Pancreatic neuroendocrine tumor progression and resistance to everolimus: the crucial role of NF-kB and STAT3 interplay.

PURPOSE: The finding of mTOR overactivation in patients affected by pancreatic neuroendocrine tumors (Pa-NETs) led to their treatment with the mTOR inhibitor everolimus. Unfortunately, the efficacy of everolimus is restricted by the occurrence of resistance. The mechanisms leading to Pa-NETs' progression and resistance are not well understood. Notably, chronic inflammation is implicated in NET development. NF-kB is involved in inflammation and drug resistance mechanisms through the activation of several mediators, including STAT3. In this respect, NF-κB and STAT3 interaction is implicated in the crosstalk between inflammatory and tumor cells. METHODS: We investigated the expression of NF-kB in different Pa-NETs by RT-qPCR and immunohistochemistry. Then, we studied the role of NF-κB and STAT3 interplay in QGP-1 cells. Subsequently, we assessed the impact of NF-κB and STAT3 inhibitors in QGP-1 cell proliferation and spheroids growth. Finally, we evaluated the implication of the NF-kB pathway in everolimus-resistant Pa-NET cells. RESULTS: We found that the increased NF-kB expression correlates  with a higher grade in Pa-NETs. The activation of the STAT3 pathway induced by TNFα is mediated by NF-kB p65. NF-kB p65 and STAT3 inhibitors decrease QGP-1 viability, spheroids growth, and Pa-NETs cell proliferation. These effects are maintained in everolimus-resistant QGP-1R cells. Interestingly, we found that NF-kB, STAT3, IL-8, and SOCS3 are overexpressed in QGP-1R compared to QGP-1. CONCLUSION: Since the NF-kB pathway is implicated in Pa-NETs' progression and resistance to everolimus, these data could explain the potential use of NF-kB as a novel therapeutic target in Pa-NET patients.

Primary cutaneous interdigitating dendritic cell sarcoma (IDCS): Report of a new case and literature review.

Interdigitating dendritic cell sarcoma is a very rare entity in the spectrum of histiocytic and dendritic cell neoplasms that mostly occurs in lymph nodes, generally presenting as solitary lymphadenopathy, but may affect every organ. Among extra nodal sites, cutaneous interdigitating dendritic cell sarcoma is exceedingly rare; to date, only 9 cases have been described in English literature. The mean age at diagnosis was 60 years, with a male-female ratio of 1,5 to 1; clinically, two different modalities of skin presentation have been reported: solitary, represented by a single red-brownish nodular lesion, or diffuse, characterized by multiple nodular lesions in one or more body districts. The extreme rarity of this sarcoma and its morphological similarity to other poorly differentiated tumors may lead to a delay in diagnosis; in particular, cutaneous localization may be difficult to differentiate from follicular dendritic cell sarcoma, Langerhans cell sarcoma, poorly differentiated squamous cell carcinoma and more generally sarcomatoid carcinoma, atypical fibroxanthoma, malignant melanoma and several sarcomas. Immunohistochemistry plays an important role in identifying this rare entity and formulating a correct histological diagnosis, fundamental requirement for choosing the best therapeutic approach. We report herein a further case of an 81-year-old Caucasian woman who presented to the Dermatology Department to remove an asymptomatic skin papule in the left temporal region, clinically diagnosed as dermatofibroma. The overall pathological and immunohistochemical features supported the diagnosis of a malignant dendritic cell tumor, consistent of interdigitating dendritic cell sarcoma.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

Surgical morbidity of total laparoscopic hysterectomy for benign disease: Predictors of major postoperative complications.

OBJECTIVE: To estimate rate of perioperative complications and to define risk factors of 30-day major (Clavien-Dindo ≥ 2) postoperative complications of total laparoscopic hysterectomy (TLH) for benign disease. STUDY DESIGN: An uncontrolled single-center single-arm retrospective study. Data of consecutive patients who have undergone TLH for pathologically confirmed benign disease between January 2000 and December 2019 have been analyzed. Perioperative surgical outcomes, occurrence of postoperative complications, readmissions, and reoperations within 30 days from surgery were registered. Univariate and multivariable analyses were performed to determine the factors associated with major (Clavien-Dindo ≥ 2) postoperative complications. RESULTS: Over the study period 3090 patients were included in the study. Conversion to open surgery occurred in 54 (1.7%) cases. Mean operative time for TLH was 87.7 (±1.7) minutes while mean estimated blood loss was 119.5 (+7.4) mL. Overall, postoperative complications were registered in 430 (13.9%) patients, and major events were observed in 208 (6.7%) of the cases. Same-hospital readmissions and reoperations within 30-day from surgery occurred in 78 (2.5%) and 28 (0.9%) patients, respectively. At multivariable analysis, endometriosis (odds ratio: 3.51, 95%CI:1.54-8.30, p = 0.02), the need for conversion to open surgery (odds ratio: 1.26, 98%CI:1.03-12.64, p < 0.001), and the occurrence of any intraoperative complication (odds ratio: 3.10, 95%CI: 1.45-21.61, p < 0.001) were found as independent risk factors for major postoperative complications. CONCLUSIONS: Total hysterectomy performed via laparoscopy is associated with acceptable major postoperative complications rate. A huge effort should be made to minimize the occurrence of intraoperative complications and the need for conversion to open surgery. Patients undergoing TLH for endometriosis should be counselled about the increased risk of major postoperative events.

The Large Uterus Classification System: a prospective observational study.

OBJECTIVE: To investigate the Large Uterus Classification System (LUCS) ability to predict surgical outcomes and complications in total laparoscopic hysterectomies (TLHs) for large uteri. DESIGN: Prospective observational study. SETTING: Two referral centres. POPULATION OR SAMPLE: Three hundred and ninety-two women who underwent TLH for a large uterus (uterine fundus at or over the transverse umbilical line). METHODS: Between 2004 and 2019, the intraoperative LUCS was estimated in all patients. The LUCS considers the uterine and adnexal vascular pedicles displacement. Type 1 is without vascular pedicles displacement. Type 2 has the cephalad displacement of adnexal vascular pedicles. The uterine vessels displacement regardless of adnexal pedicles defines Type 3. MAIN OUTCOME MEASURES: Patients' characteristics with perioperative outcomes were prospectively collected and compared between the three types of large uteri. RESULTS: Two hundred and fifty-one (64%), 82 (20.9%) and 59 (15.1%) women had Type 1, Type 2 and Type 3 uteri, respectively. Women with Type 1 uteri had a lower uterine weight, shorter operative time, less blood loss and lower complication rates than women with Types 2 and 3. The conversion rate to laparotomy in Type 1 was similar to that in Type 2 (odds ratio [OR] 0.98; 95% CI 0.32-3.56) but lower than Type 3 (OR 0.35; 95% CI 0.14-0.97); in Type 2 it was lower than Type 3, although without the conventional statistical significance (OR 0.36; 95% CI 0.13-1.13; P = 0.07). Multivariable analysis showed that the uterine Type (1 versus 2-3) was independently associated with the total complications rate (OR 2.00; 95% CI 1.09-3.68; P = 0.02). CONCLUSIONS: The LUCS appears associated with surgical outcomes and complications, potentially stratifying the surgical risk and guiding the surgical technique in TLHs for large uteri. TWEETABLE ABSTRACT: The Large Uterus Classification System may predict outcomes in total laparoscopic hysterectomy of large uteri.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients.

Merkel cell carcinoma is a rare (∼ 2000 cases/year in the USA) but aggressive neuroendocrine neoplasm of the skin. In 2008, the Merkel cell polyomavirus (MCPyV) was found to be clonally integrated in approximately 80% of Merkel cell carcinomas. The remaining 20% have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative Merkel cell carcinoma and the Merkel cell polyomavirus oncogenes that are required for virus-positive tumor growth are highly immunogenic. Indeed, antigen-specific T cells detected in patients are frequently "dysfunctional/exhausted," and the inhibitory ligand PD-L1 is often expressed by Merkel cell carcinoma cells. These data led to point our attention on the quantity and the quality of the immune response in Merkel cell carcinoma. Here, we found CD8+ lymphocytes are the only singly evaluated lymphocyte subclass that strongly influenced overall survival and disease-specific survival in Merkel cell carcinoma. In addition, we highlighted as Merkel cell polyomavirus is a strong prognostic factor and as it prompts a host immune response involving various lymphocyte subclasses (CD3, CD8, FoxP3, and PD-L1 positive) in MCC. For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

Robotic Single-Port Platform in General, Urologic, and Gynecologic Surgeries: A Systematic Review of the Literature and Meta-analysis.

BACKGROUND: Robotic platforms have recently acquired progressive importance in different surgical fields, such as urology, gynecology, and general surgery. Through the years, new surgical robots have become available as single-port robotic platform. The study is aimed to value the single-port robotic platform characteristics in different surgical specialties. METHODS: The terms "LESS" OR "single port" OR "single site" AND "robot" OR "robotic" were systematically used to search the PubMed and Scopus databases. A total of 57 studies were considered eligible for the present review. The articles included were divided according to the surgical field in which the study was conducted: General surgery (29 articles), Gynecology (18 articles), Urology (10 articles). RESULTS: Most part of the articles showed the feasibility of robotic single-port surgical procedures and described advantages in terms of cosmetic, hospital stay, and in some series even cost reduction. A meta-analysis was conducted, showing a significant increment of complications using RSP if compared with SLPS and a trend (P = 0.008) when RSP was compared with LESS. The comparison of different techniques in terms of conversion to laparotomy did not show any significant difference. CONCLUSION: Robotic single port potentially furnishes an important surgical and post-operatory improvement; however, some limits still prolong the surgical time and complication rate.

Total laparoscopic hysterectomy for enlarged uteri: factors associated with the rate of conversion to open surgery.

A hysterectomy for enlarged uteri is considered a challenge for gynaecologic surgeons, due to the limit of exposure to surgical spaces. Our objective is to investigate the different variables that may have an impact on the risk of conversion to open surgery. This is a retrospective cohort study consisting of 133 women who were submitted to surgery for uterine fibroids and who underwent total hysterectomy by laparoscopic approach attempt. The median uterus weight was 622 grams (range 301-3882) and the median maximum diameter of the bigger fibroid was 74 mm (range 33-148). We registered 13 (9.8%) cases of conversion to laparotomy. Minor and major post-operative complications were recorded in 4 (3%) and in 4 (3%) cases, respectively. After multivariable analysis, the surgeon's experience (OR: 0.24; 95% CI: 0.06-0.94, p = .027) and a maximum diameter of the biggest fibroid ≥10 cm (4.7; 1.39-15.87; p = .046), but not the uterus weight were associated with the risk of conversion to open surgery. IMPACT STATEMENT What is already known on this subject? Laparoscopic procedures for enlarged uteri are well described in literature; however, the only parameters that have been studied for the success of a laparoscopic procedure have been the uterus weight and the surgeon's experience. What do the results of this study add? This study aimed to value all the possible variables related to the successful of laparoscopic procedures; in fact, we investigated not only the uterine weight, but in our multivariate analysis, the position of the fibroids, the trocar's setting, etc. were analysed. What are the implications of these findings for clinical practice and/or further research? This study reported novel data about the feasibility of laparoscopic hysterectomy for enlarged uteri. In opposition to the literature, the uterine weight is not a predictive value for laparotomic conversion. Moreover, we discussed the possible reasons of our novel findings. It opens new perspective to create a predictive value of laparoscopic feasibility for the different types of enlarged uteri.

Technological innovation and personalized surgical treatment for early-stage endometrial cancer patients: A prospective multicenter Italian experience to evaluate the novel percutaneous approach.

OBJECTIVE: To investigate the safety, feasibility and oncological adequacy of the Percutaneous Surgical System - PSS in a consecutive series of low-risk endometrial cancer staging. STUDY DESIGN: From May 2015 to April 2017, we prospectively performed 30 consecutive percutaneous staging for low/intermediate risk endometrial cancer (FIGO stage IA G1-G2, IB G1-G2, IA G3). All patients were divided in two different groups on the basis of surgical procedure received: Group A included patients submitted to radical Class A hysterectomy and bilateral salpingo-oophorectomy; Group B concerned patients that received a lymph nodal assessment also. RESULTS: The time needed to install percutaneous instruments and suprapubic trocar was 4 min. (range 2-10). The recorded median operative time (OT) was 80 min. (range 65-120) for Gr.A and 143 min. (range 107-190) for Gr.B, in which the median time of lymph nodal assessment was 55 min. (range 20-76). The median time for hysterectomy was 60 min. (range 40-110) in all cases. Lymph nodal assessment was performed in 14 (46.6%) cases: 7 sentinel node mapping, 7 pelvic lymphadenectomy. No intraoperative complications or LPS/LPT conversions were recorded. Median discharge time was 2 days (range 1-4), 5 patients were discharged in 3rd post-op day, and only 1 patient was discharged in 4th day for fever. All patients conveyed high satisfaction with the cosmetic results. A progressive overall reduction of pain perception was observed at 24 h after surgery. Median follow-up was of 14 months (range 12-36), no recurrences have been detected. CONCLUSIONS: PSS seems to be a feasible approach for endometrial cancer staging. Larger experiences and prospective comparative studies are important to assess our assumptions and further investigate the real benefits of percutaneous surgical system.

Transvaginal contained tissue extraction after laparoscopic myomectomy: a cohort study.

OBJECTIVE: To describe the technique and report perioperative outcomes of transvaginal contained extraction of surgical specimens at laparoscopic myomectomy. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Two Italian referral centres for gynaecological minimally invasive surgery. POPULATION: Consecutive patients who underwent laparoscopic myomectomy. METHODS: Tissue extraction was accomplished following laparoscopic myomectomy in a specimen retrieval bag via a posterior colpotomy incision. If morcellation was necessary, this was performed extracorporeally, using a scalpel within the specimen retrieval pouch, whose edges were exteriorised through the vaginal introitus. MAIN OUTCOME MEASURES: Intra- and postoperative complications. RESULTS: A total of 316 women underwent transvaginal specimen retrieval with enclosed manual morcellation. The mean myomectomy specimen weight was 154 ± 128 g, and the mean operative time was 79 ± 26 minutes. No intraoperative complications occurred related to the specimen extraction or morcellation technique, or from rupture of the retrieval bag. Two (0.6%) women had a haemoperitoneum that spontaneously resolved and 16 (5.1%) had fever postoperatively. The final pathological diagnosis was benign in all cases. At the 30-day follow-up, no pelvic infection, vaginal dehiscence, or complaints of dyspareunia were recorded. CONCLUSIONS: Contained transvaginal extraction of fibroid specimens can be performed safely and efficiently in most women undergoing laparoscopic myomectomy. This technique represents a valuable minimally invasive alternative to intracorporeal morcellation. TWEETABLE ABSTRACT: Transvaginal contained morcellation at laparoscopic myomectomy is a valuable alternative to intracorporeal morcellation.

Neuroendocrine neoplasms of the head and neck and olfactory neuroblastoma. Diagnosis and classification.

Neuroendocrine neoplasms (NENs) of the head and neck are a rare group of heterogeneous epithelial neoplastic proliferations arising in virtually all of the different organs of this region, particularly in the nasal cavity, the paranasal sinuses, the nasopharynx, the larynx, the salivary glands, and the middle ear. They encompass a wide spectrum of entities ranging from very indolent neuroendocrine tumors to highly aggressive neuroendocrine carcinomas. They may represent a challenge for radiologists, oncologists, and pathologists and a correct diagnosis is crucial for the management of patients. The nomenclature and classification of cervicocephalic NENs is currently under debate and for this reason a different diagnostic terminology has been used over the years, creating confusions among clinicians and pathologists. Olfactory neuroblastoma is a rare neuroectodermal neoplasm arising in the nasal cavity showing some challenging diagnostic aspects. In this review we give an update of the more relevant criteria for diagnosing head and neck NENs and olfactory neuroblastomas focusing on the critical use of morphological parameters and immunohistochemical staining.

Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis.

We investigated whether endometrial cancer (EC) cells can express fibrinogen. Consecutive patients treated for EC were enrolled (cases). A control group of women who had hysterectomy for benign conditions was identified in a case:control ratio of 4:1. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the presence of fibrinogen and the mRNA of its three chains (α, ß, γ) in the tissue specimens from both cases and controls. Sixteen EC cases and 4 benign controls were included. Immunohistochemistry failed in one case of EC. In 12/15 (80%) cases versus 0 controls, a moderate-to-intense positivity for fibrinogen was observed (p = 0.09; OR: 32.1; 95%CI: 1.4-752.9). Six (37.5%) women among the cases versus 0 controls expressed RNA for at least one chain of fibrinogen (p = 0.25). All the cases (6/6, 100%) with positive RT-PCR had moderate-to-intense positive immunohistochemistry. Molecular and immunohistochemistry show that some cases of EC have the capability to express fibrinogen and the mRNA of at least one of its chains.

Mini-laparoscopic Sentinel Node Detection in Endometrial Cancer: Further Reducing Invasiveness for Patients with Early-Stage Disease.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy have been proposed as a safer and less morbid approach than full lymphadenectomy for patients with early endometrial cancer (EC), through either cervical or corporeal dye injection.1 (-) 4 The advantage of mini-laparoscopy is a further reduction in the overall surgical trauma for the patient. This video aims to show the feasibility of SLN biopsy using a 3-mm mini-laparoscopic approach. METHODS: A 56-year-old woman with grade 2 endometrioid EC underwent mini-laparoscopic pelvic SLN detection plus extrafascial total hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO). A two-sided superficial and deep cervical injection of indocyanine green (2 mL diluted to 1.25 mg/mL) was used for inoculation before the procedure. A 5.8-mm 0° optical camera with a near-infrared high-intensity light source for detection of fluorescence imaging was inserted through the umbilicus. Two ancillary 3-mm trocars were inserted suprapubically. The procedure was accomplished using only 3-mm instruments. RESULTS: Neither intraoperative complications nor conversion to conventional laparoscopy or open surgery occurred. The operative time was 60 min, and the estimated blood loss was 50 mL. SLN was detected bilaterally, and removal of the two identified nodes was achieved through meticulous dissection and preservation of the surrounding structures followed by TLH-BSO. No postoperative complications were registered, and the patient was discharged 24 h after surgery. An SLN ultrastaging exam was negative, and the final pathology showed a International Federation of Gynaecology and Obstetrics (FIGO) stage 1A G2 EC with a 2/21-mm myometrial invasion. CONCLUSION: Mini-laparoscopic SLN detection plus TLH-BSO is a feasible procedure that guarantees minimal surgical trauma to selected patients with early EC.

Mini-laparoscopic versus robotic radical hysterectomy plus systematic pelvic lymphadenectomy in early cervical cancer patients. A multi-institutional study.

OBJECTIVE: The aim of this study was to verify possible differences in terms of perioperative outcomes and complications between mini-laparoscopic radical hysterectomy with lymphadenectomy (mLRH) and robotic radical hysterectomy with lymphadenectomy (RRH) in patients with early cervical cancer (ECC). MATERIAL AND METHODS: In this retrospective study, thirty women with early stage cervical cancer who underwent mini-laparoscopic radical hysterectomy plus lymphadenectomy (mLRH) were compared with a cohort of thirty women who underwent robotic multiport radical hysterectomy (RRH). The study involved patients, between August 2010 and December 2012, from three Italian institutions: National Cancer Institute of Rome, University of Insubria, Varese, and the Catholic University of the Sacred Heart of Rome. RESULTS: No significant differences between groups were observed in terms of age, BMI, previous abdominal surgery or FIGO stage. Operative time, blood loss, need of blood transfusion, risk of intra- and post-operative complications, and lymph nodes yield were similar between mLRH and RRH in patients with ECC. The median length of hospital stay was 2 days in the mLRH group and 3 days in the RRH group (p < 0.05). CONCLUSIONS: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable. The decision on how to gain best access for radical hysterectomy considers the surgeon's skill and experience with the different possible approaches. Further randomized trials are needed to determine whether mini-laparoscopic techniques truly offer any advantages.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE: The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS: Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS: Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION: In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer.

BACKGROUND: Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. METHODS: Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II EC cases. RESULTS: Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ≤1 cup per month: 95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36-0.89). CONCLUSION: Coffee may protect against Type I EC in obese postmenopausal women.

Minilaparoscopic radical hysterectomy for cervical cancer: multi-institutional experience in comparison with conventional laparoscopy.

OBJECTIVE: To analyze the preliminary experience of three gynecologic oncology services with minilaparoscopic radical hysterectomy (mLRH) for the treatment of cervical cancer and to compare perioperative outcomes with those of conventional laparoscopic surgery (LRH). METHODS: Prospectively collected data on consecutive cervical cancer patients undergoing radical hysterectomy with a laparoscopic approach were analyzed retrospectively. Perioperative outcomes of women undergoing mLRH were compared to data from control patients who had undergone LRH with 5-mm instruments. Adjustment for potential selection bias in surgical approach was made with propensity score (PS) matching. RESULTS: The study cohort consisted of 257 patients, 35 undergoing mLRH and 222 undergoing LRH. The two groups were comparable in terms of demographic and tumor characteristics. No significant differences were observed between groups in terms of operative time, blood loss, lymph node yield, amount of parametrial or vaginal cuff tissue removed, and percentage of intra- or postoperative complications, both in the entire cohort and in the PS matched group. No conversions were needed from mLRH to standard laparoscopy or from minilaparoscopy to open surgery. Conversion from standard laparoscopy to open surgery was necessary in 2 patients. A shorter hospital stay was observed among women who had mLRH than in those undergoing LRH [2 (1-10) vs 4 (1-14) days, p = 0.005]. This difference remained significant after PS matching. CONCLUSION: Our preliminary study suggests that in experienced hands minilaparoscopy is a feasible and safe technique for radical hysterectomy and yields results that are equivalent to those of LRH.