KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma.

KRAS G12C mutations are found in about 12-13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD604) to further test the hypothesis in external cohorts. In the stage I IRE cohort we found a significant association between the KRAS-G12C mutation and worse DFS in multivariable analysis (HR: 2.47). In the TCGA-LUAD stage I cohort we did not find statistically significant associations between the KRAS-G12C mutation and DFS. In the MSK-LUAD604 stage I cohort we found that KRAS-G12C mutated tumours had worse RFS when compared to KRAS-nonG12C mutated tumours in univariable analysis (HR 3.5). In the pooled stage I cohort we found that KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours (HR 2.6), to KRAS wild-type tumours (HR 1.6) and to any other tumours (HR 1.8); in multivariable analysis, the KRAS-G12C mutation was associated with worse DFS (HR 1.61). Our results suggest that patients with resected, stage I LUAD with a KRAS-G12C mutation may have inferior survival outcomes..

Do we really need fine-needle biopsy needle for an ultrasound-guided biopsy of pancreatic adenocarcinoma? A retrospective study.

OBJECTIVE: Endoscopic ultrasound (EUS)-guided FNB was not demonstrated to be better than EUS fine-needle aspiration (FNA) to obtain adequate samples for diagnosis of pancreatic tumors. We report our experience using a 22-gauge needle aspiration to obtain both cytologic and histologic samples. PATIENTS AND METHODS: In a total of 232 patients (51% men), 22-gauge needles (Cook Medical) were used to obtain a cytological sample (between 2008 and 2016, Cohort A) and a cytologic and a histologic sample (between 2016 and 2019, Cohort B) to evaluate the usability of this needle to collect material for cytologic and histologic examination. MOSE was used. RESULTS: Pancreatic adenocarcinoma was diagnosed in 76/113 (68%) patients in Cohort A and in 88/119 (74%) in Cohort B. Non-diagnostic sampling occurred in 30/113 (26%) patients in Cohort A and in 25/119 (21%) in Cohort B. The median number of passages was three in both cohorts. Lesions were in the head/uncinated process 57% vs. 51% and body/tail 43% vs. 49% in Cohorts A and B, respectively; the mean tumor size was 34.5 mm (SD 10.7) in Cohort A and 35.4 mm (SD 14.7) in Cohort B. CONCLUSIONS: FNA needle (22-gauge) with adequate passes, MOSE determination and adequate processing of specimens, provided FNA and FNB specimen collection.

The lactate/pyruvate shuttle in spermatozoa: operation in vitro.

The operation of a shuttle for the transfer of reducing equivalents in the special mitochondria present in the middle piece of spermatozoa (sperm-type mitochondria, STM) was studied in reconstituted systems in vitro with mouse, rat, and rabbit STM. The redox couple lactate/pyruvate and the lactate dehydrogenase isozyme C4 are involved in the shuttle. It is active with rat and rabbit STM, while it does not work with mouse STM, probably because the influx of lactate into the mouse organelles is relatively poor. Ratios of consumption of pyruvate/lactate by STM were 21.6, 1.28, and 1.6 for mouse, rat, and rabbit organelles, respectively. The shuttle is inhibited by 0.6 mM mersalyl, a blocker of lactate transport. The operation of the shuttle would oxidize cytosolic NADH produced during aerobic glycolysis (or fructolysis) in spermatozoa of those species having an efficient lactate carrier in mitochondria.

Effect of L-malate on pyruvate dehydrogenase activity of spermatozoa.

Presence of L-malate (from 0.5 to 4 mM concentrations) in the medium produces a marked increment of pyruvate consumption by the special type of mitochondria found in the middle piece of spermatozoa (sperm-type mitochondria, STM). Pyruvate uptake by liver mitochondria is not increased by malate. A comparative study on pyruvate dehydrogenase (PDH) of STM and liver mitochondria from mouse, rat, and rabbit showed that 2 mM L-malate does not modify significantly the activity of liver PDH, while it increases markedly that of spermatozoal PDH in the three species. The differential sensitivity to L-malate appears to be a peculiar regulatory property of the PDH complex in the gametes, which contains at least one component (E1, pyruvate decarboxylase, EC 1.2.4.1) known to be a sperm-specific isozyme.

[Multiple primary tumors of the colon]. / I tumori primitivi multipli del colon.

Nine cases of multiple primary carcinomas of the large intestine are reported in order to emphasize the importance of an accurate pre-operative search of the other neoplastic lesions after a first cancer diagnosis. As the multiple carcinomas are often in various growing stages it is necessary an accurate X-ray examination for the early cancer diagnosis. It can be concluded that all "at risk" patients (including those already treated by surgery) must be yearly controlled by radiological and endoscopic examinations to assure the best long-term results.

Properties of the branched-chain 2-hydroxy acid/2-oxo acid shuttle in mouse spermatozoa.

Operation of the branched-chain 2-hydroxy acid/2-oxo acid shuttle for the transfer of reducing equivalents in mitochondria of mouse spermatozoa was studied in vitro in reconstituted systems. Results show that the branched-chain 2-oxo acids within the mitochondria are offered several metabolic pathways. (a) Decarboxylation: mouse sperm mitochondria possess high branched-chain 2-oxo acid decarboxylase activity. (b) Recycling to the cytosol by using a transport system which can be inhibited by alpha-cyano-3-hydroxycinnamate and pH 6.8. (c) Transamination to the corresponding amino acids: experiments presented indicate that leucine formed from 4-methyl-2-oxopentanoate may pass to the external phase, re-initiating the cycle. These two last possibilities would allow autocatalytic operation of the shuttle. The branched-chain 2-hydroxy acids apparently do not utilize the monocarboxylate carrier to penetrate the mitochondria.

[Double-contrast with insufflated barium-meal technic in the routine radiological study of the esophagus]. / Il doppio contrasto con la tecnica del "pasto opaco insufflato" nello studio radiologico di routine dell'esofago.

The results are reported of the esophagus double contrast examination with "Insufflated Barium Meal" technique as first part of the routine upper digestive system radiological examination. This technique gives good double contrast without those artifacts using effervescent powders and without modifying the normal radiological alimentary tract examination established way. The double contrast is administered by a special container with a built-in mouthpiece which allows the simultaneous ingestion of barium suspension and air. The esophageal mucosa can be examined as far as the distal tract where frequently the barium contrast stops using different techniques. Good results in 90% of patients have been obtained. The early detection of inflammatory and tumoral lesions has taken particular advantage in patients sometimes asymptomatic.

[Reactive lymphoreticular hyperplasia or pseudolymphoma of the stomach]. / L'iperplasia linforeticolare reattiva o pseudolinfoma dello stomaco.

Three cases of reactive lymphoreticular hyperplasia of the stomach (pseudolymphoma) are reported. The histogenesis and the radio-endoscopic aspects are illustrated and the differential diagnosis with the malignant lymphoma and the early cancer is discussed. In each case the radiological examination has shown a granular aspect in the mucosal circonferential area (moth eaten sign) with erosions and multiple ulcers (in two cases).