The molecular landscape of well differentiated retroperitoneal liposarcoma.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA sequencing, and methylation array analysis. A recurrent mutation within exon 1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p.Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair, and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31, and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumourigenesis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Outcome after ex situ or ante situm liver resection with hypothermic perfusion and auto-transplantation: A single-centre experience in adult and paediatric patients.

BACKGROUND: Evolving surgical technology and medical treatment have led to an expansion of indications to enable resection of large hepatic tumours with involvement of other abdominal structures. METHODS: Twelve extended liver and abdominal resections, either ex situ with auto-transplantation of the liver remnant or ante situm with veno-venous bypass (VVBP) were performed between 2016 and 2018. We describe our preoperative assessment, compare surgical strategies and assess outcomes. RESULTS: The median age of the 10 adult patients was 50.5 years with a majority suffering from sarcoma-like tumours. The two paediatric patients were 3 and 8 years of age, both with hepatoblastoma. Two patients underwent ex situ resections with auto-transplantation of the liver remnant, and nine patients had ante situm tumour removal with the use of VVBP in four. All patients achieved a good immediate liver function. Local infection and acute kidney injury were found in two patients. One patient underwent biliary reconstruction for bile leak. Tumour recurrence was seen in seven patients (58.3%), with four lung metastases. Five patients died from tumour recurrence (41.7%) during the follow-up. CONCLUSION: Extreme liver resections should be performed in experienced centres, where surgical subspecialties are available with access to cardiovascular support. Additionally, experience in split and living-donor liver transplantation is beneficial.

Autotransplantation of the Liver for Ex Vivo Resection of Intrahepatic Caval Leiomyosarcoma: A Case Report.

Intrahepatic caval leiomyosarcomas are rare tumors with limited therapeutic options as patients with the disease are not eligible for liver transplantation from the deceased-donor pool. Advances in surgical techniques gained in split and domino liver transplant procedures can be applied to resection of advanced tumors involving the hepatocaval confluence. Here, we describe the case of a 58-year-old white female who presented with visible abdominal wall collaterals and a palpable right subcostal tumor. Imaging revealed a 5.7 × 5.7 × 11-cm intrahepatic caval soft tissue mass extending into the hepatic veins, right renal vein, and infrarenal caval vein. The entire inferior caval vein was resected en bloc with the liver and right kidney and replaced with a blood group-identical fresh caval vein graft from a deceased donor. The splanchnic circulation was decompressed with a temporary portocaval shunt to the caval vein graft, and caudal inflow into the caval vein graft was established with a left iliac anastomosis. Ex vivo resection of the native inferior caval vein containing the intravascular tumor together with a sleeve of liver was performed under hypothermic conditions, and hepatic outflow was reconstructed with vein from the deceased donor. The liver was autotransplanted via the classical piggyback technique with uneventful portal reperfusion following a cold ischemic time of 2 hours. Histology confirmed a grade 3 leiomyosarcoma with clear resection margins. Liver function was stable, and the patient is currently alive at 2 years after resection. Follow-up imaging at 12 months was unremarkable, but local recurrence was detected on the most recent computed tomography scan. In conclusion, ex vivo resection of an intrahepatic caval leiomyosarcoma with inferior caval vein replacement by a deceased-donor caval graft and subsequent liver autotransplantation are technically demanding but provide a chance on prolonged survival.

Biphasic malignant tumours of the abdominal cavity.

Carcinosarcomas (CS) are uncommon, highly aggressive, biphasic tumours consisting of both sarcomatous and carcinomatous elements. They appear to originate from a common cell of origin, either via transformation from a single premature precursor or conversion of a mature epithelial cell through an epithelial-mesenchymal transition. CS should be considered a unique cancer subtype with cells typically displaying diffuse mitotic activity and widespread atypical mitoses predisposing to early metastasis and a tendency to local recurrence following resection. This review addresses the pathophysiology of CS and discusses its presentation, natural history and management at a variety of sites within the abdominal cavity and retroperitoneum.

Myeloid Sarcoma: Presentation, Diagnosis, and Treatment.

Myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered as a differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to very varied clinical presentations. Diagnosis is challenging and relies on a high index of suspicion as well as radiology, histology, immunophenotyping, and molecular analyses, which also are essential for risk stratification and treatment planning. Systemic chemotherapy using AML-like regimens should be commenced early, even in nonleukemic disease. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies. Prospective multicenter controlled trials are required to further refine management decisions and investigate the role of novel targeted therapies.

Psychological Prehabilitation Before Cancer Surgery: A Systematic Review.

BACKGROUND: Cancer patients experience anxiety and depression after diagnosis and during treatment. A wide range of psychological interventions have been proposed to alleviate distress, but the evidence about the perioperative effectiveness of such interventions is not clear. This systematic review examined the effect of preoperative psychological interventions or prehabilitation on the postoperative outcomes of patients undergoing surgery for cancer. METHODS: A systematic review of the published data was performed using Embase, Medline, and PsycInfo for the period from 1946 to February 2014. A total of 951 publications (case series, single case reports, and reviews) were found. Only seven of these studies included patients undergoing an operation for cancer and a preoperative psychological intervention. RESULTS: Six of the seven studies were randomized controlled trials. Four were conducted with patients who had breast cancer (n = 356). The other studies included patients with gynecologic cancer (n = 30), colorectal cancer (n = 60), and prostate cancer (n = 159). Assessment of the studies showed four to be of good quality, two to be of moderate quality, and one to be of poor quality. Interventions did not affect traditional surgical outcomes (e.g., length of hospital stay, complications, analgesia use, or mortality) but positively affected patients' immunologic function. However, psychological interventions appeared to have an impact on patients' reported outcome measures including psychological outcomes, quality of life, and somatic symptoms. CONCLUSION: Available data suggested that preoperative psychological prehabilitation may have a role for cancer patients undergoing surgery. Further evidence is needed to evaluate its role.

Outcomes Following Extended Surgery for Retroperitoneal Sarcomas: Results From a UK Referral Centre.

BACKGROUND: Primary extended resection has been proposed as the initial treatment for patients with retroperitoneal sarcoma. This approach comprises an extended en-bloc resection of the directly infiltrated organs and adjacent uninvolved organs. The results of such radical surgery have yet to be validated. This retrospective study aims to investigate this practice in a contemporary series from a referral center in the UK. METHODS: We extracted data from consecutive patients who underwent extended resectional surgery between 2009 and 2013, and investigated the type of resection performed, the effectiveness of extended surgery in providing negative microscopic margins, and the occurrence of post-surgical adverse events. RESULTS: A total of 69 patients were included. Fifty-two patients had a primary tumor (75.4 %), and in 55 patients (79.7 %) the tumor was resected en bloc with adjacent organs or structures. Colonic resection (N = 35, 50.7 %) and nephrectomy (N = 28, 40.6 %) were the most frequently performed organ resections. Organs were infiltrated in 22 patients (32 %), and there was no association between organ infiltration and patient variables and staging characteristics. Negative microscopic margins were achieved in 88.6 % of patients in this series. Postoperative complications occurred in 21 patients (30 %) and a reoperation was required in ten cases (14.5 %). No independent predictors of morbidity were identified and no 30-day postoperative deaths occurred. CONCLUSIONS: Four-fifths of patients in this series had organs removed in association with the retroperitoneal sarcoma. This approach in a specialist sarcoma unit results in negative microscopic tumor margins in up to 90 % of cases and can be performed safely.

Prognostic factors and outcome of spermatic cord sarcoma.

PURPOSE: To evaluate management and outcome in a large series of patients with spermatic cord sarcomas (SCS), a rare malignancy. METHODS: Eighty-two patients with localized SCS treated at two dedicated sarcoma units between 1992 and 2013 were included. Disease-specific survival (DSS) and crude cumulative incidence of local recurrence and distant metastases (DM) were estimated by Kaplan-Meier plots and log rank tests. RESULTS: Median follow-up was 33 months (interquartile range 13-72 months). Sixty-one patients presented with primary disease. Liposarcoma was the most common histotype, but surprisingly, 37 % of tumors were of high grade. Seventeen patients (21 %) received radiotherapy and 12 patients (15 %) chemotherapy. Five-year DSS for the whole series was 92 % [95 % confidence interval (CI) 83-97]. Five-year rates of local recurrence and DM were 26 % (95 % CI 15-42) and 24 % (95 % CI 15-38), respectively. Tumor grade was found to be a significant predictor of both DSS and DM (both p < 0.001). Quality of surgical margins was proved to affect the local outcome (p = 0.025), while the rates of distant metastases were found to differ significantly by histology (p = 0.010). Exclusively in the liposarcoma subgroup, quality of surgical margins was also directly associated with DSS (p = 0.043). CONCLUSIONS: Wide excision of the tumor is critical for cure, especially in the liposarcoma subgroup. The role of radiotherapy and chemotherapy is not established.

Pneumomediastinum after cocaine use: an unusual aetiology.

We describe an interesting case of pneumomediastinum secondary to cocaine abuse. The patient presented with severe chest pain following nasal inhalation of a large quantity of cocaine. Investigations revealed no chest injury; however oesophagitis was proven leading to a possible aetiology of oesophageal microperforation. After conservative management there was spontaneous resolution of the pneumomediastinum.

Upper gastrointestinal hemorrhage as a rare extragonadal presentation of seminoma of testis.

A rare case of a gastric presentation of a seminoma with burned out primary testicular tumor is described. The patient initially presented with upper gastrointestinal hemorrhage. Endoscopic biopsies were suggestive of seminoma, and testicular ultrasound revealed a focal lesion and testicular microcalcification. Treatment consisted of bilateral orchidectomy, followed by four cycles of etoposide and bleomycin, where a complete response was achieved. Testicular histology was consistent with the "burned out" phenomenon and no tumor cells were found. There are only two previously reported cases of extragonadal seminoma in the stomach.