Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Gastrospirillum Hominis associated chronic active gastritis: the first report from Italy.

Recently a spiral bacterium different from Helicobacter Pylori (HP) was observed in the human stomach and the name of Gastrospirillum Hominis (GH) was proposed for this organism. GH presence is reported to be not associated to HP but related to chronic active gastritis. We describe the case of a 31 year old male suffering from upper abdominal symptoms, who underwent oesophagogastroduodenoscopy, which revealed a picture of duodenal hyperemia. Gastric body showed a normal mucosa and absence of HP, while active chronic gastritis associated with HP was found in the antrum. In addition few spiral bacteria showing 4-5 spirals, larger than HP were observed within the gastric crypts and beneath the mucus layer in this site. This case represents the first report from our geographic area (Southern Italy) of the possibility of finding bacteria different from HP in the human stomach. The simultaneous HP presence does not allow us to relate the chronic active gastritis of the patient with the GH like bacteria. Our finding, however, suggests the possibility that HP and GH may be simultaneously present in the course of type B antral chronic inflammation. This association was not observed in previous investigations.

Polymorphonuclear cell function impairment in patients with Chlamydia trachomatis urogenital infections.

The phagocytic and killing functions of polymorphonuclear cells (PMNs) and monocytes in patients with culturally and serologically proven Chlamydia trachomatis urogenital infections, and the distribution of peripheral blood T cell subsets in the same patients were analysed. A significant impairment of PMNs function was observed in infected patients as compared to the control group, whereas the monocyte function was not affected. In addition, a decrease of CD4+ cells frequency was observed in these patients. Since the PMNs are the most prominent cells observed at the site of C. trachomatis infection, we suggest that a defect of PMNs function may play a role in the host susceptibility to C. trachomatis.

Rapid alternate detection system of the Rothney Astrophysical Observatory.

A new differential variable-star photometry system has been designed, constructed, and tested at the Rothney Astrophysical Observatory of the University of Calgary. The system uses a single telescope, photometer, and detector and consists of gated pulse-counting electronics synchronized to a chopped secondary mirror. The mirror is driven to four positions, permitting rapid alternate detection of a variable star, comparison star, and two sky-background regions. Within certain constraints the system is insensitive to the effects of transparency, sky-brightness, and detector-sensitivity variations occurring on time scales longer than the system's duty cycles. The system has proved effective under as much as three magnitudes of cloud and attendant sky-brightness variation.

[Total colectomy in the rat : its metabolic and functional consequences]. / La colectomia totale nel ratto: sue consequenze metaboliche e funzionali.

A number of total colectomies with end-to-end ileo-rectal anastomosis was performed in the inbred Lister rat. The following data were studied: survival rate, body weight curves, variations of appetite, thirst and diuresis, daily weight and electrolytes content of feces, intestinal transit time, histology of terminal ileum, rectum, liver and kidney. After an initial lose of body weight, rats gained their original weight at about two months after colectomy; at this time a syndrome was observed caracterized by anemia, leucocitosis with neutrophilia, ipoproteinemia, remarkable increase of thirst (up to 400%) and of water and sodium content of feces; appetite and diuresis were normal; intestinal transit tice was slightly reduced. Histologically there was a "coloni" transformation of the terminal ileum and vacuolization of the proximal renal tubules.

[Metabolic and histological changes induced in the rat by massive resection of the small intestine]. / Su alcune modificazioni metaboliche ed istologiche indotte nel ratto dalla resezione massiva del tenue.

The aim of this paper was o study the long-term changes induced in the rat as a consequence of a 90% resection of small intestine. At 6 months after operation the surviving rats were stable and showed: hypoproteinemia, hyperlipemia, and a decrease of bile flow, total lipids, and cholesterol of bile. What residual intestine concern there was an increase in length and size, and decreased transit time; stomach, duodenum and colon too showed increase size. Histologically there was hypertrophy of villi, regressive changes of pancreas and kidney, as well as deposit of iron in the kidney. The reasons for these changes are discussed.