circ_HMGCS1 modulates hepatocellular carcinoma chemoresistance via miR-338-5p/IL-7 pathway.

Hepatocellular cancer is one of the most serious types of cancer in the world, with high incidence and mortality rates. Most HCC patients with long-term chemotherapy develop chemoresistance, leading to a poor prognosis. However, the underlying mechanism of circRNAs in HCC chemoresistance remains unclear. Our research found that circ_0072391(circ_HMGCS1) expression was significantly upregulated in cisplatin-resistant HCC cells. The silence of circ_HMGCS1 attenuated the cisplatin resistance in HCC. Results showed that circ_HMGCS1 regulated the expression of miR-338-5p via acting as microRNA sponges. Further study confirmed that miR-338-5p regulated the expression of IL-7. IL-7 could remodel the immune system by improving T-cell function and antagonising the immunosuppressive network. IL-7 is an ideal target used to enhance the function of the immune system. circ_HMGCS1 exerts its oncogenic function through the miR-338-5p/IL-7 pathway. Inhibition of circ_HMGCS1/miR-338-5p/IL-7 could effectively attenuate the chemoresistance of HCC. IL-7 might be a promising immunotherapy target for HCC cancer treatment.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status.

BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study.

BACKGROUND: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD: Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS: 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION: For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.

A Prospective Study Using Propensity Score Matching to Compare Long-term Survival Outcomes After Robotic-assisted, Laparoscopic, or Open Liver Resection for Patients With BCLC Stage 0-A Hepatocellular Carcinoma.

OBJECTIVE: To compare the short- and long-term outcomes of robot-assisted (RALR), laparoscopic (LLR), or open liver resection (OLR) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Following the Balliol IDEAL classification, long-term oncological outcomes can be used to evaluate the value of minimally invasive techniques in the treatment of HCC, and to assess whether they should become a standard practice. METHODS: Data from prospective cohorts of patients with BCLC stage 0-A HCC who underwent curative liver resection using OLR, LLR, or RALR at Tongji Hospital were reviewed. The short-term and long-term oncological outcomes of these 3 different surgical approaches after adequate follow-up were compared using propensity score matching to reduce selection bias. RESULTS: Of 369 patients included in this study (71, RALR; 141, LLR; and 157, OLR), 56 patients in each of the 3 groups were chosen for further comparison, after propensity score matching. In the minimally invasive group (RALR+LLR), both the operative time and duration of Pringle's maneuver were significantly longer than those in the OLR group; however, the length of hospital stay was significantly shorter. There were no significant differences in the other intraoperative parameters and the incidence of postoperative complications among the 3 groups. HCC recurrence in the minimally invasive group when compared with the OLR group was characterized by a significantly higher proportion of single lesion or early-stage HCC. However, there were no significant differences in the 5-year disease-free survival (63.8%, 54.4%, and 50.6%) or overall survival rates (80.8%, 78.6%, and 75.7%, respectively) among the 3 groups. Clinically significant portal hypertension was the only risk factor that negatively affected the 5-year disease-free survival rate. Multivariate Cox regression analysis showed that clinically significant portal hypertension, serum alpha-fetoprotein level (≥400 ng/mL), and Edmondson-Steiner grading (III+IV) were independent risk factors for poor long-term survival. CONCLUSION: Both robotic and laparoscopic hepatectomies were safe and effective for patients with BCLC stage 0-A HCC when compared with open hepatectomy.

Perioperative and Oncological Outcomes of Robotic Versus Open Pancreaticoduodenectomy in Low-Risk Surgical Candidates: A Multicenter Propensity Score-Matched Study.

OBJECTIVES: This study aimed to perform a multicenter comparison between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). BACKGROUND: Previous comparisons of RPD versus OPD have only been carried out in small, single-center studies of variable quality. METHODS: Consecutive patients who underwent RPD (n = 1032) or OPD (n = 1154) at 7 centers in China between July 2012 and July 2020 were included. A 1:1 propensity score matching (PSM) was performed. RESULTS: After PSM, 982 patients in each group were enrolled. The RPD group had significantly lower estimated blood loss (EBL) (190.0 vs 260.0 mL; P < 0.001), and a shorter postoperative 1length of hospital stay (LOS) (12.0 (9.0-16.0) days vs 14.5 (11.0-19.0) days; P < 0.001) than the OPD group. There were no significant differences in operative time, major morbidity including clinically relevant postoperative pancreatic fistula (CR-POPF), bile leakage, delayed gastric emptying, postoperative pancreatectomy hemorrhage (PPH), reoperation, readmission or 90-day mortality rates. Multivariable analysis showed R0 resection, CR-POPF, PPH and reoperation to be independent risk factors for 90-day mortality. Subgroup analysis on patients with pancreatic ductal adenocarcinoma (PDAC) (n = 326 in each subgroup) showed RPD had advantages over OPD in EBL and postoperative LOS. There were no significant differences in median disease-free survival (15.2 vs 14.3 months, P = 0.94) or median overall survival (24.2 vs 24.1 months, P = 0.88) between the 2 subgroups. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with PDAC, RPD resulted in similar oncologic and survival outcomes as OPD.

Outcomes of Robotic Versus Laparoscopic Pancreatoduodenectomy Following Learning Curves of Surgeons: A Multicenter Study on 2255 Patients.

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

Perioperative outcomes of robot-assisted versus laparoscopic liver resection for cavernous hemangioma: a propensity score matching study.

BACKGROUND: Minimally invasive techniques have increasingly been adopted for liver resection. This study aimed to compare the perioperative outcomes of robot-assisted liver resection (RALR) with laparoscopic liver resection (LLR) for liver cavernous hemangioma and to evaluate the treatment feasibility and safety. METHODS: A retrospective study of prospectively collected data was conducted on consecutive patients who underwent RALR (n = 43) and LLR (n = 244) for liver cavernous hemangioma between February 2015 and June 2021 at our institution. Patient demographics, tumor characteristics, and intraoperative and postoperative outcomes were analyzed and compared using propensity score matching. RESULTS: The postoperative hospital stay was significantly shorter (P = 0.016) in the RALR group. There were no significant differences between the two groups in overall operative time, intraoperative blood loss, blood transfusion rates, conversion to open surgery or complication rates. There was no perioperative mortality. Multivariate analysis showed that hemangiomas located in posterosuperior liver segments and those in close proximity to major vascular structures were independent predictors of increased intraoperative blood loss (P = 0.013 and P = 0.001, respectively). For patients with hemangioma in close proximity to major vascular structures, there were no significant differences in perioperative outcomes between the two groups, with the exception that intraoperative blood loss in the RALR group was significantly less than that in the LLR group (350 ml vs. 450 ml, P = 0.044). CONCLUSIONS: Both RALR and LLR were safe and feasible for treating liver hemangioma in well-selected patients. For patients with liver hemangioma in close proximity to major vascular structures, RALR was better than conventional laparoscopic surgery in reducing intraoperative blood loss.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score.

BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Prospective validation of the Eastern Staging in predicting survival after surgical resection for patients with hepatocellular carcinoma: a multicenter study from China.

BACKGROUND: The Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection. METHODS: Patients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging. RESULTS: Among 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χ2: 408.5) and homogeneity (likelihood ratio χ2: 447.3), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.776, 0.787, and 0.768, respectively). In addition, the Eastern staging was the most informative staging system in predicting survival (Akaike information criterion: 2982.33). CONCLUSION: Using a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems.

Total Laparoscopic Resection of an Extrahepatic Mucinous Biliary Cystadenoma with Liver Involvement (with Video).

BACKGROUND: Intrahepatic mucinous biliary cystadenoma is rare, and extrahepatic MBC is even rarer. To our knowledge, total laparoscopic resection of an extrahepatic MBC that had extended intrahepatically has never been reported. PATIENTS AND METHODS: A 28-year-old female presented to our hospital with upper abdomen pain. Radiological investigations demonstrated a 7-cm multiloculated cystic lesion arising from the left hepatic bile duct extending to involve the extrahepatic biliary system down to and posterior to the back of the head of pancreas. The entire extrahepatic bile duct was involved, except for the gallbladder. Laparoscopic surgery was carried out using a five-port approach. A gourd-shaped well-defined multiloculated cyst was found extending from the extrahepatic biliary system proximally to involve the left hepatic duct intrahepatically. After cholecystectomy, the gourd-shaped cyst was opened at its narrowest part at the hepatic hilus to facilitate subsequent resectional surgery. The distal sac was dissected to the distal bile duct end at the duodenal wall and transected. The proximal sac was dissected and resected en bloc with the bifurcation of the right/left hepatic ducts, combined with left hepatectomy plus caudate lobectomy. The reconstruction was done by anastomosing the right anterior and posterior sectional bile ducts to a Roux-en-Y jejunal loop. Multiple intraoperative frozen sections demonstrated the lesion to be a benign MBC. RESULTS: The patient was discharged home 12 days after surgery. She was well on follow-up 24 months after surgery. CONCLUSION: Total laparoscopic resection is technically feasible to treat an extrahepatic MBC with intrahepatic extension.

Clinical Features of Recurrence After Hepatic Resection for Early-Stage Hepatocellular Carcinoma and Long-Term Survival Outcomes of Patients with Recurrence: A Multi-institutional Analysis.

BACKGROUND: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC. PATIENTS AND METHODS: From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence. RESULTS: Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (> 2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level > 400 ug/L, tumor size > 5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS. CONCLUSIONS: Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

Association of Preoperative Body Mass Index with Surgical Textbook Outcomes Following Hepatectomy for Hepatocellular Carcinoma: A Multicenter Study of 1206 Patients.

BACKGROUND: Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2), and high-BMI (≥ 25.0 kg/m2). The incidences of non-TO among these three groups were compared. Multivariate analyses were performed to identify whether there was any independent association between preoperative BMI and non-TO. RESULTS: Among 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P < 0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P < 0.05). CONCLUSIONS: Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.

Pathophysiological mechanisms of ALPPS: experimental model.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage strategy that may increase hepatic tumour resectability and reduce postoperative liver failure rate by inducing rapid hypertrophy of the future liver remnant (FLR). Pathophysiological mechanisms after the first stage of ALPPS are poorly understood. METHODS: An ALPPS model was established in rabbits with liver VX2 tumour. The pathophysiological mechanisms after the first stage of ALPPS in the FLR and tumour were assessed by multiplexed positron emission tomography (PET) tracers, dynamic contrast-enhanced MRI (DCE-MRI) and histopathology. RESULTS: Tumour volume in the ALPPS model differed from post-stage 1 ALPPS at day 14 compared to control animals. 18F-FDG uptake of tumour increased from day 7 onwards in the ALPPS model. Valid volumetric function measured by 18F-methylcholine PET showed good values in accurately monitoring dynamics and time window for functional liver regeneration (days 3 to 7). DCE-MRI revealed changes in the vascular hyperpermeability function, with a peak on day 7 for tumour and FLR. CONCLUSION: Molecular and functional imaging are promising non-invasive methods to investigate the pathophysiological mechanisms of ALPPS with potential for clinical application.

Nab-paclitaxel plus S-1 with or without PD-1 inhibitor in pancreatic ductal adenocarcinoma with only hepatic metastases: a retrospective cohort study.

PURPOSE: The evidence regarding programmed cell death 1 (PD-1) inhibitors on pancreatic ductal adenocarcinoma (PDAC) with metastases remains controversial. This study aimed to assess the efficacy and safety of Nab-paclitaxel plus S1 (NPS) with or without Sintilimab, a PD-1 inhibitor, in patients with PDAC with only hepatic metastases (mPDAC). METHODS: Untreated mPDAC patients who received NPS with (the combination group) or without Sintilimab (the NPS group) were retrospectively studied. Surgery was considered when the pancreatic tumor became resectable or borderline resectable on radiological examinations, and with complete metabolic response of liver metastases. RESULTS: Between October 2017 and February 2020, 32 patients were in the combination group and 34 patients in the NPS group. Successful salvage resection was achieved in 17 (25.8%) patients after tumor-downstaging (combination 12 vs. NPS 5, P = 0.03). The median overall survival (OS) was 16.8 months in the combination group and 10.0 months in the NPS group (P = 0.002). Remarkable OS benefit was observed in patients with decline in CA19-9 of ≥ 50% (16.0 vs. 6.5, P = 0.003), reduction in 18F-fluorodeoxyglucose uptake of primary tumor of ≥ 50% (16.5 vs. 10.0, P < 0. 001) and after salvage resection (20.1 vs. 11.0, P < 0. 001). No significant difference in Grade 3 or higher adverse events were seen between the two groups (40.6% vs. 32.4%, P = 0.49). CONCLUSIONS: Despite the inherent biases of this retrospective study, the addition of Sintilimab significantly improved salvage resection rates and OS compared with the NPS regimen and had a favorable safety profile in treatment naïve mPDAC patients.

Development and validation of glycolysis-related prognostic score for prediction of prognosis and chemosensitivity of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with aggressive biological behaviour. Its rapid proliferation and tumour growth require reprogramming of glucose metabolism or the Warburg effect. However, the association between glycolysis-related genes with clinical features and prognosis of PDAC is still unknown. Here, we used the meta-analysis to correlate the hazard ratios (HR) of 106 glycolysis genes from MSigDB by the cox proportional hazards regression analysis in 6 clinical data sets of PDAC patients to form a training cohort, and a single group of PDAC patients from the TCGA, ICGC, Arrayexpress and GEO databases to form the validation cohort. Then, a glycolysis-related prognosis (GRP) score based on 29 glycolysis prognostic genes was established in 757 PDAC patients from the training composite cohort and validated in 267 ICGC-CA validation cohort (all P < .05). In addition, including PADC, the prognostic value was also confirmed in other 7 out of 30 pan-cancer cohorts. The GRP score was significantly related to specific metabolism pathways, immune genes and immune cells in the patients with PADC (all P < .05). Finally, by combining with immune cells, the GRP score also well-predicted the chemosensitivity of patients with PADC in the TCGA cohort (AUC = 0.709). In conclusion, this study developed a GRP score for patients with PDAC in predicting prognosis and chemosensitivity for PDAC.

Novel Technique for Single-Layer Pancreatojejunostomy is Not Inferior to Modified Blumgart Anastomosis in Robotic Pancreatoduodenectomy: Results of a Randomized Controlled Trial.

BACKGROUND: A novel technique of single-layer continuous suturing (SCS) for pancreaticojejunostomy (PJ) during robotic pancreaticoduodenectomy (RPD), a technically straightforward procedure, has been shown to produce promising results in a previous study. The present RCT aims to show that SCS during RPD does not increase the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) when compared with modified Blumgart anastomosis (MBA). PATIENTS AND METHODS: Between January 2019 and September 2019, consecutive patients (ASA score ≤ 2) who underwent RPD were enrolled and randomized to the SCS or the MBA group. The primary endpoint was the rate of CR-POPF. A noninferiority margin of 10% was chosen. RESULTS: Of the 186 patients, 4 were excluded because PJ was not performed. The remaining 182 patients were randomized to the SCS group (n = 89) or MBA group (n = 93). CR-POPF rate was not inferior in the SCS group [SCS: 6.7%, MBA: 11.8%; 95% confidence interval (- 0.76, - 0.06), P = 0.0002]. PJ duration was significantly lower in the SCS group (P < 0.01). No significant differences were found between the two groups in operative time, estimated blood loss, postoperative hospital stay, or rates of conversion to laparotomy, morbidity, reoperation, or mortality. On subgroup analysis of patients with a soft pancreas and small main pancreatic duct, SCS significantly reduced the duration of PJ. CONCLUSIONS: This study showed that SCS was not inferior to MBA in terms of the CR-POPF rate during RPD. Registration number: ChiCTR1800020086 ( www.Chictr.org.cn ).

Preoperative Estimated Risk of Microvascular Invasion is Associated with Prognostic Differences Following Liver Resection Versus Radiofrequency Ablation for Early Hepatitis B Virus-Related Hepatocellular Carcinoma.

OBJECTIVES: The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk. METHODS: Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching. RESULTS: The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63-0.97, and HR 0.68, 95% CI 0.52-0.88, for HCC within the MC; HR 0.51, 95% CI 0.32-0.81, and HR 0.47, 95% CI 0.26-0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm). CONCLUSIONS: LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.

Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study.

BACKGROUND: Gemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA. METHODS: From January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3-4). Tumors were evaluated at baseline and thence every 4-6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov , number NCT04305288 (registration date: 12/03/2020). RESULTS: Of 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3-12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6-9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5-19.0) versus 12.0 months (95% CI, 9.3-14.8, p = 0.099). Significantly more grade 3-4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044). CONCLUSIONS: First-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.