Prostate size ≥ 100 g and its association with long-term outcomes of Retzius-sparing robot-assisted radical prostatectomy.

BACKGROUND: It is unknown whether perioperative and functional outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) may be affected by large prostate sizes (PS). METHODS: All patients treated with RS-RARP were identified and compared according to PS. The definition of PS relied on the prostatic weight at final pathology (PS < 100 g vs ≥ 100 g). Multivariable logistic regression models tested immediate and 12-month urinary continence recovery (UCR, namely, 0-1 safety pad per-day), and positive surgical margins (PSM). Multivariable Poisson log-linear regression analyses tested operative time (OT), estimated blood loss (EBL), and length of stay (LOS). The analyses relied on the database of a high-volume European institution (2010-2022). RESULTS: Of 1,555 overall patients, 1503 (96.7%) had a PS < 100 g and 52 (3.3%) had a PS ≥ 100 g. No differences were recorded in LOS (3 days), and intraoperative (1.9 vs 2.3%) as well as postoperative complications (13 vs 12%; all p values > 0.05). No significant difference was recorded in PSM (25 vs 23%, p = 0.6). In patients with PS ≥ 100 g vs < 100 g, immediate UCR rate was 42 vs 64% (p = 0.002), and 12-month UCR rate was 87 vs 88% (p = 0.3). PV ≥ 100 g independently predicted worse immediate UCR (odds ratio 0.55, 95% CI 0.30-0.98, p = 0.044), but not worse 12-month UCR (p = 0.3) or higher PSM (p = 0.7). PV ≥ 100 g independently predicted longer OT (incidence rate ratio [IRR] 1.12, 95% CI 1.10-1.15, p < 0.001) and higher EBL (IRR 1.26, 95% CI 1.24-1.28, p < 0.001), but not longer LOS (p = 0.3). CONCLUSIONS: RS-RARP is a valid option for prostate cancer treatment, even in case of very large prostates. Specifically, no significant association was recognized between PS ≥ 100 g and PSM or 12-month UCR.

Ureteroiliac fistula after oncological surgery: Case report and review of the literature.

Fistulas arising between ureters and iliac arteries (UAF) are rare pathological events and frequently require emergency treatment, as they are associated with massive haematuria and haemorrhagic shock. The medical history plays a key role in the diagnostic and therapeutic process, as it allows to include UAF among the differential diagnoses of gross haematuria. The emergency treatments of fistulas arising between the urinary system and the vascular system include the open repairing surgery or the endovascular grafting, the latter generally better tolerated by patients suffering from multiple comorbidities or not eligible for traditional surgery. Nephrostomy or ureteral stent can be used to drain the affected upper urinary tract temporarily or permanently. Herein, we reported two cases of oncological patients affected by UAF and treated successfully by endovascular procedures. Furthermore, we performed a narrative review of the literature concerning UAF and its diagnostic and therapeutic management. Although our study did not allow us to state definitive conclusion about the diagnostic and therapeutic management of UAF due to small sample size, our findings support previous experiences in favour of the treatment of fistulas with an endovascular approach.

Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature.

Pubovesical fistula (PVF) is a rare complication of radical treatments for prostate cancer (PCa), especially when a multimodal approach is performed. We present a case of PVF with extensive communication between the bladder and the pubic bones, and lymph node metastases of PCa treated by cystectomy and salvage lymphadenectomy. We describe a case of a 65-year old male patient who, after radical prostatectomy and adjuvant radiation therapy, suffered from suprapubic and perineal pain, ambulation difficulties and recurrent urinary tract infections. Cystoscopy, cystography and contrast-enhanced magnetic resonance imaging diagnosed a PVF. Choline positron emission tomography/computed tomography scan demonstrated PCa lymph node metastases. After the failure of conservative treatment, open radical cystectomy with ureterocutaneostomy diversion and salvage lymphadenectomy were performed with resolution of symptoms. At 3-month follow-up, the pelvic and perineal pain was completely regressed and 1-year later the patient was still asymptomatic. This clinical case shows efficacy and safety of combined salvage lymphadenectomy and cystectomy with urinary diversion for the treatment of late PCa node metastasis and PVF.

A Combined One-Staged Robot-Assisted Sacral Chordoma Resection.

BACKGROUND: The robotic surgery is an advanced modern minimally invasive technology, widely used in urologic oncology, and it has become useful in particular conditions. Over time, different surgical specialties made use of the robotic properties to minimize complications for high-risk procedures. A combined 1-staged robot-assisted multidisciplinary surgery with intraoperative neurophysiological monitoring can be a safe procedure to remove a sacral chordoma with low morbidity rates. CASE DESCRIPTION: A 64-year-old woman complained of a few months of drug-resistant low back and abdominal pain. The subsequent development of constipation brought the patient to undergo an abdominal computed tomography scan and magnetic resonance imaging. Radiologic investigations revealed a large size sacral mass associated with a partial destruction of the sacrum and posterior compression of the rectum. The tumor was en bloc removed by a combined 1-staged anterior laparoscopic robot-assisted and posterior open lumbosacral approach with continue intraoperative neurophysiological monitoring of sacral and pudendal plexuses. The histological diagnosis was of chordoma. After surgery, the patient reported pain relief and the total recovery of bowel dysfunction with good 11-month follow-up outcome. CONCLUSIONS: This combined technique represents a promising treatment option in selected cases. The robotic technology combined with the experience of highly qualified staff can improve the surgical result by minimizing complications. However, longer follow-up is necessary to confirm the long-term effects in terms of recurrence and survival.

Ovarian toxicity: from environmental exposure to chemotherapy.

Unlike men, who have continuous spermatogenesis throughout most of their lifetime, women are born with a fixed supply of follicles, and this number progressively declines with age until the menopause. Beside age, the speed of follicle depletion can be regulated by genetic, hormonal and environmental influences. In the course of their lives, women are exposed to multiple chemicals and radiation sources that can increase the chance of developing permanent infertility and premature ovarian failure (POF). A wealth of experimental data indicate that iatrogenic (chemotherapy, radiotherapy) and xenobiotic agents (e.g., chemicals, pharmaceuticals) are potent ovotoxicants capable of accelerating ovarian reserve depletion. In the present review we reported the negative effects exerted on mammalian ovary by some widely diffused environmental chemicals, as polycyclic aromatic hydrocarbons (PAHs) and dithiocarbamate mancozeb, and by 1-3 butadiene and 4-vinylcycloexene, two occupational chemicals known to be capable of inducing ovarian cancer and infertility. Furthermore, attention has been devoted to the consequences of chemo- and radiotherapy on the ovary, both known to affect reproductive lifespan. Our increasing understanding of metabolic alterations induced by these agents is fundamental to individuate new therapeutic strategies aimed to prevent ovarian dysfunction in fertile women.

Post-ovulatory ageing of mouse oocytes affects the distribution of specific spindle-associated proteins and Akt expression levels.

The aim of this study has been to determine the effects of in vivo post-ovulatory ageing (POA) on the distribution of spindle-associated proteins, histone H3/H4 post-translational modifications and on v-akt murine thymoma viral oncogene homolog 1 (Akt) expression levels. To this end, oocytes were retrieved 13, 29 and 33h after human chorionic gonadotrophin (hCG) treatment. The presence and distribution at the meiotic spindle of acetylated tubulin, γ-tubulin, polo kinase-1 and Ser473/Thr308 phosphorylated Akt (pAkt) as well as histone H3 and H4 acetylation and phosphorylation levels were assayed via immunofluorescence. Akt expression levels were determined via reverse transcription-polymerase chain reaction and western blotting analyses. Spindles from oocytes recovered 13h and 29h after hCG treatment showed similar levels of acetylated tubulin but ageing induced: (1) translocation of γ-tubulin from spindle poles to microtubules, (2) absence of Thr308- and Ser473-pAkt in 76% and 30% of oocytes, respectively, and (3) a significant reduction in phosphorylation levels of serine 10 on histone 3. At 29h, a significant decrease in Akt mRNA, but not in pAkt or Akt protein levels, was recorded. By contrast, protein content significantly decreased 33h after hCG. We conclude that POA impairs oocyte viability and fertilisability by altering the expression levels and spindle distribution of proteins that are implicated in cell survival and chromosome segregation. Together, these events could play a role in oocyte apoptosis.

Effects of trifluralin on the mouse ovary.

Trifluralin, a herbicide used to protect many arable and horticultural crops, was evaluated for its potential toxicity on the mammalian ovary. To this end, adult female mice were fed or not (control) with a trifluralin-enriched diet (150 mg/kg body weight/day) during gestation and lactation. After weaning, 3-week-old female mice from either trifluralin-treated or control groups were used to evaluate whether the exposure to this herbicide in utero and during lactation could induce stress responses in the ovary. It was found that trifluralin exposure caused a significantly higher level of p53, but not of pRb, in the whole ovary, and in particular in granulosa cells. TUNEL staining showed that herbicide treatment did not increase the apoptotic index of the somatic compartment. Also oocyte fertilizability was unaffected, as metaphase II oocytes retrieved from treated mice were capable of forming male and female pronuclei after in vitro fertilization as control mice. However, trifluralin determined a slightly higher number of oocytes with cytoplasmic degeneration compared with control animals. In conclusion, our results suggest that exposure to a low trifluralin dose during pregnancy and lactation does not impair oocyte quality, but can induce a stress response in ovarian somatic cells.

The fungicide mancozeb induces toxic effects on mammalian granulosa cells.

The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant.

The role of Akt signalling in the mammalian ovary.

The serine/threonine protein kinase Akt is involved in many cellular processes including cell growth, survival, proliferation and metabolism. Akt activity is modulated downstream of phosphatidylinositol-3-kinase (PI3K) in response to different extracellular stimuli. In the mammalian ovary, Akt collaborates with other kinases in the regulation of coordinate follicle and oocyte development. Akt determines the pool of primordial follicles and the transition from quiescent to growing phase. In addition, the kinase modulates granulosa cell apoptosis throughout folliculogenesis. In oocytes Akt participates in the control of meiosis resumption and, at metaphase II stage, regulates polar body emission and spindle organization. Its inhibition negatively affects preimplantation embryo development. As a consequence of such a central role, Akt dysregulation is associated with several human diseases including infertility and ovarian cancer.