Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

SDH mutations in patients affected by paraganglioma syndromes: a personal experience.

Mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are frequently involved in the development of neural crest-derived (NCD) tumors, such as pheochromocytomas (PHEOs) or paragangliomas (PGLs). In this study we report the results of sequencing analysis in leukocyte DNA of patients affected by PHEO/PGL who turned out to be SDH mutation carriers. A nonsense germline heterozygous mutation (Q109X) was found in the exon 4 of the SDHD gene in the index cases of six unrelated families affected by PHEO/PGL. Haplotype analysis showed the presence of a founder effect. Affected patients showed high clinical variability, ranging from monolateral to bilateral glomus tumors, variably associated or not with PGLs or PHEOs. A novel missense SDHD variant, T112I, was also found in one of our families. A new missense G106D mutation, involving a highly conserved amino acid, was found in two sisters affected by bilateral glomus tumors. A P81L mutation associated with abdominal and head and neck PGL was detected in three families. A G12S variant of the SDHD gene was found in one patient affected by a PHEO. The finding of this variant in 3 of 100 control subjects suggests that it is a polymorphism and not a mutation. A novel IVS2-1G>T variant was found at intron 2 of SDHD gene in one patient affected by a glomus tumor. All the tumors associated with SDHD mutations were benign. Conversely, the only mutation we found in SDHB gene (IVS3+1G>A) was associated with a malignant PHEO.

Increased risk for gallstone disease in subjects operated on for partial gastrectomy with gastro-jejunostomy (BII operation).

The prevalence of cholelithiasis has been investigated in 301 male subjects (age range 35-60 years) operated on for partial gastrectomy with gastro-jejunostomy (BII), in 277 unoperated peptic ulcer patients (age range 30-60 years) and in a control population of 281 factory's workers (age range 31-58 years). The prevalence of gallstone disease resulted significantly higher in BII operated subjects (23.9%) than in unoperated (9%) and controls (8.5%). No difference was found between unoperated peptic ulcer patients and controls. These results indicate that BII operation is a high risk condition for cholelithiasis while peptic ulcer disease does not constitute a favourable factor for gallstone formation.

Candida albicans infection of gastric ulcer frequency and correlation with medical treatment. Results of a multicenter study.

This paper reports the results of a multicenter prospective study of 188 consecutive patients affected by gastric ulcer, verified by endoscopy, in whom the frequency of a mycotic infection of the lesion was evaluated as well as the eventual influence of such pathology on the efficiency of medical treatment, the healing rate, and the healing time. A mycotic infection, defined as penetration of the periulcerous mucosa by the fungi, was found in only 13 patients (6.9%). No significant differences were found in the healing rate and healing time among these patients treated with H2-receptor antagonists and a control group of 43 matched gastric ulcer patients treated in the same period with the same therapy. It would appear from the data that mycotic infections of the gastric ulcer do not modify the efficiency of medical treatment.

[Gastrin]. / Gastrina

Gastrin is released by food rich in proteins and by vagal mechanisms. HCI and possibly secretin and glucagon inhibit gastrin release. In the wide range of actions of gastrin, stimulation of gastric acid secretion is the most important. With the advent of radioimmunochemical methods for the determination of gastrinaemia, it has been shown that gastrin exists in a number of forms of different molecular weight. To estimate the validity of gastrin radioimmunoassay it is necessary to demonstrate that decrease in antibody-bound labelled antigen is unrelated to non-specific interference by unknown substances present in serum samples, and that the antiserum reacts with endogenous hormone in an identical manner. Heterogeneity of gastrin in serum may affect the validity of the radioimmunoassay. Hypergastrinaemia associated with hyper-normochlorhydria occures in gastrinoma, hyperplasia of antral gastrin cells, diseases with delayed gastric emptying, retained antrum, short bowel syndrome,renal failure. Hypergastrinaemia associated with hypo-achlorhydria occurs in atrophic gastritis without extensive antral lesion and after vagotomy. Gastrin radioimmunoassay can be used for the mass screening of subjects with atrophic gastritis, a high risk group for gastric cancer.