"Parenchyma transection-first" strategy is superior to "tunnel-first" strategy in robotic spleen-preserving distal pancreatectomy with conservation of splenic vessels.

BACKGROUND: Creating a tunnel between the pancreas and splenic vessels followed by pancreatic parenchyma transection ("tunnel-first" strategy) has long been used in spleen-preserving distal pancreatectomy (SPDP) with splenic vessel preservation (Kimura's procedure). However, the operation space is limited in the tunnel, leading to the risks of bleeding and difficulties in suturing. We adopted the pancreatic "parenchyma transection-first" strategy to optimize Kimura's procedure. METHODS: The clinical data of consecutive patients who underwent robotic SPDP with Kimura's procedure between January 2017 and September 2022 at our center were retrieved. The cohort was classified into a "parenchyma transection-first" strategy (P-F) group and a "tunnel-first" strategy (T-F) group and analyzed. RESULTS: A total of 91 patients were enrolled in this cohort, with 49 in the T-F group and 42 in the P-F group. Compared with the T-F group, the P-F group had significantly shorter operative time (146.1 ± 39.2 min vs. 174.9 ± 46.6 min, P < 0.01) and lower estimated blood loss [40.0 (20.0-55.0) mL vs. 50.0 (20.0-100.0) mL, P = 0.03]. Failure of splenic vessel preservation occurred in 10.2% patients in the T-F group and 2.4% in the P-F group (P = 0.14). The grade 3/4 complications were similar between the two groups (P = 0.57). No differences in postoperative pancreatic fistula, abdominal infection or hemorrhage were observed between the two groups. CONCLUSIONS: The pancreatic "parenchyma transection-first" strategy is safe and feasible compared with traditional "tunnel-first strategy" in SPDP with Kimura's procedure.

Methylation patterns partition pancreatic cancer into distinct prognostic subtypes.

In the initiation and progression of pancreatic cancer, DNA methylation plays a critical role. The present study attempts to explore specific prognosis subtypes based on DNA methylation data and develop an epigenetic signature to predict the overall survival (OS) of patients with pancreatic cancer.147 samples were included in the training cohort, whereas the validation cohort included 226 samples. The 298 OS-related methylation sites in the training cohort were selected for consensus clustering, and the authors identified three subtypes with a significant difference in prognosis. Cluster1 was associated with poor OS, low-grade disease and high lymph node involvement. In addition, we identified 33 specific methylation sites in Cluster1. Subsequently, we developed a robust qualitative signature consisting of 14 methylation sites to individually predict OS in the training cohort, and the predictive accuracy of this model was confirmed in the validation cohort. Functional enrichment analysis showed that the selected genes in the model were mainly enriched in known cancer-related pathways. Patients were divided into high- and low-risk groups by the model, and a significant difference in OS was observed between these groups. Classification based on the modeling of a specific DNA methylation site can reveal the heterogeneity of pancreatic cancer and provide guidance for clinicians in predicting the prognosis of pancreatic cancer and providing personalized treatment.

Hybrid pancreatoduodenectomy in laparoscopic and robotic surgery: a single-center experience in China.

BACKGROUND: Minimally invasive surgery is beneficial for pancreatic surgery, and the indication has been expanded to pancreatoduodenectomy (PD). The aim of this study was to share our experiences with hybrid PD in laparoscopic and robotic surgery. METHODS: Sixty-four patients underwent hybrid PD in which specimen resection and gastrojejunostomy were performed through the laparoscopic route and pancreatojejunostomy and hepaticojejunostomy were performed via a robotic approach by the same surgeon at a single institution between July 2016 and June 2019. The primary endpoint was complications; secondary endpoints were operative time (OT), the length of hospital stay, and blood loss. The data for the patients were retrospectively obtained from electrical medical records. RESULTS: All patients underwent surgery with the hybrid procedure. The mean OTs and estimated blood loss (EBL) were 309.7 ± 77.6 min (range 17-620 min), 160 ± 31.7 mL (range 50-800 mL). The mean number of lymph nodes retrieved was 7.3 ± 6.7 (range 0-37), and that among 45 malignant cases was 8.42 ± 6.7 (range 1-37). The average length of postoperative stay in the hospital was 11.14 ± 7.03 days (range 6-47 days). Clinically relevant postoperative pancreatic fistulas (POPFs) occurred in 39 (60.9%) cases, and most were biochemical leak POPF (29 cases, 45.3%); only 10 (15.6%) cases were grade B/C (8 cases were Grade B and 2 cases were Grade C treated with digital subtraction angiography). Bile leakage occurred in 2 (3.1%) patients. One (1.5%) patient had a gastric fistula, and 3 (4.7%) developed postoperative delayed gastric emptying categorized as International Study Group of Pancreatic Surgery (ISGPS) Grade A. Three (4.7%) patients were readmitted for postoperative bleeding, and 2 (3.1%) died within 30 days. CONCLUSION: Hybrid PD with laparoscopic and robot surgery is safe and feasible. OT can be reduced by switching from the laparoscopic approach to the robotic procedure at the appropriate timepoint.

Transforming growth factor ß receptor signaling restrains growth of pancreatic carcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant. Efficient control of cancer growth may substantially improve the survival of PDAC patients. However, no efficient treatments are so far available. Here, we inhibited transforming growth factor ß (TGFß) receptor signaling by overexpression of a key inhibitor of this pathway, SMAD7, in the mouse pancreas, using a recently developed intraductal infusion method. Overexpression of SMAD7 significantly increased growth of both implanted PDAC and PDAC by K-ras modification. Our data thus suggest that TGFß receptor signaling restrains growth of PDAC, and modulation of TGFß receptor signaling may be an effective treatment for PDAC.

Single-port and multi-port laparoscopic left lateral liver sectionectomy for treating benign liver diseases: a prospective, randomized, controlled study.

BACKGROUND: The use of single-port laparoscopy for left-lateral liver sectionectomy (LLLS) has been reported in the literature, but the effectiveness and safety of LLLS has not been validated in randomized, controlled trials. This prospective randomized controlled trial compared the effectiveness and safety of single-port and multi-port laparoscopic LLLS for the surgical treatment of benign liver disease. METHODS: Altogether, 38 patients aged 17-65 years (16 men, 22 women) with benign liver diseases were hospitalized for elective laparoscopic LLLS between January 2010 and December 2012. Patients were randomly assigned to either single-port (n = 19) or multi-port (n = 19) laparoscopic LLLS. Main outcome measures were operative time, volume of intraoperative blood loss, complication rates, and postoperative hospitalization. RESULTS: Baseline characteristics of the two groups were comparable. Single-port and multi-port laparoscopies were successfully completed in all but one patient (1/19, 5.3 %) who required conversion from a single-port to a multi-port procedure. The two groups had similar mean operative times and volumes of intraoperative blood loss. There were no clinically significant postoperative complications or deaths. The single-port group had a significantly shorter postoperative hospitalization than the multi-port group (2.5 ± 1.7 vs. 4.0 ± 2.1 days; p < 0.05). CONCLUSIONS: Single-port laparoscopic LLLS is a technically feasible, effective, safe alternative to multi-port laparoscopy for the treatment of benign liver diseases in cautiously selected patients.

Characterization of an Ac transposon system based on apt1-m1 (Ac) on the long arm of maize chromosome 9.

Activator/Dissociation (Ac/Ds) transposable elements have been used in maize insertional mutagenesis as a complement to Mutator (Mu). In this study, to further improve the efficiency of the Ac/Ds mutagenesis system, we adopted apt1-m1 (Ac) on the long arm of chromosome 9 (9L) as a donor Ac to create an Ac insertion library. This system is based on the negative selection pressure against the donor Ac, and it was highly efficient for isolating new transposition events. We obtained 9,625 transposition events from 1083 F1 ears with an average transposition rate of 8.66 % (rates ranged from 1.11 to 29.73 %). We also adopted a modified PCR-based genome walking strategy to improve the efficiency of the new method for isolating transposon-flanking sequences. This method is more efficient than the Southern-based method that was used in previous studies. A validation step was developed to distinguish transposon tags derived from newly transposed Ac or Ds elements. Using this PCR-based method, we isolated 67 inheritable flanking sequences from the apt1-m1 (Ac) transposition library; of these, 51 were confirmed as tr-Ac-flanking sequences and 11 were tr-Ds-flanking sequences. Similar to other Ac donors from different loci, the apt1-m1 (Ac) system also exhibited a preference for short distance transposition. In this study, we have further improved the Ac mutagenesis system in maize for gene isolation and functional genomics studies.

Establishment of a mouse model for bile duct repair and tissue engineering.

Due to the lack of a suitable model, research on biliary biology is far behind that on other organs. A mouse model of common bile duct (CBD) dilation (BDD) was first established and compared with CBD ligation mice (BDL). Then, in a transplantation experiment, the dilated CBD of recipient BDD mice was injured by making an elliptical incision and repaired by transplanting a bile duct patch from donor BDD mice. Biochemical and histological changes were analyzed and cell proliferation of the bile duct grafts was determined. Slightly dilated and unblocked CBD with a diameter of 2.89±0.76 mm was obtained in BDD mice, while the CBD diameter was 0.51±0.08 mm in the Sham group and 4.71±0.64 mm in the BDL group on day 14 after surgery. The liver damage was very mild in BDD mice compared with BDL mice, proving that the BDD model could be further used for bile duct transplantation. By cross transplanting the bile duct patch from enhanced green fluorescence protein and wild-type BDD mice, it was found that the CBD injury was well repaired and the cells of the bile duct patch were completely replaced by recipient-derived cells at 12 week after the repair operation. α Smooth muscle actin, Ki67 and cytokeratin 19 immunofluorescence staining showed that the proliferation of bile duct epithelial cells and abundant active fibroblasts were found within the bile duct patch during the regeneration process. Therefore, a reliable new mouse model of bile duct injury and repair was successfully established and can be used in the study of biliary repair mechanisms and tissue engineering of biliary ducts.

Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases.

We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato-pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme-linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra-hepatic cholangio-carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p = 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child-Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 µg/L vs. 102.8 µg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p = 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p = 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP-negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.

Laparoendoscopic single-site liver resection: a preliminary report of 12 cases.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery is an emerging laparoscopic procedure previously used for cholecystectomy and appendectomy. However, few studies have examined LESS liver resection, and its benefits require investigation. This study aimed to evaluate the feasibility and safety of LESS liver resection. METHODS: From December 2009 to October 2010, 12 patients were selected for LESS liver resection with institutional review board approval. The LESS technique was performed using a transumbilical TriPort or three 5-mm trocars with a 5-mm linear or flexible laparoscope. Conventional or articulating laparoscopic instruments were used to mobilize and transect the lesions. RESULTS: The LESS liver resection procedure was successfully completed for 10 patients (83.3%), with the remaining 2 patients (16.7%) undergoing conversion to conventional multiport laparoscopy. The procedures consisted of left lateral segment resection (n = 4) and partial resection (n = 8) in addition to concomitant cholecystectomy (n = 3). The mean operative time was 80.4 min (range, 35-160 min), and the mean estimated blood loss was 45 ml (range, 20-800 min). No postoperative complications were noted except for biliary leakage (200 ml/day)in one patient. The mean hospital stay was 4.3 days (range, 2-8 days). No patient required postoperative analgesia, and the pain visual analog score 48 h after surgery was 0.53 (range, 0-2). Pathology identified 10 benign and 2 malignant liver tumors with a clear margin. CONCLUSIONS: Our preliminary data show that LESS liver resection is safe and feasible for selected patients, with potential benefits that include a fast recovery, light pain, and cosmetically acceptable scarring. However, this procedure requires advanced instruments and complicated laparoscopic techniques, with a risk of intraoperative bleeding and postoperative bile leakage.

Laparoscopic repeat resection of recurrent hepatocellular carcinoma.

BACKGROUND: The present study was designed to explore the safety and feasibility of laparoscopic re-resection of recurrent liver tumors. METHODS: Among 120 hepatocellular carcinoma patients who received laparoscopic hepatectomy, six were carefully selected to receive laparoscopic re-resection. Surgical indications were evaluated by specific selection criteria for tumor location, size, metastases, vessel invasion, and liver function. Four patients received laparoscopic partial hepatectomy, and two received laparoscopic anatomical left lateral lobe resection. Results were analyzed retrospectively. RESULTS: The six surgeries (four laparoscopic partial hepatectomies, two laparoscopic anatomical left lateral lobe resections) were successfully performed with no intraoperative complications. Mean operative time was 140.83 ± 35.69 min, mean blood loss was 283.33 ± 256.25 ml, and mean hospital stay was 5.67 ± 1.63 days. CONCLUSIONS: Our experience with carefully selected cases meeting specific criteria suggests that laparoscopic hepatic re-resection is a safe, feasible procedure that may offer multiple benefits for treating recurrent hepatocellular carcinoma.

An Improved Surgical Technique for Pure Laparoscopic Left Hemihepatectomy: Ten Years Experience in a Tertiary Center.

BACKGROUND: This study details our experience with an improved surgical technique involving the hepatic pedicle during laparoscopic left hemihepatectomy (LLH). METHODS: We describe an improved laparoscopic technique to extraparenchymally divide the left hepatic pedicle. A retrospective analysis of all of the patients who underwent laparoscopic liver procedures between 2002 and 2012 was conducted. The patients were divided into two groups, an early LLH group (ELLH group) and a recent LLH group (RLLH group), based on the surgical approach used for the left hepatic pedicle. RESULTS: A total of 72 cases of LLH (26 ELLH and 46 RLLH) were identified. The RLLH group exhibited a shorter median operative time, median length of hospital stay, and lower median blood loss compared to the ELLH group (182, 162.5-223.7 versus 232.5, 200-357.5 minutes, P < .01; 5, 4.2-7 versus 7, 6-8.7 days, P < .05; 150, 100-257.5 versus 300, 200-337.5 mL, P < .05, respectively). No perioperative mortality was observed. CONCLUSIONS: This study confirms that our improved surgical technique for LLH is practical, safe, and effective. The main advantage of this method compared to other techniques is the possibility of attaining rapid and precise control of vascular inflow, thus facilitating LLH.

Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway.

Previous population investigations have suggested that the application of curcumin may be associated with decreased incidence and improved prognosis in certain types of cancer. Forkhead box O1 (FOXO1) has been implicated in the regulation of several biological processes, including stress resistance, metabolism, DNA repair, cell cycle and apoptosis. The aims of the present study were to investigate the effects and molecular mechanisms of curcumin on the induction of anti­proliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISA­Brdu assay were used to assess cell proliferation. Reverse transcription­quantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki­67, B­cell lymphoma­2 (Bcl­2), B­cell­associated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis was detected using a Cell Death ELISA detection kit. A Caspase­3/9 Fluorescent Assay kit was used to detect caspase activity. The findings revealed that curcumin significantly decreased cell proliferation, which was associated with increased expression of the p21/CIP1 and p27/KIP1 cyclin­dependent kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl­2/Bax protein ratio and increasing caspase­9/3 activation in the pancreatic cancer cells. Using siRNA against FOXO1, and Akt inhibitor and activator, the present study confirmed that curcumin induced the expression of FOXO1 by inhibition of phosphoinositide 3­kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the anti­neoplastic effects of curcumin and justify further investigation to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer.

The differential diagnostic model for serous peptidomics in HBV carriers established by MALDI-TOF-MS analysis.

OBJECTIVES: Hepatitis B virus (HBV) can result in asymptomatic carrier (AsC) state or chronic inflammation of liver, which depends on the host immunity. We therefore investigated the peptidomic profiling in the process of HBV infection. DESIGN AND METHODS: In this study, serum from 116 HBV infected (AsC and chronic hepatitis), 60 HBV-immunized and 70 normal subjects was treated with MB-WCX (weak cation exchange based magnetic beads) kits and analyzed by the Clinprot/Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) techniques. Purified serous proteins were subjected to FT-ICR-MS analysis, and Western blot further confirmed the results. RESULTS: The specific model comprised of two peptides m/z 2882.89 and 4476.12 could distinguish HBV infected from healthy (HBV-immunized and normal) group and showed 95.5% of the sensitivity and 95.4% of the specificity by cross-validation analysis. 40/56 HBV infected and 43/50 healthy subjects could be correctly classified by the model. The area under the receiving operating curves (AUROC) of m/z 2882.89 and 4476.12, identified as subunits of fibrinogen beta chain (FBG) Bß10-42 and nucleophosmin (NPM) respectively, were both up to 0.88 when discriminating AsC from the healthy group. The expression of Bß10-42 and NPM decreased significantly in the plasma of HBV infected individuals by Western blot analysis. CONCLUSIONS: There were specific serum peptide profilings for host responses to HBV infection, and m/z 2882.89 and 4476.12 could be valuable follow-up and prognostic tools for HBV infection.

Lithotomy using cholangioscopy via the left hepatic duct orifice versus the common bile duct in laparoscopic treatment of left-sided hepatolithiasis: a comparative study.

OBJECTIVE: Laparoscopic hepatectomy is widely used in the surgical treatment of left-sided hepatolithiasis (LSH). Lithotomy using a cholangioscope usually is required for the treatment of concurrent right-sided hepatolithiasis or choledocholithiasis. The primary objective of this study was to evaluate the effectiveness and safety of gallstone elimination using cholangioscopy through the left hepatic duct (LHD) orifice versus the common bile duct (CBD). PATIENTS AND METHODS: Eligible LSH patients (n=41) were scheduled for laparoscopic left lateral segmentectomy or left hemihepatectomy with intraoperative biliary exploration using cholangioscopy through the LHD orifice (LHD group, n=23) or the CBD (CBD group, n=18) at the discretion of patients. Laparoscopic T-tube insertion was performed in selected patients. Patients were regularly followed up at monthly intervals or more frequently in the presence of any symptom. The primary outcome measures included overall operative time, duration of the cholangioscopy procedure, volume of blood loss, length of hospital stay, and frequency of procedure-related complications. RESULTS: The two groups were comparable in sex, age, symptoms, site of lesion, and gallstone comorbidities (P>.05). Of the 18 patients in the CBD group, 12 (66.7%) patients had a T-tube inserted in contrast to 1 (4.5%) patient in the LHD group. The two groups were comparable in cholangioscopy duration and volume of blood loss (P>.05), whereas the LHD group had a significantly shorter operative time than the CBD group (221.4 ± 58.6 minutes versus 171.2 ± 63.5 minutes; P<.05). The postoperative duration of hospitalization was significantly shorter in the LHD group than in the CBD group (7.5 ± 2.2 days versus 4.2 ± 1.9 days; P<.05). No patient showed any recurrence of gallstones or cholangitis during the follow-up period. CONCLUSIONS: As an effective and safe technique that is comparable to choledochotomy, LHD cholangioscopy is a preferred alternative to choledochotomy in the laparoscopic treatment of LSH because it offers patients shorter operative duration and length of hospitalization.

Outcomes of open versus laparoscopic procedure for synchronous radical resection of liver metastatic colorectal cancer: a comparative study.

BACKGROUND: The laparoscopic resection of colorectal cancer (CRC) along with synchronous liver metastases has been attempted and reported in multiple single series. In this study, we aimed to examine the feasibility, procedural safety, and oncological integrity of 1-stage totally laparoscopic procedure for the radical resection of liver metastatic CRC in a head-to-head comparison with the 1-stage open procedure simultaneously. METHODS: The patients who underwent selective 1-stage concomitant resection of CRC and synchronous liver metastases between January 2004 and December 2008 (laparoscopy group, n=13) were retrospectively enrolled in the study. Patients receiving open 1-stage resection (laparotomy group) were retrospectively included at the ratio of 1:1 (n=13 out of 71), matching the laparoscopy group in sex, age, body mass index, site and stage of primary tumor, location and size of liver metastases, and adjuvant therapies. RESULTS: All the thirteen 1-stage laparoscopic procedures were successfully completed, without conversion to open procedure or additional incision. The operative duration of laparoscopic procedure was shorter than that of open procedure (313 ± 44 vs. 350 ± 46 min, P<0.05). The volume of blood loss was comparable between the 2 groups (259 ± 111 vs. 273 ± 95 mL, P>0.05). Patients undergoing laparoscopic procedure resumed off-bed activities, bowel movement, and oral intake earlier than those undergoing open procedure, and also had a shorter hospitalization stay (8.5 ± 1.9 vs. 11.2 ± 1.8 d, P<0.05). Only 1 clinically significant adverse event occurred in a patient who developed bile leak after the laparoscopic resection. The 1-, 3-, and 5-year survival rates were comparable between the 2 groups (P>0.05). CONCLUSIONS: One-stage synchronous laparoscopic resection of liver metastatic CRC is a feasible, effective, and safe modality in specifically indicated patients, both accelerating postoperative recovery and shortening hospitalization time.

Retroperitoneal laparoscopic hepatectomy: a novel approach.

PURPOSE: Retroperitoneal laparoscopic surgery has been widely used for kidney and adrenal gland resection. However, there have not been any reports of laparoscopic hepatectomy performed using a retroperitoneal approach. Herein, we report on a successful case of laparoscopic hepatectomy using a retroperitoneal approach. Further, we discuss the key technical points, feasibility, and indications of this method. METHODS: A 48-year-old male patient with multiple hepatic metastases of the left lateral and right posterior segments of the liver following radical colon carcinoma resection underwent laparoscopic partial hepatectomy of the right posterior segment using a retroperitoneal approach, followed by laparoscopic hepatic left-lateral segmentectomy using a transabdominal approach. RESULTS: The operation time was 120 minutes and the blood loss volume was 150 mL. The patient was discharged at nine days post-surgery. There were no complications, including hemorrhage and bile leakage. CONCLUSIONS: The results of this case study provide evidence that a retroperitoneal approach is a novel, rapid, and safe method for laparoscopic hepatectomy that can be applied to the partial resection of small and superficial tumors of the right posterior segment of the liver.