Resection Of Carcinoma Research Articles

Abstract 7364: Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion

Abstract Introduction: Microvascular invasion (MVI) is a well-known prognostic factor in predicting cancer relapse after curative resection of resectable hepatocellular carcinoma (HCC).Therefore, there is a clear unmet need for a precision strategy based on cancer-specific multi-omics features to predict the MVI feature at the initial diagnosis of HCC. Methods: Using gene expression profiling for resected human HCC (Discovery cohort, n=240), we identified the transcriptomic signature predicting the MVI feature. Comprehensive analyses were performed using the dataset from the cancer dependency map (DepMap) project, including cancer-specific molecular characterization with multi-omics data, and drug sensitivity with compound screening, and integrative in-silico prediction methods to uncover MVI. The transcriptomic signature predicting the MVI feature were validated in independent translational cohorts (TCGA-LIHC; n=373, KOREA; n=188, TOKYO; n=183, MODENA; n=78, ZHONGSHAN; n=159). Results: The MVI signature with 1028 genes was identified from robust statistical testing from the discovery cohort, and robust validation for the prediction performance of the MVI signature showed significant accuracy in the validation cohort (AUC=0.865, p<0.01). Multi-omics analysis revealed aggressive tumor biology associated with the MVI signature and specified biomarkers. Conclusions: Integrative multi-omics profiling for resectable HCC uncovers biomarkers to predict MVI. A novel combination of biomarkers performs in sorting out the tumor with aggressive tumor biology. A precision strategy to discover resectable tumors beneficial from surgical resection can be established from consecutive clinical trials based on this translational study. Citation Format: Incheon Kang, Woo Young Kwon, Sung Hwan Lee. Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7364.

Feasibility and safety of robotic liver resection for huge (≥10cm) hepatocellular carcinoma in a single centre: A propensity score-matched single-surgeon study.

The applicability of robot-assisted resection for huge hepatocellular carcinoma (HCC) of ≥10cm remains contentious with limited available data. This retrospective analysis involved 337 patients who underwent robotic liver resection for HCC by a single surgeon. Propensity score matching (PSM) was employed to compare perioperative indicators between patients with regular and huge HCC. The regular HCC group exhibited a shorter median operative duration than the huge HCC group. The IWATE criteria revealed higher scores in the huge HCC group than in the regular HCC group. No significant differences were observed between the two groups in Pringle time, drainage tube removal, duration of hospital stays, blood loss volume, blood product transfusion, margin status, conversion rate to open surgery, bile leakage, in-hospital mortality, and reoperation rate. Robotic liver resection is feasible for huge HCC, with effective perioperative risk management potentially improving outcomes for subsequent minimally invasive surgeries.

Abstract 5197: Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater carcinoma

Abstract Background: Ampulla of Vater (AoV) carcinoma is a rare tumor that accounts for 20 % of periampullary cancers. Surgical resection is the only treatment that can expect cure of disease, and there is still an unmet need to predict postoperative recurrence. In this study, we investigated the novel molecular biomarkers that can predict the risk of recurrence after surgery with AoV carcinoma. Methods: In this retrospective study, we collected the surgically resected tissue and medical records of patients who were diagnosed with AoV carcinoma at Samsung Medical Center from January 2005 to December 2020. Patients were classified patients according to the initial stage and experience of tumor recurrence. Whole transcriptomic analysis using primary AOV tumor and recurred tumor tissue samples was conducted to identify the molecular biomarker for tumor recurrence. Results: A total of 40 tumor tissue from primary site in non-recurrence group, 22 tumor tissue from primary site in recurrence group, and paired 22 tumor tissue from recurrence site were analyzed. A total of 1005 genes differentially expressed between primary tumor of non-recurrence group and recurrence group were found. Gene set enrichment analysis showed that pathways related to fatty acid metabolism, adipogenesis, oxidative phosphorylation, and hypoxia were upregulated, and pathways associated with interferon gamma response, and mTOR signaling were downregulated in recurrence group. These pathways were significantly affecting the recurrence free survival which was verified with TCGA data, and we further identified some candidate genes including PIM3, IGFBP4, SLC19A1, HIF1A and CXCL11 to predict tumor recurrence . Moreover, we found candidates for single gene level biomarkers to predict early tumor recurrence in N0 stage. Low expression of UQCC3 and high expression of CLCNKB was related to early tumor recurrence. Conclusions: We found the candidates for novel molecular level biomarker to predict postoperative recurrence of AoV carcinoma. In the future, it is necessary to develop a predictive model for the risk of recurrence after surgical resection for AoV carcinoma. Citation Format: Hyemin Kim, Jin Ho Choi, Hyoung-oh Jeong, Aryoung Kim, Se-Hoon Lee, Kwang Hyuck Lee, Kyu Taek Lee, Jong Kyun Lee, Semin Lee, Joo Kyung Park. Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5197.

Abstract 6767: Multivariate analysis of ex vivo kidney 3D immune-microtumors for functional precision medicine

Abstract Immuno-oncology (IO) represents a significant paradigm shift in cancer treatment, focused on leveraging and mobilizing a patient’s own immune response and anti-tumor capabilities. Despite accounting for the majority of available treatment options, there are currently no diagnostic tests capable of predicting combination immunotherapy response in kidney cancer. We have developed a fully human 3D IO model for clinical drug efficacy prediction through multivariate analysis of the tumor-immune microenvironment (TiME) combining functional assays, artificial intelligence and multi-omics. These immune-microtumors recapitulate a patient’s unique pathophysiology and allow 3D spatio-temporal analyses of functional metrics at both bulk and single-cell resolutions. Renal cell carcinoma (RCC) resections and matched blood were collected and processed for single cell isolation of tumor and PBMCs (N=20, ISRCTN10001405). Flow cytometry (FC) and immunofluorescence (IF) were used to characterize TiME cell subpopulations (cancer, immune, stromal etc.) in pellets and 3D cultures, and to deconvolute bulk RNAseq data. Target (tumor) and effector cells (PBMCs and CD8+) were stained with fluorescent probes, activated using ɑCD3 and encapsulated in TiME-mimicking 3D matrices. 3D immune-microtumors were treated with FDA-approved regimens including immunotherapies (ipilimumab, nivolumab, pembrolizumab) and receptor-tyrosine kinase inhibitors (TKIs)(cabozantinib, lenvatinib, axitinib) as monotherapies or combination therapies. Differential drug efficacies were functionally quantified over 4 days using 3D confocal microscopy and computer vision pipelines to extract cell behavior metrics such as immune cell infiltration, immune/tumor cell migration speed, and tumor killing/viability. We devised a specialized RCC hydrogel formulation with superior viability compared to MatrigelTM alone (N=7). FC/IF/RNAseq were used to quantify relative cell subpopulations after isolation and show protein/transcriptional signature retention after 3D culture (N=7). The platform was conducive to the testing of various drugs with varying MoAs including immunotherapies, TKIs, targeted therapies and cell therapies. Treatment with pembrolizumab led to 26% higher PBMC infiltration, 14% higher CD8+ infiltration and 15% increased tumor cell death compared to control. When in combination, pembrolizumab reduced cell viability by 10% and 19% with lenvatinib and axitinib respectively (N=1). Population analyses revealed intra-patient response heterogeneity (N=7). In conclusion, we showed MoA-agnostic, patient-dependent responses to FDA-approved clinical treatment regimens via molecular and functional spatio-temporal analyses. Clinical outcome correlation is currently underway in our advanced RCC study PEAR-TREE2 as well as in breast NCT05435352 and brain NCT06038760 tumors. Citation Format: Eleonora Peerani, Keqian Nan, Demi A. Wiskerke, Thomas D. Richardson, Polina Maximchick, Jay Kearney, George R. de Fraine, Kerrie L. Loughrey, Jonathan Ient, Jessica A. Hudson, Andreas Kaffa, Aston M. Crawley, Nourdine K. Bah, Edgar G. Lopez Molina, Elli Tham, Francesco Iori, Matthew H. Williams, Maxine G. Tran, Duleek N. Ranatunga. Multivariate analysis of ex vivo kidney 3D immune-microtumors for functional precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6767.

Abstract 7518: Neoadjuvant-adjuvant pembrolizumab in resectable advanced basal cell carcinoma of the head and neck: An open-label, single-arm, phase 1b trial

Abstract Introduction: BCC is a common form of skin cancer that shares treatment-related aspects with the more well-studied skin malignancy, melanoma, including sensitivity to anti-PD-1/PD-L1 immunotherapy. However, despite major advances in peri-operative immunotherapy for melanoma, little is known regarding these strategies in BCC. This phase 1B, single-arm study evaluated neoadjuvant-adjuvant treatment with pembrolizumab (PEMBRO) together with standard of care (SOC) resection in advanced BCC of the head and neck. Methods: Eligible patients had resectable, locally advanced BCC of the head and neck, defined by at least one of the following high-risk characteristics: a measurement of ≥ 20 mm, indication for post-operative radiation, or perineural invasion (PNI) in multiple nerves. Patients were naive to hedgehog inhibitors (HHI) and had an ECOG of 0 or 1. All patients received IV PEMBRO at a dose of 200 mg every 3 weeks for a total of 4 cycles, then within 4 weeks underwent a SOC resection followed by adjuvant PEMBRO until a total of 17 cycles was completed. After the 30-day post treatment safety follow-up visit, patients were followed for up to 5 years post-operatively. The primary endpoint was pathological response rate. Secondary endpoints included RECIST response by radiographic or physical exam, adverse events (AE), and recurrence-free survival (RFS). Results: 13 patients were enrolled in the trial from July 2020 to May 2023, and received at least one dose of PEMBRO. Two patients withdrew from the trial after one dose of PEMBRO, one following treatment-related G3 hepatitis and a second due to an unrelated medical complication (cholecystitis). Out of 11 patients undergoing surgical resection, 10 patients received 4 out of 4 and 1 patient received 3 out of 4 planned cycles of neoadjuvant PEMBRO (investigator preference without new related AE). Pathological complete response (pCR) was observed in 3 patients (23%). For those with RECIST measurable disease, 2 patients demonstrated a complete response (CR), 1 patient a partial response (PR), and 5 patients showed stable disease (SD). Two patients had progressive disease (PD). One patient with a complete pathologic response had a discordant RECIST response with PD noted radiographically. All 13 patients experienced at least one AE of G1 or 2. The highest grade of related AEs were noted in 2 patients with grade 3 hepatitis and pruritus respectively that resolved with supportive therapy. As of November 2023, the median follow-up time is 17.6 months with no recurrences noted. Conclusions: Neoadjuvant-adjuvant PEMBRO shows promising efficacy and an acceptable safety profile in resectable advanced BCC of the head and neck. Given these positive results and the healthcare burden BCC accounts for, these findings warrant further study. Citation Format: Grace M. Jones, James Isaacs, Lucy Boyce Kennedy, Jennifer Ko, Allison Vidimos, Alok Vij, Christine Poblete-Lopez, Jennifer Lucas, Yee Peng Phoon, Melissa McEnery-Stonelake, Jon Meine, Thach-Giao Truong, Pauline Funchain, Brian Gastman. Neoadjuvant-adjuvant pembrolizumab in resectable advanced basal cell carcinoma of the head and neck: An open-label, single-arm, phase 1b trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7518.

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma

PurposeMagnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. MethodsWe retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. ResultsDuring a median follow-up period of 32 months (range, 4–52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5–23.1) and MVI (HR, 3.4; 95% CI, 1.0–11.3) were independent predictors of intrahepatic recurrence. ConclusionsPatients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

Extended radical resection and chest wall reconstruction for a pulmonary sarcomatoid carcinoma: a case report

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant type of non-small cell lung cancer (NSCLC), for which the treatment of choice is surgery. For peripheral PSC growing outward and invading the chest wall, a complete resection of the affected lung lobes and the invaded chest wall can improve long-term prognosis. However, when the extent of the resected chest wall is large, reconstruction is often required to reduce the risk of postoperative complications. Here, we present a case of PSC invading the chest wall treated with successful extended radical resection for lung cancer and chest wall reconstruction.Case presentationA 58-year-old male patient with a nodule in the right upper lobe that had been identified on physical examination 2 years before presentation presented to our hospital with a recent cough, expectoration, and chest pain. Imaging revealed a mass in the right upper lobe that had invaded the chest wall. Preoperative puncture pathology revealed poorly differentiated NSCLC. We performed extended radical resection for lung cancer under open surgery and reconstructed the chest wall using stainless steel wire and polypropylene meshes. The procedure was uneventful, and the patient was discharged 7 days postoperatively. Furthermore, the final pathology revealed PSC.ConclusionsThis case underscores the feasibility of surgical R0 resection in patients with PSC with chest wall invasion and no lymph node metastasis, potentially enhancing long-term outcomes. The novel aspect of this case lies in the individualized chest wall reconstruction for a large defect, using cost-effective materials that offered satisfactory structural support and postoperative recovery, thereby providing a valuable reference for similar future surgical interventions.

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

Intraoperative Techniques That Define the Mucosal Margins of Oral Cancer In-Vivo: A Systematic Review.

This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques.

Clonal analysis of metachronous double biliary tract cancers.

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Underwater endoscopic submucosal dissection performed under general anesthesia for the safe resection of superficial esophageal squamous cell carcinoma with ductal involvement.

Underwater endoscopic submucosal dissection performed under general anesthesia for the safe resection of superficial esophageal squamous cell carcinoma with ductal involvement.

Endoscopic submucosal dissection combined with endoscopic hand suturing for a laterally spreading tumor spanning the anastomosis after radical resection of a rectal carcinoma.

Endoscopic submucosal dissection combined with endoscopic hand suturing for a laterally spreading tumor spanning the anastomosis after radical resection of a rectal carcinoma.

A Randomized, Double-Blind, Phase 2 Study of Perioperative MK-4280A (Coformulation of Favezelimab and Pembrolizumab) vs Pembrolizumab in Patients with Resectable Cutaneous Squamous Cell Carcinoma (cSCC)

A Randomized, Double-Blind, Phase 2 Study of Perioperative MK-4280A (Coformulation of Favezelimab and Pembrolizumab) vs Pembrolizumab in Patients with Resectable Cutaneous Squamous Cell Carcinoma (cSCC)

Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer.

We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P < .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P < .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P < .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P < .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence. We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.

Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.

Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%). In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.

Systemic amyloid A amyloidosis of the bladder after transurethral resection of urothelial carcinoma

IntroductionAmyloid A amyloidosis of the bladder is not a major disease. We report a patient with systemic amyloid A amyloidosis of the bladder after transurethral resection of urothelial carcinoma.Case presentationAn 87‐year‐old Japanese man had bladder carcinoma. He was followed up regularly with cystoscopy. Cystoscopy revealed multiple polypoid tumors 6 months after the first transurethral resection of urothelial carcinoma. Pathologic specimens contained the amyloid A component. He had hypertrophic cardiomyopathy, valvular disorders, and arrhythmias. His cardiac disease may have resulted from amyloid A amyloidosis. We speculated the patient had systemic amyloid A amyloidosis of the heart and bladder.ConclusionWe determined the type of amyloidosis via a biopsy of the bladder tumors. Our patient had cardiac disease. Therefore, systemic amyloid A amyloidosis could have caused his cardiac disease. The pathologic findings of bladder tumors can contribute to detecting systemic amyloid A amyloidosis.

Implementation of endometrial cancer molecular subtyping into a hybrid community-academic practice.

We sought to confirm utility of our institution's modified Proactive Molecular Risk Classifier for Endometrial Cancer protocol in our daily practice, which includes mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) immunohistochemistry with in-house next-generation sequencing for POLE, TP53, and CTNNB1. We conducted a retrospective review of all patients in our institution who underwent primary endometrial carcinoma resection from the year prior to protocol implementation (PRE; October 1, 2020, to September 30, 2021) through first year of implementation (POST; October 1, 2021, to September 30, 2022) to compare the distribution of molecular and traditional staging factors using GOG-249 criteria to assign clinical risk. In total, 136 of 260 PRE patients were classified as clinically low risk (LR), of whom 31 were MMR deficient. Of the 157 LR POST patients with endometrioid-type carcinoma, 45 were MMR deficient, 5 were POLE mutant, 5 were TP53 mutant, 56 were of no specific molecular profile (NSMP), and 46 did not receive full protocol testing. Of all 79 POST NSMP endometrioid-type cases, 18 were CTNNB1 mutated and 8 showed L1CAM expression. Our protocol identified 22 (14%) of 157 LR tumors that harbored incipient intermediate- to high-risk molecular aberrations in TP53, CTNNB1, or L1CAM. Moving forward, results of ongoing trials assessing adjuvant therapy decisions based on molecular classification are necessary to confirm protocol utility and identify appropriate modifications.