Are biomarkers expression and clinical-pathological factors predictive markers of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer?

INTRODUCTION: To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. MATERIALS AND METHODS: This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. RESULTS: Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. CONCLUSION: Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Hysterectomy for Non-Prolapsed Uterus in Elderly Patients: Predictors of Prolonged Hospital Stay.

OBJECTIVE: The objective of this study was to investigate surgical outcomes and complications of hysterectomy for benign conditions other than prolapse in elderly patients and to define predictors of prolonged hospitalization. DESIGN: Retrospective analysis of prospectively collected data. SETTING: This study was conducted in an academic research center. PATIENTS: We utilized our institution surgical database to identify patients aged 60 years or more ("elderly") who underwent hysterectomy for benign conditions other than pelvic organ prolapse during a 20-year period (January 2000-December 2019). METHODS: Length of stay (LOS) of more than 2 days (90th percentile of LOS) was defined as prolonged hospitalization. Patient demographics, comorbid conditions, and surgical approach (vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), and abdominal hysterectomy (AH)) were identified. Patients treated via LH or VH were also grouped as minimally invasive surgery (MIS). Multivariable logistic regression was used to identify factors associated with prolonged LOS. RESULTS: Overall, 334 patients were included in this study, 262 (78.4%) of whom underwent LH, 42 (12.6%) VH, and 30 (9.0%) AH. Median LOS was 2 days (1-8), and 63 (18.8%) patients required prolonged LOS. Compared to AH, median hospital stay was shorter in MIS group (2 days vs. 3 days, p < 0.001). No admission variables were associated with prolonged LOS. The only independent predictors of prolonged LOS were AH (odds ratio 24.82, 95% CI 4.84-127.16) and operative time (odds ratio for 30 mins increased 11.34, 95% CI 1.63-78.78). Compared to those who underwent VH, patients having LH had a higher rate of concomitant salpingo-oophorectomy (96.6% vs. 61.9%, p < 0.001). LIMITATIONS: Retrospective single-center study design, number of patients with prolonged hospitalization, and the setting (tertiary minimally invasive gynecology referral center), which might have reduced the generalizability of our results are the limitations of this study. CONCLUSIONS: The abdominal route of hysterectomy was found as the main driver of prolonged hospitalization, reinforcing the benefits of MIS for benign hysterectomy in elderly patients with non-prolapsed uteri; the higher chance of performing concomitant salpingo-oophorectomy supports the laparoscopic approach as the first option for these patients.

Prevalence of antibodies to selected viral and bacterial pathogens in wild boar (Sus scrofa) in Campania Region, Italy.

Serum samples were collected from wild boars (Sus scrofa) harvested during the 2005-2006 hunting season in Campania, southern Italy. Samples were tested for antibodies to Leptospira interrogan, Brucella spp., Salmonella spp., Aujeszky disease virus (ADV), porcine reproductive and respiratory stress syndrome virus (PRRSV), porcine parvovirus (PPV), classical swine fever virus (CSFV), and swine vesicular disease virus (SVDV). Of the 342 serum samples tested, 15 (4.4%) were seropositive to Brucella spp., nine (2.6%) were seropositive to L. interrogans, 66 (19.3%) were seropositive for Salmonella spp., 105 (30.7%) were seropositive for ADV, 27 (7.9%) were seropositive for PPV, and 129 (37.7%) were seropositive for PRRSV. All sera tested seronegative for SVDV and CSFV antibodies. These results, recorded for the first time in Campania, support the hypothesis that wild boar are reservoirs of certain infectious agents, but some infections in wild boars originate from their domestic counterparts.

Bid cleavage, cytochrome c release and caspase activation in canine coronavirus-induced apoptosis.

A previous study demonstrated that infection of a canine fibrosarcoma cell line (A-72 cells) by canine coronavirus (CCoV) resulted in apoptosis (Ruggieri et al., 2007). In this study, we investigated the cell death processes during infection and the underlying mechanisms. We found that CCoV-II triggers apoptosis in A-72 cells by activating initiator (caspase-8 and -9) and executioner (caspase-3 and -6) caspases. The proteolytic cleavage of poly(ADP-ribose) polymerases (PARPs) confirmed the activation of executioner caspases. Furthermore, CCoV-II infection resulted in truncated bid (tbid) translocation from the cytosolic to the mitochondrial fraction, the cytochrome c release from mitochondria, and alterations in the pro- and anti-apoptotic proteins of bcl-2 family. Our data indicated that, in this experimental model, both intrinsic and extrinsic pathways are involved. In addition, we demonstrated that the inhibition of apoptosis by caspase inhibitors did not affect CCoV replication, suggesting that apoptosis does not play a role in facilitating viral release.

Shedding of Brucella abortus rough mutant strain RB51 in milk of water buffalo (Bubalus bubalis).

The objective of this study was to determine if Brucella abortus rough mutant strain RB51 (SRB51) is eliminated in buffalo milk. Thirty Brucella-free female buffaloes were used in this study: ten 4-5 years old were inoculated with the triple of the recommended calfhood dose of SRB51 by subcutaneous route, ten 2-3 years old at the first lactation were previously vaccinated twice as calves with triple the recommended calf dose of RB51, while five 4-5 years old and five 2-3 years old not vaccinated Brucella-free female buffaloes served as controls. Milk samples were taken aseptically on a daily basis for the first 30 days and weekly for the second and third months. The samples were inoculated on selective media for isolation of SRB51 and incubated for 11 days. Moreover, PCR analysis was also performed directly on milk samples. SRB51 was isolated from milk samples only during the first week post-vaccination while RB51 DNA was detected during the first week till the fourth week post-vaccination only in water buffaloes vaccinated as adults. The identification of Brucella RB51 in milk samples, strongly suggests that this Brucella vaccine could be excreted in milk of buffalo cows vaccinated as adults, while our data demonstrate that the vaccine is safe for use in buffaloes vaccinated as calves in which it was not excreted in milk.