CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Lymphoepithelioma-like Carcinoma of the Stomach: A Case Successfully Treated with Chemotherapy.

Lymphoepithelioma-like carcinoma of the stomach is a rare gastric tumour. Pathological features include undifferentiated carcinoma mixed with prominent stromal lymphoid infiltration. The incidence is significantly higher in men. Lesions occur more often in upper gastric locations, with lower numbers of lymph node metastases and better overall survival rates than other gastric carcinomas. Because of its rarity, standardised management is currently unavailable. A case of lymphoepithelioma-like carcinoma of the stomach is presented that was successfully treated with chemotherapy consisting of only two cycles of tegafur, gimeracil, and oteracil plus oxaliplatin. Key Words: Lymphoepithelioma-like carcinoma, Stomach, Chemotherapy.

Serum free light chain is associated with histological activity and cirrhosis in patients with chronic hepatitis B.

BACKGROUND: The antiviral immune response is the main cause of hepatocyte damage and inflammatory necrosis. The serum free light chain, reflecting the immune function of B-cells, is strongly associated with inflammation and disease activity. We aimed to investigate the association of serum free light chain with the progression of chronic hepatitis B. METHODS: A total of 208 eligible chronic hepatitis B patients who had undergone a liver biopsy were studied. Serum free light chains of all patients were measured by turbidimetry using an immunoassay. Liver histology was assessed according to the METAVIR scoring system (which grades the stage of fibrosis on a five-point scale, F0 = no fibrosis to F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity to A3 = severe activity). The association of serum free light chains with histological activity and fibrosis progression was evaluated. RESULTS: The concentration of serum free light chains in CHB patients increased gradually with histological activity and fibrosis progression. The intensity of histological activity was significantly correlated with the serum free kappa chain (r = 0.658, P < 0.001) and the serum free lambda chain (0.675, P < 0.001). The stages of fibrosis were correlated with the serum free kappa chain (r = 0.683, P < 0.001) and serum free lambda chain (0.664, P < 0.001). After adjusting for age, sex and other synergic factors, the serum free kappa chain remained a potential risk factor, but the serum free lambda chain was no longer associated with liver cirrhosis. Similar to FIB-4 and RPR, the serum free kappa chain exhibited excellent performance in the prediction of liver cirrhosis. The AUCs of serum free Kappa chain, FIB-4 and RPR were 0.873, 0.880 and 0.895, respectively, which were significantly higher than those of the AAR and APRI (0.718 and 0.746). CONCLUSION: Our work revealed that serum free light chains were associated with histological activity and cirrhosis in chronic hepatitis B, which could play a crucial role in the immunopathogenesis of HBV-associated cirrhosis. In addition, free kappa light chain could be a useful predictor of liver cirrhosis.

Primary leiomyoma of the inferior vena cava mimicking a cystic neoplasm of the pancreas: a case report.

Benign smooth muscle tumors of the inferior vena cava (IVC) are unusual, but mostly consist of intravenous leiomyomatosis, which arises from the uterus. Primary leiomyoma of the IVC is extremely rare. Here, we report a primary leiomyoma of the IVC, misleadingly reported as a cystic neoplasm of the pancreas in images. Immunohistochemical analysis was positive for (estrogen receptor) ER and (progesterone receptor) PR, indicating gynecologic leiomyomas. The use of ER and PR immunostaining is recommended to help distinguish between somatic and gynecologic leiomyomas, whose criteria of malignancy differ.

Complete laparoscopic cholecystectomy for a duplicated gallbladder: A case report.

INTRODUCTION: Duplication of the gallbladder (GB) is a rare congenital abnormality occurring in 1 in 4000 to 5000 births. Three types have been reported: type I (split primordial GB), type II (2 separate GBs with their own cystic ducts), and type III (triple GBs drained by 1 to 3 separate cystic ducts). Patients with a duplicated GB are usually asymptomatic and are sometimes not diagnosed on preoperative imaging, which might increase the difficulty and risk of cholecystectomy. The key to successful treatment is total removal of the duplicated GB to avoid the recurrence of disease. Intraoperative cholangiography is recommended for identifying and resecting duplicated GBs. The final diagnosis depends on the histopathology. PATIENT CONCERNS: A 62-year-old woman had recurrent upper abdominal pain and nausea for 1 year, with no fever, jaundice, or other symptoms. An ultrasound of the abdomen indicated polyps in the GB. Computed tomography (CT) revealed moderate dense structures attached to the wall of the GB and an unusual 47 × 21 mm elliptical structure with an extra tubule located above the main GB. DIAGNOSIS: A diagnosis of duplicated GB was made based on the histopathology. INTERVENTIONS: The patient underwent a laparoscopic cholecystectomy with total removal of the duplicated GB. OUTCOMES: The patient's postoperative course was uneventful and she was discharged from the hospital on the second postoperative day. She had no upper abdominal pain at the 6-month follow-up. CONCLUSION: Duplicated gallbladder is a rare congenital biliary anatomy, which is usually asymptomatic and sometimes cannot be diagnosed on preoperative imaging. With gallbladder disease, the duplicated GBs should be removed totally; a laparoscopic approach should be attempted first and cholangiography is recommended to aid in identifying and resecting the duplicated GBs. The final diagnosis depends on the histopathology. There is still insufficient evidence on the need to remove duplicated GBs found incidentally.

DHX15 Inhibits Autophagy and the Proliferation of Hepatoma Cells.

Autophagy is a highly conserved process by which superfluous or harmful components in eukaryotic cells are degraded by autophagosomes. This cytoprotective mechanism is strongly related to various human diseases, such as cancer, autoimmune diseases, and diabetes. DEAH-box helicase 15 (DHX15), a member of the DEAH box family, is mainly involved in RNA splicing and ribosome maturation. Recently, DHX15 was identified as a tumor-related factor. Although both autophagy and DHX15 are involved in cellular metabolism and cancer progression, their exact relationship and mechanism remain elusive. In this study, we discovered a non-classic function of DHX15 and identified DHX15 as a suppressive protein in autophagy for the first time. We further found that mTORC1 is involved in DHX15-mediated regulation of autophagy and that DHX15 inhibits proliferation of hepatocellular carcinoma (HCC) cells by suppressing autophagy. In conclusion, our study demonstrates a non-classical function of DHX15 as a negative regulator of autophagy related to the mTORC1 pathway and reveals that DHX15-related autophagy dysfunction promotes HCC cell proliferation, indicating that DHX15 may be a target for liver cancer treatment.

Spindle cell hemangioma of the spleen: A case report.

RATIONALE: Spindle cell hemangioma (SCH) is considered a benign vascular lesion. It typically develops as a solitary nodule or multiple masses located in the dermal or subcutaneous layers of the distal extremities. To the best of our knowledge, there are no prior reports of SCH in the spleen. PATIENT CONCERNS: A 41-year-old male was admitted to our hospital with recurrent headaches, nausea, and vomiting persisting for 5 days. Ultrasound, computed tomography, and magnetic resonance imaging revealed multiple space-occupying lesions in the spleen, and the biggest lesion was 4.8 cm × 5.4 cm in size. INTERVENTIONS: The patient underwent laparoscopic splenectomy. DIAGNOSIS: A diagnosis of spindle cell hemangioma of the spleen was made based on the histopathology. OUTCOMES: No evidence of local recurrence or distant metastases was observed over 4-year follow-up. LESSONS: Splenic SCH may exhibit relatively high proliferative activity and be comorbid with epithelioid hemangioendothelioma or angiosarcoma, raising the possibility of malignant potential. However, the patient remained alive and disease-free 4 years after the operation. The nature of SCH in deep soft tissues requires further study.

Sarcomatoid carcinoma of the pancreas: A case report.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive epithelial tumor that has both epithelial and mesenchymal features. It is characterized by sarcomatous elements with evidence of epithelial differentiation. And the term "sarcomatoid carcinoma" is often confused with "carcinosarcoma". CASE SUMMARY: We present a case of SCP with lymph node metastasis in a 59-year-old male patient. He had experienced darkening of the urine, scleral icterus, and fatigue for 4 weeks. Computed tomography and magnetic resonance imaging revealed a mass in the pancreatic head, and laboratory tests revealed elevated serum bilirubin levels. The patient underwent pancreaticoduodenectomy after biliary decompression. Histologically, spindle cells with marked nuclear atypia and brisk mitotic activity arranged in a storiform or fascicular pattern were present in the bulk of the tumor. Immunohistochemical analysis found that the spindle cells exhibited strong diffuse positivity for epithelial markers, indicative of epithelial differentiation. Accordingly, the pathologic diagnosis of the pancreatic neoplasm was SCP. CONCLUSION: Although sarcomatoid carcinomas and carcinosarcomas have different pathologic features, both have epithelial origin.

Myxoid and reticular angiomatoid fibrous histiocytoma: a case confirmed by fluorescence in situ hybridization analysis for EWSR1 rearrangement.

Angiomatoid fibrous histiocytoma (AFH) is a tumor of intermediate malignancy and undefined lineage, mostly arising in the extremities of young patients. However, AFH may rarely display uncommon clinical and morphologic features, such as older age at presentation, occurrence outside somatic soft tissues and alterations in the architectural patterns, stromal matrix and cytomorphology, causinga great diagnostic challenge for practicing pathologists. Herein, we present a case of AFH with unusual histologic features arising in the right hip of a 37-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma mimicking myoepithelioma, extraskeletal myxoid chondrosarcoma, or myxoid liposarcoma. The tumor cells focally expressed desmin with a dendritic-like cell process staining pattern and CD68. Fluorescence in situ hybridization analysis confirmed the rearrangement of the EWSR1 gene. This report further expands the clinicopathologic spectrum of AFH and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants.

Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway.

The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.

[Significance of P504s in distinction between solid pseudopapillary tumor of pancreas and pancreatic neuroendocrine tumors].

OBJECTIVE: To study the significance of P504s in differential diagnosis between solid pseudopapillary tumor of the pancreas (SPTP) and pancreatic neuroendocrine tumors (PanNET). METHODS: Forty-three patients with SPTP and 41 patients with PanNET encountered during the period from 2007 to 2014 were recruited. Immunohistochemical study for vimentin, CD10, chromogranin A, synaptophysin, beta-catenin, CD99 and P504s in SPTP and PanNET was performed. The diagnostic value of P504s in differentiating SPTP from PanNET was analyzed. RESULTS: Immunohistochemical study showed that vimentin, CD10, chromogranin A, synaptophysin and CD99 were expressed both in SPTP and PanNET. All cases of SPTP showed granular cytoplasmic expression of P504s, whereas those of PanNET were negative. CONCLUSION: P504s is a sensitive and useful marker for SPTP and can be used in the distinction between SPTP and PanNET.

The Prevalence of Helicobacter pylori Infection Decreases with Older Age in Atrophic Gastritis.

The clinical pathological characteristics of 3969 adult patients with chronic atrophic gastritis were retrospectively studied. The positivity of intestinal metaplasia and dysplasia in atrophic gastric specimens increased with age; however, H. pylori positivity and inflammatory activity decreased significantly with increased age. H. pylori infection was present in 21.01% of chronic atrophic gastritis patients, and 92.33% of the subjects with H. pylori infection were found to have simultaneous inflammatory activity. The intestinal metaplasia and dysplasia positivity markedly increased as the degree of gastric atrophy increased. In conclusion, the incidence of H. pylori infection decreased with age and correlated significantly with inflammatory activity in atrophic gastritis patients. The intestinal metaplasia and dysplasia positivity notably increased as the degree of gastric atrophy increased. Large population-based prospective studies are needed to better understand the progression of CAG.

RDW to platelet ratio: a novel noninvasive index for predicting hepatic fibrosis and cirrhosis in chronic hepatitis B.

OBJECTIVE: To develop a simple predictive model for significant fibrosis and cirrhosis in chronic hepatitis B (CHB) using the routine hematological parameters of a complete blood count. METHODS: A total of 458 eligible CHB patients who had undergone a liver biopsy were randomly divided into two cohorts: an estimation group (n = 310) and a validation group (n = 148). Liver histology was assessed according to the Metavir scoring scheme. All common demographics, hematological parameters, HBeAg status, HBV DNA, and liver biochemistry were analyzed. RESULTS: Based on routinely available clinical parameters (age, sex, HBeAg status, HBV DNA, common hematological parameters of a complete blood cell count), a model for predicting significant fibrosis (Metavir score ≥2) in the estimation group was derived using platelets and red cell distribution width (RDW), and another model for predicting cirrhosis (Metavir score = 4) was derived using platelets, RDW and hemoglobin. A novel index, the RDW to platelet ratio (RPR), was developed to amplify the opposing effects of liver fibrosis on the RDW and platelets. The AUCs of the RPR for predicting significant fibrosis and cirrhosis were 0.825 and 0.884, respectively, which is superior to the AAR, FIB-4 and APRI in the estimation group. Compared with the two derived models, the RPR has a comparable predictive power for significant fibrosis and cirrhosis. Using optimized cutoffs (0.10 and 0.16), the RPR accurately predicted 63.1% of cases with significant fibrosis and 73.7% of cases with cirrhosis and accurately excluded 85.5% of the cases with mild fibrosis and 93.0% of the cases with no cirrhosis. CONCLUSION: The RPR, a routinely available, inexpensive and easily calculated index, can predict significant fibrosis and cirrhosis in CHB patients with relatively high accuracy. The application of this index may reduce the need for liver biopsy in CHB patients.

Solitary fibrous tumor of the liver: a case report.

Hepatic solitary fibrous tumor (SFT) is a rare tumor originating from the mesenchyme. Here we report a new case of SFT in the liver and review the clinical presentation, radiological and operative findings, diagnosis, treatment, and outcome. The patient was a 59-year-old man who presented with progressive fatigue for 3 months and an abdominal mass for 3 days. On laboratory tests, no abnormality was detected except that abdominal ultrasonography revealed a 9.0 × 6.2 cm hypoechogenic mass in the left lobe of the liver. A computed tomographic scan confirmed a hypodense lesion in the left lobe of the liver. The patient underwent left hepatectomy. SFT was diagnosed on the basis of histopathological findings. The patient was free from all symptoms and had no signs of local recurrence after 24 months' follow up.

[Expression of GADD153 in follicular tumors of thyroid and comparison with CK19, Galectin-3 and HBME-1].

OBJECTIVE: To study immunohistochemical expression of GADD153 and assess its usefulness as markers in the differential diagnoses in follicular tumors of the thyroid. METHODS: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 34 cases of follicular thyroid adenomas (FTA), 46 cases of follicular thyroid carcinomas (FTC), 29 cases of follicular variant papillary carcinomas (FVPC). RESULTS: (1) GADD153 was expressed in cell nucleus with positive or strong positive expression in FTC, and no or weak expression in FTA and FVPC. The positive expressions of GADD153 were present in 38 of 46(82.6%) in FTC, 11 of 34(32.4%) in FTA and three of 29(10.3%) in FVPC, the positive expression rate in FTC was obviously higher than that in FTA and in FVPC, the differences were statistically significant (χ² = 20.80 and 37.48; P < 0.01). (2) CK19, Galectin-3 (Gal-3) and HBME-1 were all expressed in the cytoplasm, the positive expressions of CK19, Gal-3 and HBME-1 were present in 54.3% (25/46), 67.4% (31/46) and 58.7% (27/46) in FTC; 50.0% (17/34), 29.4% (10/34) and 32.4% (11/34) in FTA; 100% (29/29), 93.1% (27/29) and 89.7% (26/29) in FVPC, the differences were statistically significant as well (χ² = 21.20 and 8.22; P < 0.01). (3) According to the expressions of CK19, Gal-3, HBME-1 and GADD153, we divided the results into low expression group (0 or 1+) and high expression group (2+ or 3+), the sensitivity and the specificity were calculated. in FTA, the sensitivity were 26.5%, 8.8%, 2.9% and 11.8%; the specificity were 50.7%, 52.0%, 54.7% and 58.7%. in FTC, the sensitivity were 19.6%, 26.1%, 23.9% and 65.2%; the specificity were 41.3%, 57.1%, 62.0% and 92.1%. in FVPC, the sensitivity were 96.6%, 82.8%, 79.3% and 3.4%; the specificity were 77.5%, 81.3%, 85.0% and 57.5%. CONCLUSIONS: The sensitivity and the specificity of GADD153 expression are well for diagnosing FTC, and CK19, Gal-3, HBME-1 are well for FVPC. The four markers when used in combination, are better to identify the follicular tumors of the thyroid.

Focal nodular hyperplasia of the liver: pathological analysis of 11 cases.

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign tumor-like lesion of the liver, predominantly affecting women. Its etiology is obscure and its pathogenesis is poorly understood. FNH should be differentiated from other benign and malignant hepatic lesions. The aim of this study was to explore the pathological characteristics of FNH of the liver. METHODS: Eleven patients with FNH were studied retrospectively by using hematoxylin and eosin, immunohistochemical and histochemical staining. RESULTS: In 8 female and 3 male FNH patients aged 19 to 54 years (mean 32), most of lesions showed central scars macroscopically. Microscopically 8 patients were found of classical type, 2 were of telangiectic type, and 1 was of mixed type. CONCLUSION: FNH is an uncommon benign hyperplastic lesion of the liver. It should be differentiated from hepatocellular adenoma, alpha-fetoprotein negative hepatocellular carcinoma, and fibrolamellar carcinoma.