Efficacy of treatment based on TKIs in combination with PD-1 inhibitors for unresectable recurrent hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: The recurrence occurs within 5 years in up to 70% of hepatocellular carcinoma (HCC) patients who received radical liver resection, and most patients are no longer suitable for repeat surgery. There are limited treatment options for unresectable recurrent HCC. This study aimed to explore the potential efficacy of treatment based on TKIs in combination with PD-1 inhibitors for unresectable recurrent HCC. METHODS: Forty-four patients with unresectable recurrent HCC after radical surgery between January 2017 and November 2022 were retrospectively collected and screened. All patients received the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors, and 18 of these patients received trans-arterial chemoembolization (TACE) or TACE combined with radiofrequency ablation (RFA). Two patients who received TKIs in combination with PD-1 inhibitors eventually obtained repeat surgery, with one patient undergoing a repeat hepatectomy and one patient receiving a liver transplant. RESULTS: The median survival for these patients was 27.0 months (95% confidence interval [CI] 21.2, 32.8), with a 1-year overall survival (OS) rate of 83.6% (95% CI 77.9%, 89.3%). Median progression-free survival (PFS) was 15.0 months (95.0% CI 12.1, 17.9), with a 1-year PFS rate of 77.0% (95% CI 70.6%, 83.4%). The two patients who underwent repeat surgery had a survival time of 34 and 37 months after the combined treatment with no recurrence, respectively, as of November 2022. CONCLUSION: The combination of TKIs and PD-1 inhibitors for unresectable recurrent HCC is effective and can prolong the survival of patients in this group.

Long-term survival and portal vein patency with novel PVTT surgery approach in advanced HCC patients with Vp3/4 PVTT following combination therapy of TKIs and PD-1 inhibitors.

BACKGROUND: It is controversial whether patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) should undergo salvage surgery following the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors. This study aimed to elucidate the efficiency and safety of salvage surgery following combination therapy, while also summarizing a novel surgical approach for Vp3/4 PVTT. METHODS: Between April 2019 and December 2022, a consecutive series of unresectable HCC patients with PVTT who received salvage surgery following combination therapy were enrolled. Evaluation included perioperative and long-term follow-up outcomes. The complete removal of Vp3/4 PVTT was achieved using a novel surgical approach characterized by "longitudinal incision and transverse suturing" and "angle-to-straight conversion". RESULTS: Forty patients including 22 patients with Vp3 and 18 patients with Vp4 were included. Long-term follow-up showed similar rates of portal vein patency (Vp3: 95.5%, Vp4:94.4%, p = 0.900), and 3-year portal vein patency rates were 95.0%. There were no significant differences observed in combination therapy-related adverse events (p = 0.253) and perioperative complications (p = 0.613) between the Vp3 and Vp4 groups. The recurrence patterns were similar between the two groups (p = 0.131). There were no significant differences in overall survival (OS) and recurrence-free (RFS) survival between the Vp3 and Vp4 groups (OS p = 0.457, RFS p = 0.985). Patients who achieved a pathological complete response had significantly better RFS (p = 0.011). CONCLUSION: Salvage surgery after combination therapy demonstrated favorable efficacy and safety. The novel surgical approach for PVTT can effectively achieve complete removal of PVTT and ensured long-term portal vein patency.

Comparison of survival benefit between salvage surgery after conversion therapy versus surgery alone for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

BACKGROUND: Salvage surgery after conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody has shown improved survival benefits in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We aimed to compare the survival benefits in a retrospective cohort of patients with HCC with PVTT who underwent salvage surgery after conversion therapy and surgery alone. METHODS: From January 2015 to October 2021, we selected patients diagnosed with HCC with PVTT who underwent liver resection at Chinese PLA General Hospital. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. RESULTS: The 6-, 12-, and 24-month recurrence-free survival rates in the conversion and surgery alone groups were 80.3% vs 36.5%, 65.4% vs 29.4%, and 56% vs 21%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. CONCLUSIONS: For patients with HCC with PVTT, surgery after conversion therapy is in relationship with increased survival in comparison with surgery alone.

Improving the Surgical Effect for Primary Liver Cancer with Intraoperative Fluorescence Navigation Compared with Intraoperative Ultrasound.

BACKGROUND This study aimed to compare the application value of intraoperative fluorescence navigation technology (FNT) and intraoperative ultrasound (IOUS) in primary liver cancer surgery. MATERIAL AND METHODS Fifty consecutive patients with primary liver cancer scheduled to receive surgical treatment were divided into FNT group and IOUS group. FNT and IOUS were separately used to guide tumor resection and detect new cancerous lesions in the 2 groups. The complete tumor resection rate (R0) resection rate, length of the tumor distance from cutting edge, the diagnostic efficacy of cancerous nodules and the fluorescence imaging characteristics of different types tumors were recorded. RESULTS The R0 resection rate was 100% (25 out of 25 patients) in the FNT group and 96% (24 out of 25 patients) in the IOUS group. In the FNT group, 1 case (4%, 1 out of 25 patients) had cancer tissue that was less than 1 cm from the cutting edge, compared to 7 cases (28%, 7 out of 25 patients) in the IOUS group (P=0.049), which was a significant difference. In the remaining livers of 50 consecutive patients, FNT found 5 new cancerous nodules with a sensitivity of 71.4%, a specificity of 11.1%, and a false-positive rate of 88.9%; for IOUS the results were 42.9%, 88.9%, 11.1%. The fluorescence imaging characteristics of all well-differentiated hepatocellular carcinomas were tumor tissue imaging, but all other types of tumors were ring imaging around the tumor. CONCLUSIONS FNT can improve the R0 resection rate, ensure a safe distance between tumor and cutting edge and can identify more new cancerous nodules compared to IOUS. Thus, FNT could improve the surgical treatment effect for primary liver cancer and hopefully further improve the prognosis of patients.

CCNI2 promotes pancreatic cancer through PI3K/AKT signaling pathway.

Globally, pancreatic cancer is recognized as one of the deadliest malignancies that lacks effective targeted therapies. This study aims to explore the role of cyclin I-like protein (CCNI2), a homolog of cyclin I (CCNI), in the progression of pancreatic cancer, thereby providing a theoretical basis for its treatment. Firstly, the expression of CCNI2 in pancreatic cancer tissues was determined through immunohistochemical staining. The biological role of CCNI2 in pancreatic cancer cells was further assessed using both in vitro and in vivo loss/gain-of-function assays. Our data revealed that CCNI2 expression was abnormally elevated in pancreatic cancer, and clinically, increased CCNI2 expression generally correlated with reduced overall survival. Functionally, CCNI2 contributed to the malignant progression of pancreatic cancer by promoting the proliferation and migration of tumor cells. Consistently, in vivo experiments verified that CCNI2 knockdown impaired the tumorigenic ability of pancreatic cancer cells. Moreover, the addition of phosphatidylinositol 3-kinase (PI3K) inhibitors could partially reverse the promoting effect of CCNI2 on the malignant phenotypes of pancreatic cancer cells. CCNI2 promoted pancreatic cancer through PI3K/protein kinase B (AKT) signaling pathway, indicating its potential as a prognostic marker and therapeutic target for pancreatic cancer.

Whole-exome sequencing identifies a set of genes as markers of hepatocellular carcinoma early recurrence.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by a high recurrence rate and poor prognosis. In recent years, the therapeutic regimen of programmed cell death protein 1 (PD-1) antibody combined with multi-targeted tyrosine kinase inhibitors (mTKIs) has achieved better results in the clinical application of hepatocellular carcinoma. Whole-exome sequencing can reflect the mutational characteristics of patients' exons and guide the clinical selection of molecular targeting drugs more accurately, which is in line with the concept of precision medicine. METHODS: We performed exome sequencing on 63 patients with HCC treated with radical surgery at our hospital and collected their clinical indexes and postoperative follow-up data. Using machine learning, a prediction model for recurrence within 1 year was constructed and the model was presented in a nomogram. Patients treated with PD-1 antibodies in combination with mTKIs after relapse were grouped by prognosis, and the valuable mutated genes were screened according to whole-exome sequencing data. The tumor tissue immune cells were analyzed using the UCSC Xena database. The expressions of target proteins were verified by Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC), respectively, on commercial HCC cell lines and pathological specimens of hepatocellular carcinoma collected clinically. RESULTS: The proportion of patients who relapsed within a year was 41% and the prognosis of those patients was poor. The characteristic exon mutation profile with a high frequency of variants in multiple mucin genes was present in Chinese HCC patients. Multiple nidi and 30 exon variants were brought into the prediction model with an area under the curve (AUC) = 0.94. MUC6 gene mutation was obvious in patients with an early recurrence, and MUC3A and MUC4 gene mutations were evident in patients with poorer responses to PD-1 antibodies combined with mTKIs. Those three mucins were negatively correlated with immune infiltrating cells. CONCLUSIONS: We depicted the exon characteristics of hepatocellular carcinoma in the Chinese population and established a predictive model for recurrence within 1 year after radical surgical treatment. Moreover, we found that mucins were worthy targets of hepatocellular carcinoma.

Factors influencing the prognosis patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma undergoing salvage surgery after conversion therapy.

Background: The aim of this study was to investigate the prognostic factors influencing the outcome of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (HCC) receiving salvage surgery after conversion therapy based on tyrosine kinase inhibitors (TKIs) and anti-programmed death-1 (PD-1) antibodies. Methods: From June 2018 to December 2022, patients receiving salvage surgery after conversion therapy based on PD-1 and TKIs at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were retrospectively recruited for this study. Overall survival (OS) and recurrence-free survival (RFS) were observed as the primary end point in the Cox analysis of prognostic factors among this study. Results: The 6- and 12-month RFS rates were 77.0% and 64.8%, respectively, while the 6-, 12-, 24-, and 36-month OS rates were 98.4%, 93.4%, 76.8%, and 69.8%, respectively. The median OS and RFS were not reached. On multivariable Cox regression analyses, low serum alpha fetoprotein (AFP) level (≤20 ng/mL) after conversion therapy [hazard ratio (HR) 0.186, 95% CI: 0.039-0.887; P=0.035) and microvascular invasion (MVI) grade II (HR 3.054, 95% CI: 1.000-9.329; P=0.050) were independent factors associated with a higher OS and RFS. Conclusions: For patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) HCC, lower AFP level after conversion therapy (<20 ng/mL) and MVI II were associated with a higher OS and lower RFS rate, respectively.

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.

Construction and Validation of a Ferroptosis-Related lncRNA Signature as a Novel Biomarker for Prognosis, Immunotherapy and Targeted Therapy in Hepatocellular Carcinoma.

Recently, immunotherapy combined with targeted therapy has significantly prolonged the survival time and improved the quality of life of patients with hepatocellular carcinoma (HCC). However, HCC treatment remains challenging due to the high heterogeneity of this malignancy. Sorafenib, the first-line drug for the treatment of HCC, can inhibit the progression of HCC by inducing ferroptosis. Ferroptosis is associated with the formation of an immunosuppressive microenvironment in tumours. Moreover, long non-coding RNAs (lncRNAs) are strongly associated with ferroptosis and the progression of HCC. Discovery of ferroptosis-related lncRNAs (FR-lncRNAs) is critical for predicting prognosis and the effectiveness of immunotherapy and targeted therapies to improve the quality and duration of survival of HCC patients. Herein, all cases from The Cancer Genome Atlas (TCGA) database were divided into training and testing groups at a 6:4 ratio to construct and validate the lncRNA signatures. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression analyses were used to screen the six FR-lncRNAs (including MKLN1-AS, LINC01224, LNCSRLR, LINC01063, PRRT3-AS1, and POLH-AS1). Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses demonstrated the optimal predictive prognostic ability of the signature. Furthermore, a nomogram indicated favourable discrimination and consistency. For further validation, we used real-time quantitative polymerase chain reaction (qRT-PCR) to analyse the expression of LNCSRLR, LINC01063, PRRT3-AS1, and POLH-AS1 in HCC tissues. Moreover, we determined the ability of the signature to predict the effects of immunotherapy and targeted therapy in patients with HCC. Gene set enrichment analysis (GSEA) and somatic mutation analysis showed that ferroptosis-related pathways, immune-related pathways, and TP53 mutations may be strongly associated with the overall survival (OS) outcomes of HCC patients. Overall, our study suggests that a new risk model of six FR-lncRNAs has a significant prognostic value for HCC and that it could contribute to precise and individualised HCC treatment.

Prognosis and Tumour Immune Microenvironment of Patients With Hepatocellular Carcinoma by a Novel Pyroptosis-Related lncRNA Signature.

Worldwide, hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. However, the survival rate of patients with HCC continues to be poor. The recent literature has revealed that long non-coding RNAs (lncRNAs) and the occurrence of pyroptosis can perform a substantial task in predicting the prognosis of the respective condition along with the response to immunotherapy among HCC patients. Thus, screening and identifying lncRNAs corelated with pyroptosis in HCC patients are critical. In the current study, pyroptosis-related lncRNAs (PR-lncRNAs) have been obtained by co-expression analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regression assessments have been performed to develop a PR-lncRNA prognostic model. The risk model was analysed using Kaplan-Meier analysis, principal component analysis (PCA), functional enrichment annotation, and a nomogram. The risk model composed of five PR-lncRNAs was identified as an independent prognostic factor. The tumour immune microenvironment (TIME) was assessed using model groupings. Finally, we validated the five PR-lncRNAs in vitro using a quantitative real-time polymerase chain reaction (qRT-PCR).

Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report.

Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient's survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.

Surgery After Conversion Therapy With PD-1 Inhibitors Plus Tyrosine Kinase Inhibitors Are Effective and Safe for Advanced Hepatocellular Carcinoma: A Pilot Study of Ten Patients.

BACKGROUND AND AIMS: Immunotherapy with PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) has been proven to be effective against advanced hepatocellular carcinoma (HCC). The aim of this study was to identify the feasibility and safety of subsequent salvage surgery after this combination therapy. METHODS AND PATIENTS: A retrospective analysis was performed on patients with primary HCC with major vascular invasion between 2018 and 2019. All cases were treated with a combination of a PD-1 inhibitor and TKI agents and subsequent surgery. RESULTS: A total of 10 HCC cases with major vascular invasion met the successful conversion criteria after the combination therapy, and eight patients underwent subsequent salvage surgery after both radiology and 3D quantitative oncological assessment. Partial response (PR) was recorded in 7 of 10 patients and complete response (CR) in 3 of 10 patients before salvage surgery. Salvage surgery included right hepatectomy, left hepatectomy, and anatomic segmental hepatectomy. The mean intraoperative blood loss was 1,650 ml (50-3,000 ml). No complications beyond Clavien-Dindo level III or postoperative mortality were observed. The viable tumor cell rate of the PR cases (modified response evaluation criteria in solid tumors, mRECIST) varied from 1.5% to 100%, and only one patient had pathology-proven pathological complete response (pCR). The postoperative median follow-up time was 19.7 months (9.1-24.9 months). The 12-month recurrence-free survival rate of all cases who underwent salvage surgery was 75%. CONCLUSION: Salvage surgery was effective and safe after conversion therapy with PD-1 inhibitors plus TKIs and may increase the long-term oncological benefit for patients with unresectable HCC.

Bifunctional cleavable probes for in situ multiplexed glycan detection and imaging using mass spectrometry.

In situ analysis of glycans is of great significance since they mediate a range of biological activities. Aberrant changes of glycosylation are closely related to cancer onset and progression. In this work, bifunctional laser cleavable mass probes (LCMPs) were developed for in situ glycan detection from both cells and tissues using laser desorption ionization mass spectrometry (LDI-MS). Specific recognition of glycans was achieved by lectins, and inherent signal amplification was achieved by the conversion of the detection of glycans to that of mass tags which overcame the low ionization efficiency and complicated mass spectra of glycans. Multiplexed glycan profiling was easy to implement due to the simple and generic synthetic route to LCMPs and serial alternative mass tags, which offers high sensitivity, low interference and in situ detection of glycans. Moreover, as an excellent inherent matrix, LCMPs facilitated direct glycan detection from the cell surface and tissue imaging using LDI-MS. Intrinsic and fine glycan distribution in human cancer and paracancerous tissues was strictly demonstrated by MS imaging to explore the correlation between glycosylation and various cancers. This approach presented a versatile LDI-MS based platform for fast and in situ multiplexed glycan engineering, thus providing a new perspective in glycobiology and clinical diagnosis.

Two cases of intrahepatic cholangiocellular carcinoma with high insertion-deletion ratios that achieved a complete response following chemotherapy combined with PD-1 blockade.

BACKGROUND: Insertion-deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. CASE PRESENTATION: Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of TP53 and PTEN that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation JAK2, whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. CONCLUSIONS: These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation.

Retrospective study on the effects of the prognosis of patients treated with extracorporeal membrane oxygenation combined with continuous renal replacement therapy.

BACKGROUND: Patients undergoing extracorporeal membrane oxygenation (ECMO) treatment often have severe fluid overload and electrolyte imbalances and may even suffer acute kidney injury (AKI). It is often necessary to use continuous renal replacement therapy (CRRT). In this study, we aimed to retrospectively analyze the prognosis of patients treated with ECMO combined with CRRT and to find the independent factors that affect the survival rate. METHODS: There were 32 patients who were treated with ECMO combined with CRRT in our hospital from January 2007 to December 2017 who were analyzed. All of the patients were divided into a survival group and death group. The clinical indicators and biochemical indexes of the two groups were observed, and their differences were compared. Multivariate logistic regression analysis was carried out to determine the independent risk factors. RESULTS: The fluid balance at ECMO day 3, SOFA score and lactate at CRRT initiation, sequential organ failure assessment (SOFA) score at ECMO weaning, CRRT duration, ECMO to CRRT interval, mechanical ventilation (MV) duration, length of ICU, and overall hospital length of stay were statistically significant (P<0.05). The clinical biochemical indexes at CRRT initiation and ECMO weaning [serum creatinine, pH, white blood cell (WBC), hemoglobin (Hb), bilirubin]; patient's age, gender and BMI; and the fluid balance at ECMO days 1 and 7 were not statistically significance (P>0.05). The fluid balance at ECMO day 3 and lactate at CRRT initiation by multivariable logistic regression analysis were independent risk factors affecting patient prognosis. CONCLUSIONS: The fluid balance at ECMO day 3 and lactate at CRRT initiation are the prognosis independent risk factors for ECMO + CRRT patients.

Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy.

AIM: To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy. METHODS: We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis. RESULTS: A total of 269 (49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy, including 71 (13.17%) cases of grade A pancreatic fistula, 178 (33.02%) cases of grade B, and 20 (3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula (POPF) and the following factors: age, hypertension, alcohol consumption, smoking, history of upper abdominal surgery, preoperative jaundice management, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, operative time, intraoperative blood transfusion, Braun anastomosis, and pancreaticoduodenectomy (with or without pylorus preservation). Conversely, a significant correlation was observed between POPF and the following factors: gender (male vs female: 54.23% vs 42.35%, P = 0.008), diabetes (non-diabetic vs diabetic: 51.61% vs 39.19%, P = 0.047), body mass index (BMI) (≤ 25 vs > 25: 46.94% vs 57.82%, P = 0.024), blood glucose level (≤ 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%, P = 0.002), pancreaticojejunal anastomosis technique (pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis: 57.54% vs 35.46%, P = 0.000), diameter of the pancreatic duct (≤ 3 mm vs > 3 mm: 57.81% vs 38.36%, P = 0.000), and pancreatic texture (soft vs hard: 56.72% vs 29.93%, P = 0.000). Multivariate logistic regression analysis showed that gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy. CONCLUSION: Gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

Application of single-layer mucosa-to-mucosa pancreaticojejunal anastomosis in pancreaticoduodenectomy.

AIM: To investigate the simplicity, reliability, and safety of the application of single-layer mucosa-to-mucosa pancreaticojejunal anastomosis in pancreaticoduodenectomy. METHODS: A retrospective analysis was performed on the data of patients who received pancreaticoduodenectomy completed by the same surgical group between January 2011 and April 2014 in the General Hospital of the People's Liberation Army. In total, 51 cases received single-layer mucosa-to-mucosa pancreaticojejunal anastomosis and 51 cases received double-layer pancreaticojejunal anastomosis. The diagnoses of pancreatic fistula and clinically relevant pancreatic fistula after pancreaticoduodenectomy were judged strictly by the International Study Group on pancreatic fistula definition. The preoperative and intraoperative data of these two groups were compared. χ(2) test and Fisher's exact test were used to analyze the incidences of pancreatic fistula, peritoneal catheterization, abdominal infection and overall complications between the single-layer anastomosis group and double-layer anastomosis group. Rank sum test were used to analyze the difference in operation time, pancreaticojejunal anastomosis time, postoperative hospitalization time, total hospitalization time and hospitalization expenses between the single-layer anastomosis group and double-layer anastomosis group. RESULTS: Patients with grade A pancreatic fistula accounted for 15.69% (8/51) vs 15.69% (8/51) (P = 1.0000), and patients with grades B and C pancreatic fistula accounted for 9.80% (5/51) vs 52.94% (27/51) (P = 0.0000) in the single-layer and double-layer anastomosis groups. Although there was no significant difference in the percentage of patients with grade A pancreatic fistula, there was a significant difference in the percentage of patients with grades B and C pancreatic fistula between the two groups. The operation time (220.059 ± 60.602 min vs 379.412 ± 90.761 min, P = 0.000), pancreaticojejunal anastomosis time (17.922 ± 5.145 min vs 31.333 ± 7.776 min, P = 0.000), postoperative hospitalization time (18.588 ± 5.285 d vs 26.373 ± 15.815 d, P = 0.003), total hospitalization time (25.627 ± 6.551 d vs 33.706 ± 15.899 d, P = 0.002), hospitalization expenses (116787.667 ± 31900.927 yuan vs 162788.608 ± 129732.500 yuan, P = 0.001), as well as the incidences of pancreatic fistula [13/51 (25.49%) vs 35/51 (68.63%), P = 0.0000], peritoneal catheterization [0/51 (0%) vs 6/51 (11.76%), P = 0.0354], abdominal infection [1/51 (1.96%) vs 11/51 (21.57%), P = 0.0021], and overall complications [21/51 (41.18%) vs 37/51 (72.55%), P = 0.0014] in the single-layer anastomosis group were all lower than those in the double-layer anastomosis group. CONCLUSION: Single-layer mucosa-to-mucosa pancreaticojejunal anastomosis appears to be a simple, reliable, and safe method. Use of this method could reduce the postoperative incidence of complications.

Integrin αvß6 sustains and promotes tumor invasive growth in colon cancer progression.

AIM: To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular matrices. METHODS: An immunohistochemical study of integrin αvß6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS: High immunoreactivity for αvß6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin αvß6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both αvß6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing αvß6 in the tumorigenicity assay. Flow cytometry was applied to analyze αvß6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on αvß6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced αvß6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION: Integrin αvß6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin ανß6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.