The follicle-stimulating hormone receptor (FSHR) is expressed in human sperm and it may be considered as molecular marker of the detrimental effects related to the physiopathology of testicular varicocele

Localization of the follicle-stimulating hormone receptor (FSHR), has been always closely related to the testis and ovary. FSH/FSHR role in Sertoli cell, has been known, however, the sites of FSH action within the male reproductive system are not resolved yet. Few studies have raised the intriguing possibility that germ cells may exhibit FSHR, all the reports point to Sertoli cells as the exclusive FSH target cells in testis. Besides, the attention has been always paid on the FSHR several polymorphisms which affect receptor sensitivity and expression. The presence of FSHR in germinal cells from spermatogonia to spermatocytes, including round spermatids is controversial or excluded. The mechanisms by which testicular varicocele affects fertility remain undetermined. Recently, our studies showed that the disease causes damage in sperm at the molecular level opening a new chapter in the already multifaceted physiopathology of varicocele. Samples used in this study were from normozoospermic and from diagnosed varicocele of grade III on the left testis patients. To date four FSHR isoforms were discovered, FSHR1, FSHR2, FSHR3 and FSHR4. The activity of FSHR1 is mediated by G proteins, which activate adenylate cyclase. FSHR2 and FSHR3 also bind FSH, but this does not result in activation of adenylate cyclase. FSHR4 does not bind FSH. By western blot analysis, we showed that healthy sperm express FSHR1, FSHR2 and FSHR3 while FSHR4 is almost absent. Varicocele does not express FSHR2. Immunofluorescence assay evidences FSHR localization prevalently at the midpiece level, which was strongly reduced in varicocele sperm. Responses to different FSH concentrations on motility and survival were significantly reduced in varicocele respect to the normal sperm, probably due to the lower FSHR1 expression and FSHR2 absence. The FSHR significance in human male gamete also emerged from the acrosome reaction histochemical studies, during FSH treatment which significantly induced the process. Our data showed for the first time that human sperm express the FSHR and constrain the need of further studies on the molecular anatomy of human male gamete both in healthy and in pathological conditions related to the male genital apparatus, considering the high couple infertility linked to the male. The translation of these new researches in the clinic surgery of testicular varicocele needs to be taken into account since molecular alterations in sperm imply a decline in the acquisition of fertilizing ability, and to date controversies exist on the opportunity to intervene surgically

Robotic versus open Ivor-Lewis esophagectomy: A more accurate lymph node dissection without burdening the leak rate

BackgroundRobotic-assisted minimally invasive esophagectomy (RAMIE) combines the beneficial effects of minimally invasive surgery on postoperative complications, especially on pulmonary ones, with the safety of the anastomosis performed in open surgery. Moreover, RAMIE could allow a more accurate lymphadenectomy. MethodsWe reviewed our database to identify all patients with adenocarcinoma of the esophagus treated by Ivor-Lewis esophagectomy in the period January 2014 to June 2022. Patients were divided according to the thoracic approach into RAMIE and open esophagectomy (OE) groups. We compared the groups for early surgical outcomes, 90-day mortality as well as R0 rate, and the number of lymph nodes harvested. ResultsWe identified 47 patients in RAMIE and 159 patients in the OE group. Baseline characteristics were comparable. Operative time was significantly longer for RAMIE procedures (p < 0.01); however, we did not observe the difference in overall (RAMIE 55.5% vs. OE 61%, p = 0.76) and severe complications rate (RAMIE 17% vs. OE 22.6%, p = 0.4). The anastomotic leak rate was 2.1% after RAMIE and 6.9% after OE (p = 0.56). We did not report the difference in 90-day mortality (RAMIE 2.1% vs. OE 1.9%, p = 0.65). In the RAMIE group, we observed a significantly higher number of thoracic lymph nodes harvested, with a median of 10 lymph nodes in the RAMIE group versus 8 in the OE group (p < 0.01). ConclusionsIn our experience, RAMIE has morbimortality rates comparable to OE. Moreover, it allows a more accurate thoracic lymphadenectomy which results in a higher thoracic lymph nodes retrieval rate

Treatment of EGJ Cancer within or outside clinical trials: Does the setting matter? A monocentric prospective observational study

Introduction: RCTs support neoadjuvant chemoradiotherapy (nCRT) followed by surgery in Locally Advanced Esophago-Gastric Junction (LA-EGJ) adenocarcinoma. However, RCTs are performed in highly controlled settings with limited representativeness of real-life patients (RLS). Aim: To compare the outcomes in RLS and clinical trial settings. Methods: The outcomes of RLS, which comprised 125 patients consequently treated for LA-EGJ adenocarcinoma between 2012 and 2017, were compared with the phase II trial (PIIS), performed on 65 patients from 2003 to 2011. Results: About half of RLS (51.2%) were treated with nCRT according to VR-protocol, 20.8% with standard-CRT according to CROSS/Al-Sarraf, 20% with CT alone. pCR was 36.8%, 28.6% and 9.1% after VR-protocol, standard-CRT, and chemotherapy respectively (p=0.082), while three-year overall survival (OS) was 58.6% (95% CI 43.2-71.1%), 32.8% (14.6-52.4%) and 44.8% (21.3-65.9%) respectively (p=0.030). With respect to PIIS, RLS had a higher proportion of cN+ (94% versus 54%; p<0.001), and a lower proportion of pCR after CT/CRT (23% versus 39%; p=0.041). Three-year OS was slightly higher, although not significantly, in PIIS (58.9%, 45.1-70.2%) than RLS (47.9%, 37.4-57.7%) and nearly identical to 3-year OS in RLS treated with VR-protocol. Discussion/conclusion: Real-life patients with EGJ adenocarcinoma have more advanced cancer at baseline, lower pathologic response to neoadjuvant treatment than patients enrolled in clinical trials, but similar survival

The "Weekday Effect" on Enhanced Recovery after Surgery Protocol for Gastrectomy

Introduction: While enhanced recovery after surgery (ERAS) protocol demonstrated to improve outcomes after gastrectomy, some papers evidenced a detrimental effect on postoperative morbidity related to the "weekday effect." We aimed to understand whether the day of gastrectomy could affect postoperative outcomes and compliance with ERAS items. Methods: We included all patients that underwent gastrectomy for cancer between January 2017 and September 2021. Cohort was divided considering the day of surgery: Early group (Monday-Wednesday) and Late group (Thursday-Friday). Compliance with protocol and postoperative outcomes were compared. Results: Two hundred twenty-seven patients were included in Early group, while 154 were in Late group. The groups were comparable in preoperative characteristics. No significant difference in pre/intraoperative and postoperative ERAS items' compliance was apparent between Early and Late groups, with most items exceeding the 70% threshold. Median length of stay was 6.5 days and 6 days in Early and Late groups (p = 0.616), respectively. Morbidity was 50% in both groups, with severe complications that occurred in 13% of Early patients and 15% of Late patients. Ninety-day mortality was 2%, and it was similar between the two groups. Conclusions: In a center with a standardized ERAS protocol, the weekday of gastrectomy has no significant impact on the success of each ERAS item and on postoperative surgical and oncological outcomes

Feasibility and safety of an enhanced recovery protocol (ERP) for upper GI surgery in elderly patients ( 65\u200975\ua0years) in a high-volume surgical center

Enhanced recovery protocols (ERP) have demonstrated their efficacy after esophagectomy and gastrectomy but little is known about their feasibility and safety in elderly patients. Patients submitted to Ivor-Lewis esophagectomy or gastrectomy for cancer between January 2016 and June 2019 were divided into three age groups: young-age group, YG (<= 65 years, n = 130); middle-age group, MG (66-74 years, n = 101); old-age group, OG (>= 75 years, n = 74). The groups were compared for adherence to our ERP, morbidity and mortality rates. After esophagectomy, adherence to ERP was comparable between the three groups, overall morbidity was higher in OG, without statistically significant difference, while the incidence of cardiac complications was significantly higher in OG (p = 0.02). After gastrectomy, OG presented a lower adherence to urinary catheter removal and to early mobilization. No difference in overall morbidity rate was observed (p = 0.13). The median length of stay was comparable both after esophagectomy (p = 0.075) and gastrectomy (p = 0.07). Multivariable analysis showed that age >= 75 years was not associated with a higher risk of ERP failure either after esophagectomy (p = 0.59) or after gastrectomy (p = 0.83). After esophagectomy, the risk of failure of the ERP program was higher for patients with ASA grade 3-4 (p = 0.03) and for those with postoperative complications (p < 0.001) while after gastrectomy only postoperative complications were associated to higher risk of ERP failure (p < 0.001). In our series, adherence to ERP protocol of patients >= 75 years old was similar to that of younger patients after esophagectomy and gastrectomy, without a significant increase in morbi-mortality rates