Vascular challenges from pancreatoduodenectomy in the setting of coeliac artery stenosis

Coeliac artery stenosis due to median arcuate ligament compression or atherosclerotic disease is a frequently unrecognised challenge to recovery after pancreatoduodenectomy. The described case illustrates management with intraoperative superior mesenteric artery to hepatic artery bypass graft that led to haemorrhagic challenges postoperatively but ultimately a good recovery. Aspects of preoperative diagnosis, preoperative intervention and intraoperative management options are reviewed. Surgeons need to possess these tools to prevent complications from coeliac artery stenosis when pancreatoduodenectomy is required

Ideal Outcome After Pancreatoduodenectomy:A Transatlantic Evaluation of a Harmonized Composite Outcome Measure

OBJECTIVE: The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden. BACKGROUND: Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO). METHODS: This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications-Clavien-Dindo ≥3, (3) postoperative pancreatic fistula-International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay &gt;75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models. RESULTS: Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P &lt;0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO. CONCLUSIONS: The newly developed composite outcome measure "Ideal Outcome" can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.</p

Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)

INTRODUCTION: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC. METHODS: One hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at \u3c40 or breast cancer \u3c50 years of age). RESULTS: Frequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants. CONCLUSION: Type and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies

The State of Immunotherapy in Hepatobiliary Cancers

Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options

Morbidity and Mortality after Surgery for Retroperitoneal Sarcoma

Retroperitoneal sarcoma (RPS) is a rare disease with over 100 histologic types and accounts for 10–15% of all soft tissue sarcomas. Due to the rarity of RPS, sarcoma centers in Europe and North America have created the Transatlantic RPS Working Group (TARPSWG) to study this disease and establish best practices for its management. Current guidelines dictate complete resection of all macro and microscopic disease as the gold standard for patients with RPS. Complete extirpation often requires a multi-visceral resection. In addition, recent evidence suggests that en bloc compartmental resections are associated with reduced rates of local recurrence. However, this approach must be balanced by the potential for added morbidity. Strategies to mitigate postoperative complications include optimization of the patient through improved preoperative nutrition and pre-habilitation therapy, referral to a high-volume sarcoma center, and implementation of enhanced recovery protocols. This review will focus on the factors associated with perioperative complications following surgery for RPS and outline approaches to mitigate poor surgical outcomes in this patient population

Is American College of Surgeons NSQIP organ space infection a surrogate for pancreatic fistula?

BACKGROUND: In the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), pancreatic fistula has not been monitored, although organ space infection (OSI) data are collected. Therefore, the purpose of this analysis was to determine the relationship between ACS NSQIP organ space infection and pancreatic fistulas. STUDY DESIGN: From 2007 to 2011, 976 pancreatic resection patients were monitored via ACS NSQIP at our institution. From this database, 250 patients were randomly chosen for further analysis. Four patients were excluded because they underwent total pancreatectomy. Data on OSI were gathered prospectively. Data on pancreatic fistulas and other intra-abdominal complications were determined retrospectively. RESULTS: Organ space infections (OSIs) were documented in 22 patients (8.9%). Grades B (n = 26) and C (n = 5) pancreatic fistulas occurred in 31 patients (12.4%); grade A fistulas were observed in 38 patients (15.2%). Bile leaks and gastrointestinal (GI) anastomotic leaks each developed in 5 (2.0%) patients. Only 17 of 31 grade B and C pancreatic fistulas (55%), and none of 38 grade A fistulas were classified as OSIs in ACS NSQIP. In addition, only 2 of 5 bile leaks (40%) and 2 of 5 GI anastomotic leaks (40%) were OSIs. Moreover, 3 OSIs were due to bacterial peritonitis, a chyle leak, and an ischemic bowel. CONCLUSIONS: This analysis suggests that the sensitivity (55%) and specificity (45%) of organ space infection (OSI) in ACS NSQIP are too low for OSI to be a surrogate for grade B and C pancreatic fistulas. We concluded that procedure-specific variables will be required for ACS NSQIP to improve outcomes after pancreatectomy

Trends in Textbook Outcomes over Time: Are Optimal Outcomes Following Complex Gastrointestinal Surgery for Cancer Increasing?

Background: The use of composite measures like "textbook outcome" (TO) may provide a more accurate measure of surgical quality. We sought to determine if TO has improved over time and to characterize the association of achieving a TO with trends in survival among patients undergoing complex gastrointestinal surgery for cancer. Methods: Medicare beneficiaries who underwent pancreas, liver, or colon resection for a cancer diagnosis between 2004 and 2016 were identified using the SEER-Medicare database. Rates of TO (no complication, extended length of stay, 90-day readmission, or 90-day mortality) were assessed over time. Results: Among 94,329 patients, 6765 (7.2%), 1985 (2.1%), and 85,579 (90.7%) patients underwent resection for primary pancreatic, hepatic, or colon cancer, respectively. In total, 53,464 (56.7%) patients achieved a TO; achievement of TO varied by procedure (pancreatectomy: 48.1% vs. hepatectomy: 55.2% vs. colectomy: 57.4%, p < 0.001). The proportion of patients achieving a textbook outcome increased over time for all patients (2004-2007, 53.3% vs. 2008-2011, 56.5% vs. 2012-2016, 60.1%) (5-year increase: OR 1.16 95%CI 1.13-1.18) (p < 0.001). Survival at 1-year following pancreatic, liver, or colon resection for cancer had improved over time among both patients who did and did not achieve a postoperative TO. TO was independently associated with a marked reduction in hazard of death (HR 0.44, 95%CI 0.43-0.45). The association of TO and survival was consistent among patients stratified by procedure. Conclusion: Less than two-thirds of patients undergoing complex gastrointestinal surgery for a malignant indication achieved a TO. The likelihood of achieving a TO increased over time and was associated with improved survival

Transcriptome Analysis of Human Endogenous Retroviruses at Locus-Specific Resolution in Non-Small Cell Lung Cancer

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide. Among its subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the most common, accounting for more than 85% of lung cancer diagnoses. Despite the incredible efforts and recent advances in lung cancer treatments, patients affected by this condition still have a poor prognosis. Therefore, novel diagnostic biomarkers are needed. Recently, a class of transposable elements called human endogenous retroviruses (HERVs) has been found to be implicated in cancer development and later employed as novel biomarkers for several tumor types. In this study, we first ever characterized the expression of HERVs at genomic locus-specific resolution in both LUAD and LUSC cohorts available in The Cancer Genome Atlas (TCGA). Precisely, (i) we profiled the expression of HERVs in TCGA-LUAD and TCGA-LUSC cohorts; (ii) we identified the dysregulated HERVs in both lung cancer subtypes; (iii) we evaluated the impact of the dysregulated HERVs on signaling pathways using neural network-based predictions; and (iv) we assessed their association with overall survival (OS) and relapse-free survival (RFS). In conclusion, we believe this study may help elucidate another layer of dysregulation that occurs in lung cancer involving HERVs, paving the way for identifying novel lung cancer biomarkers