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A letter to the editor is presented which is concerned with the use of calcitonin in the treatment of painful diabetic neuropathy.

Background: Colorectal cancer (CRC) is a leading cause of death in rural America. Rural populations are large and heterogeneous, yet patient-related drivers of inequities in CRC access are understudied. This study aimed to identify vulnerable rural populations at lower odds of undergoing elective CRC surgery., Methods: Evaluation of the Policy Map and United States Census Bureau identified factors associated with poor surgical access in the most populous states (by total rural population). To assess whether these identified factors were associated with reduced access to elective CRC surgery, the 2007 to 2020 National Inpatient Sample was used to evaluate 69,212 hospitalizations of rural patients undergoing CRC surgery. Rural was defined as counties with a population of <250,000. Multivariable logistic regression models assessed predictors of elective CRC surgery. Patient- and hospital-level factor interactions were specified a priori., Results: More than 72% of hospitalizations of rural patients were elective. Multivariate regression analysis demonstrated that older age, multimorbidity, Black race, Latino-Hispanic ethnicity, Medicaid insurance, and rural hospitals predicted lower odds of elective CRC surgery. On interaction analyses, high-risk patients were less likely to undergo elective CRC surgery in urban facilities relative to rural., Conclusion: In this large study of rural dwellers, ethnoracial minorities, elders, and Medicaid beneficiaries had profoundly less access to elective CRC surgery, especially when care was received in urban settings. Future studies should focus on exploring actionable social drivers of health in these rural populations. Findings underscore the need for multilevel interventions to enhance rural access to equitable and quality surgical cancer care., (Copyright © 2024. Published by Elsevier Inc.)

Aim: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers., Methods: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy., Results: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity., Conclusion: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation., (© 2023. The Author(s).)

Background and Objectives : Vulvovaginal infections pose significant health challenges for women, necessitating effective treatment approaches. This retrospective observational study aimed at investigating the efficacy of collagen-based vaginal ovules therapy, specifically Plurigin Ovules, in restoring cervical epithelialization and reducing inflammation in mycotic, viral, and bacterial cervico-vaginitis. Materials and Methods : A total of 398 women with cervico-vaginitis were included in the study, categorized into three groups: bacterial cervico-vaginitis (Group A), viral cervico-vaginitis (Group B), and fungal cervico-vaginitis (Group C). Participants received vaginal therapy with Plurigin Ovules for three months. Vaginal health parameters were assessed at baseline (T0) and after six months (T1) using various diagnostic tests and analyzed with appropriate statistical tests. Results : Significant improvement in cervico-vaginitis was observed in all three groups. At T1, 87.7% patients of Group A, 66.7% of Group B, and 71.5% of Group C achieved infection resolution (all p < 0.05). Positive colposcopy results decreased across all groups ( p < 0.001). Positive vaginal swabs and altered vaginal pH decreased in group A and C ( p < 0.001). Positive HPV tests decreased in Group B ( p < 0.001). Positive Pap tests and clinical examinations decreased significantly across all groups ( p < 0.001). The odds ratios were calculated to reveal the significant associations between these diagnostic outcomes. The therapy was well-tolerated, and no major adverse events were reported. Conclusion : Plurigin Ovules exhibited promising therapeutic outcomes in the three cervico-vaginitis conditions studied. Bacterial cervico-vaginitis showed the most significant improvement, followed by fungal and viral cervico-vaginitis. These findings emphasize the potential of Plurigin Ovules as an effective therapeutic option for cervico-vaginal inflammation and infection, highlighting its role in promoting re-epithelialization and reducing inflammatory processes in the cervix and vagina.

Background: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B 3 ) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear., Methods: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life., Results: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups., Conclusions: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.)., (Copyright © 2023 Massachusetts Medical Society.)

This cross-sectional study aimed to evaluate the prevalence of postpartum depression and the associated risk factors in a sample of Italian women at three months after delivery. Eighty women were screened by completing the Edinburgh Postnatal Depression Scale (EPDS). Women with a score ≥10 were evaluated as positive and other variables were detected through the administration of the Postpartum Depression Predictors Inventory.The prevalence of postpartum depression in the sample was 11.25% (EPDS score >10). A statistically significant relationship was found between the predisposition to postnatal depression and various risk factors such as prenatal depression, stressful life experiences marital problems. Furthermore, strong emotional and instrumental support from the partner and a good economic status can represent protective factors. It is essential to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account, and adequate screening programs are implemented.Impact Statement What is already known on this subject? Pregnancy can cause emotional stress for women with consequent development, in some cases, of mood disorders such as postpartum depression. What do the results of this study add? According to this study, women suffering from postpartum depression showed a significant tendency to anxiety and depression, low perceived support from the partner, and low socio-economic status. What are the implications of these findings for clinical practice and/or further research? It would be desirable to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account and adequate screening programs are implemented.

Purpose: Cancer-related cognitive impairment (CRCI) has been reported in non-central nervous system neoplasms survivors. The purpose of this study was to evaluate the perception of cognitive decrement in patients undergoing surgical and / or medical therapy for gynecological cancers., Methods: All women diagnosed with primary gynecological cancer and undergoing active medical treatment have been enrolled in a prospective study. Before starting treatment (T1) and 6 months after the end of treatment (T2), patients were interviewed to evaluate the effects of cancer treatment on perceived cognitive function (using FACT-Cog -version 3), on depression (using Beck Depression Inventory-II test) and on quality of life (using EORTC-QLQC-30). Age, education level, marital status, lifestyle, menopausal state at diagnosis, cancer type, cancer FIGO stage, treatment modality was also recorded. The differences between baseline and post-treatment results have been evaluated with Student's t test. The results have been stratified by the menopausal state at diagnosis, type of tumor (endometrial, cervical, ovarian, vulvar) disease stage and type of treatment (chemotherapy or radiotherapy)., Results: Seventy-three patients were included. A significant reduction in perceived cognitive impairments was demonstrated at T2 (CogPCI: 61.35 ± 13.83 vs 55.05 ± 16.56; p < 0.05). On the contrary, a significant improvement was shown in depression state (BDII: 21.14 ± 11.23 vs 12.82 ± 12.33, p < 0.005). The menopausal state at surgery, tumor site, stage and treatment modality seem to influence the variables analyzed., Conclusion: CRCI is a true risk also in gynecological cancer survivors. The cognitive impairment does not seem to be dependent on depression state after treatment or to a menopausal condition. Assessing cognitive decline in cancer survivorship is essential for ensuring the optimum quality of life and functioning.

Background: Research examining skin disease in heart and lung transplant recipients in Australia is limited. This study aims to determine the spectrum of skin diseases encountered in Australian heart and lung transplant recipients, their effect on quality of life, and potential risk factors for skin cancer., Methods: Ninety-four participants were recruited from an Australian heart and lung transplant centre between March and December 2016. The participants were asked to fill out a questionnaire which included the Dermatology Life Quality Index and were examined for malignant and non-malignant skin disease. The association of study variables with the presence of skin cancer and Dermatology Life Quality Index score were examined using logistic regression analysis., Results: A dermatological diagnosis was made in 82 patients (87%). Actinic keratosis was the most common diagnosis, affecting 50 participants (53%), followed by skin cancer (41; 44%) and warts (14; 15%). Other non-malignant skin diseases were less common. Risk factors associated with skin cancer on multivariate modelling included age at transplantation and a history of ≥5 post-transplant skin cancers. Skin disease had a negative effect on the quality of life of a minority of patients., Conclusion: Actinic keratosis and skin cancer are very frequent in Australian heart and lung transplant recipients and more common than non-malignant skin diseases. Routine dermatological surveillance at regular intervals is advised., (© 2020 S. Karger AG, Basel.)

Objective: Evaluate the effects of carboxy-methyl-beta-glucan on cervical epithelialization and on the vaginal microbiota in patients with HPV infection or low-grade cervical preneoplastic lesion (CIN 1)., Materials and Methods: Seven-hundred eighty-four women with positive HPV tests or diagnosed with CIN 1 were enrolled in a retrospective case-control study. All the recruited women performed, at baseline and after 6 months, Pap test, HPV test, evaluation of vaginal health according to the Amsel criteria, colposcopy, and punch biopsy. The study population was then divided into 2 groups in relation to the therapy performed during the follow-up period. Group A performed treatment with vaginal gel based on carboxy-methyl-beta-glucan (1 application/day for 20 days per month for 3 months). Group B was the control group., Results: The patients of group A had a significant improvement in the ectopia pattern and a greater number of cases with metaplasia in the maturation phase with a significant increase in Lugol uptake. In the experimental group, a significant improvement in the pH indices, a negative Swift test and a resolution of the leucorrhoea were observed. A negative result of the 37.1% Pap test and the 39.9% HPV test (vs. 15.2% and 16.5%, respectively) were demonstrated in the treatment group with respect to the control group. A negativization of the colposcopic pictures was observed with a reduction in the amount of CIN 1 found higher in the treatment group., Conclusions: Vaginal therapy based on carboxy-methyl-beta-glucan has been able to improve overall vaginal health; this effect seemed to positively impact the risk of persistence and progression of CIN., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Giada Lavitola et al.)

Introduction: Colposcopy represents the second step of the diagnostic approach of cervical intraepithelial lesions. Limits of colposcopy in studying cervix are essentially related to cervical anatomy. Nowadays, endocervical courettage is the standard technique to examine endocervix. Endocervicoscopy is a new imaging technique for the diagnostic work-up of endocervix in patients with cervical intraepithelial neoplasia (CIN)., Objective: To evaluate endocervicoscopy accuracy to identify and grade cervical intraepithelial lesion in comparison to other procedures employed into the diagnostic workup of cervical pathology., Methods: A total of 634 women who performed colposcopy, endocervicoscopy and cytological or histological sampling were included in a retrospective study. The agreement between the endocervicoscopic and the colposcopic impressions, minor and major changes, and between these imaging techniques and histological diagnosis was assessed for the entire cohort. χ2 test and k statistic were used in the statistical analysis., Results: The extension of the lesion resulted significantly greater at endocervicoscopy than at colposcopy. We showed a statistically significant association between colposcopy and endocervicoscopy findings. Overall, the correlation of minor or major findings between colposcopy and endocervicoscopy was statistically significant with a p value for all parameters <0.0001. Description of mosaic/punctuation, cuffed crypt (gland) openings and ridge sign showed a high k value (k = 0.68 [95% CI 0.64-0.73], k = 0.80 [95% CI 0.75-0.85], k = 0.78 [95% CI 0.64-0.90], respectively). The sensitivity (70.1%) and the specificity (77.0%) of endocervicoscopy for all CIN lesions were lower than colposcopy., Conclusion: Endocervicoscopy turned out to be a good method to identify and grade CIN lesions in a subset of patients where colposcopy was not satisfactory. It allowed us to overcome one of the limits of colposcopy in the evaluation of the squamo-columnar junction and to establish the real extension of the lesion into cervical cancer., (© 2020 S. Karger AG, Basel.)

Importance: There is limited research examining the incidence of nonmelanoma skin cancer (NMSC) in heart and lung transplant recipients in Australia., Objective: To determine the frequency of and risk factors for NMSC in a cohort of Australian heart and lung transplant recipients., Design, Setting, and Participants: A retrospective cohort study was conducted at an Australian tertiary center where heart and lung transplants are performed between March 21 and December 14, 2016. A consecutive sample of 94 patients who underwent heart and/or lung transplant presenting for outpatient dermatologic review were evaluated. Data analysis was conducted between April 18 and October 30, 2017., Exposures: Risk factors examined for association with posttransplantation NMSC included age at the time of transplantation, sex, skin phenotype, UV radiation exposure, history of allograft rejection, history of smoking, history of skin cancer prior to transplant, and transplant type., Main Outcomes and Measures: The primary outcome measure was the occurrence of posttransplantation NMSC. The probabilities of developing NMSC in general, and squamous cell carcinoma and basal cell carcinoma specifically, were separately summarized based on Kaplan-Meier analysis. Association of risk factors with development of NMSC was examined using univariable and multivariable Cox proportional hazards regression analysis., Results: Of the 94 study participants, 58 (62%) were men; median age at transplantation was 51.9 years (range, 15.1-69.7 years). There were 801 posttransplantation skin cancers in 57 (61%) of the patients who underwent heart and/or lung transplant. The probabilities for NMSC were 41% (95% CI, 31%-53%) at 5 years and 67% (95% CI, 55%-78%) at 10 years; for basal cell carcinoma, 27% (95% CI, 18%-38%) at 5 years and 53% (95% CI, 40%-67%) at 10 years; and for squamous cell carcinoma, 33% (95% CI, 24%-45%) at 5 years and 62% (95% CI, 50%-74%) at 10 years. On multivariable analysis, older age at transplantation was associated with the development of NMSC (hazard ratio [HR], 1.07/1 year; 95% CI, 1.04-1.10; P < .001) and history of pretransplant skin cancer was associated with development of basal cell carcinoma (HR, 4.56; 95% CI, 1.67-12.42; P = .003). A Fitzpatrick skin type III to VI was associated with a decreased risk of NMSC (HR, 0.42; 95% CI, 0.24-0.74; P = .003). Sex, transplanted organ, UV radiation exposure, and history of allograft rejection were not associated with an increased risk of skin cancer., Conclusions and Relevance: In this study of Australian heart and lung transplant recipients, there was a probable high frequency of NMSC. Routine dermatologic surveillance at frequent intervals is advised for similar populations.

Introduction. HPV infection is a highly infectious disease; about 65% of partners of individuals with genital warts will develop genital condylomatosis. Only in 20-30% it regresses spontaneously and relapse rates range deeply (9-80%). Echinacea extracts possess antiviral and immunomodulator activities. The aim of this study was to evaluate the efficacy of the therapy, using a formulation based on HPVADL18® (on dry extracts of 200 mg Echinacea Purpurea (EP) roots plus E. Angustifolia (EA)), on the posttreatment relapse incidence of genital condylomatosis. Materials and Methods. It is a prospective single-arm study. Patients with a satisfactory and positive vulvoscopy, colposcopy, or peniscopy for genital condylomatosis were divided into two random groups and subjected to destructive therapy with Co2 Laser. Group A (N=64) immediately after the laser therapy started a 4-month treatment with oral HPVADL18®; Group B (N=61) did not undergo any additional therapy. Patients were subjected to a follow-up after 1, 6, and 12 months. Differences in relapse incidence between the two groups during follow-up controls were evaluated by χ 2-test; the groups were stratified by age, gender, and condylomatosis extension degree. Results and Discussion. Gender, age, and condyloma lesions' extension degree showed no statistically significant differences between the two trial groups. The relapse incidence differs statistically between the two studied groups and progressively decreases during the 12 months after treatment in both groups. Statistically significant reduction of relapse rates has been shown in Group A in patients over 25 years old. This difference is significant for both men and women. The relapse incidence is superior in case of extended condylomatosis. Conclusions. In conclusion, the presence of a latent infection causes condylomatosis relapse; in order to reduce the relapse risk an induction of a protective immune response seems to be essential to allow rapid viral clearance from genital areas surrounding lesion and treatment zones. Echinacea promotes this process. EP and EA dry root extracts seem to be a valid adjuvant therapy in reducing relapse incidence of lesions in patients treated for genital condylomatosis.

[This corrects the article DOI: 10.18632/oncotarget.25049.].

Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need. A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients. Caspase-4 quantification was also assessed in the lung tumor mass of 98 paired NSCLC patients compared to 10 non-tumor lung tissues (i.e. tuberculosis). Circulating caspase-4 was detected in both healthy and NSCLC patients; however at different range values: 2.603-3.372 ng/ml for NSCLC patients (95% CI) compared to 0.3994-0.6219 ng/ml for healthy subjects (95% CI). The sensitivity of the test ranged from 97.07% to 100%; the specificity was 88.1% with a positive predictive value of 92.54%, accuracy of 95.19% and AUC of 0.971. Smokers (95% CI, 0.3947-0.6197 ng/ml) and COPD patients (95% CI, 1.703-2.995 ng/ml) showed intermediate values of circulating caspase-4. Tissue levels of caspase-4 in the tumor mass showed that 72 (72.7%) out of 99 patients were positive. More importantly, higher levels (cut-off value = 0.307 ng/ml) of caspase-4 in the tumor mass were associated to reduced overall survival (median 0.92 years) compared to NSCLC patients with lower levels (median 3.02 years). We report for the first time caspase-4 as a novel diagnostic and prognostic biomarker, opening new therapeutic perspectives for NSCLC patients., Competing Interests: CONFLICTS OF INTEREST MT, RPA, AP, AS and RS are co-founders of ImmunePharma S.r.l., academic spin-off at the University of Salerno, Department of Pharmacy (DIFARMA). ImmunePharma S.r.l. counts on the following patents: RM2014A000080 and PCT/IB2015/051262. The other authors have no conflicts of interest to disclose.

Purpose: The aim of this study was to evaluate the effects of antiviral therapy on liver stiffness measurement (LSM)., Methods: Two hundred HBV patients were enrolled from four hospital centers in southern Italy; median age was 50.7 (25-75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine patients were treated with nucleos(t)ide analogs, while 51 patients were untreated. The cutoffs of the LSM, related to the fibrosis stages, were as follows: non-advanced fibrosis ≤ 8.1 kPa and advanced fibrosis ≥ 8.2 Kpa., Results: At baseline, the median value of LSM was 14.1 kPa for advanced fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24 months from the start of therapy. The treated patients (68% received Entecavir and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p < 0.001) in non-advanced fibrosis and of 6 kPa (p < 0.001) in advanced fibrosis/cirrhosis. In the patients not undergoing antiviral treatment, no statistically significant change of the LSM was observed (p = 0.26). A logistic binary regression model showed that the only independent factor associated with a significant change in the LSM was the liver stiffness value at baseline (odd ratio 2.855; 95% CI 1.456-5.788; (p = 0.007)., Conclusion: Long-term antiviral therapy induced a significant reduction of liver stiffness measurement and this result may be related to the reduction of liver fibrosis.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification., In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities. The knowledge of key histologic and molecular characteristics may help pathologists in achieving a correct diagnosis thus leading to an adequate therapeutic approach., (Copyright © 2018 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy. The Rotterdam criteria indicate four distinct phenotypes. In phenotypes with the typical ovarian morphology (ovarian volume ≥10 ml) the sensibility to clomiphene citrate (CC) ovulation therapy was demonstrated inversely proportional to the ovarian volume. In this retrospective study we evaluated the influence of ovarian volume on the success rate of CC ovulation induction in women with anovulatory phenotype 2 characterized only by the presence of hyperandrogenism and anovulation (ANOV + HA). Statistical analysis was conducted by stratifying patients both on the basis of CC dose (Group 1: n = 37, 50 mg; Group 2: n = 9, 100 mg; and Group 3: n = 12, 150 mg) and on the basis of response to therapy. Eighty women were evaluated but overall only 58 women (72.5%) reached ovulation. In the phenotype studied, we didn't find any correlations between ovarian volume and the chance of ovulation with the gradient increase in CC; furthermore, ovarian volume was comparable in CC responders and non-responders. Our study has shown that in the phenotype 2 examined, ovarian volume did not have any predictive value of the dosage required to induce ovulation. The significance of this result is discussed.

Aim of our study was to assess the ovulation rate, with mid-luteal progesterone level and ultrasound follicles monitoring, in PCOS CC-resistant patients undergone transvaginal hydrolaparoscopy ovarian drilling. A prospective observational study was carried out in 123 PCOS, infertile, CC-resistant patients who undergone THL ovarian drilling. Each woman was evaluated by hormonal measurement, and ultrasound evaluation during 6 months follow-up. Progesterone serum levels were assessed on days 20-24 of the cycle after surgical treatment. Pg levels >3 ng/mL were considered as ovulation. Ovulation frequency and the highest mean follicular diameters during the monitoring were recorded. 117 patients complete the study, since six patients were lost to follow-up. Mean follicular diameter during ovulation monitoring was 16.37 mm. Ovulation rate at the follow up was 64.1% one month after treatment, 79.5% after three months and 82.9% after six months. 28 patients conceived during follow-up period. Pregnancy rate was 70.1%. Our study has shown that THL ovarian drilling improves ovulation and pregnancy rate in women with CC-resistant PCOS. We believe that this approach should be offered as second-line therapy at all PCOS CC-resistant women who fail the medical methods of ovulation induction.

Sonic Hedgehog (Shh) pathway regulates embryonic development of different organs including the thyroid gland. The aberrant activation of Shh signaling has been found in several types of cancer and according to recent evidences it represents an important regulator of tumor-stroma interaction. In this study, we have analyzed expression, activation and molecular mechanisms regulating the Shh pathway and its involvement in the modulation of tumor stroma interaction in anaplastic thyroid cancer (ATC) cells. Our results suggest that Shh signaling undergoes a dual mechanism of induction in ATC cells: 1) a basal non-canonical Smo-dependent activation of Gli transcription factor that is partly caused by interaction with the RAS/BRAF/MEK oncogenic pathway and is characterized by the absence of Shh ligand expression in thyroid cancer cells and 2) a paracrine response of cancer cells to Shh ligand secreted by tumor stroma (fibroblasts and mesenchymal stromal cells, MSCs) inducing cancer cell migration and in vitro tumorigenesis. Our data therefore suggest Shh as a potential novel therapeutic target in aggressive thyroid cancers., Competing Interests: CONFLICTS OF INTEREST None.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in gynecology. In PCOS patients vascularization parameters are altered. Transvaginal hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS patients. In this study, we assessed the effect of ovarian drilling using THL on ovarian volume (OV) and vascularization index (VI) using 3D power Doppler ultrasonography in CC-resistant PCOS patients. A case-control study on 123 CC-resistant PCOS women who underwent THL ovarian drilling was performed. Patients underwent 3D ultrasound and power Doppler to measure VI, flow index (FI), vascularization flow index (VFI) and to evaluate OV before and after the procedure, at six months, and on the early follicular phase of the menstrual cycle. After THL ovarian drilling, OV and power Doppler flow indices were significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72 cm 3 , p < 0.01; VI: 2.50 versus 4.81, p < 0.01; VFI: 1.10 versus 2.16, p < 0.01; FI: 32.05 versus 35.37, p < 0.01). In conclusion, THL ovarian drilling seems to reduce OV and 3D power Doppler indices, and could therefore be a viable alternative to LOD in PCOS patients resistant to medical therapy.

Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease., Competing Interests: Conflicts of Interest: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Background: Cervical cancer (CC) treatments impact quality of life (QoL) and sexual function (SF) of survivors. Treatment options to reduce sexual dysfunction are limited. The aim of this study was to assess the effectiveness of ospemifene in CC survivors with clinical signs and symptoms of vulvovaginal atrophy (VVA) focusing on their QoL and SF., Materials and Methods: Fifty-two patients with previous diagnosis of stage I-IIa CC suffering from VVA and treated with ospemifene were enrolled into a single arm prospective study. Patient underwent 6 months of therapy. At baseline and after 6 months all subjects performed Vaginal Health Index (VHI). The SF and QoL were measured by The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) and the Cervical Cancer Module (CXC-24)., Results: After treatment a significant improvement of each parameter of VHI has been demonstrated. Global health status and emotional and social functioning scores improved significantly. On the contrary, general symptoms scales did not show significant difference from baseline data. Sexual activity, sexual vaginal functioning, body image, and sexual enjoyment scores increased significantly., Conclusion: Ospemifene seems to be effective in decreasing the VVA symptoms in CC survivors.

Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutic target in non-small cell lung cancer. To date, few reports have been provided related to ALK-rearranged late recurrence and sensitivity to the treatment with specific ALK inhibitors. We report a case of a 35-year-old man who underwent a right lower lobe lobectomy for lung adenocarcinoma, and treated with the platinum-based chemotherapy regimen. After 10 healthy years, he developed a lung nodule in the same site as the previous. Cytopathologic diagnosis was lung adenocarcinoma. Furthermore, the pulmonary nodule was considered a late recurrence in relation to the lymph node involvement, the same histotype and the site, ALK fluorescence in situ hybridization test and epidermal growth factor receptor analysis were performed on the formalin-fixed paraffin-embedded specimens of the previous resected tumor, because of inadequacity cytologic sample. Being positive for ALK rearrangement, the patient was treated with crizotinib with a good response. To the best of our knowledge, it is the first case of a late relapse of ALK-positive lung adenocarcinoma sensitive to crizotinib in the literature.

Purpose: DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer., Methods: Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method., Results: The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies., Conclusion: dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)

Carcinoids are tumors that originate from diffuse neuroendocrine system cells (APUD cells) and represent 1-2% of all pulmonary tumors. Although surgical resection remains the mainstay of treatment, bronchoscopic radical resection of typical carcinoids in selected cases exhibiting endoluminal growth and small implant base has also been explored. Bronchoscopic removal of endobronchial lesions may also reduce the risk of post-obstructive infections and improve pulmonary function, allowing the patient to undergo surgery in better clinical and respiratory state. In this paper we have evaluated the impact on surgical planning and outcome of preoperative bronchoscopic resection in treatment of endobronchial typical carcinoids. Our observations further support the role of bronchoscopic treatment before surgery in endobronchial typical carcinoids., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

In this report we describe a case of pulmonary epithelioid hemangioendothelioma (PEH) in a young woman. The neoplasm manifested with dry cough, chest pain, finger clubbing, and multiple bilateral pulmonary nodules on chest x-ray and computed tomographic (CT) scan. She underwent thoracoscopy, and the histological features of the lung biopsies were initially interpreted as consistent with a not-well-defined interstitial lung disease. Our patient was clinically and radiologically stable over a period of four years, after which the disease progressed to involve not only the lung but also mediastinal lymph nodes, liver and bone. Fiberoptic bronchoscopy showed subtotal occlusion of the right middle and lower lobe bronchi. The histologic examination of bronchial biopsies revealed a poorly differentiated neoplasm immunohistochemically positive for vimentin and vascular markers CD31, CD34 and Factor VIII. A diagnosis of malignant hemangioendothelioma was made. Positron emission tomography (PET) is more sensitive than CT scan and bone scintigraphy in detecting PEH metastases. Furthermore, 18-fluorodeoxyglucose (FDG) uptake seems to be related to the grade of malignancy of PEH lesions. Therefore, we suggest that FDG-PET should be included in the staging system and follow-up of PEH.

Objectives: To compare surgical outcomes of different types of intracorporeal sutures for laparoscopic posterior myomectomy, by a prospective randomized study., Study Design: Prospective randomized study on 47 patients with single posterior intramural myoma (4-7cm in diameter) undergoing laparoscopic myomectomy. The patients enrolled were divided into two groups, one operated using conventional suture in double strand, and the other with bidirectional barbed suture Stratafix. The main outcome measures were suturing time, peri-operative variables, and post-operative adhesions in both groups., Results: The mean operative time was shorter with the Stratafix™ than with the conventional suture (66.3±8.2 vs. 73±8min; p=0.005). Suturing time was significantly shorter in the Stratafix™ than in the control group (8.8±2.4 vs. 15.5±2.8min; p=0.001). Intraoperative bleeding was significantly less in the Stratafix group (p=0.0012). Conversely, there was no statistically significant difference for postoperative adhesions between the two groups (26.7% vs. 21.4% p=0.5)., Conclusions: The use of barbed suture may reduce operative time, suturing time, and blood loss. No difference in post operative adhesions was found., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The main objective of our study was to evaluate the colposcopist ability to correctly identify the worst area of a cervical lesion where biopsy should be performed; the secondary objective was to investigate the influence of the colposcopist skill in grading cervical preneoplastic lesions., Methods: 296 patients referred for colposcopy were enrolled in a prospective study. All patients were randomized in two groups: in the first group, "senior group", the colposcopy was performed by an experienced colposcopist; in the second group, "junior group", the colposcopy was performed by a less experienced colposcopist. A detailed colposcopic description, including a grading of the lesion, was completed for each case. During the colposcopic exam patients underwent two direct biopsies; each biopsy was labeled with letter A (suspicious area with most severe grade) or B (suspicious area with less severe grade) according to the judgment of the colposcopist. An experienced pathologist reanalyzed the histological slides, after routine diagnosis., Results: The senior group identify the worst area of the cervical lesion in statistical significant higher rates than junior group. Specimen A resulted representative of the higher-grade lesion (A > B) in 73.7 % (N = 28) in senior group and in 48.4 % (N = 15) in junior group; while in 26.3 % (N = 10) the higher-grade lesion corresponded to specimen B (A < B) in senior group and in 51.6 % (N = 16) in junior group (p < .05)., Conclusion: The ability of a colposcopist in grading cervical lesion depends on his experience.