Effectiveness of no drainage after elective day-case laparoscopic cholecystectomy, even with intraoperative gallbladder perforation: a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) has been carried out as day-case surgery. Current guidelines do not mention the role of drainage after LC. In particular, data stay blank with no prospective study on drainage management when gallbladder perforation (GP) accidentally occurs intraoperatively. METHODS: A randomized controlled trial was conducted to compare clinical outcomes of drainage and no drainage after elective day-case LC. Intraoperative GP was recorded. The primary and secondary outcomes were major and minor complications, respectively. RESULTS: Two hundred patients were randomized. No major complications occurred in either group. In secondary outcomes, nausea/vomiting, pain, hospital stay, and cost were similar in the drainage group and no drainage group; postoperative fever, WBC, and CRP levels were significantly lower in the no drainage group. GP occurred in 32 patients. Male patients with higher BMI and CRP and abdominal pain within 1 month were more likely to occur GP. Subgroup analysis of GP, primary outcomes, and most secondary outcomes had no difference. Postoperative WBC and CRP were higher in the drainage group. Postoperative fever occurred in 63 patients. Univariate analysis of fever showed that blood loss, drainage, postoperative WBC, CRP, and hospital stay were significant. Multivariable logistic regression analysis demonstrated that drainage was an independent risk factor for fever after LC (OR 3.418, 95% CI 1.392-8.390; p = 0.007). CONCLUSIONS: No drainage after elective day-case LC is safe and associated with fewer complications, even in intraoperative GP. The trial proves that drainage is an independent risk factor for postoperative fever. The use of a drain after LC may lead to an unsuccessful day-case procedure by causing fever, elevated CRP, and extended hospital stay (NCT03909360).

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.

Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids.

BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.

Imbedding pancreaticojejunostomy used in pure laparoscopic pancreaticoduodenectomy for nondilated pancreatic duct.

BACKGROUND: LPD has been cautiously regarded as feasible and safe for resection and reconstruction. However, anastomosis of the remnant pancreas is still thought to be a critical obstacle to the dissemination of LPD in general practice. This study presents a new technique of pancreaticojejunostomy for nondilated pancreatic duct and evaluates its safety and reliability. METHODS: From July 2014 to June 2015, a total of 52 patients underwent LPD with the new technique. A modified technique of duct-to-mucosa PJ was performed with transpancreatic interlocking mattress sutures, named the imbedding duct-to-mucosa PJ. Then the morbidity and mortality was calculated. RESULTS: This technique was applied in 52 patients after LPD all with nondilated pancreatic duct (1-3 mm). The mean operation time was 4.6 h (range, 3.5-8.3 h) and the median time for the anastomosis was 37 min (range, 24-53 min). Operative mortality was zero, and morbidity was 21.2 % (n = 11), including hemorrhage (n = 3, 5.8 %), biliary fistula (n = 1, 1.9 %), pulmonary infection (n = 1, 1.9 %), delayed gastric emptying (n = 2, 3.8 %), abdominal abscess caused by biliary fistula or PF formation (n = 2, 3.8 %), and POPF (n = 2, 3.8 %). Two patients developed a pancreatic fistula (one type A, one type B) classified according to the International Study Group on Pancreatic Fistula. CONCLUSIONS: The described technique is a simple and safe reconstruction procedure after LPD, especially for patients with nondilated pancreatic duct.

The paradigm of tumor shrinkage and rapid liver remnant hypertrophy for conversion of initially unresectable colorectal liver metastasis: a case report and literature review.

BACKGROUND: For colorectal liver metastasis (CRLM) patients, hepatic resection is currently the sole cure offering the chance of long-term survival. Tumor shrinkage and planned liver remnant hypertrophy are the two key strategies for conversion of initially unresectable CRLM. First conducted in 2012, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver growth. As a means to induce hypertrophy, portal vein embolization (PVE) has been widely applied before extending hepatectomy. Recently, Peng et al. present a new approach of terminal branches portal vein embolization (TBPVE), offering an efficient way to amplify FLR and making chances for surgery in 2 weeks. CASE PRESENTATION: We reported a 61-year-old woman with synchronous hepatic metastasized carcinoma of the colon sigmoideum underwent TBPVE after 6 cycles of neoadjuvant therapy in order to perform a planned right trisectionectomy. Rapid liver remnant hypertrophy and remarkable tumor shrinkage were achieved, and laparoscopic sigmoidectomy and right trisectionectomy were successfully performed. The postsurgical course was uneventful and 7 months of recurrence-free survival have been witnessed. CONCLUSIONS: The dual tactics of tumor shrinkage and planned rapid liver remnant hypertrophy will make concerted efforts to further increase the clinical candidacy for curative resection, which are valuable for further investigation.

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.

Total mesopancreas excision for pancreatic head cancer: analysis of 120 cases.

OBJECTIVE: To evaluate the feasibility and safety of total mesopancreas excision (TMpE) in the treatment of pancreatic head cancer. METHODS: The clinical and pathological data of 120 patients with pancreatic head cancer who had undergone TMpE in our center from May 2010 to January 2014 were retrospectively analyzed. RESULTS: The mean operative time was (275.0±50.2) min and the average intra-operative blood loss was (390.0±160.5) mL. Post-operative complications were reported in 45 patients, while no peri-operative death was noted. The specimen margins were measured in three dimensions, and 86 patients (71.6%) achieved R0 resection. CONCLUSIONS: TMpE is safe and feasible for pancreatic head cancer and is particularly helpful to increase the R0 resection rate.

"Total arterial devascularization first" technique for resection of pancreatic head cancer during pancreaticoduodenectomy.

Integrated resection of the pancreatic head is the most difficult step in radical pancreaticoduodenectomy (RPD) in patients with the portal vein (PV) and superior mesenteric vein (SMV) invasion or oppression by the tumor. This study introduced a new idea and skill named the "total arterial devascularization first" (TADF) technique and its applications in RPD. Three arterial blood supplies of pancreatic head were obstructed before dissection of veins. The critical steps included exposure of the anterior surface of the abdominal aorta (AA) by completely transecting neural and connective tissue between superior mesenteric artery (SMA) and pancreatic mesounsinate, and transection of the mesounsinate from the origin of SMA to the root of the celiac trunk. From January 2012 through May 2013, a total of 58 patients with PV/SMV invasion or oppression underwent RPD using this technique. The median operative time was 5.1 h (ranging 4.5-8.1 h). The median intraoperative blood loss was 450 mL (ranging 200-900 mL). No intraoperative and postoperative bleeding of pancreatic head region occurred. Among the 58 patients, 21 were subjected to vessel lateral wall angiectomy or angiorrhaphy, and 10 to angiectomy and end-to-end anastomosis. The incidence of postoperative bleeding, postoperative pancreatic fistula and biliary fistula was 5.2%, 6.8%, and 1.7%, respectively. No patients died 3 months after operation. The TADF technique is a new method for intricate RPD and could improve the security of surgery and reduce intraoperative bleeding, which is expected to become standardized surgical approach for RPD.

[The role of preoperative TACE on hepatocellular carcinoma located in caudate lobe].

OBJECTIVE: To evaluate the effect of preoperative transarterial chemoembolization (TACE) on hepatocellular carcinoma located in caudate lobe. METHODS: Totally 29 cases of caudate lobe hepatocellular carcinoma admitted from January 2001 to December 2010 were analyzed retrospectively. Among the 29 patients, 23 were male and the other 6 were female. The median age was 52 years. According to receiving preoperative TACE or not, the 29 cases were divided into two groups: preoperative TACE plus surgery (group A, n = 11) and surgery only (group B, n = 18). The surgical results and long-term survival were compared between two groups. RESULTS: After TACE, the diameter of the tumour reduced by over 33.3% in 3 patients, 10.0% to 33.3% in 6 patients, and less than 10.0% in 2 patients. The duration of surgery and intraoperative blood loss in group A were (298 ± 39) minutes and (1031 ± 310) ml, respectively. The duration of surgery and intraoperative blood loss in group B were (281 ± 54) minutes and (868 ± 403) ml, respectively. No significant difference was found in terms of these two groups (t = 1.006, P = 0.324; t = 1.223, P = 0.232). In addition, 6 cases in group A developed complications and 4 cases in group B did so. Only one patient died because of postoperative complication, and this patient belonged to group A. No significant difference was found between two groups (χ(2) = 0.028, P = 0.868; χ(2) = 0.633, P = 0.426). The 5-year survival rate was 56.8% in group A and 34.9% in group B. The difference did not reach significant difference (P = 0.132). CONCLUSIONS: For hepatocellular carcinoma located in caudate lobe, preoperative TACE does not significantly increase the surgical difficulty and impair the safety. In addition, preoperative TACE has the tendency to provide benefit to long-term survival.

Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection.

BACKGROUND: The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. METHODS: We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease-free survival (DFS), surgery-related outcomes, and surgical approaches were collected. RESULTS: A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p < 0.001). There was no significance in OS (p = 0.790), DFS (p = 0.580), and surgery-related outcomes (all p > 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery-related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). CONCLUSIONS: Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery-related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

Hotspots and difficulties of biliary surgery in older patients.

ABSTRACT: With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Case report: A de novo ERBB3 mutation develops in a gallbladder cancer patient carrying BRCA1 mutation after effective treatment with olaparib.

Background: Gallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentation: The patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. Conclusion: Olaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

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.

Mucoepidermoid carcinoma of the pancreas: a case report and a review of literature.

Mucoepidermoid carcinoma of the pancreas is rare. Here, a 63-year-old woman with left upper abdominal pain and abdominal distension is presented. Her mucoepidermoid carcinoma was located at the left upper abdomen, arising from the pancreatic body and tail without invasion of pancreatic capsule. On pathologic examination, the tumor consisted of three types of cells, the majority being poorly differentiated adenocarcinoma cells with mucin products in their cytoplasm, and some moderately differentiated adenocarcinoma with a tendency to form ducts. In addition, there were epidermoid cells and intermediate undifferentiated cells. She survived for 12 months after surgery.

Lactate promotes the growth of patient-derived organoids from hepatopancreatobiliary cancers via ENO1/HIF1α pathway and does not affect their drug sensitivities.

The long culture duration of patient-derived organoids (PDOs) have severely limited their clinical applications. The aim of this study was to determine the effect of lactate supplementation on the growth, genetic profiles and drug sensitivities of PDOs from hepatopancreatobiliary tumors. LM3, Huh7, Panc02, and RBE cell lines were cultured as organoids in the presence or absence of lactate, and total protein was extracted to measure the expression of α-enolase (ENO1), hypoxia-inducible factor-1α (HIF1α), AKT, and PI3 kinase (PI3K). Thirteen hepatopancreatobiliary tumor specimens were collected during surgical resection and cultured as PDOs with or without L-lactate. Hematoxylin and eosin (H&E) staining and immunohistochemical staining were performed on the original tissues and PDOs to compare their pathological structures, and their genetic profiles were analyzed by whole-exome sequencing (WES). The sensitivity of the PDOs to gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infigratinib, and lenvatinib were evaluated in terms of cell viability. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with PDOs to test the sensitivity of PDOs to tislelizumab. The addition of 20 mM lactate significantly promoted the growth of LM3 and Huh 7 organoids by 217% and 36%, respectively, compared to the control group, and the inhibition of lactate transporter decreased their growth. The HIF1α/ENO1/AKT/PI3K pathway was also activated by lactate. The inhibition of enolase also partly decreased the growth of organoids treated with lactate. Furthermore, 20 mM lactate increased the viability of 9 PDOs from 135% to 317% without affecting their pathological features. The genetic similarity, in terms of single nucleotide variations, insertions, and deletions, between original tissues and lactate-treated PDOs ranged from 83.2% to 94.1%, and that between the untreated and lactate-treated PDOs was at least 93.2%. Furthermore, the addition of lactate did not significantly change the dose-response curves of the PDOs to chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitor, especially for the drugs to which the cells were sensitive. Thus, lactate can be added to the culture medium of PDOs to promote their growth without altering their genetic profiles and drug sensitivities.

Hepatopancreatoduodenectomy for advanced biliary malignancies.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers (GBCs). However, HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates. The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies. METHODS: The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved. A case-control analysis was conducted at our department. Patients with advanced GBC who underwent HPD (HPD-GBC group) were compared with a control group (None-HPD-GBC group). Baseline characteristics, preoperative treatments, tumor pathologic features, operative results, and prognosis were assessed. RESULTS: Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department. Significant postoperative complications (grade III or greater) and postoperative pancreatic fistula were observed in 24 (42.1%) and 15 (26.3%) patients, respectively. One postoperative death occurred in the present study. Overall survival (OS) was longer in patients with advanced cholangiocarcinoma than in those with GBC (median survival time [MST], 31 months vs . 11 months; P   <  0.001). In the subgroup analysis of patients with advanced GBC, multivariate analysis demonstrated that T4 stage tumors ( P  = 0.012), N2 tumors ( P  = 0.001), and positive margin status ( P  = 0.004) were independently associated with poorer OS. Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors ( P  < 0.001). CONCLUSION: HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced high- volume center. For patients with advanced GBC without an N2 or T4 tumor, HPD can be a preferable treatment option.

[Binding pancreatic duct to mucosa anastomosis].

OBJECTIVE: To study the feasibility of binding pancreatic duct to mucosa anastomosis (BDM)-a complementary procedure to both binding pancreaticojejunostomy and binding pancreaticogastrostomy. METHODS: (1) Animal experimental study:gastrostomy and jejunostomy were performed on six adult New Zealand rabbits. The gastrostomy and jejunostomy shared a same stent (rubber urethral catheter, silicone tube or plastic infusion tube). Both ends of the stent were placed in gastric and enteric cavity. Purse-string suture was performed around the stent before the jejunum and the stomach were brought together for fixation by few stitches. And to observe whether the purse-string suture around a plastic tube, rubber tube or silicon tube inserted into jejunum and/or stomach can prevent leaking out of the jejunal or gastric content to cause peritonitis. (2) Clinically 7 patients were performed with BDM anastomosis. The procedure was consisted of five steps: preparation of the pancreatic stump;preparation of the jejunum; preparation of the fixing sutures between the pancreatic stump and the jejunum; implementation of the anastomosis; lastly, fixation of the jejunum beside the pancreas stump. Post-operative periodic examination of the blood amylase and the amylase in the abdominal drainage. Pancreatic fistula was classified in to two categories: parenchymal fistula (pancreatic cut surface fistula) and anastomotic leakage. RESULTS: Animal experiment did not show any leakage around the plastic tube or silicon tube inserted into jejunum and(or) stomach. There was no anastomotic leak in all the patients. There was transient increase of amylase in two cases, but the volume of drainage did not exceed 50 ml/d and the recovery of the patients was not affected. CONCLUSIONS: BDM is a simple, safe and easy procedure to perform. It provides to the surgeons with a new option in different situations to achieve the most ideal surgical result.

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid.

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan-Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.