Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome.

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. It is caused by mutations in the NALCN gene that encodes a voltage-independent, cation channel permeable to NM, K+ and Ca2+ and forms a channel complex with UNCSO and UNC79. So far, only 4 homozygous mutations have been found in 11 cases belonging to 4 independent consanguineous families. We studied a Sardinian family with 2 siblings presenting dysmorphic facies, hypotonia, psychomotor retardation, epilepsy, absent speech, sleep disturbance, hyperkinetic movement disorder, cachexia and chronic constipation. Polymorphic generalized seizures started at 4 and 6 years, respectively. Anti-epileptic drugs (AEDs) therapy was efficient for female proband's epilepsy, but the male still has weekly seizures. Whole exome sequencing identified 2 novel truncating mutations in NALCN allowing to assess the clinical phenotype to IHPRF1. This is the fifth family reported worldwide, and these are the first European cases with IHPRF1 syndrome with biallelic truncating mutations of NALCN.

Factors influencing outcome in gastric cancer involving muscularis and subserosal layer.

AIMS: The prognostic factors for advanced gastric carcinoma without serosal invasion (pT2 AGC) are not clear. In terms of prognosis, pT2 AGC is considered intermediate between early gastric cancer (EGC) and gastric carcinoma with serosal invasion. METHODS: From January 1985 to December 2000, 182 patients with pT2 AGC underwent curative gastric resection in our Department. Prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: Univariate analysis demonstrated that gender, tumour location, lymph node involvement, Borrmann type, number of lymph nodes involved, venous infiltration and extent of lymphadenectomy were significantly related to the prognosis. Multivariate analysis revealed that extent of lymph node metastasis (N1 vs N0 relative risk (RR) of recurrences=3.96, p<0.05; N2 vs N0 RR=6.55, p<0.05), and extent of lymphadenectomy (D1 vs D2 RR=3.2, p<0.01) were independent prognostic factors. In a subset of patients in which venous infiltration was analysed, this factor was also significant (RR=3.9, p<0.05). CONCLUSIONS: Our study shows that lymph node involvement and venous infiltration are important prognostic factors for pT2 AGC and, as such, adjuvant chemotherapy could be useful in this group of patients. An extensive lymph node dissection, minimum D2, should always be performed in order to reduce the risk of recurrence.

[Correlation between chronic gastritis of the gastric stump, Helicobacter pylori infections and iron deficiency after gastrectomy for gastric cancer]. / Correlazione tra gastrite cronica del moncone, infezione da Helicobacter pylori e carenza di ferro dopo gastrectomia per cancro gastrico.

Atrophic chronic gastritis and Helicobacter pylori infection are considered possible causes of iron deficiency anemia, and sideropenic anemia is also frequent after subtotal gastrectomy. In this study, thirty-three patients who underwent subtotal gastrectomy for primary adenocarcinoma of stomach were follow-up for at least 3 years, and included in this analysis. The presence of atrophic gastritis and H. pylori infection were detected by biopsy sampling and endoscopy every year after surgery. The iron status was evaluated by the assay of serum ferritin, serum iron and hemoglobin level. Statistical analysis revealed that atrophic gastritis was associated with lower iron serum levels, and gastric stump H. pylori infection was related to lower serum ferritin levels; on the contrary, no correlation of these factors with sex, age, malabsorption symptoms and stage of tumor was found. Atrophic chronic gastritis and Helicobacter pylori infection seem to play an important role as possible causes of post gastrectomy anaemia.

[Trends in stomach carcinoma. A statistical analysis of 1204 cases]. / Il carcinoma dello stomaco in prospettiva. Analisi statistica di 1.204 casi.

The authors report a retrospective analysis of their experience of gastric cancer. One thousand two hundred and four patients, observed between 1977 and 1994, of whom 1,094 underwent surgery, were studied. Data analysis was performed, dividing this period as follows: 1977-1982, 1983-1988, 1989-1994. The results reveal that, over time, substantial changes occurred both in tumor characteristics and surgical approach. With regards to tumor characteristics, the disease weighs heavily, even if it is less frequent than in the past (25% reduction), striking younger subjects and presenting in increasingly more aggressive forms [higher frequency of proximal (+11.4%) and diffuse forms (+18.1%), reduction of advanced forms (-11.6%) not proportional to the increase of early forms (+64.5%), as well as increase of cases with a short clinical history (+15.2%)]. In terms of surgical approach, while the use of conservative surgery was reduced during the study period, extensive procedures were more widely used, particularly in the curative treatment of advanced tumors (subtotal gastrectomies: reduction of 39.5%; total gastrectomies: increase of 106%). The increasing use of extended surgery is linked to the modifications occurred in tumor characteristics and in pre and post-operative management rather then to changes in surgical approach. It must be noted, however, that such technical advances have not yielded an improvement in survival (p = n.s.); as such, it is likely that gastric cancer has became a more aggressive disease and, therefore, has counterbalanced the benefits of early diagnosis and extended exeresis.

[Clinicopathological features of advanced gastric cancer. Report on 400 operated cases]. / Caratteristiche cliniche e patologiche del cancro gastrico molto avanzato. Risultati in 400 casi operati.

In the present study the Authors report the clinical and pathological characteristics of highly advanced cases of gastric carcinoma. Of 1204 primary gastric cancer cases observed between 1977 and 1994 at the Second Department of Surgery, University of Siena, 400 cases treated by non-curative surgery were selected for this study: 174 explorative laparotomies, 76 by-pass and 150 resective operations, of which 98 relatively non-curative and 52 absolutely non-curative resections. The clinical and pathological features of these cases were compared with curative resection cases. Of several variables examined at univariate analysis, tumor site, macroscopic aspect, tumor size, depth in gastric wall and lymph nodal involvement significantly influenced the operative rate and the rate of non-curative operations (p < 0.001). With reference to non-curative cases, the diffusion pattern of neoplasm, besides the above mentioned variables, significantly affected the resectability rate: distant metastases, and particularly peritoneal spread, involved a lower resection rate if compared to cases with loco-regional diffusion (p < 0.001).