Evaluating postoperative hernia incidence and risk factors following pelvic exenteration.

Pelvic exenteration (PE) is a technically challenging surgical procedure. More recently, quality of life and survivorship following PEs are being increasingly acknowledged as important patient outcomes. This includes evaluating major long-term complications such as hernias, defined as the protrusion of internal organs through a facial defect (The PelvEx Collaborative in Br J Surg 109:1251-1263, 2022), for which there is currently limited literature. The aim of this paper is to ascertain the incidence and risk factors for postoperative hernia formation among our PE cohort managed at a quaternary centre. METHOD: A retrospective cohort study examining hernia formation following PE for locally advanced rectal carcinoma and locally recurrent rectal carcinoma between June 2010 and August 2022 at a quaternary cancer centre was performed. Baseline data evaluating patient characteristics, surgical techniques and outcomes was collated among a PE cohort of 243 patients. Postoperative hernia incidence was evaluated via independent radiological screening and clinical examination. RESULTS: A total of 79 patients (32.5%) were identified as having developed a hernia. Expectantly, those undergoing flap reconstruction had a lower incidence of postoperative hernias. Of the 79 patients who developed postoperative hernias, 16.5% reported symptoms with the most common symptom reported being pain. Reintervention was required in 18 patients (23%), all of which were operative. CONCLUSION: This study found over one-third of PE patients developed a hernia postoperatively. This paper highlights the importance of careful perioperative planning and optimization of patients to minimize morbidity.

Perioperative outcomes of cytoreductive surgery for tumours of colorectal or appendiceal origin with ovarian involvement.

BACKGROUND AND OBJECTIVES: Ovarian metastases (OM) are a common site for metastases in gastrointestinal tumours with peritoneal disease. This study aimed to evaluate perioperative complications between patients with and without OM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal/colorectal cancer. METHODS: Female patients undergoing CRS ± HIPEC for appendiceal/colorectal tumours at a single centre from 2009 to 2020 were analysed. Patients were grouped according to presence or absence of OM at the time of CRS. RESULTS: The study included 318 patients, 72 (22.6%) had OM. Operation duration was longer for patients with OM (332 vs. 276 min, p < 0.0001). Patients with OM achieved higher rates of complete cytoreduction (93% vs. 79%, p = 0.006) despite a higher peritoneal carcinomatosis index (13 vs. 7, p < 0.001) and were more likely to require a blood transfusion (32% vs. 19%, p = 0.024) and a stoma (24% vs.10%, p = 0.005). Increasing age and presence of abdominal symptoms were independent predictors of major and all-cause morbidity, respectively. The presence of abdominal symptoms was independently associated with all-cause morbidity in the OM group. CONCLUSION: These results may assist with preoperative counselling. Prospective multicentre datasets are needed to evaluate morbidity in one- versus two-stage approaches for those with abdominal symptoms and OM.

Appendiceal pseudomyxoma peritonei: predictors of recurrence and iterative surgery.

AIM: Appendiceal pseudomyxoma peritonei (PMP) is a rare entity, with recurrence rates up to 26% despite optimal cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence specific to PMP originating from non-infiltrative appendiceal mucinous neoplasms (low grade - LAMN and high grade - HAMN) is lacking. The aim of this study was to identify patterns of recurrence and predictive factors for patients appropriate for iterative surgery. METHOD: A bi-institutional retrospective analysis was performed on patients undergoing complete cytoreduction and HIPEC for PMP derived from perforated LAMN or HAMN. Multivariate logistic regression was performed to identify independent predictors for re-do CRS. Five-year overall survival (OS) was stratified according to surgical intervention, and 5-year disease-free survival (DFS) was stratified according to histological PMP grade. Cox regression analysis was performed to identify independent predictors for OS and DFS. RESULTS: Sixty of 239 (25.1%) patients developed peritoneal recurrence between 2007 and 2020. The median time to recurrence was 20.7 months. The risk of disease recurrence was highest with high-grade PMP (P <0.001) and increasing PCI (P <0.001). Patients with high-grade histology from their index procedure and aged over 60 years were less likely to be offered iterative surgery on multivariate analysis. Patients who underwent iterative CRS and HIPEC had a 5-year survival of 100%. CONCLUSION: Iterative CRS and HIPEC is feasible in selected patients with recurrent PMP, displaying good oncological outcomes. Age, index histology and level of abdominal quadrant involvement are predictive of proceeding to re-do surgery.

Prognostic Impact of Tumor-Infiltrating Lymphocytes in Primary and Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: There is increasing literature emerging on the significance of tumor-infiltrating lymphocytes in colorectal cancer. However, there have been inconsistent findings, secondary to small patient numbers and varied methods for identifying these lymphocytes. OBJECTIVE: The aim of this study was to determine the prognostic and predictive power of tumor-infiltrating lymphocytes in colon, rectal (in neoadjuvant setting), and metastatic colorectal cancer. DATA SOURCES: A comprehensive search of PubMed and Embase was undertaken from January 2006 to December 2016. STUDY SELECTION: The inclusion criteria included a description of the tumor-infiltrating lymphocyte subset(s) assessed with reporting of associated short- and long-term outcomes. MAIN OUTCOME MEASURES: The main outcome measures, were disease-free and overall survival. RESULTS: A total of 25 studies were included, 15 for primary colorectal cancer (4719 patients), 7 for locally advanced rectal cancer (727 patients), and 3 studies for metastatic colorectal cancer (418 patients). High CD3, CD8, FoxP3, and CD45RO densities were associated with improved overall survival for primary colorectal cancer, with pooled estimated HRs of 0.88, 0.81, 0.70, and 0.63 (all p < 0.001) respectively. Furthermore, in locally advanced rectal cancer, the levels of CD8 cells were a significant predictor of good tumor regression grade after chemoradiotherapy. LIMITATIONS: The retrospective nature of included studies and the significant interstudy heterogeneity were limitations. CONCLUSIONS: There is increasing evidence that tumor-infiltrating lymphocytes play an important role in predicting prognosis in colorectal cancer and tumor regression after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clinical researchers are now in a unique position to build on this work to identify robust predictive markers to stratify patients not only to currently available therapies but also to immunotherapy, which has demonstrated success in improving patient outcomes.

An Update on Immunotherapy for Solid Tumors: A Review.

In recent years, it has been demonstrated that immunotherapy is an effective strategy for the management of solid tumors. The origins of immunotherapy can be traced back to the work of William Coley, who elicited an immune response against sarcoma by injecting patients with a mixture of dead bacteria. Significant progress has been made since, with immune markers within the tumor now being used as predictors of cancer prognosis and manipulated to improve patient survival. While surgery remains central to the management of most patients with solid malignancies, it is important that surgeons consider the different immunotherapy strategies that can be employed to manage disease. Here, we highlight how the immune system influences tumorigenesis and bring attention to how current and future immunotherapies can serve as an adjunct to surgery.

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

BACKGROUND: Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. OBJECTIVE: The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. DESIGN: A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. SETTINGS: This study is based on a binational colorectal cancer audit database. PATIENTS: Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. RESULTS: A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). LIMITATIONS: This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. CONCLUSIONS: The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

BACKGROUND: Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. OBJECTIVE: The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. DESIGN: This was a retrospective cohort study. SETTING: This study was conducted at a quaternary referral center. PATIENTS: Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. MAIN OUTCOME MEASURES: The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. RESULTS: Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. LIMITATIONS: Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. CONCLUSIONS: Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at http://links.lww.com/DCR/A515.

Recurrent common bile duct stones as a late complication of endoscopic sphincterotomy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) has become well established as a modality for the management of common bile duct stones (CBDS), especially in the setting of associated cholangitis. Our study aims to determine the rate of long term morbidity of recurrent CBDS post ES. METHODS: A retrospective analysis of patients who underwent ERCP and ES (ERCP+ES) was undertaken on a prospectively maintained database from 1998 to 2012 at the Northern Hospital, Melbourne. Primary CBDS were defined as those detected at least 6 months after complete clearance of the CBD. Prior cholecystectomy was a requirement for inclusion and patients with primary CBD stones in the setting of an intact sphincter were excluded. RESULTS: A total of 1148 patients underwent ERCP, of which 573 had an ES. Fifty-one patients underwent an ES prior to developing primary CBDS (8.9%). The time to recurrence ranged from 6 months to 15 years (mean 3.3 years). The number of procedures per patient ranged from 2 to 11, with 51% requiring 3 or more ERCPs. Factors associated with primary CBDS recurrence included a dilated CBD > 12 mm, stricture of the major papilla post ES to 2 - 5 mm and presence of the ampulla within or on the edge of a duodenal diverticulum. CONCLUSION: The results demonstrate that ERCP + ES has an inherent long-term complication of recurrent primary CBDS formation. While this can be managed with repeat ERCP, the advent of laparoscopic bile duct exploration should lead us to re-examine the role of ERCP + ES in younger patients.

Outcome and Salvage Surgery Following "Watch and Wait" for Rectal Cancer after Neoadjuvant Therapy: A Systematic Review.

BACKGROUND: Currently there is no reliable test to predict pathological complete response following neoadjuvant chemoradiotherapy for rectal cancer. However, there is increasing interest in using clinical complete response as a surrogate marker, allowing a subset of patients with locally advanced rectal cancer to be allocated into a "watch and wait" pathway. Little is known about the oncological safety of the "watch and wait" approach or the rate of salvage surgery in cases of tumor regrowth. This information is critical for the implementation of this approach. OBJECTIVE: The aim of this study is to assess the rate of salvage surgery and associated oncological outcomes for patients who develop a tumor regrowth with the "watch and wait" approach. DATA SOURCES: Relevant studies were identified through PubMed, Embase, and Google Scholar search. STUDY SELECTION: A systematic review was undertaken of studies assessing patients selected for the "watch and wait" approach according to PRISMA guidelines. MAIN OUTCOME MEASURES: The associated tumor regrowth, salvage surgery, and disease-free and overall survival rates were assessed. RESULTS: Five retrospective and 4 prospective observational studies were included into the analysis, with a total of 370 patients in the "watch and wait" group, of which 256 (69.2%) had persistent clinical complete response. Of those who had tumor regrowth, salvage surgery was possible in 83.8%. There was no difference in overall survival and disease-free survival between patients who received immediate surgery and the "watch and wait" group. LIMITATIONS: The limitations of this study include its retrospective nature and small sample size. Furthermore, there is significant heterogeneity between study protocols, including the short median follow-up, given that tumor regrowth and distant metastasis may manifest at a later time point. CONCLUSION: The majority of patients with tumor regrowth can be salvaged with definite surgery after "watch and wait." However, there is insufficient evidence to draw firm conclusions on the oncological safety of this approach; therefore, it is currently not the standard of care for locally advanced rectal cancer.

A systematic review of minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally a maximally invasive operation with a large abdominal incision and multi-visceral resections. However, to minimize abdominal wall morbidity and improve functional recovery, some centres have adopted a minimally invasive (MI) approach in select cases. The primary aim of this systematic review and meta-analysis was to assess the evidence for safety and patient selection for minimally invasive approaches to CRS and HIPEC with curative intent. METHODS: A PRISMA-compliant systematic review was performed using three electronic databases: Ovid MEDLINE, EMBASE and Web of Science. Data regarding postoperative morbidity was meta-analysed. RESULTS: Thirteen studies met the inclusion criteria (N = 462 MI patients), all of which were retrospective in design. Six studies included an open comparison group. Pseudomyxoma peritonei, mesothelioma and ovarian carcinoma made up the majority of cases (>90%), with a PCI < 10 listed as a prerequisite to selection across all studies. On pooled analysis there was no difference in major morbidity between MI and open groups (OR 0.52 95% CI 0.18-1.46, P = 0.33). There was one perioperative death reported in the MI group. Length of stay appeared shorter in the MI group (median range MI: 4-11 v Open: 7-13 days). Short-term recurrence and overall survival between both groups also appeared no different. CONCLUSION: Minimally invasive CRS and HIPEC appears feasible and safe in appropriately selected patients. Clear histological stratification and longer term follow up is required to determine oncological safety, particularly in more aggressive tumours such as colorectal peritoneal metastases.

The utility of ctDNA in colorectal cancer with peritoneal metastases.

BACKGROUND: The development of peritoneal metastases (PM) in patients with colorectal cancer (CRC) connotates a poor prognosis. Circulating tumour (ctDNA) is a promising tumour biomarker in the management CRC. This systematic review aimed to summarize the role of ctDNA in patients with CRC and PM. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic review of the literature until June 2022 was performed. Studies reporting on the utility of ctDNA in colorectal PM were included. A total of eight eligible studies were identified including a total of 167 patients. RESULTS: The findings from this review suggest an evolving role for ctDNA in CRC with PM. ctDNA can be isolated from both plasma and peritoneal fluid, with peritoneal fluid preferred as the liquid biopsy of choice with higher mutation detection rates. Concordance rates between tissue and plasma/peritoneal ctDNA mutation detection can vary, but is generally high. ctDNA has a potential role in monitoring anti-EGFR treatment response and resistance, as well as in predicting future prognosis and recurrence. The detection of ctDNA in plasma of patients with isolated PM is also possibly suggestive of occult systemic disease, and patients exhibiting such ctDNA positivity may benefit from systemic treatment. Limitations to ctDNA mutation detection may include the size of peritoneal lesions, as well as the fact that PM poorly shed ctDNA. CONCLUSION: While these findings are promising, further large-scale studies are needed to better evaluate the utility of ctDNA in this subset of patients.

Parenteral nutrition after cytoreductive surgery for peritoneal malignancy: Should it be administered routinely?

PURPOSE/BACKGROUND: Cytoreductive surgery (CRS) is complex abdominal surgery that is used to treat peritoneal malignancy. CRS is associated with major morbidity and efforts to address this include optimisation of perioperative care. There is variation in international protocols on the nutritional management after CRS, in particular whether parenteral nutrition (PN) should be routinely or selectively administered. HYPOTHESIS/AIM: This study assessed parenteral nutrition use, factors associated with PN requirement and nutritional outcomes in a centre that selectively uses PN after CRS. METHODS/INTERVENTIONS: A retrospective analysis was undertaken on patients who underwent cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) at Peter MacCallum Cancer Centre between 1st January 2015 and 31st December 2020 using data entered into a prospectively maintained database. Patient characteristics, nutritional status, oncological parameters, operative details and postoperative outcome data were retrieved. Categorical variables were compared using the chi-squared test and continuous data was compared using a non-parametric Mann-Whitney U-test. A p-value <0.05 was considered statistically significant. Cox regression analysis was performed to identify independent predictors of requiring PN and postoperative weight change over admission. RESULTS: A total of 222 patients who had CRS between were included (mean age 56 years; female 61.3%). Preoperative nutritional characteristics of participants included a mean body mass index (BMI) of 27.6 kg/m2 and the majority (77.9%) were not at nutritional risk pre-operatively with a Patient Generated Subjective Global Assessment (PG-SGA) score of category A. A high proportion of patients had surgery for colonic adenocarcinoma (58.1%), received HIPEC (87.4%) and achieved complete cytoreduction (82%). Postoperative parenteral nutrition was required for 65 patients (29.3%). The most frequent indication for PN was postoperative ileus (63.1%) with the mean (SD) time to commencing PN being postoperative day 5. Factors associated with the requirement for postoperative PN included preoperative albumin (OR 0.89; p = 0.015), weight loss >5% of body weight in the 6 months prior to admission (OR 2.2; p = 0.05), higher PCI score (OR 1.048; p = 0.005), number of anastomoses completed (OR 1.766; p = 0.017) and development of any postoperative complication (OR 2.71; p = 0.009). PN use was not associated with postoperative weight change. CONCLUSION: Most patients undergoing CRS did not require post-operative PN. Nutritional and operative factors may identify patients who are likely to need PN after surgery. Selective use of PN did not impact on postoperative weight change.

Anastomotic Leak in Colorectal Surgery: Predictive Factors and Survival.

<br><b>Introduction:</b> Anastomotic leak (AL) is a serious complication following colorectal surgery.</br> <br><b>Aim:</b> The aim of this study was to identify factors associated with the development of AL and to analyze its impact on survival.</br> <br><b>Materials and methods:</b> All consecutive adult colorectal cancer resections performed between 2007 and 2020 with curative intent and anastomosis formation were included from a prospectively maintained database. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).</br> <br><b>Results:</b> There were 6837 eligible patients. The rate of AL was 2.2% and 4.0% in patients with colon and rectal cancer, respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (odds ratio 2.293, p = 0.009). Emergency surgery (p = 0.015), surgery at a public hospital (p = 0.002), and an open surgical approach (p = 0.021) were all associated with a significantly higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (4.4% <i>vs.</i> 1.3%, p < 0.001). In rectal cancer patients, AL was associated with neoadjuvant chemoradiotherapy (p = 0.038) and male gender (p = 0.002). The anastomosis formation technique (hand-sewn <i>vs.</i> stapled) did not impact the rate of AL (p = 0.116 and p = 0.198 with colon and rectal cancer, respectively).</br> <br><b>Discussion:</b> Clinicians should be cognizant of the predictive factors for AL and should consider early intervention for at-risk patients.</br>.

Predictive Factors for Anastomotic Leak in Colorectal Surgery: A Bi-National Database Study.

IntroductionAnastomotic leak (AL) is a serious complication following colorectal surgery. This study aimed to identify factors associated with the development of AL and analyze its impact on survival.Materials and MethodsAll consecutive adult colorectal cancer resections with curative intent and anastomosis formation were included from a prospectively maintained bi-national database between 2007 and 2020. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).ResultsThere were 7566 eligible patients. The rate of AL was 2.3% and 4.4% in patients with colon and rectal cancer respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (Odds ratio 1.999, p = 0.017). Emergency surgery (p = 0.013), surgery at a public hospital (p < 0.01), and an open surgical approach (p = 0.002) were all significantly associated with a higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (6.8% vs 1.6%, p < 0.05). In rectal cancer patients, ultra-low anterior resections had the highest risk of AL (4.6%), and associations were found with neoadjuvant chemotherapy (p = 0.011), surgery in a public hospital (p = 0.019), and an open approach (p = 0.035). Anastomosis formation technique (hand-sewn vs stapled) did not impact on rate of AL.DiscussionClinicians should be cognizant of the predictive factors for AL and consider early intervention for patients at risk of this.

Colorectal cancer in younger adults from a Bi-National Colorectal Cancer Audit registry.

BACKGROUND: The incidence of colorectal cancer (CRC) in younger adults (<50 years old) is rising worldwide, at a rate of 1% per annum since mid-1980s. The clinical concern is that younger adults may have more advanced disease leading to poorer prognosis compared to their older cohort due to lack of screening. Therefore, the aim of this study is to assess the incidence and short-term outcomes of colorectal cancer in younger adults. METHODS: This is a retrospective study from a prospectively maintained bi-national database from 2007 to 2018. RESULTS: There were 1540 younger adults diagnosed with CRC, with a rise from 5.8% in 2007 to 8.4% in 2018. Majority had lower American Society of Anaesthesiologists (ASA) scores (89%), rectal cancers (46.1%) and higher tumour stage (65.4%). As a consequence, they were likely to have higher circumferential resection margin positivity (6%, P = 0.02) and to receive adjuvant chemotherapy (57.1%, P < 0.001) compared to their older cohort. Multivariate analysis showed disadvantaged socioeconomic status (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.37-7.94, P < 0.001) and increasing tumour stage (OR 14.9, 95% CI 1.89-116.9, P < 0.001) were independent predictors for circumferential resection margin positivity whereas being female (OR 0.71, 95% CI 0.53-0.95, P = 0.02), higher ASA score (OR 175.3, 95% CI 26.7-1035.5, P < 0.001), urgent surgery (OR 2.75, 95% CI 1.84-4.11, P < 0.001) and anastomotic leak (OR 5.02, 95% CI 3.32-7.58, P < 0.001) were predictors of inpatient mortality. CONCLUSION: There is a steady rise in the incidence of colorectal cancer in younger adults. Both physicians and younger adults should be aware of the potential risk of colorectal cancer (CRC) and appropriate investigations performed so not to delay the diagnosis.

Molecular and genomic characterisation of a panel of human anal cancer cell lines.

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.

Inguinal lymph node dissection for penile cancer: a contemporary review.

Penile cancer is an uncommon disease associated with significant psychological and physical morbidity. Penile cancer has an expectable pattern of spread in a stepwise fashion, from inguinal to pelvic lymph nodes (PLN) then distant spread. Patients with penile cancer have variable survival, with patients with a low burden of nodal metastatic disease having lasting survival with surgical management, however patients with a large amount of locoregional metastatic disease having a worse prognosis. The current management options for patients with metastatic lymph node disease in penile cancer aims to reduce the morbidity associated with radical inguinal lymph node (ILN) surgery with appropriate risk stratification to optimise oncological control of the disease. This article describes current challenges in managing the inguinal region in patients with penile squamous cell carcinoma (SCC).

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.