucocorticoids exert feedback suppression on hypothalamus and pituitary, Thereby the release of CRH and ACTH are suppressed which results in bilateral adrenal cortical atrophy, at the same time patients is having features of latrogenic Cushing syndrome.The interesting part of this case is excess glucocorticoids have exerted cross feedback suppression on hypothalamus and pituitary resulting in suppression of release of GHRH, GH and LHRH, LH and FSH also from hypothalamus and pituitary thereby resulting in growth retardation as well as hypogonadotrophic hypogonadism. Combination of feedback and cross feedback effect of excess glucocorticoids are seen in one patient which is an interesting part of the case.