Prediction of short-term surgical complications in women undergoing pelvic exenteration for gynecological malignancies.

OBJECTIVE: Pelvic exenteration (PE) is an extensive surgery associated with high rates of postoperative morbidity and mortality. The absence of well-defined preoperative selection criteria to identify patients eligible for PE prompted the assessment of pre-operative predictors of 30-day major surgical complications. METHODS: Demographics and surgical characteristics of patients undergoing PE for gynecologic cancer in a single institution between 01/2004-12/2016 were reviewed. Postoperative complications within 30 days following surgery were graded using the Accordion grading system. Logistic regression was used to analyze potential risk factors for severe postoperative complications. RESULTS: A total of 138 patients were included in the cohort. Forty-five patients underwent total PE, 52 anterior PE, and 41 posterior PE. Among the 137 patients with follow-up, a severe postoperative complication was experienced by 37 patients (27.0%) and 3 patients (2.2%) experienced death within 90 days. The most frequent grade 3 complications were complications of urinary reconstruction (n = 15), wound dehiscence (n = 9), and abdominal abscess requiring intervention with drain or return to the operating room (n = 6). On multivariable analysis, independent predictors of severe postoperative complications were anterior or total PE (adjusted odds ratio (aOR): 11.66, 95% CI 2.56-53.18), pre-operative hemoglobin ≤10 mg/dl (aOR 2.70, 95% CI 1.02-7.14) and presence of 3+ comorbidities (aOR: 2.76, 95% CI 1.07-7.10). CONCLUSIONS: Major complications after exenteration are common. Surgical complexity and patient selection play a considerable role in predicting complications. These data can be used to better risk stratify patients undergoing PE.

Locally advanced cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome.

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus.

A laparoscopic risk-adjusted model to predict major complications after primary debulking surgery in ovarian cancer: A single-institution assessment.

OBJECTIVE: To develop and validate a simple adjusted laparoscopic score to predict major postoperative complications after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (AEOC). METHODS: From January 2006 to June 2015, preoperative, intraoperative, and post-operative outcome data from patients undergoing staging laparoscopy (S-LPS) before receiving PDS (n=555) were prospectively collected in an electronic database and retrospectively analyzed. Major complications were defined as levels 3 to 5 of MSKCC classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n=370) and was validated on the remaining one-third patients (n=185). RESULTS: Major complication rate was 18.3% (102/555). Significant predictors included in the scoring system were: poor performance status, presence of ascites (>500cm(3)), CA125 serum level (>1000U/ml), and high laparoscopic tumor load (predictive index value, PIV ≥8). The mean risk of developing major postoperative complications was 3.7% in patients with score 0 to 2, 13.2% in patients with score 3 to 5, 37.1% in patients with score 6 to 8. In the validation population, the predicted risk of major complications was 17.8% (33/185) versus a 16.7% (31/185) observed risk (C-statistic index=0.790). CONCLUSION: This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt tailored strategies on individual basis.

Secondary cytoreductive surgery in patients with isolated platinum-resistant recurrent ovarian cancer: a retrospective analysis.

OBJECTIVE: To analyze the impact of secondary cytoreductive surgery (SCS) on survival outcome in a retrospective series of isolated platinum-resistant recurrent ovarian cancer. METHODS: We evaluate a consecutive series of 268 ovarian cancer patients with platinum-resistant relapse. Isolated recurrence was defined as the presence of a single nodule, in a single anatomic site, and was observed in 27 cases (10.1%). In all women the presence of isolated relapse was assessed at radiological evaluation, and surgically confirmed in the SCS group. RESULTS: Among the 27 patients with isolated recurrence, 16 (59.3%) received chemotherapy alone, and 11 (40.7%) complete SCS followed by non-platinum based chemotherapy. No significant differences were observed in the distribution of baseline clinico-pathological characteristics, pattern of recurrent disease, duration of PFI, and type of salvage chemotherapy between the two groups. In the SCS group, 6 patients (54.5%) showed isolated peritoneal relapse and 5 women (45.4%) showed isolated lymph nodal recurrence, and were treated with peritonectomy and lymphadenectomy, according with site of relapse. Two post-operative complications (18.2%) occurred: asymptomatic lymphocele and groin wound dehiscence. SCS significantly prolonged median time to first progression (12 months vs 3 months; p-value=0.016), median time to second progression (8 months vs 3 months; p-value=0.037), and post-relapse survival (PRS) (32 months vs 8 months; p-value=0.002). Residual tumor at 1st surgery (X(2)=5.690; p-value=0.017), duration of PFI (X(2)=5.401; p-value=0.020), and complete SCS (X(2)=4.250; p-value=0.039) retains independent prognostic role for PRS in multivariate analysis. CONCLUSIONS: SCS prolongs PRS compared to chemotherapy alone in isolated platinum-resistant recurrent ovarian cancer.

Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience.

OBJECTIVE: To evaluate the prognostic impact of routinely use of staging laparoscopy (S-LPS) in patients with primary advanced epithelial ovarian cancer (AEOC). METHODS: All women were submitted to S-LPS before receiving primary debulking surgery (PDS) or neoadjuvant treatment (NACT). The surgical and survival outcome were evaluated by univariate and multivariate analysis. RESULTS: Among 300 consecutive patients submitted to S-LPS no complications related to the surgical procedure were registered. The laparoscopic evaluation showed that almost half of the patients (46.3%) had a high tumor load. One-hundred forty-eight (49.3%) women were considered suitable for PDS and the remaining 152 (50.7%) were submitted to NACT. The percentages of complete (residual tumor, RT=0) and optimal (RT<1cm) cytoreduction of PDS and interval debulking surgery (IDS) were 62.1% and 57.5%, 22.5% and 27.7%, respectively, p=0.07. The post-operative complications of NACT/IDS group were lower than PDS group (p=0.01). The median progression free survival in women with RT=0 at PDS was 25 months (95% CI, 15.1-34.8), which was statistically significant longer than in all other patients, irrespective of the type of treatment they received (p=0.0001). At multivariate analysis, residual disease (p=0.011) and performance status (p=0.016) maintained an independent association with the PFS. CONCLUSIONS: Including S-LPS in a tertiary referral center for the management AEOC does not appear to have a negative impact in terms of survival and it may be helpful to individualize the treatment avoiding unnecessary laparotomies and surgical complications.

Critical proliferation-independent window for basic fibroblast growth factor repression of myogenesis via the p42/p44 MAPK signaling pathway.

In many cell types including myoblasts, growth factors control proliferation and differentiation, in part, via the mitogen-activated protein kinase (MAPK) pathway (also known as the extracellular regulated kinase (Erk) pathway). In C2C12 myoblast cells, insulin-like growth factor-1 and basic fibroblast growth factor (bFGF) activate MAPK/Erk, and both growth factors promote myoblast proliferation. However, these factors have opposing roles with respect to differentiation; insulin-like growth factor-1 enhances muscle cell differentiation, whereas bFGF inhibits the expression of the muscle-specific transcription factors MyoD and myogenin. Cells treated with bFGF and PD98059, a specific inhibitor of the MAPK pathway, show enhanced expression of the muscle-specific transcription factors MyoD and myogenin as compared with cells not exposed to this inhibitor. Inhibiting MAPK activity also enhances myoblast fusion and the expression of the late differentiation marker myosin heavy chain. Basic FGF mediated repression of muscle-specific genes does not result from continued cell proliferation, since bFGF-treated cells progress through only one round of cell division. We have identified a critical boundary 16 to 20 h after plating during which bFGF induced MAPK activity is able to repress myogenic gene expression and differentiation. Thus, the targets of MAPK that regulate myogenesis are functional at this time and their identification is in progress.

Characterization of proteins in detergent-resistant membrane complexes from Madin-Darby canine kidney epithelial cells.

We previously isolated detergent-resistant membrane complexes (DRMs) that were not solubilized after extraction of Madin-Darby canine kidney cells with Triton X-100 on ice. The complexes were rich in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol (GPI)-anchored proteins. In this study, we examined the protein composition of DRMs and further characterized the detergent solubility of these structures. Eight to ten cell-surface proteins, including proteins from both apical and basolateral membranes, were recovered in DRMs. Most DRM proteins, however, were not exposed to the surface of whole cells, and we did not detect the complex of cell-surface proteins described by Sargiacomo et al. in a similar study [Sargiacomo, M., et al. (1993) J. Cell Biol. 122, 789-807]. Almost all proteins in DRMs were solubilized by Triton X-100 at temperatures above 30 degrees C or by octyl glucoside on ice. In contrast, a GPI-anchored protein, placental alkaline phosphatase, was mostly solubilized by Triton X-100 after extraction at 10 degrees C. This protein was insoluble in ice-cold Triton X-100 when first delivered to the plasma membrane and remained so for at least 6 h after synthesis. A fraction of the lipids in DRMs remained insoluble after extraction with Triton X-100 at 37 degrees C. DRM lipids were not solubilized by octyl glucoside, suggesting that this detergent selectively extracts proteins from DRMs.