Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods.

OBJECTIVE: Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods. METHODS: This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004-2013 and 2014-2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004-2013, and 50 published from 2014-2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I2=95%) overall gastrointestinal complications (15% vs 21%; p=0.36; I2=98%), infectious diseases (16% vs 13%; p=0.62; I2=93%), overall respiratory complications (12% vs 12%; p=0.88; I2=91%), overall urinary complications (6% vs 12%; p=0.06; I2=94%), or thromboembolic events (5% vs 3%; p=0.25; I2=63%). Also, no differences were found in intensive care unit (ICU) admissions (89% vs 28%; p=0.06; I2=99%), reoperations (8% vs 7%; p=0.50; I2=37%), or deaths (3% vs 3%; p=0.77; I2=57%). CONCLUSIONS: Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.

Uterine torsion and intrauterine growth restriction: Case report and systematic literature review.

PURPOSE: Uterine torsion (UT) in pregnancy is a rare condition in obstetric practice. It is defined as a rotation of the uterus of more than 45° around its long axis. Presentations are varied and, most of the time, this condition is recognized at laparotomy or cesarean section (CS). The aim of this study is to summarize the latest evidence about UT in pregnancy. METHODS: A systematic research of the literature was conducted fetching all papers published from March 2006 to June 2020. We collected data regarding clinical features, treatment, and feto-maternal outcomes. Finally, we reported data of a case of UT associated with intrauterine growth restriction (IUGR) diagnosed and treated at our institution. RESULTS: According to our search strategy, 38 articles were included. In 66% of the cases, acute symptomatology was present at the onset, most frequently abdominal pain was reported. In one-third of the cases, UT was diagnosed during CS without clinical suspicion. Only in two cases, including our case, IUGR was reported. Most (66%) of the cases presented a 180° torsion. In the majority of the cases, a CS was performed also with a deliberate or accidental posterior hysterotomy. One and six cases of maternal and fetal death were, respectively, reported. CONCLUSION: UT is an infrequent obstetric condition but should be considered in case of abdominal pain, vomiting, or shock presentation during pregnancy. It could lead to a reduction in uterine blood flow contributing to poor placental perfusion, even though more evidence is needed to clarify this link.

Clear cell degeneration associated with endometriosis of abdominal wall after cesarean section: A case report and systematic review of literature.

AIM: The scar of cesarean section (CS) is the most common site of abdominal wall endometriosis (AWE), whose tumor degeneration has been reported in an increasing number of cases; the most frequent histological type is clear cell carcinoma (CCC). METHODS: We conducted a systematic research of the literature, collecting data regarding the evidence on tumor degeneration from AWE after CS. Moreover, we reported a case of clear cell borderline tumor (CCBT) originating from AWE. RESULTS: We included data of 37 patients with diagnosis of CCC. The average time between the last CS and the diagnosis of CCC was around 15 years. Overall, 26.0% and 73.9% patients received exclusive local abdominal resection of the lesion and additional surgery, respectively. Lymph nodes involvement was detected in 26.0 % patients and adjuvant chemotherapy was administered in 52.0 % cases. During follow-up period, 15.2% patients died of disease, 32.6% had no evidence of disease, and 17.4% recurred. We diagnosed a CCBT arose in a patients with AWE and a personal history of several surgical procedures for endometriosis, a CS and a subsequent transverse laparotomy. We performed an open bilateral ovariectomy and a large excision of the endometriotic abdominal lesion. CONCLUSION: Tumor degeneration from AWE seems to be a real occurrence with an increasing number of events. Considering the lack of risk factors and diagnostic instruments for tumor degeneration, the removal of AWE localization could be advisable, even though there was long average time between the trigger surgery and the tumor finding.

Current Treatment Options for Cervical Leiomyomas: A Systematic Review of Literature.

Background and objectives: Cervical leiomyomas are a rare benign disease. Although they are mainly treated surgically, currently, there is not a standardized treatment for cervical leiomyomas. This study aims to summarize current literature evidence about treatment options for cervical leiomyomas. Materials and methods: A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, including observational prospective and retrospective studies, case series and case reports. We collected data regarding studies related to treatment options for cervical leiomyomas, evaluating the following aspects: study design, population, treatment type, rate of surgical complications, and fertility outcome. Results: According to literature research, 38 articles were included. Among 214 patients, the weighted average age was 39.4 years-old; 23 patients were pregnant. Most of the leiomyomas (78%) were extracervical; in 22% of cases (29 patients) were intracervical; 188 patients (88%) received surgical treatment, 6 (3%) received exclusive conservative management and 21 (10%) underwent interventional radiology treatment. One hundred twenty-seven patients (67.5%) underwent myomectomy, while 54 (28.7%) and 7 (3.7%) hysterectomy and trachelectomy, respectively. Cervical myomectomy was performed by open surgery in 21 out of 127 cases (16.5%), while in 92 (72.4%) and 6 (4.7%) patients the surgical approach was performed by traditional and robot-assisted laparoscopy, respectively. The total rate of surgical complications was 5.6%. Conclusion: Surgery is the primary therapeutic option for cervical leiomyomas with a low rate of surgical complications. Interventional radiology techniques have reported promising but still limited results.

Validation of an enhanced recovery after surgery protocol in gynecologic surgery: an Italian randomized study.

BACKGROUND: The enhanced recovery after surgery concept, which was introduced 20 years ago, is based on a multimodal approach to improve the functional rehabilitation of patients after surgery. OBJECTIVE: This study aimed to validate an enhanced recovery after surgery protocol in gynecologic surgery for both benign and malignant diseases (endometrial cancer and advanced ovarian cancer) and to measure the adherence to the enhanced recovery after surgery protocol items in a randomized trial setting. STUDY DESIGN: In this trial (NCT03347409), we randomly assigned patients to undergo standard perioperative care or enhanced recovery after surgery protocol. The primary outcome is a shorter length of stay in favor of the enhanced recovery after surgery protocol. Secondary outcomes include measurement of adherence to the enhanced recovery after surgery protocol items: comparison of postoperative pain, vomiting, and nausea; anesthesiologic and surgical complications up to 30 days after surgery; rate of readmissions; the time to event in hours for bowel movements, flatus, drinking, hunger, eating, and walking; and the quality of recovery using a validated questionnaire (QoR-15). Finally, we explored the length of stay in the prespecified subgroups at randomization, based on the type of surgical access and gynecologic disease. RESULTS: A total of 168 women were available for analysis: 85 women (50.6%) were assigned to the standard perioperative care group, and 83 women (49.4%) were assigned to the enhanced recovery after surgery protocol group. The 2 groups were similar for age, body mass index, comorbidities, anesthesiological risk, smoking habits, surgical access, and complexity of surgical procedures. Seventy-two patients (42.9%) underwent surgery for benign disease, 48 (28.6%) for endometrial cancer, and 48 (28.6%) for ovarian cancer. Women in the enhanced recovery after surgery protocol group had a shorter length of stay (median: 2 [interquartile range, 2-3] vs 4 [interquartile range, 4-7] days; P<.001). A decreased rate of postoperative complications was noted for the enhanced recovery after surgery protocol group, as well as an earlier time to occur for all the events. Mean adherence to protocol items was 84.8% (95% confidence interval, 79.7-89.8), and we registered a better satisfaction in the enhanced recovery after surgery protocol group. The shortening of the length of stay was confirmed also in the prespecified subgroup analysis. CONCLUSION: Application of the enhanced recovery after surgery protocol in gynecologic surgery translated to a shorter length of stay regardless of surgical access and type of gynecologic disease. Adherence to the enhanced recovery after surgery protocol items in the setting of a randomized trial was high.

Laparoscopic management of a large urethral leiomyoma.

INTRODUCTION AND HYPOTHESIS: A 42-year-old female presented with a 12-cm mass bulging the anterior vaginal wall and causing urgency urinary incontinence and bulk symptoms. METHODS: Imaging showed a tumor originating from the dorsal and cranial part of the urethra and developing in the vesicouterine space and vesicovaginal septum, dislocating the bladder ventrally and the uterus cranial-dorsally. RESULTS: Tranvaginal biopsy showed a benign leiomyoma. A laparoscopic approach with development of the vesicouterine space permitted a safe partial morcellation of the myoma. After the bladder and vaginal wall had been completely freed, further caudal dissection was conducted with isolation of the distal cranio-dorsal portion of the urethra. The dissection plane with the vaginal wall was developed up to the caudal margin of the urethral myoma almost corresponding to the vulvar plane, and total excision of the lesion was performed. CONCLUSION: Laparoscopic management of urethral leiomyomas that develop into the vesicouterine space and vesicovaginal septum is feasible and safe also for very large lesions.

Adnexal torsion with normal ovary in the third trimester of a twin pregnancy: Case report and literature review.

Management of adnexal torsion in a dichorionic diamniotic pregnancy at 32 weeks is presented. Adnexal torsion is a rare condition in pregnancy, particularly during late third trimester and with normal ovary and tube. The size of a twin uterus at late third trimester prevented a laparoscopic approach. A longitudinal laparotomic incision below the umbilicus permitted detorsion and fixation of the adnexa. To our knowledge, this is the first case reported in a late twin pregnancy.

Parenchymal liver metastasis in advanced ovarian cancer: Can bowel involvement influence the frequency and the related mortality rate?

OBJECTIVE: This retrospective study estimates the frequency of parenchymal liver metastasis (PLM) and the overall survival (OS) rate of patients with FIGO Stage IIIC-IV Advanced Epithelial Ovarian Cancer (EOC) with bowel involvement. STUDY DESIGN: Between November 2008 and July 2020, all consecutive patients with FIGO Stage IIIC-IV EOC who underwent Visceral Peritoneal Debulking and bowel resection(s) at the Gynaecological Oncology Unit of "Centro di Riferimento Oncologico (CRO)", Aviano, Italy, without evidence of PLM at pre-operative imaging assessment, were included in the study. The presence and the time of the onset of PLM during the follow-up period were detected by diagnostic imaging (CT-scan, Ultrasound and PET). The OS of patients with and without PLM was compared. Considering the bowel's layers, the association between depth of bowel involvement, number of PLM, and the relative OS rate was evaluated. RESULTS: The median follow-up period was 47.3 (12-138) months. PLM occurred in 24/72 (33.0%) cases; the average onset time of PLM was 13 months. PLM was associated with increased significant mortality risk and an average OS of 33.2 versus 56.8 months (p < 0.001). The risk of developing PLM correlated directly with the depth of bowel involvement. However, there was no statistical difference between the layers in terms of OS at the end of the observational period. CONCLUSIONS: PLM occurred more frequently among patients with EOC and bowel involvement. The PLM arose within 15 months of follow-up and the frequency increased according to the depth of involvement. Particularly, the difference is remarkably higher starting from muscular layer where the total number of PLM arose significantly (p = 0.02). Although there was no significant difference among the infiltrated bowel layers in terms of OS, patients with bowel involvement up to muscular had a dramatic reduction in the OS rate during the first 30 months of follow-up.

Proximate Composition and Fatty Acid Profile of Gilthead Seabream (Sparus aurata) Fed with Pelvetia canaliculata-Supplemented Diets: An Insight towards the Valorization of Seaweed Biomass.

Seaweeds are a sustainable source of protein and lipids that may be used to replace fish by-products in aquaculture feed. This study aimed at using the macroalgae Pelvetia canaliculata as an ingredient in gilthead seabream (Sparus aurata) feed, either as freeze-dried powder or as algae residue (waste) that was obtained after the supplementation of sunflower oil. The formulated diets and the fish muscle were analyzed concerning the proximate composition and the fatty acid profile. The health lipid indices hypocholesterolemic/hypercholesterolemic (h/H), atherogenic (AI), thrombogenic (TI), as well as n-3/n-6 and polyunsaturated fatty acid/saturated fatty acid (PUFA/SFA) ratios were calculated. Additionally, the peroxidizability index (PI) was determined. No differences were observed in the proximate composition of fish muscle regardless of the diet used. Fish fed a diet supplemented with 10% of algae waste (W10) stand out for the highest content in oleic acid (C18:1 n-9), and the lowest in both linoleic (C18:2 n-6) and palmitic (C16:0) fatty acids. All fish samples showed values of health lipid indices within the limits recommend for a nutritional balanced diet. These results highlight that fish fed diets supplemented with P. canaliculata are sources of healthy lipids that might be consumed on a regular basis to prevent cardiovascular diseases.

Risks factors for anastomotic leakage in advanced ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to summarise the available evidence on the pre- and intra-operative risk factors for anastomotic leakage (AL) after bowel resection and anastomosis for ovarian cancer (OC). STUDY DESIGN: We searched online databases from Pubmed, Scopus, ScienceDirect, and Cochrane Library from inception to October 2020. Pre- and intra-operative risk factors for AL were considered as the primary outcomes. Research heterogeneity and bias were evaluated by I2 and by the Newcastle Ottawa scale, respectively. The study was registered with PROSPERO, CRD42018095225. RESULTS: The overall AL rate after OC surgery (median ± SD) was 5.3 ± 12% (277 AL on 5178 anastomoses). Thirteen non-randomised studies were included in the meta-analysis enrolling a total of 3274 patients. Pre albumin level ≤ 3 gr/dl, multiple bowel resections and primary cytoreductive surgery were associated with a significantly high risk of AL with a pooled OR of 5.29 (95% CI: 1.51-18.59), OR = 4.4 (95% CI: 1.19-16.66) and OR = 1.71 (95% CI: 1.05-2.77), respectively. Optimal cytoreduction, ASA score, ascites, and protective stoma were not associated with an increased risk of AL. CONCLUSION: Based on the best available evidence, preoperative albumin level <3 gr/dl, multiple bowel resections and primary cytoreductive surgery were associated with an increased risk for AL after bowel surgery for OC.

DICOM-MIABIS integration model for biobanks: a use case of the EU PRIMAGE project.

PRIMAGE is a European Commission-financed project dealing with medical imaging and artificial intelligence aiming to create an imaging biobank in oncology. The project includes a task dedicated to the interoperability between imaging and standard biobanks. We aim at linking Digital imaging and Communications in Medicine (DICOM) metadata to the Minimum Information About BIobank data Sharing (MIABIS) standard of biobanking. A very first integration model based on the fusion of the two existing standards, MIABIS and DICOM, has been developed. The fundamental method was that of expanding the MIABIS core to the imaging field, adding DICOM metadata derived from CT scans of 18 paediatric patients with neuroblastoma. The model was developed with the relational database management system Structured Query Language. The integration data model has been built as an Entity Relationship Diagram, commonly used to organise data within databases. Five additional entities have been linked to the "Image Collection" subcategory in order to include the imaging metadata more specific to the particular type of data: Body Part Examined, Modality Information, Dataset Type, Image Analysis, and Registration Parameters. The model is a starting point for the expansion of MIABIS with further DICOM metadata, enabling the inclusion of imaging data in biorepositories.

Artificial intelligence, radiomics and other horizons in body composition assessment.

This paper offers a brief overview of common non-invasive techniques for body composition assessment methods, and of the way images extracted by these methods can be processed with artificial intelligence (AI) and radiomic analysis. These new techniques are becoming more and more appealing in the field of health care, thanks to their ability to treat and process a huge amount of data, suggest new correlations between extracted imaging biomarkers and traits of several diseases as well as lead to the possibility to realise an increasingly personalized medicine. The idea is to suggest the use of AI applications and radiomic analysis to search for features that may be extracted from medical images [computed tomography (CT) and magnetic resonance imaging (MRI)], and that may turn out to be good predictors of metabolic disorder diseases and cancer. This could lead to patient-specific treatments and management of several diseases linked with excessive body fat.

Extra-abdominal ovarian cancer presenting with breast metastases at diagnosis: Case report and literature review.

OBJECTIVE: Malignant ovarian tumours are diagnosed at an advanced stage in the majority of cases. However, only a small percentage present as extra-abdominal, non-lymph-node solid metastases, as in the breast, and they are usually cases of relapse. The discovery of mono- or bilateral breast lesions with peritoneal carcinosis and/or abdomino-pelvic lesions can be cumbersome in the differential diagnosis of primary tumours. This article aims to summarize current evidence on the detection of breast metastases at diagnosis of ovarian cancer. STUDY DESIGN: A systematic review of the literature in Scopus, PubMed/MEDLINE, ScienceDirect and the Cochrane Library, including case reports and case series, was undertaken. Data regarding study features; population characteristics; clinical, radiological and histological assessment of the disease; treatment and follow-up were collected. In addition, a case report of a patient managed at the authors' centre is provided. RESULTS: According to the search strategy, 16 articles (18 patients) were included in this review. Serous ovarian, fallopian tube or primary peritoneal cancer was detected in 61% of cases, while another type or a non-specified type of epithelial ovarian cancer was detected in 27.7% of cases; there was one case with granulosa cell tumour of the ovary and one case with mucinous ovarian tumour of low malignant potential. Breast metastases were mainly monolateral (66.6%), with other extra-abdominal sites of disease in the majority of the cases. A minority of patients (16.6%) received treatment for primary breast cancer with a subsequent diagnosis of ovarian cancer. Concomitant breast and abdominal surgery can be an option. PAX8, WT1 and CA125 immunohistochemical staining can aid in differential diagnosis. CONCLUSION: Breast metastases of malignant ovarian tumours must be promptly recognized to ensure proper treatment. Specific immunohistochemical analysis can be a decisive assessment in uncertain cases.

Impact of endometrial sampling technique and biopsy volume on the diagnostic accuracy of endometrial cancer.

BACKGROUND: Histotype and tumor grading of endometrial cancer are the most important factors that have to be assessed by preoperative endometrial sampling, and their concordance with the final surgical and definitive histological findings is of paramount importance. We aim to compare histotype and tumor grading concordance of various endometrial sampling techniques (ESTs) and to investigate the role of endometrial volume biopsy. METHODS: We performed a retrospective analysis of patients with apparent early stage endometrial cancer collecting demographic, clinical data, type of EST, pathological characteristics of endometrial biopsies and final specimens. We classified ESTs as dilation and curettage (D&C), diagnostic hysteroscopy with D&C, outpatient hysteroscopy and operative hysteroscopy with or without D&C. Diagnostic and operative hysteroscopy were performed with Bettocchi's 5 mm hysteroscope. We evaluated concordance for histotype, and tumor grading, and we performed subgroup analysis based on the technique and final tumor grading. Concordance was classified from good, moderate, sufficient, fair, poor and none using Cohen k-statistic. Finally, we investigated the existence of independent risk factors for discordant tumor grading using multivariate binary logistic regression. RESULTS: We collected 148 patients and of these 131 (88.5%) were diagnosed with endometrioid histotype and 65 (44%), 46 (31%) and 37 (25%) respectively with well, moderate and poor differentiated tumors. Atypical hyperplasia (AH) was detected preoperatively in 28 patients (19%). Histotype concordance was fair (k=0.35) and tumor grading concordance was moderate (k=0.45); particularly, concordance was fair in well-differentiated cases (k=0.38); concordance was moderate in moderate- and poor-differentiated cases (k=0.52) and good (k=0.71). Operative hysteroscopy showed moderate concordance for histotype (k=0.41), while grading concordance was fair for G1 (k=0.41), moderate for G2 (k=0.58) and good for G3 (k=0.72), regardless the use of D&C. Preoperative volume biopsy did not impact the concordance of tumor grading, while the adoption of operative hysteroscopy (with or without D&C) decreased the risk of grading discordance in G3 tumors (HR 0.17; 95% CI: 0.03-0.94; P=0.04). Conversely, time elapsed from diagnosis to treatment in well-differentiated tumors increased the risk of discordant results (HR 1.06; 95% CI: 1.02-1.52; P=0.04). CONCLUSIONS: Operative hysteroscopy demonstrated the best tumor grading concordance, especially in poor-differentiated tumors. The volume of biopsy did not affect the tumor grading concordance.

Opportunistic salpingectomy during postpartum contraception procedures at elective and unscheduled cesarean delivery.

OBJECTIVE: To compare intra- and postoperative surgical complications of opportunistic bilateral total salpingectomy during postpartum permanent contraception procedures in elective and unscheduled cesarean delivery. STUDY DESIGN: We conducted a retrospective cohort study (2010-2017) of women who had postpartum permanent contraception procedures during cesarean delivery, and we collected baseline characteristics, scheduling of delivery (elective versus unscheduled), operative time, estimated blood loss (EBL) and surgical complications (bleeding, iatrogenic injury, infection, anemia and relaparotomy). We classified patients according to contraceptive technique: bilateral total salpingectomy, bilateral partial salpingectomy with or without fimbriae, and other methods. RESULTS: Five hundred twenty-eight women underwent postpartum permanent contraception procedures, 245 (46.4%) had bilateral total salpingectomy, 239 (45.3%) had bilateral partial salpingectomy, and 48 (8.3%) underwent other methods. We did not find differences in baseline characteristics, operative time and EBL among postpartum permanent contraception groups. Unscheduled cesarean delivery did not influence the choice of postpartum permanent contraception technique (p=.22). Postpartum permanent contraception-related intraoperative bleeding occurred in 1 (0.4%) and 2 (0.9%) patients, respectively, in bilateral total and partial salpingectomy group (p=.23). Postoperative complications were 13 (5.3%) and 6 (2.5%), respectively, in bilateral total and partial salpingectomy groups (p=.11). Subgroup analysis confirmed no differences for intra- and postoperative complications during unscheduled cesarean delivery. We noted a 4.3-min increase in operative time for total salpingectomy after multivariate analysis (p<.01). CONCLUSION: At maternal request for postpartum permanent contraception during cesarean delivery, bilateral total salpingectomy can be a safe and feasible method even in case of unscheduled cesarean delivery. IMPLICATIONS STATEMENT: Our results suggest that bilateral total salpingectomy during any cesarean delivery may be an acceptable choice for its higher contraceptive efficacy and risk-reduction effect for ovarian cancer, at the price of a small increase in operative time.

Multivariate analysis of prognostic factors in primary squamous cell vulvar cancer: The role of perineural invasion in recurrence and survival.

OBJECTIVE: to assess the prognostic role in recurrence and survival of perineural invasion (PNI) in vulvar squamous cell cancer (VSCC). METHODS: Patients underwent primary surgery for VSCC from January 2009 to December 2016 served as the study cohort. We collected demographic, clinical, pathological characteristics and follow-up data, and we compared them among PNI-negative versus -positivepatients. We calculated disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier and univariate log-rank test. We conducted a multivariate analysis with cox-proportional hazard models for DFS and OS, including age, tumor size, depth of invasion, free tumor margin <8 mm, high-grade histology, lymph vascular space invasion, PNI, extracapsular lymph nodal disease, lymph nodal ratio >0.2 and FIGO Stage 2009 (Early I-II versus Advanced III-IV). RESULTS: We found 74 patients with a PNI prevalence of 31.1%. The 5-year DFS was favourable for PNI-negative patients (72% versus 18%; p = 0.00). The 5-year OS was 75% versus 35% in favor of PNI-negative patients (p = 0.00). The subgroup analysis conducted among stage confirmed a decreased DFS and OS in PNI-positive patients. Multivariate analysis showed that PNI (HR 2.74; CI95% 1.10-7.13; p = 0.03) and extracapsular lymph nodal disease (HR 13.54; CI95% 2.87-64.07; p = 0.01) are independent prognostic factors for earlier recurrence. OS was significantly reduced in case of PNI (HR 4.93; CI95% 1.33-18.35; p = 0.01) and extracapsular lymph nodal disease (HR 10.63; CI95% 1.65-68.57; p = 0.01). CONCLUSIONS: PNI is an independent prognostic factor for aggressive behavior and unfavorable course in VSCC and should be considered in adjuvant treatment planning.

Canine oral primary melanoma cells exhibit shift to mesenchymal phenotype and phagocytic behaviour.

Canine oral malignant melanoma (COMM) is a potentially lethal cancer disease. We established primary cell lines from mostly amelanotic primary COMM and metastases and assessed lesions and derived cells for Melan A, PNL2 and CD146 expression. Then, migration and invasion of CD146-enriched vs -depleted COMM cells were analysed. Epithelial-to-mesenchymal transition (EMT) was addressed by Vimentin-staining and MMP2/MMP9 zymography. Phagocytic behaviour was analysed by histopathological examination and phagocytosis assay. While Melan A- and PNL2-staining yielded inconsistent data, 100% of COMM sections and primary cells showed CD146 expression, suggesting that this protein may serve as a prognostic marker. An overall correlation between CD146-expression and migration/invasion was not observed. All primary cell lines consistently expressed Vimentin and secreted biologically active MMP2, indicating that they had undergone EMT. Importantly, COMM sections exhibited cell-in-cell structures, and all primary cell lines exhibited phagocytic activity, supporting the concept that cell cannibalism may have a role in COMM progression.