Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer.

BACKGROUND: To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. METHODS: This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial. RESULTS: Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. CONCLUSIONS: The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity.

Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: The Role of Immune-related Factors.

BACKGROUND/AIM: Treatment of locally advanced cervical cancer (LACC) consists of concomitant chemoradiation or neoadjuvant chemotherapy (NACT) plus radical surgery (RS). This study analyzed the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), tumor infiltrating lymphocytes (TILs), and PD-L1 expression in LACC patients, treated with NACT+RS. PATIENTS AND METHODS: We prospectively analyzed 37 LACC patients treated from December 2016 to September 2019. Patients were submitted to pelvic examination, biopsy and imaging. RESULTS: In 65% of cases, a nodal involvement was present at pre-treatment MRI. All cancers showed the presence of stromal TILs and PD-L1 staining of inflammatory cells. No significant correlations were found between clinicopathological parameters and the number of TILs and PDL-1 at baseline. After NACT, 29 patients (78%) were submitted to RS; 28% of patients showed pathological complete response, 62% partial response and 10% stable disease. Seven (24%) patients reported a positive node. Patients with high levels of stromal TILs and low NLR and PLR showed a significantly better response to NACT. No significant correlation was observed between PD-L1 expression and response to NACT. CONCLUSION: The number of TILs, the expression of PDL1, and NLR and PLR ratios correlate significantly with the response of LACC patients to NACT.

Efficacy of Antibiotic Prophylaxis for Hysteroscopy: A Meta-Analysis of Randomized Trials.

OBJECTIVE: To assess the efficacy and side effects of antibiotic prophylaxis compared with placebo or no treatment in women undergoing hysteroscopy. DATA SOURCES: A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through December 31, 2018. METHODS OF STUDY SELECTION: The search included a combination of the following terms: "hysteroscopy," "endoscopic surgery," "antibiotic prophylaxis." The following outcomes were selected: postoperative fever, infection rate, pelvic inflammatory disease (PID) and abscess occurrence, postoperative antibiotic requirement, and side effects occurrence (lower abdominal pain, vomiting, diarrhea, anaphylactic reaction). A random-effects model was used at meta-analysis. Study quality and bias risk were assessed with the Cochrane tool. TABULATION, INTEGRATION, AND RESULTS: Five randomized controlled trials comparing efficacy of antibiotic prophylaxis with placebo or no treatment were included in the meta-analysis. Overall, pooled incidence of events was very low in both groups (fever, 3.79% vs 1.8%; overall infection, .52% vs .58%; postoperative antibiotic therapy, 1.18% vs 1.32%; and lower abdominal pain, 12.46% vs 9.31%). Moreover, the incidence of serious infections requiring further actions (PID or abscess) appeared to be extremely low (.2% in pretreated women and none in control groups). No one trial individually or the pooled analysis showed a statistically significant benefit of antibiotics prophylaxis over placebo for the outcome considered. CONCLUSION: The use of antibiotics appears not to be beneficial to prevent infection after hysteroscopy; however, the lack of high-quality studies makes it difficult to draw firm conclusions. Considering the very low infection rate highlighted after hysteroscopic procedures, a difference will probably never be proven in a randomized trial. A larger population and program data to confirm these results are therefore warranted.

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

OBJECTIVE: To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. METHODS: We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. RESULTS: The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. CONCLUSIONS: Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

Management of Endometriomas.

Ovarian endometriomas affect 17 to 44% of women with endometriosis, and are often associated with pelvic pain and infertility. Treatment options include expectant management, medical and/or surgical treatment, and in vitro fertilization and embryo transfer (IVF-ET). The choice of treatment depends mostly on the associated symptoms. In most cases, surgery is the preferred choice, since endometriomas do not respond to medical treatment, which may only treat associated pain. In case of infertility, IVF-ET may be a suitable alternative to surgery, particularly when there is no associated pain. According to the best available scientific evidence, laparoscopic excision of the endometrioma wall should be considered the procedure of choice. Concerns have been raised as to the possibility that surgical excision may damage the ovarian reserve, but recent evidences demonstrate that part of the damage may be due to the presence of the endometrioma itself. Indication to surgical treatment should balance the possible risks of damaging the ovarian reserve with the advantages of surgery in terms of satisfactory pain relief rates and pregnancy rates, and of obtaining tissue specimen for ruling out the rare cases of unexpected ovarian malignancy. A score system to guide the clinician in the decision to perform or withhold surgery is presented.

Bulky mesonephric adenocarcinoma of the uterine cervix treated with neoadjuvant chemotherapy and radical surgery: report of the first case.

AIMS AND BACKGROUND: Malignant mesonephric adenocarcinoma of the uterine cervix is a rare occurrence with few cases described in the literature. Although surgery seems to be effective in the treatment of early-stage tumor, no cases describing outcomes of locally advanced stage are available. METHODS: We report the first case of a patient with International Federation of Obstetrics and Gynecologists stage IIB mesonephric adenocarcinoma undergoing neoadjuvant chemotherapy and radical surgery. CONCLUSIONS: Despite the inherent limitation of a single description of a case, our experience supports the utilization of neoadjuvant chemotherapy in patients with malignant mesonephric adenocarcinoma of the uterine cervix. Further prospective multi-institutional studies are needed.

Dealing naturally with stumbling blocks on highways and byways of TRAIL induced signaling.

In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside.

Ovarian cancer: interplay of vitamin D signaling and miRNA action.

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.

Complete remission after neoadjuvant chemotherapy of an advanced vulvar cancer patient: a case report.

Invasive vulvar cancer has an incidence of 1-2/100 000 women per year and squamous cell carcinoma accounts for approximately 85-90% of all vulvar cancers. Surgery has long been considered as the standard treatment, followed by chemotherapy in case of lymph node involvement. This approach is not only disfiguring, but also carries with it an operative mortality of up to 10%. Several studies have assessed the feasibility of radio-chemotherapy as definitive therapy and/or a neoadjuvant procedure. Nonetheless, combined radio-chemotherapy is associated with considerable toxicity. This study reports our experience with an unconventional schedule of neoadjuvant chemotherapy (topotecan and cisplatin) without radiotherapy in a patient with locally advanced vulvar cancer (International Federation of Gynecology and Obstetrics stage IIIA) who experienced complete clinical remission, followed by minimal surgical treatment.