Sarcomatoid carcinoma of the pancreas (Review).

Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature.

Extended Left Hemihapatectomy with Right Hepatic Artery Reconstruction for Primary Hepatic Neuroendocrine Neoplasm: A Brief Report.

BACKGROUND rimary hepatic neuroendocrine neoplasms (PHNEN) are exceedingly rare tumors with atypical clinical manifestations, accounting for less than 0.5% of all neuroendocrine tumors. Currently, there is a lack of consensus on their management, and guidelines do not recommend postoperative chemotherapy for patients with stage G1/G2 disease after curative resection. We present a case report of PHNEN, outlining its diagnostic challenges, treatment strategy, and clinical outcomes. CASE REPORT A 31-year-old man presented with jaundice and was initially diagnosed with suspected IgG4-related disease, which initially appeared to respond to steroid therapy, but manifested worsening jaundice 4 months after initial treatment. Subsequent evaluation revealed a PHNEN NET G2 with lymph node metastasis and invasion of the right hepatic artery; and involvement of the hepatic duct at the hepatic hilum, primarily the left hepatic duct. The patient underwent extended left hemi-hepatectomy with caudate lobe resection, bile duct resection, and lymphadenectomy, followed by reconstruction of the right hepatic artery. Postoperatively, the patient received adjuvant chemotherapy consisting of capecitabine (1000 mg bid D1-14) and temozolomide (200 mg qn D10-14) for 6 cycles. Currently, the patient remains disease free 43 months after treatment. CONCLUSIONS PHNEN presents diagnostic challenges due to its rarity and lack of specific markers. Surgical resection remains the cornerstone of treatment, with chemotherapy being considered in select cases with high-risk features. Further research is needed to refine treatment approaches and improve outcomes for patients with PHNEN.

A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer.

BACKGROUND: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. METHODS: In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. RESULTS: Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. CONCLUSION: Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

Evaluation of Large Language Model Performance and Reliability for Citations and References in Scholarly Writing: Cross-Disciplinary Study.

BACKGROUND: Large language models (LLMs) have gained prominence since the release of ChatGPT in late 2022. OBJECTIVE: The aim of this study was to assess the accuracy of citations and references generated by ChatGPT (GPT-3.5) in two distinct academic domains: the natural sciences and humanities. METHODS: Two researchers independently prompted ChatGPT to write an introduction section for a manuscript and include citations; they then evaluated the accuracy of the citations and Digital Object Identifiers (DOIs). Results were compared between the two disciplines. RESULTS: Ten topics were included, including 5 in the natural sciences and 5 in the humanities. A total of 102 citations were generated, with 55 in the natural sciences and 47 in the humanities. Among these, 40 citations (72.7%) in the natural sciences and 36 citations (76.6%) in the humanities were confirmed to exist (P=.42). There were significant disparities found in DOI presence in the natural sciences (39/55, 70.9%) and the humanities (18/47, 38.3%), along with significant differences in accuracy between the two disciplines (18/55, 32.7% vs 4/47, 8.5%). DOI hallucination was more prevalent in the humanities (42/55, 89.4%). The Levenshtein distance was significantly higher in the humanities than in the natural sciences, reflecting the lower DOI accuracy. CONCLUSIONS: ChatGPT's performance in generating citations and references varies across disciplines. Differences in DOI standards and disciplinary nuances contribute to performance variations. Researchers should consider the strengths and limitations of artificial intelligence writing tools with respect to citation accuracy. The use of domain-specific models may enhance accuracy.

Novel insights into the pathogenesis of thyroid eye disease through ferroptosis-related gene signature and immune infiltration analysis.

Thyroid eye disease (TED) has brought great physical and mental trauma to patients worldwide. Although a few potential signaling pathways have been reported, knowledge of TED remains limited. Our objective is to explore the fundamental mechanism of TED and identify potential therapeutic targets using diverse approaches. To perform a range of bioinformatic analyses, such as identifying differentially expressed genes (DEGs), conducting enrichment analysis, establishing nomograms, analyzing weighted gene correlation network analysis (WGCNA), and studying immune infiltration, the datasets GSE58331, GSE105149, and GSE9340 were integrated. Further validation was conducted using qPCR, western blot, and immunohistochemistry techniques. Eleven ferroptosis-related DEGs derived from the lacrimal gland were originally screened. Their high diagnostic value was proven, and diagnostic prediction nomogram models with high accuracy and robustness were established by using machine learning. A total of 15 hub gene-related DEGs were identified by WGCNA. Through CIBERSORTx, we uncovered five immune cells highly correlated with TED and found several special associations between these immune cells and the above DEGs. Furthermore, EGR2 from the thyroid sample was revealed to be closely negatively correlated with most DEGs from the lacrimal gland. High expression of APOD, COPB2, MYH11, and MYCN, as well as CD4/CD8 T cells and B cells, was verified in the periorbital adipose tissues of TED patients. To summarize, we discovered a new gene signature associated with ferroptosis that has a critical impact on the development of TED and provides valuable insights into immune infiltration. These findings might highlight the new direction and therapeutic strategies of TED.

Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.

BACKGROUND: A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear. METHODS: We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs). RESULTS: One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004-1.017, p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005-1.026, p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002-1.011, p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001-1.014, p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010, p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004-1.535, p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028-1.288, p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers. CONCLUSIONS: Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.

A Comparative Study of Laparoscopic and Open Approaches for Right Hemihepatectomy in Hepatocellular Carcinoma Patients: Safety and Short-Term Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, with China reporting over half of global cases. While traditional open liver resection is effective, it often results in large incisions and significant complications. Laparoscopic hepatectomy, particularly for right hemi-hepatectomy, features smaller incisions and quicker recovery, but its widespread adoption is hindered by its procedural complexity and a steep learning curve. This study compares the safety and efficacy of laparoscopic versus open right hemi-hepatectomy with an anterior approach in 57 patients with HCC. MATERIAL AND METHODS The data of patients with HCC who underwent treatment at our center from January 2016 to December 2020 were retrospectively analyzed. RESULTS We included a total of 57 patients with histopathologically-confirmed HCC - 23 in the laparoscopic group and 34 in the open group. Operation time was significantly shorter in the open group than in the laparoscopic group (234.5±66.9 vs 297.0±74.9, P=0.002). Intraoperative bleeding was significantly less in the laparoscopic group (P=0.042). There were no statistically significant differences in postoperative complications between the 2 groups. Postoperative hospital stay was significantly shorter in the laparoscopic group (12 days vs 15 days, P=0.044). There was no significant difference in postoperative overall survival (OS) and disease-free survival (DFS) between the 2 groups (P>0.05). CONCLUSIONS In patients with hepatocellular carcinoma, the laparoscopic right hemi-hepatectomy with the anterior approach technique has the same safety and comparable short-term outcomes as open surgery.

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients.

OBJECTIVE: To determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients. METHODS: Clinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection. RESULTS: 244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group. CONCLUSION: Acute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients. SUMMARY: Clinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.

Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know.

Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.

A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas.

SMARCA1is a mammalian imitation switch (ISWI) gene that encodes for SNF2L. SNF2L is involved in regulating cell transition from a committed progenitor state to a differentiated state. Although many papers have detailed the correlation between SMARCA1 and different cancers, no pan-cancer analysis has been conducted to date. We started by exploring the potential carcinogenic role of SMARCA1 across 33 carcinomas using the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEx) databases. The expression of SMARCA1 was significantly elevated in some tumor types but not in others. There was a distinct relationship between SMARCA1 expression and patient prognosis. S116 phosphorylation levels were up-regulated in both lung adenocarcinoma and uterine corpus endometrial carcinoma. The expression level of SMARCA1 was positively correlated with cancer-associated fibroblasts infiltration in a number of tumors, such as colon adenocarcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma. It was also associated with CD8+ T-cell infiltration in head and neck squamous cell carcinoma and lung adenocarcinoma. Furthermore, SMARCA1 is involved in chromatin remodeling and protein processing-associated mechanisms. Our study presents an initial assessment and illustration of the carcinogenic role of SMARCA1 in different carcinomas.

Bile is a reliable and valuable source to study cfDNA in biliary tract cancers.

Objective: The aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC). Methods: A total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling. Results: Bile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, the consistency between bile supernatant and tumor tissue was 90.00% (18/20), that between bile pellet and tumor tissue was 85.00% (17/20), and that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of TERC, IL7R, RICTOR, and TERT). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant. Conclusion: The consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC.

Comprehensive bioinformatic analysis of MMP1 in hepatocellular carcinoma and establishment of relevant prognostic model.

Matrix metalloproteinase 1 (MMP1) encodes endopeptidases associated with degradation of multiple components of the extracellular matrix. This function has increasingly been considered to play a major proteolysis role in tumor invasion and metastasis. However, the relationship between MMP1 gene expression, tumor-immune microenvironment and prognosis in hepatocellular carcinoma patients remains mostly unclear. This study focused on a comprehensive analysis of MMP1 in hepatocellular carcinoma, specifically the prognosis and tumor-immune microenvironment. MMP1 expression was analyzed using TCGA database and clinical samples. MMP1 associated mechanisms, pathways, mutations and prognosis in hepatocellular carcinoma were evaluated. We also analyzed the tumor-immune microenvironment and corresponding treatments. Our research demonstrated that MMP1 expression was upregulated in patients with hepatocellular carcinoma and correlated with poor survival. A prognostic model was established and its performance evaluated. We also found and report various correlations between MMP1 and immune-related cells/genes, as well the potential therapeutic agents. These findings indicate that MMP1 can potentially be a promising prognostic biomarker and indicator of the tumor-immune microenvironment status in hepatocellular carcinoma.

Pancreatic adenocarcinoma associated immune-gene signature as a novo risk factor for clinical prognosis prediction in hepatocellular carcinoma.

Pancreatic adenocarcinoma (PAAD) has high mortality and a very poor prognosis. Both surgery and chemotherapy have a suboptimal therapeutic effect, and this caused a need to find new approaches such as immunotherapy. Therefore, it is essential to develop a new model to predict patient prognosis and facilitate early intervention. Our study screened out and validated the target molecules based on the TCGA-PAAD dataset. We established the risk signature using univariate and multivariate Cox regression analysis and used GSE62452 and GSE28735 to verify the accuracy and reliability of the model. Expanded application of PAAD-immune-related genes signature (-IRGS) on other datasets was conducted, and the corresponding nomograms were constructed. We also analyzed the correlation between immune-related cells/genes and potential treatments. Our research demonstrated that a high riskscore of PAAD-IRGS in patients with PAAD was correlated with poor overall survival, disease-specific survival and progression free interval. The same results were observed in patients with LIHC. The models constructed were confirmed to be accurate and reliable. We found various correlations between PAAD-IRGS and immune-related cells/genes, and the potential therapeutic agents. These findings indicate that PAAD-IRGS may be a promising indicator for prognosis and of the tumor-immune microenvironment status in PAAD.

Development of nomogram models of inflammatory markers based on clinical database to predict prognosis for hepatocellular carcinoma after surgical resection.

BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.

A Meta-Analysis and Systematic Review of Normothermic and Hypothermic Machine Perfusion in Liver Transplantation.

BACKGROUND: The gap between the demand and supply of donor livers is still a considerable challenge. Since static cold storage is not sufficient in marginal livers, machine perfusion is being explored as an alternative. The objective of this study was to assess (dual) hypothermic oxygenated machine perfusion (HOPE/D-HOPE) and normothermic machine perfusion (NMP) in contrast to static cold storage (SCS). METHODS: Three databases were searched to identify studies about machine perfusion. Graft and patient survival and postoperative complications were evaluated using the random effects model. RESULTS: the incidence of biliary complications was lower in HOPE vs. SCS (OR: 0.59, 95% CI: 0.36-0.98, p = 0.04, I2: 0%). There was no significant difference in biliary complications between NMP and SCS (OR: 0.76, 95% CI: 0.41-1.40, p = 0.38, I2: 55%). Graft and patient survival were significantly better in HOPE than in SCS (HR: 0.40, 95% CI: 0.23-0.71, p = 0.002, I2: 0%) and (pooled HR: 0.43, 95% CI: 0.20-0.93, p = 0.03, I2: 0%). Graft and patient survival were not significantly different between NMP and SCS. CONCLUSION: HOPE/D-HOPE and NMP are promising alternatives to SCS for donor liver preservation. They may help address the widening gap between the demand for and availability of donor livers by enabling the rescue and transplantation of marginal livers.

Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma.

Immune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7-14.3). Median overall survival was 13.0 months (95% CI NE-NE), 9.0 months(95% CI 6.3-11.7)and 3.0 months (95% CI 1.9-4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI 2.9-7.1, p < 0.001), 4.0 months (95% CI 2.8-5.2) and 2.0 months (95% CI 1.7-2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1-91.6, p < 0.001; 54.3%, 95% CI 36.6-71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI NE-NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI 0.9-3.1) and sintilimab group (2.0 months, 95% CI 0.8-3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.

Preoperative nomogram for microvascular invasion prediction based on clinical database in hepatocellular carcinoma.

The presence of microvascular invasion (MVI) is a critical determinant of early hepatocellular carcinoma (HCC) recurrence and prognosis. We developed a nomogram model integrating clinical laboratory examinations and radiological imaging results from our clinical database to predict microvascular invasion presence at preoperation in HCC patients. 242 patients with pathologically confirmed HCC at the Ningbo Medical Centre Lihuili Hospital from September 2015 to January 2021 were included in this study. Baseline clinical laboratory examinations and radiological imaging results were collected from our clinical database. LASSO regression analysis model was used to construct data dimensionality reduction and elements selection. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with MVI and finally a nomogram for predicting MVI presence of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Survival analysis indicated that the probability of overall survival (OS) and recurrence-free survival (RFS) were significantly different between patients with MVI and without MVI (P < 0.05). Histopathologically identified MVI was found in 117 of 242 patients (48.3%). The preoperative factors associated with MVI were large tumor diameter (OR = 1.271, 95%CI: 1.137-1.420, P < 0.001), AFP level greater than 20 ng/mL (20-400 vs. ≤ 20, OR = 2.025, 95%CI: 1.056-3.885, P = 0.034; > 400 vs. ≤ 20, OR = 3.281, 95%CI: 1.661-6.480, P = 0.001), total bilirubin level greater than 23 umol/l (OR = 2.247, 95%CI: 1.037-4.868, P = 0.040). Incorporating tumor diameter, AFP and TB, the nomogram achieved a better concordance index of 0.725 (95%CI: 0.661-0.788) in predicting MVI presence. Nomogram analysis showed that the total factor score ranged from 0 to 160, and the corresponding risk rate ranged from 0.20 to 0.90. The DCA showed that if the threshold probability was > 5%, using the nomogram to diagnose MVI could acquire much more benefit. And the net benefit of the nomogram model was higher than single variable within 0.3-0.8 of threshold probability. In summary, the presence of MVI is an independent prognostic risk factor for RFS. The nomogram detailed here can preoperatively predict MVI presence in HCC patients. Using the nomogram model may constitute a usefully clinical tool to guide a rational and personalized subsequent therapeutic choice.

Extended pancreato-duodenectomy coupled with adjuvant chemotherapy for SMARCB1/INI1 deficient pancreatic carcinoma: A case report and literature review.

INTRODUCTION: SMARCB1/INI1 gene deletion appears to be associated with a rare, malignant and aggressive form of pancreatic carcinoma whose diagnosis is challenging. Our objective is to illustrate that the tumor may masquerade as a duodenal papillary carcinoma, be difficulty to identify on diagnostic imaging and that making an accurate diagnosis may be challenging, however surgical resection may be possible. CASE REPORT: We present a case of a 24-year old male patient presenting with jaundice and itchy skin, elevated TBIL, AST, ALP and CA125. A 2.2 × 1.7 cm pancreatic nodule, later diagnosed as a SMARCB1/INI deficient pancreatic carcinoma was detected on Endoscopic Ultrasound - Fine Needle Aspiration (EUS-FNA). The patient was successfully treated with extended pancreato-duodenectomy coupled with adjuvant chemotherapy, a 7 × 5 × 5 cm tumor resected. DISCUSSION: SMARCB1/INI deficient pancreatic carcinoma has been reported in couple of other articles. However, unlike other cases, in our case identification and accurate assessment of the tumor was particularly difficulty both on imaging and during operation. Our patient has thus far had a positive outcome with no recurrence. CONCLUSION: For rare forms of pancreatic carcinoma, identification and assessment of the tumor size may be challenging on imaging and during operation. However, careful assessment should be performed before ruling out surgical resection. Furthermore, adjuvant chemotherapy may be beneficial to the patient.