Validation of an enhanced recovery after surgery protocol in gynecologic surgery: an Italian randomized study

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Cisplatin Cytotoxicity in Human Testicular Germ Cell Tumor Cell Lines Is Enhanced by the CDK4/6 Inhibitor Palbociclib

Background: Cisplatin-based chemotherapy is the mainstay of pharmacological treatment of testicular germ cell tumors (TGCTs) that, together with early diagnosis, surgery, and/or radiotherapy, has dramatically improved the prognosis. However, under the pressure of such pharmacological therapy (both classical cytotoxic drugs and targeted therapy), cancer cells may develop resistance. Thus, combination therapy that may include cytotoxic drugs and targeted therapy could offer an advantage to curing cancers. Here, we investigated the in vitro and in vivo antitumor activity of cisplatin, as a single-agent or in combination with palbociclib. Patients and methods: The cell viability of Ntera-2/cl.D1 (NT2/D1) and 833K after exposure to palbociclib and/or cisplatin was evaluated by MTT dye reduction assay and by ATPLite Luminescence Assay. Gene and protein expression was evaluated by quantitative reverse transcription polymerase chain reaction and by western blot. Flow cytometric cell-cycle analysis was performed, as well. The in vivo experiments were conducted on NT2/D1 xenografts in AB zebrafish embryos exposed to the drugs. Results: Palbociclib and cisplatin decreased TGCT cell viability both in vitro and in vivo. This effect was additive when cells were exposed to the drug combination. In the NT2/D1 cell lines, the drug combination also exerted a positive effect with regard to delaying cell recovery after the toxic insult. In the combination experiments, cisplatin-induced cell accumulation in G2/M was predominant compared with the palbociclib effect. Conclusions: These results could provide the rationale for developing further studies to improve the pharmacological treatment of TGCTs, but they must be demonstrated in a dedicated clinical trial

Laparoscopic management of a large urethral leiomyoma

Introduction and hypothesis: A 42-year-old female presented with a 12-cm mass bulging the anterior vaginal wall and causing urgency urinary incontinence and bulk symptoms. Methods: Imaging showed a tumor originating from the dorsal and cranial part of the urethra and developing in the vesicouterine space and vesicovaginal septum, dislocating the bladder ventrally and the uterus cranial-dorsally. Results: Tranvaginal biopsy showed a benign leiomyoma. A laparoscopic approach with development of the vesicouterine space permitted a safe partial morcellation of the myoma. After the bladder and vaginal wall had been completely freed, further caudal dissection was conducted with isolation of the distal cranio-dorsal portion of the urethra. The dissection plane with the vaginal wall was developed up to the caudal margin of the urethral myoma almost corresponding to the vulvar plane, and total excision of the lesion was performed. Conclusion: Laparoscopic management of urethral leiomyomas that develop into the vesicouterine space and vesicovaginal septum is feasible and safe also for very large lesions. © 2019, The International Urogynecological Association

Patterns of Recurrence and Clinical Outcome of Patients with Stage IIIC to Stage IV Epithelial Ovarian Cancer in Complete Response after Primary Debulking Surgery Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery: An Italian Multicenter Retrospective Study

OBJECTIVE: The objective of this retrospective study was to assess the clinical outcome of patients with advanced epithelial ovarian cancer in complete response after primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (IDS]). METHODS: The authors reviewed the hospital records of 384 patients who underwent PDS (n = 322) or IDS (n = 62) and who were in complete response after primary treatment. RESULTS: Optimal (residual disease [RD] < 1 cm) and complete (no gross RD) cytoreduction rates were higher after IDS than after PDS (71.0% vs 55.9%; P = 0.001 and 51.6% vs 35.7%, respectively; P = 0.02). Tumor recurred in 73.0% of the 322 complete responders after PDS versus 87.1% of the 62 complete responders after IDS (P = 0.01). The IDS group showed a higher recurrence rate within 6 months (11.3% vs 3.1%: P = 0.01) and a trend to higher recurrence rate between 6 and 12 months (30.6% vs 19.9%). Tumor recurred in 57.4% of the 115 completely cytoreduced patients after PDS versus 87.5% of the 32 completely cytoreduced patients after IDS (P = 0.001). The IDS group showed a trend to higher recurrence rate within 6 months (6.2% vs 1.7%) and a higher recurrence rate between 6 and 12 months (37.5% vs 15.6%; P = 0.01). Two-year, 5-year, and 7-year progression-free survival were 65.8%, 40.8%, and 39.3% for completely cytoreduced patients after PDS versus 43.8%, 12.5%, and 12.5% for completely cytoreduced patients after IDS (P = 0.001); and 2-year, 5-year, and 7-year overall survival were 96.4%, 69.3%, and 50.4% for the former versus 87.1%, 41.8%, and 32.6% for the latter (P = 0.001). CONCLUSIONS: The clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups

Impact of Bevacizumab-containing Primary Treatment on Outcome of Recurrent Ovarian Cancer: An Italian Study

The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred

Neoadjuvant Platinum-based Chemotherapy Followed by Radical Hysterectomy for Stage Ib2-IIb Adenocarcinoma of the Uterine Cervix - An Italian Multicenter Retrospective Study

AIM: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. PATIENTS AND METHODS: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). RESULTS: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. CONCLUSION: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix