Comparison of percutaneous microwave/radiofrequency ablation liver partition and portal vein embolization versus transarterial chemoembolization and portal vein embolization for planned hepatectomy with insufficient future liver remnant.

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.

The short- and long-term outcomes of laparoscopic pancreaticoduodenectomy combining with different type of mesentericoportal vein resection and reconstruction for pancreatic head adenocarcinoma: a Chinese multicenter retrospective cohort study.

BACKGROUND: The results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs. METHODS: Patients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared. RESULTS: In total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS. CONCLUSIONS: In LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.

Practice Patterns and Perioperative Outcomes of Laparoscopic Pancreaticoduodenectomy in China: A Retrospective Multicenter Analysis of 1029 Patients.

OBJECTIVE: The aim of the study was to analyze the outcomes of patients who have undergone laparoscopic pancreaticoduodenectomy (LPD) in China. SUMMARY BACKGROUND DATA: LPD is being increasingly used worldwide, but an extensive, detailed, systematic, multicenter analysis of the procedure has not been performed. METHODS: We retrospectively reviewed 1029 consecutive patients who had undergone LPD between January 2010 and August 2016 in China. Univariate and multivariate analyses of patient demographics, changes in outcome over time, technical learning curves, and the relationship between hospital or surgeon volume and patient outcomes were performed. RESULTS: Among the 1029 patients, 61 (5.93%) required conversion to laparotomy. The median operation time (OT) was 441.34 minutes, and the major complications occurred in 511 patients (49.66%). There were 21 deaths (2.43%) within 30 days, and a total of 61 (5.93%) within 90 days. Discounting the effects of the early learning phase, critical parameters improved significantly with surgeons' experience with the procedure. Univariate and multivariate analyses revealed that the pancreatic anastomosis technique, preoperative biliary drainage method, and total bilirubin were linked to several outcome measures, including OT, estimated intraoperative blood loss, and mortality. Multicenter analyses of the learning curve revealed 3 phases, with proficiency thresholds at 40 and 104 cases. Higher hospital, department, and surgeon volume, as well as surgeon experience with minimally invasive surgery, were associated with a lower risk of surgical failure. CONCLUSIONS: LPD is technically safe and feasible, with acceptable rates of morbidity and mortality. Nonetheless, long learning curves, low-volume hospitals, and surgical inexperience are associated with higher rates of complications and mortality.

How to Perform Total Laparoscopic Duodenum-Preserving Pancreatic Head Resection Safely and Efficiently with Innovative Techniques.

BACKGROUND: Although rapid progress has been achieved in laparoscopic pancreaticoduodenectomy (PD) over the last decade, laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) remains a challenging surgery that has been rarely reported due to not only requiring complicated pancreaticojejunostomy (PJ) but also ensuring sufficient blood supplies to duodenum and common bile duct (CBD). We completed LDPPHR for 22 patients safely and efficiently with innovative techniques. PATIENTS AND METHODS: Clinical outcomes, including rate of conversion to laparotomy, time of residual pancreatic duct reconstruction, incidence of postoperative complications, and time of hospital stay, were collected for 22 consecutive patients who underwent LDPPHR with innovative techniques as follows: application of indocyanine green (ICG) to visualize and preserve CBD and the vessels supplying the duodenum and CBD, Hong's PJ, and pancreatic duct end-to-end anastomosis (ETEA) for the residual pancreas. RESULTS: All surgeries were performed successfully under laparoscopy except for one case. The duration of ETEA was significantly shorter than PJ (18.2 ± 5.1 min versus 27.5 ± 8.3 min, p < 0.05). There was no significant difference in incidence of postoperative complications between the Hong's PJ and ETEA group. The overall incidence of postoperative pancreatic fistula (POPF) in the Hong's PJ and ETEA group was 23.5% and 20%, respectively, without grade C fistula. All complications were resolved after conservative treatment. CONCLUSIONS: By utilizing intraoperative ICG navigation, LDPPHR is a minimally invasive, safe, and efficient approach for chronic pancreatitis with pancreatic head stones by using pancreatic duct ETEA and benign or low-grade malignant tumors of the pancreatic head by using Hong's PJ.

Betulinic acid induces apoptosis of gallbladder cancer cells via repressing SCD1.

Gallbladder cancer (GBC) is the most common and aggressive malignancy of the biliary tract. Betulinic acid (BetA) has been reported to have anti-inflammatory and antitumor effects; however, the effect of BetA on GBC is still unknown. In this study, we investigated the effect of BetA on five GBC cell lines and found that BetA significantly inhibited the proliferation of NOZ cells but had little inhibitory effect on other GBC cells. BetA disturbed mitochondrial membrane potential and induced apoptosis in NOZ cells. Real-time polymerase chain reaction analysis revealed that stearoyl-coenzyme A desaturase 1 (SCD1) was highly expressed in NOZ cells but low expressed in other GBC cells. BetA inhibited SCD1 expression in a concentration-dependent manner in NOZ cells. Downregulation of SCD1 expression by RNA interference inhibited the proliferation of NOZ cells and induced cell apoptosis. Moreover, BetA inhibited the growth of xenografted tumors and suppressed SCD1 expression in nude mice. Thus, our results showed that BetA induced apoptosis through repressing SCD1 expression in GBC, suggesting that BetA might be an effective agent for the treatment of patients with GBC that highly expresses SCD1.

WITHDRAWN: Individualized and pancreatic duct diameter-based strategy for pancreaticoenteric anastomosis during pancreaticoduodenectomy.

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Pure laparoscopic radical resection for type IIIa hilar cholangiocarcinoma.

BACKGROUND: Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1-4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma. METHODS: The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed. RESULTS: This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC). CONCLUSIONS: Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We present a video of the described procedure.

Binding pancreaticogastrostomy in laparoscopic central pancreatectomy: a novel technique in laparoscopic pancreatic surgery.

BACKGROUND: Even though more and more cases of laparoscopic central pancreatectomy (LCP) are reported (Machado et al. in Surg Laparosc Endosc Percutan Tech 23(6):486-490, 2013; Hong et al. in World J Surg Oncol 10:223, 2012; Gonzalez et al. in JOP 14(3):273-276, 2013, Zhang et al. in J Laparoendosc Adv Surg Tech A 23(11):912-918, 2013; Sucandy et al. in N Am J Med Sci 2(9):438-441, 2010; Sa Cunha et al. in Surgery 142(3):405-409, 2007), the management for pancreatic stumps remains the most technically challenging part which is the same as in pancreatoduodenectomy (PD), making it the bottleneck for laparoscopic pancreatic surgery. In open surgery, various pancreatic reconstruction techniques designed for either pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG) have been attempted to reduce the postoperative pancreatic fistula (POPF), including the binding anastomosis, invented by our team, i.e., binding PG (BPG) and binding PJ, which have been proved to be effective to reduce the POPF (Hong et al. 2012; Peng et al. in Ann Surg 245(5):692-698, 2007; Peng et al. in Updates Surg 63(2):69-74, 2011). However, despite of this, few reports are seen addressing such technique for laparoscopic surgery even though laparoscopic pancreatic surgery is more performed. After a previous successful laparoscopic BPG in a case of laparoscopic CP (LCP; Hong et al. 2012) and more than 50 cases of open PD and CP (Peng et al. 2011), we further performed laparoscopic BPG in 10 consecutive cases of LCP with satisfactory outcomes. OBJECTIVE: To explore the feasibility and efficacy of LCP with BPG. METHODS: Between October 2011 and July 2014, LCP with laparoscopic BPG was performed in ten consecutive patients with lesions of benign or low malignancy at the pancreatic neck. Operative and pathological data, complications, hospital stay and details on the surgical techniques were introduced. RESULTS: The operations were successfully performed in all the ten cases, with no conversions. The tumor size ranged from 2.0-3.0 to 2.5-3.0 cm, average (2.50 ± 0.35) to (2.66 ± 0.35) cm, and the diameter of pancreatic duct was (1.6-2.1) mm, average (1.71 ± 0.17) mm. Operation time was 170-250 (198.50 ± 25.82) min, and blood loss was 20-300 (125 ± 107.31) mL. Three cases had grade A pancreatic fistula (PF), and one case had delayed gastric emptying, which were all managed with conservative treatment. Upper GI bleeding occurred in one case which was cured with second operation, time for the recovery of bowl movement was 3-5 (4.2 ± 0.8) days, the time for semifluid dieting was 6-10 (8.2 ± 1.5) days, and the hospital stay was 8-20 (12.8 ± 4.63) days. The postoperative fast blood sugar was (6.3 ± 1.6) mmol/L with the normal diet, which was not significantly different from the preoperative data (5.3 ± 0.5) mmol/L (P > 0.05). The postoperative pathology was as follows: five cases of cystic serous adenoma, one case of intraductal papillary mucinous neoplasm, two cases of neuroendocrine tumor, and two cases of solid pseudopapillary tumor of pancreas. All the patients were followed up for 7-40 months, no recurrence happened, and no new incidence of diabetes or insufficiency of pancreatic exocrine function occurred. CONCLUSIONS: LCP with BPG is feasible and safe; the advantages lie in its minimal invasiveness, the efficacy for avoiding PF, and the preservation of the pancreatic endocrine and exocrine function insufficiency, making it an ideal procedure for the benign or low-malignant lesions at the pancreatic neck.

Indocyanine green retention is a potential prognostic indicator after splenectomy and pericardial devascularization for cirrhotic patients.

BACKGROUND: Splenectomy and pericardial devascularization (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and specificity than the Child-Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD. METHODS: From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classification, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively. RESULTS: Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function compensation was 31.2%, which offered a sensitivity of 68.4% and a specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were significantly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of postoperative liver function recovery (P=0.020). CONCLUSIONS: ICGR15 has outperformed the Child-Pugh classification for assessing liver function in cirrhotic patients with portal hypertension. ICGR15 may be a suitable prognostic indicator for cirrhotic patients after SPD.

Comparison of two laparoscopic splenectomy plus pericardial devascularization techniques for management of portal hypertension and hypersplenism.

OBJECTIVE: Our research was conducted to analyze the outcomes of two laparoscopic splenectomy plus pericardial devascularization (LSPD) techniques in the management of portal hypertension (PTH) and hypersplenism. METHODS: Between May 2012 and May 2013, 41 patients with PTH and hypersplenism undergoing LSPD were retrospectively analyzed. Of them, 29 patients received LSPD by LigaSure Vessel Sealing System (LVSS) and Endo-GIA universal endoscopic vascular linear staplers (Endo-GIA) (EG Group) and 12 patients received LSPD by LVSS and Hem-o-Lock (HL Group). Operating time, intraoperative blood loss, postoperative course, and hospitalization costs were compared between the two LSPD combination techniques. RESULTS: There were no significant differences in preoperative patient characteristics of the two groups. Significantly less operating time, intraoperative blood loss, and postoperative complications were observed in EG Group. The incidence of portal vein thrombosis was lower in the EG Group (3.4 vs. 8.3%), as well as the incidence of pancreatic fistula (0 vs. 8.3%). Upper gastrointestinal hemorrhage was not observed in either group. Uncontrolled bleeding warranted conversion to open surgery in one case in EG Group (conversion rate 3.4%) and in two cases in HL Group (conversion rate 16.7%). Two patients (16.7%) in HL Group underwent successful emergency exploratory laparotomy due to uncontrolled intraabdominal bleeding postoperatively. No re-operation was needed in EG Group. Two patients experienced liver failure after surgery in each group. Of those, three patients were managed successfully and one patient refused further therapy. While the overall complication rate was significantly lower in EG Group (17.2 vs. 58.3%, P < 0.05), overall hospitalization costs remained significantly higher for EG Group. CONCLUSION: The results suggest that the modified Endo-GIA and LVSS technique is a safe and effective combination approach to LSPD with shorter operative time, less intraoperative blood loss, lower conversion rate to laparotomy, shorter hospital stay, better recovery, and lower postoperative complication rate compared with the Hem-o-Lock and LVSS approach. Higher hospitalization expenses associated with the Endo-GIA and LVSS approach.

Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress.

Chemotherapy drugs themselves may act as stressors to induce adaptive responses to promote the chemoresistance of cancer cells. Our previous research showed that sirtuin 1 (SIRT1) was overexpressed in pancreatic cancer patients and deregulation of SIRT1 with RNAi could enhance chemosensitivity. Thus, we hypothesized that SIRT1 might facilitate chemoresistance in pancreatic cancer cells through regulating the adaptive response to chemotherapy-induced stress. In the present study, SIRT1 in PANC-1, BXPC-3, and ASPC-1 cells was upregulated after treatment with gemcitabine. Moreover, the decrease in SIRT1 activity with special inhibitor EX527 had a synergic effect on chemotherapy with gemcitabine in PANC-1 and ASPC-1 cell lines, which significantly promoted apoptosis, senescence, and G0 /G1 cycle arrest. Western blot results also showed that SIRT1, acetylated-p53, FOXO3a, and p21 were upregulated after combined treatment, whereas no obvious change was evident in total p53 protein. To further confirm the role of SIRT1 in clinical chemotherapy, SIRT1 was detected in eight pancreatic cancer tissues acquired by endoscopy ultrasonography guided fine needle aspiration biopsy before and after chemotherapy. Compared to before chemotherapy, SIRT1 was significantly increased after treatment with gemcitabine in six cases. Thus, our results indicated a special role for SIRT1 in the regulation of adaptive response to chemotherapy-induced stress, which is involved in chemoresistance. Moreover, it indicates that blocking SIRT1 activity with targeting drugs might be a novel strategy to reverse the chemoresistance of pancreatic cancer.

Partial hepatectomy for primary hepatic melanoma: a report of two cases and review of the literature.

Malignant melanoma is an extremely aggressive cancer arising from melanocytes, associated with the development of metastases in up to 20% of patients. Although the liver is a frequent metastatic site of malignant melanoma, primary hepatic melanoma (PHM) is rare. The treatment of PHM is controversial, and the prognosis for affected patients remains poor. We present two PHM patients who underwent partial hepatectomy at our institution and review the clinical and pathological data from these cases. Our results suggest that it is difficult to make a preoperative diagnosis of PHM without pathological results. For patients with resectable PHM, surgical resection is a potentially curative treatment.

Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1α through regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells.

Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)/hypoxia-inducible factor 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer.

The Synergy of Gene Targeting Drug Icaritin Soft Capsule with Immunomodulator and TACE Brings New Hope for Drug Combination in Patients with Advanced Liver Cancer: A Case Report and Literature Review.

At present, the average five-year survival rate of liver cancer in China is only 12.1%. The reason for this association lies in the diagnosis at its middle or/and advanced stage of liver cancer for lacking special clinical symptoms in almost 70% of patients without the chance of effective surgical resection. Epidemiological studies have shown that there are only 30% of patients with an initial diagnosis of liver cancer have the opportunity to undergo radical surgery. Therefore, systematic and comprehensive treatment would play an important role in liver cancer treatment at its middle or/and advanced stage, and the related therapeutic schedule still needs further improvement and optimization. We applied a gene-targeted drug of Icaritin soft capsule in the treatment of a liver cancer patient at its advanced stage. And the level of AFP was found to decrease to 6.4ng/mL from 10.86ng/mL; meanwhile, MRI showed that the primary tumor significantly reduced in size, with shrinking of the hepatogastric space, hepatic aortic side, and renal artery side lymph nodes. After treatment with TACE and Icaritin, the patient had no discomfort and no longer experienced abdominal pain and bloating and gained three kilograms of weight. The therapeutic effect of Icaritin-targeted drugs was completely demonstrated during the later treatment follow-up. That is to say, the multiple anti-tumor characteristics of Icaritin with good safety were fully displayed in this case, and it can be used in combination with other drugs to treat hepatocellular carcinoma in the clinical setting. The results show that Icaritin can put some effects on the combined treatment of patients with liver cancer.

Textbook outcome as a composite outcome measure in laparoscopic pancreaticoduodenectomy: a multicenter retrospective cohort study.

BACKGROUND: Textbook outcome (TO) is a composite outcome measure for surgical quality assessment. The aim of this study was to assess TO following laparoscopic pancreaticoduodenectomy (LPD), identify factors independently associated with achieving TO, and analyze hospital variations regarding the TO after case-mix adjustment. METHODS: This multicenter cohort study retrospectively analyzed 1029 consecutive patients undergoing LPD at 16 high-volume pancreatic centers in China from January 2010 to August 2016. The percentage of patients achieving TO was calculated. Preoperative and intraoperative variables were compared between the TO and non-TO groups. Multivariate logistic regression was performed to identify factors independently associated with achieving TO. Hospital variations regarding the TO were analyzed by the observed/expected TO ratio after case-mix adjustment. Differences in expected TO rates between different types of hospitals were analyzed using the one-way analysis of variance test. RESULTS: TO was achieved in 68.9% ( n =709) of 1029 patients undergoing LPD, ranging from 46.4 to 85.0% between different hospitals. Dilated pancreatic duct (>3 mm) was associated with the increased probability of achieving TO [odds ratio (OR): 1.564; P =0.001], whereas advanced age (≥75 years) and concomitant cardiovascular disease were associated with a lower likelihood of achieving TO (OR: 0.545; P =0.037 and OR: 0.614; P =0.006, respectively). The observed/expected TO ratio varied from 0.62 to 1.22 after case-mix adjustment between different hospitals, but no significant hospital variations were observed. Hospital volume, the surgeon's experience with open pancreaticoduodenectomy and minimally invasive surgery, and surpassing the LPD learning curve were significantly correlated with expected TO rates. CONCLUSION: TO was achieved by less than 70% of patients following LPD. Dilated pancreatic ducts, advanced age, and concomitant cardiovascular disease were independently associated with achieving TO. No significant hospital variations were observed after case-mix adjustment.

Application of binding pancreatogastrostomy in laparoscopic central pancreatectomy.

BACKGROUND: The feasibility of binding pancreaticogastrostomy in laparoscopic central pancreatectomy is not known. METHODS: In October 2011, a female patient with a pancreatic neck mass received laparoscopic central pancreatectomy with binding pancreaticogastrostomy. RESULTS: The operation was successful. No complications occurred. The operative time was 210 min. Blood loss was 120 ml. On day 11 after the operation, the patient was discharged. The postoperative pathological result showed a 2 × 2 × 2-cm solid pseudopapillary tumor of the pancreas with intrapancreatic infiltration. The surgical margin was negative. CONCLUSIONS: Laparoscopic central pancreatectomy with binding pancreaticogastrostomy might be feasible, facilitating further study in laparoscopic pancreatoduodenectomy. TRIAL REGISTRATION: This study was waived from trial registration because it is a retrospective analysis of medical records.

Siglec-15 Regulates the Inflammatory Response and Polarization of Tumor-Associated Macrophages in Pancreatic Cancer by Inhibiting the cGAS-STING Signaling Pathway.

Tumor-associated macrophages especially M2 phenotype macrophages play an important role in tumor progression and the formation of immunosuppressive tumor microenvironment. Previous studies indicated that infiltration of a large number of M2-macrophages was positively associated with a low survival rate and poor prognosis of patients with pancreatic ductal cancer. However, the mechanisms responsible for M2-macrophage polarization remain unclear. Recently, Siglec-15 appears as an emerging target for the normalization of the tumor immune microenvironment. Hence, we detected the Sigelc-15 expression on macrophages by using qPCR and Western blot assay and found that the expression of Siglec-15 was upregulated on M2 macrophages induced by IL-4 and conditioned media from pancreatic ductal cancer. In addition, after knocking out Siglec-15, the expression of M2 phenotype macrophage biomarkers such as Arg1 and CD206 was significantly downregulated. Besides, in our study we also found that Siglec-15 could upregulate the glycolysis of macrophage possibly by interacting with Glut1 to regulate the M2-macrophage polarization. The regulation was also partly dependent on STING, and Glut1-related glycose metabolism was involved in regulating cGAS/STING signaling. When utilizing a subcutaneous transplantation mouse model, we observed that knocking out of Siglec-15 or co-injecting tumor cells with macrophage from Siglec-15 KO mice could significantly inhibit the growth of subcutaneous tumors in mice. Taken together, these findings suggest that Siglec-15 is essential for the M2-macrophage polarization to shape an immune suppressive tumor microenvironment in pancreatic cancer and makes it an attractive target for pancreatic cancer immunotherapy.

Incidence of postoperative pancreatic fistula after using a defined pancreaticojejunostomy technique for laparoscopic pancreaticoduodenectomy: A prospective multicenter study on 1033 patients.

OBJECTIVE: This prospective multicenter study aimed to study the incidence of postoperative pancreatice fistula using a defined technique of pancreaticojejunostomy (PJ) in laparoscopic pancreaticoduodenectomy (LPD). BACKGROUND: PJ is a technically challenging and time-consuming procedure in LPD. Up to now, only a few small sample size studies have been reported on various PJ techniques in LPD, none of which has widely been accepted by surgeons. METHODS: This prospective study enrolled consecutive patients who underwent LPD using a defined technique of PJ at four institutions in China between January 2017 and December 2020. RESULTS: Of 1045 patients, after excluding 12 patients (1.2%) due to conversion to open surgery, 1033 patients were analysed. The males comprised of 57.12% (590/1033), and females 42.88% (443/1033), with a mean age of 59.00 years. The mean ± s.d. operation time was (270.2 ± 101.8) min. The median time for PJ was 24min (IQR = 20.0-30.0). The overall incidence of postoperative pancreatic fistula was 12.6%, including 67 patients (6.5%) with Grade A biochemical leak, 50 patients (4.8%) with Grade B, and 13 patients (1.3%) with Grade C pancreatic fistulas. The overall incidence of major complications (Clavien-Dindo score ≥3) was 6.3% and the 30-day mortality was 2.8%. CONCLUSION: The pancreaticojejunostomy technique for LPD was safe, simple and reproduceable with favorable clinical outcomes. However, further validations using high-quality RCTs are still required to confirm the findings of this study.

ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma.

Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming.