Bone marrow metastatic neuroendocrine carcinoma with unknown primary site: A case report and review of the literature.

BACKGROUND: Metastatic neuroendocrine carcinoma (NEC) of bone marrow is uncommon. Here, we report a case of bone marrow metastatic NEC with an unknown primary site. CASE SUMMARY: A 73-year-old Chinese woman was admitted to our hospital because marked chest distress and asthma lasting 1 d on March 18, 2018. She was initially diagnosed with pulmonary infection, cardiac insufficiency, thrombocytopenia and severe anemia. Following treatment with antibiotic therapy, diuresis and blood transfusion, the patient's symptoms greatly improved. After bone marrow examinations, the patient was diagnosed with bone marrow metastatic NEC, bone marrow necrosis (BMN) and secondary myelofibrosis (MF). Further imaging workup did not show the primary tumor, we presumed that the primary site might regress spontaneously or merely be unexplored due to lack of positron emission tomography with gallium peptide. Everolimus (10 mg/d) was added to the treatment and the best supportive and symptomatic therapies were also administered. Unfortunately, the patient's condition continued to deteriorate and she died on May 15, 2018. CONCLUSION: Bone marrow invasion of NEC is rare and our patient who suffered from bone marrow metastatic NEC as well as secondary BMN and MF had an extremely poor prognosis. Bone marrow biopsy plays an important role in the diagnosis of solid tumors invading bone marrow.

Single-cell atlas of diverse immune populations in the advanced biliary tract cancer microenvironment.

Immunotherapies have been explored in treating solid tumors, albeit with disparate clinical effects in distinct cancer types. Systematic interrogation of immune cells in the tumor microenvironment (TME) is vital to the prediction of immunotherapy response and the development of innovative immunotherapeutics. To comprehensively characterize the immune microenvironment in advanced biliary tract cancer (BTC), we utilized single-cell RNA sequencing in unselected viable cells from 16 matched samples, and identified nineteen cell subsets from a total of 45,851 cells, in which exhausted CD8+ T cells, macrophages, and dendritic cells (DCs) in BTC were shown to augment and communicate within the TME. Transcriptional profiles coupled with T cell receptor (TCR) sequences revealed that exhausted CD8+ T cells retained clonal expansion and high proliferation in the TME, and some of them highly expressed the endoplasmic reticulum stress (ER) response gene, XBP1, indicating the role of ER stress in remodeling TME. Functional assays demonstrated that XBP1 and common immune checkpoints (PD1, TIGIT) were significantly upregulated in CD8+ T cells cocultured within the TME of BTC cells (GBC-SD, HCCC-9810). When treating the coculture groups with the specific inhibitor of IRE1α-XBP1 (4µ8C), the downregulation of TIGIT was observed in the treatment group. Collectively, comprehensive transcriptome profiling provides deep insights into the immune atlas in advanced BTC, which might be instrumental in exploring innovative immunotherapy strategies.

The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice.

BACKGROUND & AIMS: Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota. METHODS: Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion. RESULTS: We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival. CONCLUSION: We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).

Development and validation of a nomogram to predict overall survival in patients with incidental gallbladder cancer: A retrospective cohort study.

Objective: The aim of this study was to develop and validate a nomogram to predict the overall survival of incidental gallbladder cancer. Methods: A total of 383 eligible patients with incidental gallbladder cancer diagnosed in Shanghai Eastern Hepatobiliary Surgery Hospital from 2011 to 2021 were retrospectively included. They were randomly divided into a training cohort (70%) and a validation cohort (30%). Univariate and multivariate analyses and the Akaike information criterion were used to identify variables independently associated with overall survival. A Cox proportional hazards model was used to construct the nomogram. The C-index, area under time-dependent receiver operating characteristic curves and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Results: T stage, N metastasis, peritoneal metastasis, reresection and histology were independent prognostic factors for overall survival. Based on these predictors, a nomogram was successfully established. The C-index of the nomogram in the training cohort and validation cohort was 0.76 and 0.814, respectively. The AUCs of the nomogram in the training cohort were 0.8, 0.819 and 0.815 for predicting OS at 1, 3 and 5 years, respectively, while the AUCs of the nomogram in the validation cohort were 0.846, 0.845 and 0.902 for predicting OS at 1, 3 and 5 years, respectively. Compared with the 8th AJCC staging system, the AUCs of the nomogram in the present study showed a better discriminative ability. Calibration curves for the training and validation cohorts showed excellent agreement between the predicted and observed outcomes at 1, 3 and 5 years. Conclusions: The nomogram in this study showed excellent discrimination and calibration in predicting overall survival in patients with incidental gallbladder cancer. It is useful for physicians to obtain accurate long-term survival information and to help them make optimal treatment and follow-up decisions.

Does splenectomy significantly improve the prognosis of hepatocellular carcinoma patients with hypersplenism? A systematic review and meta-analysis.

BACKGROUND: Whether hepatocellular carcinoma (HCC) patients with hypersplenism can benefit from splenectomy is unclear. This study aimed at exploring the efficacy and safety of concurrent splenectomy for HCC patients with hypersplenism. METHODS: PubMed, EMBASE and Web of Science databases were systematically searched to compare data on the combination of hepatectomy or transhepatic arterial infusion (TAI) with splenectomy (the splenectomy group) with data on hepatectomy or TAI alone (the non-splenectomy group) for the treatment of HCC with hypersplenism. Prospective clinical trials or retrospective cohort studies from inception to May 10, 2020 were considered eligible for this analysis. The relevant outcomes, including patients' demographics, clinicopathologic characteristics, perioperative indices and long-term outcomes, were independently extracted by two investigators. Publication bias for overall survival (OS) and disease-free survival (DFS) was qualitatively assessed by funnel plots and quantitatively evaluated by Begg's and Egger's tests. RESULTS: Nine retrospective studies including 1,650 patients were analyzed. Short-term outcomes suggested that the incidence rate of postoperative complications, including portal or splenic vein thrombosis [odds ratio (OR) =26.28, P<0.001] and pancreatic injury (OR =14.89, P=0.001), was significantly higher in the splenectomy group, whereas the perioperative mortality rate was similar between the splenectomy and non-splenectomy groups (P=0.541). Long-term outcomes indicated that the occurrence of variceal re-hemorrhage (OR =0.31, P<0.001) and tumor progress or recurrence (OR =0.62, P=0.001) was markedly reduced for patients who underwent splenectomy, while the long-term mortality rates were not statistically different between the two groups (P=0.087). The prognostic evaluation revealed that the OS and DFS were comparable between the splenectomy and non-splenectomy groups [for OS: hazard ratio (HR) =0.77, 95% confidence interval (CI): 0.53-1.13; for DFS: HR =0.87, 95% CI: 0.63-1.19]. Funnel plots suggested an HRs symmetric distribution for OS and DFS. Begg's and Egger's tests confirmed that there was no significant HR publication bias for OS and DFS. CONCLUSIONS: Due to the significant progress in surgical techniques and perioperative care, concomitant splenectomy should be considered as an optional treatment for some HCC patients with hypersplenism.

Coexistence of breakpoint cluster region-Abelson1 rearrangement and Janus kinase 2 V617F mutation in chronic myeloid leukemia: A case report.

BACKGROUND: The Janus kinase 2 (JAK2) V617F mutation is common in patients with breakpoint cluster region-Abelson1 (BCR-ABL1)-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in BCR-ABL1-positive chronic myeloid leukemia (CML) patients. Here, we report a CML patient with both a BCR-ABL1 rearrangement and JAK2 V617F mutation. CASE SUMMARY: A 45-year-old Chinese woman was admitted to our department with a history of significant thrombocytosis for 20 d. Color Doppler ultrasound examination showed mild splenomegaly. Bone marrow aspiration revealed a karyotype of 46, XX, t(9;22)(q34;q11.2) in 20/20 metaphases by cytogenetic analysis, rearrangement of BCR-ABL1 (32.31%) by fluorescent polymerase chain reaction (PCR) and mutation of JAK2 V617F (10%) by PCR and Sanger DNA sequencing. The patient was diagnosed with CML and JAK2 V617F mutation. Following treatment with imatinib for 3 mo, the patient had an optimal response and BCR-ABL1 (IS) was 0.143%, while the mutation rate of JAK2 V617F rose to 15%. CONCLUSION: Emphasis should be placed on the detection of JAK2 mutation when CML is diagnosed to distinguish JAK2 mutation-positive CML and formulate treatment strategies.

Prognostic prediction and diagnostic role of intercellular adhesion molecule-1 (ICAM1) expression in clear cell renal cell carcinoma.

The intercellular adhesion molecule-1 (ICAM1) has been reported to function in multiple malignancies, but its effect on clear cell renal cell carcinoma (ccRCC) hasn't been discussed yet. This study aimed to identify the potential role of ICAM1 in prognostic prediction and early diagnosis of ccRCC. ICAM1 expression was inspected by immunohistochemistry and correlated with clinicopathologic variables. Association between protein expression and cancer-specific survival (CSS) of ccRCC patients was evaluated and the value of area under the receiver operating characteristics (ROC) curve (AUC) was calculated to measure the protein's diagnostic accuracy. ICAM1 was positively immunostained in 83.2% of 173 ccRCC tissues, but negatively immunostained in all the para-cancerous normal epitheliums of renal tubules. High ICAM1 expression was significantly related to male sex (P = 0.00241), T3/T4 stage (P = 0.02249), non-N0M0 stage (P = 0.03797) and positive renal pelvis invasion (P = 0.04227). Kaplan-Meier survival analysis illustrated that high ICAM1 expression was significantly correlated to a decreased CSS (P = 0.00006). Multivariate Cox analysis indicated that ICAM1 was an independent predictor for CSS of patients (P = 0.00451). Furthermore, the AUC value of ICAM1 in diagnosing ccRCC was 0.916 (P < 0.00001). In conclusion, high ICAM1 expression on tumor cells indicates a poor outcome of patients and ICAM1 is likely to be an independent predictor for the prognosis of ccRCC. Moreover, ICAM1 has a high AUC value and may be a potential and useful diagnostic marker.