Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells

Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining.

C1 inhibitor mitigates peritoneal injury in zymosan-induced peritonitis

Peritonitis, due to a fungal or bacterial infection, leads to injury of the peritoneal lining and thereby forms a hazard for the long-term success of PD, and remains a lethal complication in PD patients. This study investigated whether C1 inhibitor (C1-INH) could protect against the progression of peritoneal injuries with five daily administrations of zymosan after mechanical scraping of rat peritoneum to mimic fungal peritonitis. Severe peritoneal injuries were seen in this model, accompanied by fibrinogen/fibrin exudation and peritoneal deposition of complement activation products such as activated C3 and C5b-9. However, intraperitoneal injection of C1-INH decreased peritoneal depositions of activated C3 and C5b-9, ameliorated peritoneal thickening and reduced influx of inflammatory cells and prevented production of peritoneal fibrous layers with both one and two doses of C1-INH each day. Our results suggest that C1-INH might be useful to protect against peritoneal injuries after causes of peritonitis such as fungal infections. This clinically available agent may thus help extend the duration of PD.

Removal of the uterus through the vagina with the replacement of ligatures with hemostatic tweezers

Having described the methods of removing the uterus through the vagina using tweezers and pointing out the advantages of tweezers over ligatures (simplicity, speed and easier operation technique: the postoperative period is shorter) and their disadvantages (the possibility of bleeding after removing the tweezers, bedsores on the peritoneal lining of the intestines and in the vagina), author proceeds to describe his case of canceris colli uteri, where he produced extirpatio uteri per vaginam in the manner of Pan-Doyen.

Malignant effusions

In this chapter, malignant effusions are first defined and then characterized into either ascites, where fluid collects in the layers of the peritoneal lining, and malignant pleural effusion where fluid collects within the pleural space in the lining of the lung. The aetiology and common presenting symptoms of both are outlined, before treatment strategies are considered. For both, this generally consists of drainage of the fluid using specific techniques which are described. Methodologies for managing effusions outside of simple drainage are also covered, along with a brief review of the evidence supporting them.

Abdominal cocoon: a surgical challenge

Encapsulating peritoneal sclerosis (EPS) or sclerosing peritonitis best described as abdominal cocoon is a complex syndrome characterized by formation of a thick fibrocollagenous membrane that totally encloses the small intestinal loops. The etiology is varied and multifactorial. This complex disease is usually associated with continuous peritoneal dialysis (PD), tuberculosis, post renal transplant, or with long term use of beta blockers. A few cases may even be idiopathic in origin. The pathogenesis is attributed to conversion of epithelial cells from the peritoneal lining to mesenchymal cells leading to a formation of a thick membrane. The clinical features range from abdominal pain due to altered gut motility to frank features suggestive of intestinal obstruction. Making a pre-operative diagnosis is the biggest challenge in abdominal cocoon. However computerized tomography provides enough information to arrive at a diagnosis. Surgical intervention continues to remain the final option in an unremitting intestinal obstruction despite the role of conservative therapy using drugs proposed for treatment. The focus of management is early diagnosis and treatment in order to halt the progression to a frank cocoon. The paper reviews the etiopathogenesis and management of this intricate condition.

BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma

BackgroundMalignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM yet exist. In the search for novel therapeutic target candidates in PeM, we performed a comprehensive integrative multi-omics analysis of 19 treatment-naïve PeM tumors.ResultsThe analysis identified PeM tumors withBAP1loss to form a distinct molecular subtype characterized by distinct expression patterns of genes involved in chromatin remodeling, DNA repair pathway, and immune checkpoint receptor activation. This PeM subtype could potentially benefit from immune checkpoint, PARP, or HDAC inhibition therapies.ConclusionsOur findings uncoverBAP1as a trackable prognostic and predictive biomarker, and refine PeM disease classification. This integrated molecular characterization provides a comprehensive foundation for developing PeM precision medicine.

Ectopic Hepatocellular Carcinoma Arising from the Peritoneum in a Patient with a History of Oropharyngeal Cancer: A Case Report

A subphrenic mass was noted on a surveillance computed tomography (CT) scan of a 65-year-old man who had achieved complete remission of oropharyngeal cancer after concurrent chemoradiotherapy. The mass was 3.2 cm in size and showed a multilobular enhancing pattern along the peritoneal lining. The patient was negative for hepatitis B surface antigen and anti-hepatitis C virus antibody. His carcinoembryonic antigen level was within the normal range. Contrast-enhanced CT revealed no mass in the liver. He underwent surgery, and a pale yellowish soft tumor measuring 3.8 × 3.2 × 1.2 cm was resected. Histologically, the tumor was confirmed to be a hepatocellular carcinoma. Currently, he is doing well, and has been followed up without any signs of recurrence.

Incidence of peritoneal carcinomatosis in recurrent plasmacytoid urothelial carcinomas (PUC) of the bladder: A retrospective analysis of patient outcomes at M. D. Anderson Cancer Center (MDACC).

297 Background: PUC are a rare subset of urothelial cancers with a paucity of available literature regarding their clinical behavior. Methods: Retrospective analysis of outcomes among all patients (pts) with predominant PUC (pPUC) seen at MDACC from 1999-2010. Results: 31 pts with pPUC histology were identified (median age:63.5yrs; 83.3% male; TNM stage:cT1N0,n=4;cT2N0,n=8;cT3b-4aN0,n=6; cT4b, N+ or M+ n = 13). Median survival for all pts was 17.7mo (Stage I-III vs IV: 38.1 vs 13.3mo). Of 18 pts with potentially surgically resectable PUC (<=pT4aN0M0) 7 received neoadjuvant chemotherapy,10 had initial surgery, and one was treated with TURBT alone. Despite pathologic downstaging in 67% of pts treated with neoadjuvant chemotherapy relapses were common and there was no difference in survival between pts treated with neoadjuvant chemotherapy compared to initial surgery, even though adjuvant chemotherapy was given in 7 patients. Only 1 pt in pCR remains in remission >18 mo after surgery. The most common site of recurrence was in the peritoneum (13/18pts), with relapses occurring even in those with pCR at surgery. At least 4 pts developed CNS involvement with lepto-meningeal disease. In pts presenting with metastatic disease who were treated with chemotherapy, the median survival was 12.6 months. Conclusions: Plasmacytoid bladder tumors are a very aggressive subset with overall poor outcomes. Though chemotherapy sensitive with downstaging seen with neoadjuvant chemotherapy, there are few long-term survivors. There is a strong predilection for recurrences along the peritoneal lining, and peritoneal carcinomatosis should remain high on a clinician’s differential when patients develop obstructive bowel symptoms.

Müllerian Serous Cystadenoma of the Scrotum Following Orchiopexy

A 24-year-old man presented himself with a nodular lesion of about 1 cm diameter at the site of a previous orchiopexy associated with surgery for cryptorchism. Histopathology revealed the lesion to be adenomatous and confined to the scrotum. Histological and immunohistological features were not consistent neither with median raphe cysts or cutaneous adenomas nor with the intrascrotal adenomas of the rete testis, epididymis, nor with (malignant) mesotheliomas. However, the lesion did compare well with serous (papillary) cystadenomas of the testis or paratestis. These adenomas are thought to originate in remnants of the Müllerian system or of peritoneal lining altered by Müllerian metaplasia. This implies that the scrotal adenoma may have developed from an implant of such elements during orchiopexy 14 years ago. Complete excision of the lesion appears to be an adequate therapy.

Cryptorchidism in common eutherian mammals

Cryptorchidism is failure of one or both testes to descend into the scrotum. Primary fault lies in the testis. We provide a unifying cross-species interpretation of testis descent and urge the use of precise terminology. After differentiation, a testis is relocated to the scrotum in three sequential phases: abdominal translocation, holding a testis near the internal inguinal ring as the abdominal cavity expands away, along with slight downward migration; transinguinal migration, moving a cauda epididymidis and testis through the abdominal wall; and inguinoscrotal migration, moving a s.c. cauda epididymidis and testis to the bottom of the scrotum. The gubernaculum enlarges under stimulation of insulin-like peptide 3, to anchor the testis in place during gradual abdominal translocation. Concurrently, testosterone masculinizes the genitofemoral nerve. Cylindrical downward growth of the peritoneal lining into the gubernaculum forms the vaginal process, cremaster muscle(s) develop within the gubernaculum, and the cranial suspensory ligament regresses (testosterone not obligatory for latter). Transinguinal migration of a testis is rapid, apparently mediated by intra-abdominal pressure. Testosterone is not obligatory for correct inguinoscrotal migration of testes. However, normally testosterone stimulates growth of the vaginal process, secretion of calcitonin gene-related peptide by the genitofemoral nerve to provide directional guidance to the gubernaculum, and then regression of the gubernaculum and constriction of the inguinal canal. Cryptorchidism is more common in companion animals, pigs, or humans (2–12%) than in cattle or sheep (≤1%). Laboratory animals rarely are cryptorchid. In respect to non-scrotal locations, abdominal testes predominate in cats, dogs, and horses. Inguinal testes predominate in rabbits, are common in horses, and occasionally are found in cats and dogs. S.c. testes are found in cattle, cats and dogs, but are most common in humans.