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Background: Idiopathic calcium nephrolithiasis (ICN) is a common condition with a complex phenotype influenced by both environmental and genetic factors. In our study we investigated the association of allelic variants with the history of nephrolithiasis., Methods: We genotyped and selected 10 candidate genes potentially related to ICN from 3046 subjects participating in the INCIPE survey cohort (Initiative on Nephropathy, of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points), a study enrolling subjects from the general population in the Veneto region in Italy., Results: Overall, 66 224 variants mapping on the 10 candidate genes were studied. A total of 69 and 18 variants in INCIPE-1 and INCIPE-2, respectively, were significantly associated with stone history (SH). Only two variants, rs36106327 (chr20:54 171 755, intron variant) and rs35792925 (chr20:54 173 157, intron variant) of the CYP24A1 gene were observed to be consistently associated with ICN. Neither variant has been previously reported in association with renal stones or other conditions. Carriers of CYP24A1 variants showed a significant increase in the ratio of 1,25 (OH) 2 vitamin D to 25 (OH) vitamin D compared with controls ( P  = .043). Although not associated with ICN in this study, the rs4811494 CYP24A1 variant that was reported to be causative of nephrolithiasis was very prevalent in heterozygosity (20%)., Conclusion: Our data suggest a possible role for CYP24A1 variants in the risk of nephrolithiasis. Genetic validation studies in larger sample sets will be necessary to confirm our findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: This study aimed to analyse the possibility of surgical rescue of intrabreast tumour recurrence (IBTR) following conservative operation for breast cancer, i.e. quadrantectomy, axillary dissection and radiotherapy., Methods: Of 2544 patients treated with this approach, 209 presented with an IBTR as the first and only sign of relapse. Some 197 patients were considered suitable for further surgery; 12 were inoperable. Six patients declined operation., Results: Reoperative surgery was total mastectomy in 134 patients (70 per cent) and further local resection in 57 (30 per cent). Median follow-up after second surgery was 73 (range 1-192) months. The overall survival probability at 60 months was 70 per cent after mastectomy and 85 per cent following further local excision. There was no difference in disease-free survival between the two operative groups. Second IBTR was more common at 5 years in the re-excision group (19 versus 4 per cent)., Conclusion: Since the type of surgery did not seem to affect survival, breast conservation can be considered in selected patients with IBTR.

Background: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment., Purpose: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment., Methods: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches., Results: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure., Conclusions: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Background: The 67-kd laminin receptor is a cell-surface protein that binds laminin with high affinity. In vitro studies suggest that this protein is involved in the progression of human tumors to invasive cancers (metastasis), but there have been few in vivo studies. Identification of such proteins would allow development of therapies aimed at interfering with their mechanisms of action., Purpose: This large retrospective study was designed to investigate the association of expression of this laminin receptor molecule with established prognostic factors and overall survival in breast carcinoma patients., Methods: We immunohistochemically stained archival paraffin-embedded sections of 1160 primary breast carcinomas, using an immunoperoxidase technique and the MLuC5 monoclonal antibody, which is specific for the 67-kd laminin receptor. Specimens were obtained from consecutive surgeries performed from January 1968 through December 1971. Patients with negative lymph nodes or involved regional nodes had been treated with surgery alone; those with positive axillary nodes had received surgery and radiotherapy. No chemotherapy had been administered until disease recurrence. The statistical analysis was carried out using the logrank method for the survival curves and the actuarial life table to calculate survival rates according to the different prognostic variables., Results: We found statistically significant associations between laminin receptor expression and young age (P < .001), premenopausal status (P = .001), positive axillary lymph nodes (P = .01), peritumoral lymphatic invasion (P = .02), and the diameter of the tumor (P = .05). Moreover, the association of expression of the receptor protein with poor prognosis, as indicated by survival curves, was statistically significant (P < .01). For patients with receptor-negative tumors, the survival rate was 50% at 20 years; for those with receptor-positive tumors, the survival rate was 50% at 13 years. Multivariate analysis showed the laminin receptor to be an independent prognostic factor (P = .005), indicating its predictive value in relation to overall survival., Conclusions: Our data suggest that the 67-kd laminin receptor is associated with the metastatic process., Implications: These preliminary findings also suggest that hormones may have a regulatory role in the in vivo expression of the 67-kd laminin receptor, which supports the hypothesis that hormone therapy might inhibit expression of the receptor. Studies of expression of this receptor in tumors of patients with extremely different sex hormone levels (e.g., men and pregnant women) are in progress.

Many surgeons favour total gastrectomy (TG) 'de principe' in the treatment of gastric cancer, but final demonstration of its advantage over subtotal gastrectomy (SG) is still lacking. We analysed survival after curative TG or SG within groups of patients stratified according to the main prognostic variables as found in multivariate analysis, i.e., nodal status, degree of invasion of the gastric wall, patient age and sex. Our series consisted of 361 patients treated by curative SG and 41 by curative TG, admitted to the Istituto Nazionale Tumori of Milan between 1965 and 1979. In patients with lymph node involvement survival appeared to be significantly better (P = 0.0005) after SG. However, stratifying for age it was found that the benefit was limited to patients over 60 years old. No significant difference in survival was found in the group without nodal involvement (N -) and invasion of the wall to the serosa or beyond. No statistical comparison was possible in N - groups with invasion confined to mucosa, submucosa or muscularis propria because of the small number of such patients who underwent TG. We conclude that SG still represents the standard reference operation for gastric carcinoma provided that a safe proximal margin of resection is guaranteed.