Primary pure squamous cell carcinoma of the gallbladder.

SummarySquamous cell carcinoma (SCC) is an uncommon and frequently aggressive subtype of gallbladder cancer known for its poor outcomes compared with other gallbladder tumours. Gallbladder SCC typically presents as higher grade and more advanced than adenocarcinoma, resulting in lower estimated survival. Early recognition of these tumours is ideal, but infrequently achieved. Herein is a case of a male patient in his 80s with new onset abdominal pain who was initially diagnosed with cholecystitis, but diagnostic imaging revealed a gallbladder mass. Surgical resection and pathology revealed pure SCC of the gallbladder without local organ invasion or metastatic disease. Pure SCC histology of the gallbladder is rare, with limited studies on clinical presentation, natural history, and optimal treatment.

Comparison of epidural infusion versus intrathecal morphine block as part of enhanced recovery after open pancreatoduodenectomy.

BACKGROUND AND OBJECTIVES: The accepted approach to pain management following open pancreatoduodenectomy (PD) remains controversial, with the most recent enhanced recovery after surgery (ERAS) protocols recommending epidural anesthesia (EA). Few studies have investigated intrathecal (IT) morphine, combined with transversus abdominis plane (TAP) blocks. We aim to compare the different approaches to pain management for open PD. METHODS: Patients who underwent open PD at our institution from 2020 to 2022 were included in the study. Patient characteristics, pain management, and postoperative outcomes between EA, IT morphine with TAP blocks, and TAP blocks only were compared using univariate analysis. RESULTS: Fifty patients were included in the study (58% male, median age 66 years [interquartile range, IQR: 58-73]). Most patients received IT morphine (N = 24, 48%) or EA (N = 18, 36%). The TAP block-only group required higher doses of postoperative narcotics while hospitalized (p = 0.004) and at discharge (p = 0.017). The IT morphine patients had a shorter median time to Foley removal (p = 0.007). Postoperative pain scores, non-opioid administration, postoperative bolus requirements, postoperative outcomes, and length of stay were similar between pain modalities. CONCLUSIONS: IT morphine and EA showed comparable efficacy with superior results compared to TAP blocks alone. Integration of IT morphine into PD ERAS protocols should be considered.

Disparities in Surgical Treatment of Resectable Pancreatic Adenocarcinoma at Minority Serving Hospitals.

INTRODUCTION: Minority serving hospitals (MSH) are those serving a disproportionally high number of minority patients. Previous research has demonstrated that treatment at MSH is associated with worse outcomes. We hypothesize that patients treated at MSH are less likely to undergo surgical resection of pancreatic adenocarcinoma compared to patients treated at non-MSH. METHODS: Patients with resectable pancreatic cancer were identified using the National Cancer Database. Institutions treating Black and Hispanic patients in the top decile were categorized as an MSH. Factors associated with the primary outcome of definitive surgical resection were evaluated using multivariable logistic regression. Univariate and multivariable survival analysis was performed. RESULTS: Of the 75,513 patients included in this study, 7.2% were treated at MSH. Patients treated at MSH were younger, more likely to be uninsured, and higher stage compared to those treated at non-MSH (P < 0.001). Patients treated at MSH underwent surgical resection at lower rates (MSH 40% versus non-MSH 44.5%, P < 0.001). On multivariable logistic regression, treatment at MSH was associated with decreased likelihood of undergoing definitive surgery (odds ratio 0.91, P = 0.006). Of those who underwent surgical resection, multivariable survival analysis revealed that treatment at an MSH was associated with increased morality (hazard ratio 1.12, P < 0.001). CONCLUSIONS: Patients with resectable pancreatic adenocarcinoma treated at MSH are less likely to undergo surgical resection compared to those treated at non-MSH. Targeted interventions are needed to address the unique barriers facing MSH facilities in providing care to patients with pancreatic adenocarcinoma.

Risk factors and outcomes in patients undergoing minimally invasive hepatectomy with unplanned conversion: a contemporary NSQIP analysis.

BACKGROUND: Minimally invasive techniques are growing for hepatectomies. Laparoscopic and robotic liver resections have been shown to differ in conversions. We hypothesize that robotic approach will have decreased conversion to open and complications despite being a newer technique than laparoscopy. METHODS: ACS NSQIP study using the targeted Liver PUF from 2014 to 2020. Patients grouped based on hepatectomy type and approach. Multivariable and propensity scored matching (PSM) was used to analyze the groups. RESULTS: Of 7767 patients who underwent hepatectomy, 6834 were laparoscopic and 933 were robotic. The rate of conversions was significantly lower in robotic vs laparoscopic (7.8% vs 14.7%; p < 0.001). Robotic hepatectomy was associated with decreased conversion for minor (6.2% vs 13.1%; p < 0.001), but not major, right, or left hepatectomy. Operative factors associated with conversion included Pringle (OR = 2.09 [95% CI 1.05-4.19]; p = 0.0369), and a laparoscopic approach (OR = 1.96 [95% CI 1.53-2.52]; p < 0.001). Undergoing conversion was associated with increases in bile leak (13.7% vs 4.9%; p < 0.001), readmission (11.5% vs 6.1%; p < 0.001), mortality (2.1% vs 0.6%; p < 0.001), length of stay (5 days vs 3 days; p < 0.001), and surgical (30.5% vs 10.1%; p < 0.001), wound (4.9% vs 1.5%; p < 0.001) and medical (17.5% vs 6.7%; p < 0.001) complications. CONCLUSION: Minimally invasive hepatectomy with conversion is associated with increased complications, and conversion is increased in the laparoscopic compared to a robotic approach.

Unsuspected gastric glomus tumour.

Gastric glomus tumours (GGTs) are rare predominantly benign, mesenchymal neoplasms that commonly arise from the muscularis or submucosa of the gastric antrum and account for <1% of gastrointestinal soft-tissue tumours. Historically, GGT has been difficult to diagnose preoperatively due to the lack of unique clinical, endoscopic and CT features. We present a case of an incidentally identified GGT in an asymptomatic man that was initially considered a neuroendocrine tumour (NET) by preoperative fine-needle aspiration biopsy with focal synaptophysin reactivity. An elective robotic distal gastrectomy and regional lymphadenectomy were performed. Postoperative review by pathology confirmed the diagnosis of GGT. GGTs should be considered by morphology as a differential diagnosis of gastric NET on cytology biopsy, especially if there is focal synaptophysin reactivity. Additional staining for SMA and BRAF, if atypical/malignant, can help with this distinction. Providers should be aware of the biological behaviour and treatment of GGTs.

Extended postoperative thromboprophylaxis after pancreatic resection for pancreatic cancer is associated with decreased risk of venous thromboembolism in the minimally invasive approach.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with increased venous thromboembolism (VTE). We sought to compare rates of bleeding complications and VTE in patients receiving extended postoperative thromboprophylaxis (EPT) to those who did not, and identify risk factors for VTE after pancreatectomy for PDAC. METHODS: This is a retrospective review of pancreatectomies for PDAC. EPT was defined as 28 days of low molecular weight heparin. Multivariable analysis (MVA) was performed to identify independent risk factors of VTE. RESULTS: Of 269 patients included, 142 (52.8%) received EPT. Of those who received EPT, 7 (4.9%) suffered bleeding complications, compared to 6 (4.7%) of those who did not (p = 0.938). There was no significant difference in VTE rate at 90 days (2.8% vs. 2.4%, p = 0.728) or at 1 year (6.3% vs. 7.9%, p = 0.624). On MVA, risk factors for VTE included worse performance status, lower preoperative hematocrit, R1/R2 resection, and minimally invasive (MIS) approach. Among those who received EPT, there was no difference in VTE rate between MIS and open approach. CONCLUSIONS: EPT was not associated with a difference in VTE risk or bleeding complications. MIS approach was associated with a higher risk of VTE; however, this was significantly lower among those who received EPT.

Management of Clinical T2N0 Esophageal and Gastroesophageal Junction Adenocarcinoma: What Is the Optimal Treatment?

BACKGROUND: The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma includes neoadjuvant chemoradiation and surgery. The optimal treatment for clinical T2N0M0 (cT2N0) disease is debated. This study aims to determine the optimal treatment in these patients. METHODS: The National Cancer Database was used to identify patients who underwent surgery for cT2N0 esophageal and GEJ adenocarcinoma from 2004 to 2017. Patients were grouped into surgery-alone, neoadjuvant therapy (NAT), and adjuvant therapy (AT) groups. Subgroups of high-risk patients (tumor ≥ 3 cm, poor differentiation, or lymphovascular invasion) and patients upstaged after upfront surgery were identified. Kaplan-Meier method and Cox proportional hazard ratios were used to compare overall survival. RESULTS: Of 2160 patients included, 957 (44.3%) underwent surgery-alone, 821 (38.0%) underwent NAT and surgery, and 382 (17.7%) underwent surgery and AT. One thousand six hundred nineteen (75.0%) patients had high-risk features. Six hundred fourteen (45.9%) patients were upstaged after upfront surgery. In the overall cohort, AT was associated with improved survival compared to NAT (HR 0.618, p < 0.001) and surgery-alone (HR 0.699, p < 0.001). There was no difference in survival between NAT and surgery-alone (HR 1.132, p = 0.112). Similar results were observed in high-risk patients. Patients upstaged after upfront surgery who received AT had improved survival compared to those initially treated with NAT (HR 0.613, p < 0.001). CONCLUSION: This analysis suggests that cT2N0 esophageal and GEJ adenocarcinomas may not benefit from the intensive multimodality therapy utilized in locally advanced disease. Selective use of AT for patients who are upstaged pathologically, or have high-risk features, is associated with improved outcomes.

Predictors of Conversion During Minimally Invasive Gastrectomy for Malignancy.

INTRODUCTION: Implementation of minimally invasive gastrectomy (MIG) for malignancy is increasing. However, risk factors for conversion to open surgery during laparoscopic and robotic gastrectomy are poorly understood. This study aimed to determine the risk factors for, and impact of, conversion during oncologic resection. METHODS: The National Cancer Database (NCDB) was used to identify patients with clinical stage I-III gastric cancer from 2010 to 2017. Chi-squared test and t-test were used to compare the robotic versus laparoscopic groups. Propensity score weighted multivariable logistic regression was used to evaluate factors associated with conversion to open surgery. RESULTS: Of 6990 patients identified, 5702 (81.6%) underwent a laparoscopic resection and 1288 (18.4%) underwent robotic-assisted resection. Conversion rates were 14.7% and 7.8% for laparoscopic and robotic gastrectomy, respectively. The robotic approach was associated with lower likelihood of conversion compared to laparoscopic approach (odds ratio [OR] = 0.470, P < 0.001). Other factors predictive of conversion included tumor size >5 cm compared to <2 cm (OR 1.714, P = 0.010), total gastrectomy compared to partial gastrectomy (OR 2.019, P < 0.001), antrum/pylorus (OR 2.345, P < 0.001), and body (OR 2.152, P < 0.001) tumors compared to cardia tumors. Compared to those treated with laparoscopic and robotic gastrectomy, patients who underwent conversion experienced significantly longer hospital length of stay and higher rates of positive surgical margins. CONCLUSIONS: Laparoscopic gastrectomy was associated with a higher conversion rate compared to robotic gastrectomy. Conversion to open surgery was associated with a significantly longer length of stay and higher rates of positive margins. Identification of risk factors for conversion can aid in appropriate modality selection.

Albumin-bilirubin score is superior to platelet-albumin-bilirubin score and model for end-state liver disease sodium for predicting posthepatectomy liver failure.

BACKGROUND: Risk stratification for patients undergoing hepatectomy can be attempted using established models. This study compares the platelet-albumin-bilirubin (PALBI) score with albumin-bilirubin (ALBI) and model for end-stage liver disease sodium (MELD-Na) for predicting posthepatectomy liver failure (PHLF) and 30-day mortality. METHODS: The 2014-2018 NSQIP database was queried for patients who underwent elective hepatectomy. Multivariable logistic regressions assessed associations of posthepatectomy outcomes with patient and clinical characteristics. Predictive accuracy of the grading systems was evaluated using receiver operator characteristic (ROC) curves and calculating area under the curve (AUC). RESULTS: Severe PHLF (Grade B/C) and mortality were present in 2.58% (N = 369) and 1.2% (N = 171) of patients who underwent hepatectomy (N = 13 925), respectively. ALBI Grade 2/3 had a stronger association with severe PHLF (odds ratio [OR] = 1.62, p < 0.01) and mortality (OR = 2.06, p < 0.005) than PALBI Grade 2/3 (OR = 1.14, p = 0.43 for PHLF and OR = 2.01, p < 0.005 for mortality) or MELD-Na ≥10 (OR = 1.29, p = 0.25 for PHLF and OR = 1.84, p < 0.03). ALBI had a higher AUC (0.671) than PALBI (0.625) and MELD-Na (0.627) for predicting severe PHLF. ALBI had a higher AUC (0.695) than PALBI (0.642) for predicting 30-day mortality. CONCLUSIONS: ALBI was a more accurate predictor of severe PHLF and 30-day mortality than MELD-Na and PALBI for patients who underwent hepatectomy.

Bile leak incidence, risk factors and associated outcomes in patients undergoing hepatectomy: a contemporary NSQIP propensity matched analysis.

BACKGROUND: Despite advances in surgical technique, bile leak remains a common complication following hepatectomy. We sought to identify incidence of, risk factors for, and outcomes associated with biliary leak. STUDY DESIGN: This is an ACS-NSQIP study. Distribution of bile leak stratified by surgical approach and hepatectomy type were identified. Univariate and multivariate factors associated with bile leak and outcomes were evaluated. RESULTS: Robotic hepatectomy was associated with less bile leak (5.4% vs. 11.4%; p < 0.001) compared to open. There were no significant differences in bile leak between robotic and laparoscopic hepatectomy (5.4% vs. 5.3%; p = 0.905, respectively). Operative factors risk factors for bile leak in patients undergoing robotic hepatectomy included right hepatectomy [OR 4.42 (95% CI 1.74-11.20); p = 0.002], conversion [OR 4.40 (95% CI 1.39-11.72); p = 0.010], pringle maneuver [OR 3.19 (95% CI 1.03-9.88); p = 0.044], and drain placement [OR 28.25 (95% CI 8.34-95.72); p < 0.001]. Bile leak was associated with increased reoperation (8.7% vs 1.7%, p < 0.001), 30-day readmission (26.6% vs 6.8%, p < 0.001), 30-day mortality (2% vs 0.9%, p < 0.001), and complications (67.2% vs 23.4%, p < 0.001) for patients undergoing MIS hepatectomy. CONCLUSION: While MIS confers less risk for bile leak than open hepatectomy, risk factors for bile leak in patients undergoing MIS hepatectomy were identified. Bile leaks were associated with multiple additional complications, and the robotic approach had an equal risk for bile leak than laparoscopic in this time period.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Robotic gastrointestinal surgery: learning curve, educational programs and outcomes.

The use of the robotic platform for gastrointestinal surgery was introduced nearly 20 years ago. However, significant growth and advancement has occurred primarily in the last decade. This is due to several advantages over traditional laparoscopic surgery allowing for more complex dissections and reconstructions. Several randomized controlled trials and retrospective reviews have demonstrated equivalent oncologic outcomes compared to open surgery with improved short-term outcomes. Unfortunately, there are currently no universally accepted or implemented training programs for robotic surgery and robotic surgery experience varies greatly. Additionally, several limitations to the robotic platform exist resulting in a distinct learning curve associated with various procedures. Therefore, implementation of robotic surgery requires a multidisciplinary team approach with commitment and investment from clinical faculty, operating room staff and hospital administrators. Additionally, there is a need for wider distribution of educational modules to train more surgeons and reduce the associated learning curve. This article will focus on the implementation of the robotic platform for surgery of the pancreas, stomach, liver, colon and rectum with an emphasis on the associated learning curve, educational platforms to develop proficiency and perioperative outcomes.

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Novel response to neoadjuvant anti-PD1 therapy for a patient with retrocaval melanotic schwannoma.

Melanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symptoms related to nerve compression and mass effect. Due to the rarity of these lesions, they can be initially misidentified as melanocytomas, pigmented dermatofibrosarcoma protuberans, neurofibromas or malignant melanomas. Surgical excision is the mainstay of treatment with limited benefit from adjuvant systemic chemotherapy or radiation. Modern treatments with immune checkpoint blockade have demonstrated significant improvements in progression-free and overall survival for a variety of cancer histologies; however, anti-PD1 therapy has yet to be evaluated in patients with melanotic schwannoma. This report demonstrates a significant improvement in symptomatology and tumor stability with neoadjuvant anti-PD1 therapy for a retrocaval melanotic schwannoma initially masquerading as malignant melanoma. This report demonstrates the potential benefit of a novel therapeutic option for patients with melanotic schwannoma.

Novel Application of Iterative Hyperthermic Intraperitoneal Chemotherapy for Unresectable Peritoneal Metastases from High-Grade Appendiceal Ex-Goblet Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PMs) from appendiceal ex-goblet adenocarcinoma (AEGA) are associated with a poor prognosis. While cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong survival, the majority of patients are ineligible for complete cytoreduction. We describe a novel approach to the management of such patients with iterative HIPEC (IHIPEC). METHODS: Patients with signet ring/poorly differentiated AEGA with high Peritoneal Cancer Index (PCI) and extensive bowel involvement underwent IHIPEC with mitomycin C at 6-week intervals for a total of three cycles. Survival outcomes for these patients were compared with patients with high-grade appendiceal tumors matched for tumor burden who were treated with other conventional approaches, i.e. systemic chemotherapy only (SCO) or complete CRS + HIPEC. RESULTS: Between 2016 and 2019, seven AEGA patients with high PCI (median 32.5 [range 21-36]) underwent 18 IHIPEC cycles (median cycles per patient 3 [2-3]) in combination with systemic chemotherapy (median 2 lines [1-3], 12 cycles [10-28]). IHIPEC was delivered laparoscopically in 14/18 cases. Postoperatively, the median length of stay was 1 day (1-8 days), no procedure-related complications were reported, and five (28%) 90-day readmissions for bowel obstruction were documented. Median overall survival after IHIPEC was better compared with a matched group of patients (n = 16) receiving SCO (24.6 vs. 7.9 months; p = 0.005), and similar to those (n = 7) who underwent CRS + HIPEC (24.6 vs. 16.5 months; p = 0.62). CONCLUSIONS: IHIPEC in combination with systemic chemotherapy is tolerable, safe, and may be associated with encouraging survival outcomes compared with SCO in selected patients with high-grade, high-burden AEGA PM.

Robotic pancreaticoduodenectomy decreases the risk of clinically relevant post-operative pancreatic fistula: a propensity score matched NSQIP analysis.

BACKGROUND: A single-institution study demonstrated robotic pancreaticoduodenectomy (RPD) was protective against clinically-relevant postoperative pancreatic fistula (CR-POPF) compared to open pancreaticoduodenectomy (OPD). We sought to compare the national rate of CR-POPF by approach. METHODS: Procedure-targeted pancreatectomy Participant User Data File was queried from 2014 to 2017 for all patients undergoing pancreaticoduodenectomy. A modified fistula risk score was calculated and patients were stratified into risk categories. Multivariate logistic regression and propensity score matching was used. RESULTS: The rate of CR-POPF (15.6% vs. 11.9%; p = 0.026) was higher in OPD compared to RPD. On subgroup analysis, OPD had higher CR-POPF in high risk patients (32.9% vs. 19.4%; p = 0.007). On multivariable analysis OPD was a predictor of increased CR-POPF (Odds Ratio [OR] = 1.61 [1.15-2.25]; p = 0.005). Other operative factors associated with increased CR-POPF included soft pancreatic texture (OR = 2.65 [2.27-3.09]; p < 0.001) and concomitant visceral resection (OR = 1.41 [1.03-1.93]; p = 0.031). Increased duct size (reference <3 mm) was predictive of decreased CR-POPF: 3-6 mm (OR = 0.70 [0.61-0.81]; p < 0.001) and ≥6 mm (OR = 0.47 [0.37-0.60]; p < 0.001). Following propensity score matching, RPD continued to be protective against the occurrence of CR-POPF (OR = 1.54 [1.09-2.17]; p = 0.013). CONCLUSIONS: This is the largest multicenter study to evaluate the impact of RPD on POPF. It suggests that RPD can be protective against POPF, especially for high risk patients.

Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy.

Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.