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Background: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. Methods: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV (+) and (−) patients were compared. Results: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV (+) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV (+) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (−) patients. There was no significant difference between the HAV (+) and (−) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV (+) and (−) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV (+) group. Conclusions: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV (+). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively. [ABSTRACT FROM AUTHOR]

Background: The role of the robotic approach for pancreaticoduodenectomy has not been well established with robust data. This study aimed to reappraise feasibility and justification of robotic pancreaticoduodenectomy (RPD) over time. Methods: A total of 500 patients undergoing RPD were enrolled and divided into early (first 250 patients) and late (last 250 patients) groups for a comparative study. Results: The conversion rate was 8.8% overall and was significantly lower in the late group (5.6% vs. 12.0%; p =.012). The overall median intraoperative blood loss was 130 mL. Radicality of resection was similar between early and late groups. The overall surgical mortality after RPD was 1.3%. The overall surgical morbidity and major complication was 44.1% and 13.2%, respectively, and similar between early and late groups. Chyle leakage was the most common complication after RPD (25.0%), followed by postoperative pancreatic fistula (POPF). The POPF rate was 8.6% overall, with 5.9% in the early group and 11.0% in the late group, p =.051. The overall delayed gastric emptying rate was 3.5%. The late group had better survival outcomes than those of the early group after RPD for ampullary adenocarcinoma (p =.027) but not for pancreatic head adenocarcinoma. Conclusions: Reappraisal of this study has confirmed that RPD is not only technically feasible without increasing surgical risks but also oncologically justified without compromising survival outcomes for both pancreatic head and other periampullary cancers over time. Moreover, RPD is associated with the benefits of low surgical mortality, blood loss, and delayed gastric emptying. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD. Non-gellable 13% P407 sol became in-situ gellable with adding 2.0-2.5% HPMC and mucoadhesibility was further imporved with adding 0.3% HA-L (low MW) or HA-H (high MW). Optimized 0.5% HPβCD-solubilized TES P407-based thermogellable hydrogels with enhancement of mucoadhesion for prolonging ocular delivery comprised 13% P407, 2.5% HPMC, and 0.3% HA-L or HA-H. Furthermore, rheological measurements under simulated eye blinking confirmed that non-thixotropic properties of optimized hydrogels could be spreaded evenly and retain a greater amount of drug-loaded hydrogels on the ocular surface for a longer period to prolong drug delivery. Compared with conventional eye drops, the prolonged residence time of optimized hydrogels from ex vivo and in vivo studies were observed, indicating relationships between rheological properties and in vivo performances. It was concluded that P407-based thermosensitive hydrogels with reducing concentration of P407 and enhancing mucoadhesion was successfully formulated by adding 2.5% HPMC and 0.3% HA in 13% P407 for potentially accomplishing effective clinical treatment of DED. [ABSTRACT FROM AUTHOR]

Aim: Whether to execute pancreaticoduodenectomy or not for older people could pose a dilemma. This study clarifies the safety and justification of robotic pancreaticoduodenectomy (RPD) for older individuals over 80.Methods: A total of 500 patients undergoing RPD were divided into group O (≥ 80 y/o) and group Y (< 80 y/o) for comparison.Results: There were 62 (12.4%) patients in group O. Surgical mortality was 1.6% for overall patients and higher in group O, 6.5% vs 0.9%; p = 0.001. The surgical complication was comparable between groups O and Y. Delayed gastric emptying and bile leakage were higher in group O, 9.7% vs 2.5%; p = 0.004, and 6.5% vs 0.9%; p = 0.001, respectively. Length of stay was also longer in group O, with a median of 26 vs 19 days; p = 0.001. Survival outcome after RPD was poorer in group O for overall periampullary adenocarcinomas, with a 5-year survival of 48.1% vs 51.2%; p = 0.025 and also for the subgroup of pancreatic head adenocarcinoma, with a 3-year survival of 27.4% vs 42.5%; p = 0.030.Conclusion: RPD is safe and justified for the selected octogenarians and even nonagenarians, whoever is fit for a major operation. Nevertheless, pancreatic head cancer and higher mortality risk for the aged over 80 with advanced ASA score ≥ 3 should be informed as part of counselling in offering RPD. [ABSTRACT FROM AUTHOR]

Background: Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity. Methods: In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs). The anti-CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti-cancer moiety of the BsAb provided these BsAb-armed T cells with the cancer-targeting ability, which transformed the naïve T cells into cancer-specific BsAb-armed T cells. Results: With this technology, a large amount of cancer-specific BsAb-armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb-armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF-α and IFN-γ) were dramatically released from the BsAb-armed T cells after engaging cancer cells, resulting in a remarkable anti-cancer efficacy. Notably, the BsAb-armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors. Conclusions: Collectively, the BsAb-armed T cell technology represents a simple, time-saving, and highly safe method to generate highly pure cancer-specific effector T cells, thereby providing an affordable T cell immunotherapy to patients. [ABSTRACT FROM AUTHOR]

In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic cancer cell line) was significantly increased compared with the other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: The exploration of molecular characteristics has emerged as a prominent trend to advance precision medicine. The utilization of genetic testing to guide therapy is integral to precision medicine. This study aims to investigate the potential patient populations for the reimbursement of next-generation sequencing (NGS) and assess the budget impact from the perspective of Taiwan's single insurer, the National Health Insurance Administration. Methods: To comprehend the scope for medicines with companion diagnostics (CDx) involved, we analyze the U.S. Food and Drug Administration-approved/cleared diagnostic tests, conduct a literature review to identify medicines approved by the European Medicines Agency that require a CDx, and identify the medicines with CDx involved covered by the National Health Insurance (NHI) in Taiwan. Subsequently, we explore the potential reimbursement indications for NGS testing and conduct a budget impact analysis to evaluate the expected financial impact for the NHI over a five-year period. Furthermore, sensitivity analyses are conducted to deal with uncertainty. Results: We have compiled 13 cancer types for which NGS can serve as a companion diagnostic. These encompass non-small-cell lung cancer, colorectal cancer, breast cancer, ovarian cancer, biliary tract cancer, acute myeloid leukemia, acute lymphoblastic leukemia, melanoma, cholangiocarcinoma, prostate cancer, pancreatic cancer, gastrointestinal stromal tumor, and thyroid cancer/medullary thyroid cancer. The implementation of NGS reimbursement in NHI will benefit 25,000 to 30,000 patients undergoing targeted therapies. The projected incremental budget impact ranges from TWD570 million to TWD650 million (USD19 million to USD22 million) over five years. Conclusions: This study focuses on evaluating the financial impact of incorporating NGS testing into NHI reimbursement for relevant cancer drug indications. The findings can serve as references for the planning of reimbursement policies. However, with the advancement of precision medicine, it is foreseeable that there will be a broader range of applications for NGS, and its cost will gradually decrease. [ABSTRACT FROM AUTHOR]

The study of robotic pancreaticouodenectomy (RPD) focusing on delayed gastric emptying (DGE) is seldom reported. This study explored the incidence of DGE in RPD with extracorporeal hand-sewn gastrojejunostomy involving downward positioning of the stomach. Patients with periampullary lesions undergoing RPD or open pancreaticouodenectomy (OPD) were included for comparison. A variety of clinical factors were evaluated for the risk of developing DGE. There were 409 (68.2%) RPD and 191 (31.8%) OPD in this study. DGE occurred in 7.7% of patients after pancreaticoduodenectomy, with 4.4% in RPD and 14.7% in OPD, p < 0.001. Nausea/vomiting (12.6% vs. 6.3%) and jaundice (9.9% vs. 5.2%) were significant preoperative risk factors for DGE, while malignancy (8.7% vs. 2.2%) and lymph node involvement (9.8% vs. 5.6%) were significant pathological risk factors. Intraoperative blood loss > 200 c.c. was the other factor related to DGE (11.2% vs. 4.4% in those with blood loss ≤ 200 c.c.). None of the postoperative complications was significantly associated with DGE. Hospital stay was significantly longer in the group with DGE (median, 37 vs. 20 days in the group without DGE). After multivariate analysis by binary logistic regression, compared with OPD, RPD was the only independent factor associated with a lower incidence of DGE. RPD with extracorporeal hand-sewn antecolic, antiperistaltic, and inframesocolic gastrojejunostomy via a small umbilical wound involving careful downward positioning of the stomach was associated with a low incidence of DGE and presented as the most powerful independent predictor of this condition. [ABSTRACT FROM AUTHOR]

Background and Aims: There is no consensus on the superiority of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP). Methods: Data of patients undergoing RDP and LDP were prospectively collected and compared. Results: There were 65 RDP and 112 LDP. RDP took a shorter operation time than LDP. Overall, DP with splenectomy took a longer operation time than that with spleen preservation. This difference was only significant in LDP group. In both RDP and LDP groups, splenectomy was associated with increased blood loss, as compared with spleen preservation. No significant differences were observed in surgical morbidity between RDP and LDP. The hospital cost in RDP was almost double that of LDP, with a median of 13,404 versus 7765 USD. Conclusion: LDP is comparable to RDP in regard to surgical outcomes. LDP with spleen preservation is highly recommended whenever possible and feasible for benign or low malignant lesions in terms of lower costs and less blood loss. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most common causes of death in Taiwan. Previous studies have shown that more than 90% of pancreatic cancer cells presented epidermal growth factor receptor (EGFR) cell marker, and this marker is thought to be important as it is related to activation of cancer cell proliferation, angiogenesis, and cancer progression. Moreover, tumor-associated fibroblasts were involved in tumor proliferation and progression. In this study, we fabricated an anti-EGFR and anti-fibroblast activation protein bispecific antibody-targeted liposomal irinotecan (BS−LipoIRI), which could specifically bind to pancreatic cancer cells and tumor-associated fibroblasts. The drug encapsulation efficiency of BS−LipoIRI was 80.95%, and the drug loading was 8.41%. We proved that both pancreatic cancer cells and fibroblasts could be targeted by BS−LipoIRI, which showed better cellular uptake efficacy compared to LipoIRI. Furthermore, an in vivo mouse tumor test indicated that BS−LipoIRI could inhibit pancreatic cancer growth up to 46.2% compared to phosphate-buffered saline control, suggesting that BS−LipoIRI could be useful in clinical cancer treatment. [ABSTRACT FROM AUTHOR]

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by right–left reversal of visceral organs and dextrocardia; the use of robotic pancreaticoduodenectomy (RPD) may be challenging in these patients. A male patient presented with jaundice; imaging studies revealed a bile duct tumor and SIT with variant celiacomesenteric trunk and multiple vascular anomalies. RPD was carried out cautiously and successfully. The trocar port design mirrored that of a normal patient. Pathological examination revealed extrahepatic bile duct adenocarcinoma, classified as pT3N1M0, stage IIB. The patient recovered uneventfully. Although difficult, RPD is technically feasible in an SIT patient with cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. Methods: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. Results: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). Conclusion: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results. [ABSTRACT FROM AUTHOR]

Therapeutic efficacies of orally administrated hydrophobic chemodrugs are decreased by poor water solubilities and reduced oral bioavailabilities by P-glycoprotein (P-gp) and CYP450. In this study, CPT11 alone or combined with dual-function inhibitors (baicalein (BA) silymarin (SM), glycyrrhizic acid (GA), and glycyrrhetinic acid (GLA)) of P-gp and CYP450 loaded in a lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENP) to improve the solubility and inhibit the elimination by P-gp and CYP450. Results revealed that the LBSNENP composed of Capryol 90, lecithin/Tween 80/Cremophor EL, and propylene glycol at a weight ratio of 18:58:24 (designated PC90C10P0) was optimally selected. Encapsulating CPT11 with PEO-7000K in PC90C10P10/30 further enhanced the resultant hydrogel to be gastro-retainable and to release CPT11 in a sustained manner. Pharmacokinetic study of CPT11-loaded PC90C10P0 administered orally revealed an absolute bioavailability (FAB, vs. intravenous CPT11) of 7.8 ± 1.01% and a relative bioavailability (FRB1, vs. oral solution of CPT11) of 70.7 ± 8.6% with a longer half-life (T1/2) and mean residence time (MRT). Among the dual-function inhibitors, SM was shown to be the most influential in increasing the oral bioavailability of CPT11. SM also increased the plasma concentration of the SN-38 active metabolite, which formed from the enhanced plasma concentration of CPT11. It is concluded that treatment with CPT11 loaded in PC90C10P0 with or without solubilization with SM could expose tumors to higher plasma concentrations of both CPT11 and SN-38 leading to enhancement of tumor growth inhibition with no signs of adverse effects. [ABSTRACT FROM AUTHOR]

Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcomes of preventive covered stent placement at the gastroduodenal artery stump in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy. Methods: Between July 2006 and September 2018, patients undergoing computed tomography angiography or diagnostic angiography for sentinel hemorrhage after pancreaticoduodenectomy were retrospectively reviewed. Patients having angiogram-negative angiography and undergoing preventive covered stent placement or conservative treatment were included. Clinical outcomes, technique success, and complications were evaluated. Results: A total of 25 patients (mean age 62.5 years) were evaluated, including 15 patients underwent preventive covered stent placement at the gastroduodenal artery stump and 10 patients received conservative treatments. The clinical success rates were 50% (5/10) and 86.7% (13/15) for conservative treatments and covered stent groups, respectively (p = 0.07). In the conservative treatment group, delayed massive hemorrhage occurred in five patients, two of whom died of recurrent bleeding due to gastroduodenal artery pseudoaneurysm within 16 days, and two had intraluminal hemorrhage within 5 days. In the covered stent group, one patient had inferior pancreaticoduodenal artery pseudoaneurysm 1 day after the placement of the covered stent, and one had recurrent bleeding due to duodenal ulcer within 14 days. The 30-day mortality was 40% (4/10) and 0 in the conservative treatment and covered stent groups, respectively (p = 0.02). The difference in the overall survival was nonsignificant between the two groups (p = 0.23). Conclusions: The preventive covered stent placement at the gastroduodenal artery stump is safe and reduces delayed massive hemorrhage and short-term mortality in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNA (lncRNA) mediates the pathogenesis of various diseases, including cancer and cardiovascular, infectious, and metabolic diseases. This study examined the role of lncRNA NTT in the development and progression of cancer. Methods: The expression of NTT was determined using tissues containing complementary DNA (cDNA) from patients with liver, lung, kidney, oral, and colon cancers. The expression of cis- acting genes adjacent to the NTT locus (CTGF , STX7 , MYB , BCLAF1 , IFNGR1 , TNFAIP3 , and HIVEP2) was also assessed. We used knockdown and chromatin immunoprecipitation (ChIP) assays to identify the cis- acting genes that interact with NTT. Results: NTT was most significantly downregulated in hepatocellular carcinoma (HCC), while a higher NTT level correlated with a shorter survival time of patients with HCC. Multivariate analysis indicated NTT was not an independent predictor for overall survival. MYB was significantly upregulated, and its increased expression was associated with dismal survival in HCC patients, similar to the results for NTT. NTT knockdown significantly decreased cellular migration. ChIP of HCC cell lines revealed that NTT is regulated by the transcription factor ATF3 and binds to the MYB promoter via the activated complex. Additionally, when NTT was knocked down, the expression of MYB target genes such as Bcl-xL , cyclinD1 , and VEGF was also downregulated. NTT could play a positive or negative regulator for MYB with a context-dependent manner in both HCC tissues and animal model. Conclusion: Our study suggests that NTT plays a key role in HCC progression via MYB -regulated target genes and may serve as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Pancreaticoduodenectomy, so‐called "Whipple operation," is a time‐consuming and technically demanding complex operation. Traditionally, this procedure has been performed most usually by open approach, which results in a large and painful wound. With the introduction of laparoscopic and robotic surgery, minimally invasive surgery (MIS) has emerged as a worldwide trend to improve wound cosmesis and to minimize wound pain. Although MIS for pancreaticoduodenectomy has also been attempted at some centers, the role of MIS, either robotic or laparoscopic approach, has not been well‐established for complex pancreaticoduodenectomy. Given that laparoscopic pancreaticoduodenectomy has been limited by its technical complexity and the high level of advanced laparoscopic skills required for pancreatic reconstruction, a robotic surgical system is introduced to overcome several limitations related to the laparoscopic approach. Providing high‐quality three‐dimensional (3‐D) vision, high optical magnification, articulation of robotic instruments, greater precision with suture targeting, and elimination of surgeon tremor, robotic surgical systems innovatively perform more delicate and complex procedures involving extensive dissection and suturing techniques such as pancreaticoduodenectomy. Although associated with longer operative time, robotic pancreaticoduodenectomy (RPD) has been claimed to have the benefits of less delayed gastric emptying, less blood loss, shorter length of postoperative stay, and lower wound infection rate, as compared with the traditional open pancreaticoduodenectomy (OPD). Moreover, RPD seems to be not only technically feasible but also justified without compromising the survival outcomes for pancreatic head and ampullary adenocarcinomas. Therefore, RPD could be recommended not only to surgeons but also to patients in terms of surgical feasibility, surgical outcomes, and patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer. Methods: A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups. Results: At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years. Conclusion: During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy. [ABSTRACT FROM AUTHOR]

Background: To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC). Methods: In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients. Results: Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC. Conclusions: Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups. [ABSTRACT FROM AUTHOR]

This study is to clarify the feasibility and justification of robotic pancreaticoduodenectomy (RPD) by comparing the outcomes between RPD and open pancreaticoduodenectomy (OPD) groups. All perioperative data and outcomes were prospectively collected. There were 304 (63.9%) RPD and 172 (36.1%) OPD. The median operation time was longer in RPD group than OPD (7.5 vs 7.0 h). The blood loss was much lower in RPD group, with a median of 130 vs. 400 c.c. in OPD group. Based on Clavien–Dindo classification, grade 0 (no complication) was 51.8% in RPD group, higher than 43.2% in OPD. Delayed gastric emptying was only 3.5% in RPD group, much lower than 13.6% in OPD. Wound infection rate was also lower in RPD group, 3.2% vs. 7.7% in OPD. The postoperative hospital stay was shorter in RPD group, with a median of 20 days, vs. 24 days in OPD. There was no significant difference regarding the lymph node yield, surgical mortality, postoperative pancreatic fistula, postpancreatectomy hemorrhage, chyle leakage and bile leakage between RPD and OPD groups. For pancreatic head adenocarcinoma, the survival outcome was better in RPD group, with 1-year, 3-year, and 5-year survival of 82.9%, 45.3%, and 26.8% respectively, as compared with 63.8%, 26.2%, and 17.4% in OPD. RPD is not only feasible but also justified without increasing the surgical risks and compromising the survival outcomes. Moreover, RPD might provide benefits of less blood loss, less delayed gastric emptying, lower wound infection rate and shorter length of postoperative stay, as compared with OPD. [ABSTRACT FROM AUTHOR]

Background/Purpose: Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life‐threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD. Methods: This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death). Results: Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m2, chronic steroid use, preoperative serum albumin <3.0 mg/dL, soft pancreas, operative time ≥480 minutes, and intraoperative transfusion. The c‐statistic of our risk scoring model for Grade C POPF using these risk factors was 0.77. The score was significantly higher in Grade C POPF than in Grade B POPF (P <.001) or none/biochemical leak (P <.001). Conclusions: This prospective study showed risk factors for Grade C POPF after PD. [ABSTRACT FROM AUTHOR]

Background: Chyle leakage is a well‐known but poorly characterized complication after pancreaticoduodenectomy (PD). No study examined the chyle leakage after robotic PD (RPD). Methods: Data regarding chyle leakage were prospectively collected and analyzed from patients undergoing RPD or open PD (OPD). Results: The study included 118 RPD and 165 OPD. Overall chyle leakage rate was 12.0%, with 13.6% for RPD and 10.9% for OPD. Chyle leakage was eventually resolved in all patients through conservative treatment. The drainage volumes were significantly higher in chyle leakage group from postoperative days (PODs) 1‐7, with a median of 240 mL on POD 1 and POD 7, as compared to 160 mL on POD 1 and 70 mL on POD 7 for those without chyle leakage. The number of lymph nodes involved and resected and pancreatic head adenocarcinoma affected the risk of developing chyle leakage, whereas the surgical approach used (RPD or OPD) did not. Conclusions: Chyle leakage after PD is not rare, and it can eventually be resolved through conservative treatment. The extent and radicality of the surgery probably have a significant effect on the risk of developing chyle leakage, but the surgical approach used does not. [ABSTRACT FROM AUTHOR]

Background: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. Methods: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. Results: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. Conclusions: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive. [ABSTRACT FROM AUTHOR]

Background: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD).Methods: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group).Results: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group.Conclusions: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection. [ABSTRACT FROM AUTHOR]

Background: Gangliocytic paraganglioma (GP) is rare and difficult to be differentiated from other periampullary neoplasms. The clinical characteristics and optimal treatment of periampullary GPs have not been clarified.Methods: The data pool for the analysis comprised of cases of periampullary GP encountered in our institution and sporadic cases reported in the English literature.Results: A total of 117 cases with periampullary GP were studied, including 2 from our institute, and among them, duodenal GP was the most common (53.0%). GP size ranged from 0.7 to 19.0 cm, with a median of 2.2 cm. The most common presenting symptom for overall periampullary GPs was epigastric pain in 49.5% cases, followed by gastrointestinal bleeding in 35.4% cases. Most (84.1%) of the periampullary GPs were benign, whereas 15.9% were malignant. Metastasis was noted in 26.3% of periampullary GPs, with 14.5% showing lymph node metastasis and 1.8% showing liver metastasis. Of the periampullary GP cases included, 30.1% were treated with pancreaticoduodenectomy, 40.6% with local excision, and 17.7% with endoscopic resection.Conclusions: Periampullary GP should be considered as a tumor with malignant potential. Endoscopic resection is the treatment of choice for most of the duodenal GPs, whereas pancreaticoduodenectomy is recommended for GPs with possible malignancy, such as large size, with submucosal invasion, or pancreatic GP. [ABSTRACT FROM AUTHOR]

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Background: In 10%‐18% of mild‐type hemophilia A (HA) patients, mutations cannot be found by routine DNA analysis. Objective: We aimed to identify the genetic defects by mRNA analysis of F8 gene in mild HA patients without mutation in exonic DNA. Patients and methods: From 2006 to 2016, we identified F8 exon mutations in 39 of 49 mild HA patients using routine genetic testing. We then evaluated the 10 remaining patients from six unrelated families without exonic DNA mutation by performing cDNA sequence analysis. Results: Nine of the 10 (90%) patients were confirmed to have F8 gene mutation. Eight patients from four unrelated families were notably found to have presence of an aberrant 675‐bp fragment. Sequencing of this fragment showed that there were two separate new alternative splicing exons of 35 bp and 55 bp within intron 18, which formed a 90‐bp insertion between exon 18 and exon 19 (E18ins90bpE19) in the mRNA. Based on direct sequencing, this alternative splicing transcript appears to have resulted from deep intronic variant c.5999‐277G>A of intron 18. Conclusions: Our study suggests that deep intronic variant of c.5999‐277G>A may be a hot spot mutation for mild hemophilia patients without mutation in exonic DNA. [ABSTRACT FROM AUTHOR]

The mucosal immune system is the host's first line of defense against invasion by foreign pathogens. Gelatin nanoparticles (GNPs) are suitable carriers for the delivery of antigens via various routes of administration. In the present study, GNPs were modified with polyethyleneimine (PEI), a positively charged polymer. Then, ovalbumin (OVA) and polyinosinic:polycytidylic acid (poly(I:C)), an immunostimulant, were adsorbed onto the surface of the positively charged GNPs. We assessed whether GNPs could act as an effective mucosal vaccine that is capable of inducing both mucosal and systemic immune responses. The results showed that GNPs effectively adsorbed OVA/poly(I:C), facilitated cellular uptake by RAW 264.7 macrophage cells and murine bone marrow‐derived dendritic cells (BMDCs) in vitro, and led to increased expression of the maturation markers CD80 and CD86 on BMDCs. Furthermore, GNPs induced increased secretion of proinflammatory cytokines in both RAW 264.7 and BMDCs. C57BL/6 mice that were intranasally twice‐immunized with OVA/poly(I:C)‐loaded GNPs produced high levels of serum OVA‐specific IgG antibodies and secretory IgA in nasal and lung lavage. Spleen cells from immunized mice were collected and re‐stimulated with OVA, and results showed significantly augmented production of IFN‐γ, IL‐4, IL‐5, and IL‐6 in mice that received OVA/poly(I:C)‐loaded GNPs. Moreover, intranasal immunization with OVA/poly(I:C)‐loaded GNPs resulted in the inhibition of EG7 tumor growth in C57BL/6 mice. Taken together, these results indicate that nasal administration of OVA/poly(I:C)‐loaded GNPs elicited effective mucosal and systemic immune responses, which might be useful for further applications of antigen delivery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1228–1237, 2019. [ABSTRACT FROM AUTHOR]

Background: Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate.Methods: From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients.Results: The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017).Conclusion: The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection. [ABSTRACT FROM AUTHOR]

Initially, he developed mildly pruritic rashes after starting the anti-hepatitis C virus (HCV) treatment with oral ledipasvir/sofosbuvir once daily for 9 weeks; however, the skin rashes have deteriorated and persisted after completion of a 12-week treatment course. To the Editor, Direct-acting antiviral agents (DAAs) drastically increase the tolerability to and efficacy of the chronic hepatitis C treatment compared to the historic regimen of pegylated interferon and ribavirin. Pharmacokinetic interactions between Simeprevir and Ledipasvir in treatment-naive hepatitis C Virus genotype 1-infected patients without cirrhosis treated with a Simeprevir-Sofosbuvir-Ledipasvir regimen. [Extracted from the article]

Anti-mPEG/anti-human epidermal growth factor receptor 2 (HER2) bispecific antibodies (BsAbs) non-covalently bound to a docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micellar drug delivery system (LsbMDDs) were endowed with active targetability to improve the chemotherapeutic efficacy of DTX. DTX-loaded mPEGylated LsbMDDs formulations were prepared using lecithin/DSPE-PEG(2K or 5K) nanosuspensions to hydrate the thin film, and then they were subjected to ultrasonication. Two BsAbs (anti-mPEG/anti-DNS or anti-HER2) were simply mixed with the LsbMDDs to form BsAbs-LsbMDDs formulations, respectively, referred as the DNS-LsbMDDs and HER2-LsbMDDs. Results demonstrated that the physical characteristics of the BsAbs-LsbMDDs were similar to those of the plain LsbMDDs but more slowly released DTX than that from the LsbMDDs. Results also showed that the HER2-LsbMDDs suppressed the growth of HER2-expressing MCF-7/HER2 tumors, increasing the amount taken up via an endocytosis pathway leading to high drug accumulation and longer retention in the tumor. In conclusion, the BsAbs-LsbMDDs preserved the physical properties of the LsbMDDs and actively targeted tumors with a drug cargo to enhance drug accumulation in tumors leading to greater antitumor activity against antigen-positive tumors. [ABSTRACT FROM AUTHOR]

Anti-mPEG/anti-human epidermal growth factor receptor 2 (HER2) bispecific antibodies (BsAbs) non-covalently bound to a docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micellar drug delivery system (LsbMDDs) were endowed with active targetability to improve the chemotherapeutic efficacy of DTX. DTX-loaded mPEGylated LsbMDDs formulations were prepared using lecithin/DSPE-PEG(2K or 5K) nanosuspensions to hydrate the thin film, and then they were subjected to ultrasonication. Two BsAbs (anti-mPEG/anti-DNS or anti-HER2) were simply mixed with the LsbMDDs to form BsAbs-LsbMDDs formulations, respectively, referred as the DNS-LsbMDDs and HER2-LsbMDDs. Results demonstrated that the physical characteristics of the BsAbs-LsbMDDs were similar to those of the plain LsbMDDs but more slowly released DTX than that from the LsbMDDs. Results also showed that the HER2-LsbMDDs suppressed the growth of HER2-expressing MCF-7/HER2 tumors, increasing the amount taken up via an endocytosis pathway leading to high drug accumulation and longer retention in the tumor. In conclusion, the BsAbs-LsbMDDs preserved the physical properties of the LsbMDDs and actively targeted tumors with a drug cargo to enhance drug accumulation in tumors leading to greater antitumor activity against antigen-positive tumors. [ABSTRACT FROM AUTHOR]