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Background Investigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types. Patients and methods A surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN. Results Cancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78. Conclusion Defective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.

Background Results of computed tomography body composition (CTBC) predicting long-term outcomes of gastric cancer have been mixed and the plausible mechanism remains elusive. Methods We retrospectively enrolled a cohort of stage III gastric cancer who had undergone curative-intent gastrectomy. Clinicopathological variables, preoperative CTBC including abdominal muscle, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and nutritional and inflammatory index were taken together to construct prognostic analysis. In vitro tests using co-culture system of gastric cancer cell lines and visceral adipocytes were conducted. Results A total of 191 eligible patients were enrolled. By multivariate analysis, SAT and VAT/ SAT ratio were prognostic factors of disease-free survival, while sarcopenia was not. SAT remained as a prognostic factor of overall survival. SAT index was positively correlated with prognostic nutritional index, while VAT HU was positively correlated with platelet-to-lymphocyte ratio. Expression of adiponectin receptor 1 and 2 (AdipoR1, R2), and peroxisome proliferator-activated receptor (PPAR) α, β/δ, ɤ of patients with higher VAT/SAT ratio were decreased as compared to those with lower VAT/SAT ratio. Proliferation of gastric cancer cells co-cultured with adipocytes was increased by 50–100% and accompanied by down-regulation of mRNAs of AdipoR1, 2, PPARα, β/δ, ɤ, and pro-apoptotic genes, as compared to their controls. Conclusion SAT and VAT played exactly opposite prognostic roles of locally advanced gastric cancers, which might work through modulation of AdipoR1, 2 and PPARα, β/δ, ɤ. Preoperative CTBC, supplementary to classic TNM system, helps clinicians tailor individualized adjuvant therapy and/or nutritional support.

Esophageal cancer survival has improved owing to improvements in surgical techniques and preoperative chemoradiation. Excessive alcohol consumption is a shared risk factor for esophageal cancer and chronic alcoholic pancreatitis. Puestow’s procedure is a treatment choice for pain relief and pancreatic duct decompression. It is logical to perform Puestow’s procedure on patients undergoing esophagectomy with underlying chronic pancreatitis to preserve pancreatic function and restore quality of life in the setting of improved esophageal cancer overall survival. Herein, we report our preliminary experience with two patients who underwent both of these procedures during the same operation and achieved acceptable outcomes.

BACKGROUND Laparoscopic cholecystectomy (LC) with associated procedures and endoscopic retrograde cholangiopancreatography (ERCP) have been the standard treatments for both common and rare biliary diseases. Mirizzi syndrome (MS) is a rare and complex biliary condition. We report our experience with MS treatment and investigate the value of laparoscopic procedures and ERCP in patient management. METHODS From 2004 to 2017, 100 consecutive patients with MS were diagnosed by ERCP and underwent surgery in a referral center. Sixty patients were treated with intended LC, and 40 patients were treated with open cholecystectomy (OC). The clinical manifestations, ERCP and associated procedures, surgical procedures, and postoperative outcomes were investigated. RESULTS The surgical mortality rate was 1%, while the surgical morbidity rate was 15%. The patients treated with intended LC suffered from less morbidity (5%). The percentage of postoperative residual biliary stones was 32% (n = 32), and only three patients underwent re-operation (laparotomy) for stone removal. The laparotomy conversion rate in the intended LC group was 16.7% (10/60). The length of hospitalization for the patients with successful LC was significantly shorter than that for the patients with conversion and intended OC. Csendes classification was a risk factor for conversion from LC to OC (type I vs types II to V, P

BACKGROUND The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings. METHODS All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute-and-chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed. RESULTS Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC-to-LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P

The clinical impact of nutrition therapy in critically ill patients has been known for years, and relevant guidelines regarding nutrition therapy have emphasized the importance of proteins. During critical illness, such as sepsis or the state following major surgery, major trauma, or major burn injury, patients suffer from a high degree of stress/inflammation, and during this time, metabolism deviates from homeostasis. The increased degradation of endogenous proteins in response to stress hormones is among the most important events in the acute phase of critical illness. Currently published evidence suggests that adequate protein supplementation might improve the clinical outcomes of critically ill patients. The role of sufficient protein supplementation may even surpass that of caloric supplementation. In this review, we focus on relevant physiological alterations in critical illness, the effects of critical illness on protein metabolism, nutrition therapy in clinical practice, and the function of specific amino acids.

Background Submucosal tumors (SMTs) of different etiologies exist from esophagus to rectum. Esophagogastric junction (EGJ) is one of the known difficult locations for tumor resection. Although minimally invasive surgery (MIS) is a well-established approach for gastrointestinal surgery, there is no consensus that MIS for resection of SMTs around EGJ is superior to laparotomy. We tried to clarify the factors that determine the surgeons’ choices between these two approaches. Methods From January 2002 to June 2016, 909 patients with SMTs underwent resection in our department. Among them, 119 patients (13%) had SMTs around EGJ were enrolled by retrospective review. The clinicopathological features and tumor-related parameters were reviewed and analyzed. Results The cohort was stratified into three groups according to the extent of gastrectomy and surgical approaches. The three groups are as following: major gastrectomy (n = 13), minor gastrectomy by laparotomy (n = 51), and minor gastrectomy with MIS (n = 55). The average tumor size was significantly larger in the major gastrectomy group than in the two minor gastrectomy groups; however, there was no difference between the two minor gastrectomy groups (5.33 cm, 4.07 cm, and 3.69 cm, respectively). The minor gastrectomy with MIS required least hospital stay and operation duration also. We re-stratify the two minor gastrectomy groups (n = 106) according to the orientation of SMTs around the EGJ into 4 zones. Most of SMTs located on the greater curvature side of the EGJ were resected with MIS (82% versus 18%), whereas SMTs in the other zones were resected more often by laparotomy (59% versus 41%). There was no surgical mortality within the cohort, while minor gastrectomy with MIS yielded least number of leakages among the three groups. Conclusions For SMTs around the EGJ, larger tumors (diameter of more than 5 cm) are more likely to be resected with major gastrectomy. To resect SMTs around the EGJ in a wedge-like (minor gastrectomy) fashion, tumors located other than the greater curvature side were more often resected by laparotomy. However, MIS yielded acceptable safety and surgical outcomes compared to conventional laparotomy for SMTs around the EGJ of the same size.

The present study aimed to conduct a prognosis analysis of Taiwanese patients with metastatic gastrointestinal stromal tumors (GISTs), who are resistant to or were unable to tolerate imatinib or sunitinib, and were subsequently treated with regorafenib. The study considered the survival, potential prognostic factors and safety of these Taiwanese patients. A total of 28 patients with pre-treated metastatic GIST, receiving regorafenib treatment, were analyzed between April 2014 and December 2017. Data were collected prospectively, and patients were followed up for a median of 14.8 months. It was reported that 50% (10/20) of male patients and 50% (4/8) of female patients demonstrated response and clinical benefit to regorafenib. The median progression-free survival (PFS) and overall survival (OS) time in all patients receiving regorafenib were 4.4 and 29.3 months, respectively. Good performance status and disease control mediated by regorafenib were independently associated with a more favorable PFS time. Good performance status, higher pre-treated albumin level, lower neutrophil:lymphocyte ratio (NLR) and lower platelet:lymphocyte ratio (PLR) were independent favorable predictors of OS time. Overall, poor performance status and poor disease control predicted a less favorable PFS time in Taiwanese patients with GISTs, who were pre-treated with regorafenib. Meanwhile poor performance status, high NLR, PLR and low albumin level predicted a less favorable OS time.

Objective A video coaching (VC) system has been developed in surgical education. This study compares the educational effect on technical and nontechnical skills of the VC method for teaching laparoscopic surgery. Design We conducted a prospectively randomized study of an education program to teach laparoscopic procedures. Setting The study was performed at the Chang Gung Memorial Hospital, a university hospital in Taiwan. Participants We enrolled sixteen first- or second-year surgical residents.The participants were randomized into VC and conventional teaching (CT) groups, and their surgical skills were judged by the Global Operation Assessment of Laparoscopic Skills (GOALS) and the Objective Structured Assessment of Technical Skills (OSATS). Nontechnical skills were evaluated by the Non-Technical Skills for Surgeons (NOTSS) assessment and self-efficacy questionnaires (SEQs). After the program, posttraining scores were compared to assess improvements. Results The 16 enrolled participants finished the entire course and completed all the videos during the study period. Comparing the VC and CT groups, we found that the pretraining GOALS, OSATS, NOTSS and SEQ scores were similar between both groups. However, after training, the OSATS score gain was higher in the VC groupthan in the CT group (9.25 ± 2.05 vs. 6.50 ± 1.51, p=0.009). Regarding nontechnical skills, the NOTSS score improved more in the VC group than in the CT group (5.50 ± 0.93 vs. 4.25 ± 0.89, p=0.015). The SEQ score was also higher in the VC group (32.13 ± 2.10) than in the CT group (29.50 ± 1.77), with a significant difference (p=0.018). Conclusion VC can help surgeons build their expertise using a more accessible method. Additionally, VC can shorten the learning curve and improve self-efficacy, thereby contributing to surgeons' education.

Autoimmune pancreatitis (AIP) is a rare disease, which comprises two distinct forms of steroid response chronic pancreatitis. AIP type 2 with no association to IgG level and more confined to the pancreas makes it hard to differentiate with pancreatic cancer preoperatively. Here, we present two cases that were preoperatively diagnosed as pancreatic cancer but turn out to be AIP type 2. The first case is a 55-year-old male with epigastric pain, body weight loss and obstructive jaundice. He also had elevated liver enzyme, but tumor marker and IgG4 level were within normal range. The image studies showed the pancreatic head mass. The pylorus-preserving pancreaticoduodenectomy was performed. The second case is a 35-year-old female with epigastric pain and fever. The laboratory data were within the normal range except elevated C-reactive protein level. The magnetic resonance cholangiopancreatography showed a lobulated mass at the pancreatic tail with regional lymphadenopathy. The laparoscopic distal pancreatectomy with splenectomy was arranged for suspect pancreatic neoplasm. In summary, we had reviewed several studies and concluded several steps to help differential AIP to pancreatic cancer. This may help reduce the unnecessary pancreatic resection in the future.

Introduction: Splenectomy is an important and potentially curative treatment for immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has replaced open splenectomy (OS) as the standard approach. The prognostic role of platelet count and the clinical indication of preoperative platelet transfusion are not entirely clear. Methods: We designed a study to explore the prognostic impact of surgical methods, platelet count, and platelet transfusion in a large, single-institute, long-term cohort of ITP patients. Result: In 118 ITP patients, there was no difference between OS and LS in response and surgical complications. The overall response rate was 77% and the complete response (CR) rate was 70%. Patients with a CR had a trend towards a higher baseline platelet count. A stable platelet count 14–28 days after splenectomy was associated with a sustained long-term response. Patients requiring preoperative platelet transfusion had a lower preoperative platelet count and were more likely to need postoperative transfusion of red blood cells and platelets. They also had a lower postoperative platelet count than the nontransfusion group. Relapse-free survival did not differ. Conclusions: Baseline and postoperative platelet counts are apparently associated with the treatment response to splenectomy but the difference did not reach statistical significance. Preoperative platelet transfusion did not overcome the disadvantage of thrombocytopenia and was not recommended when other preparative measures are available.

Numerous strategies for perioperative nutrition therapy for patients undergoing pancreaticoduodenectomy (PD) have been proposed. This systematic review aimed to summarize the current relevant published randomized controlled trials (RCTs) evaluating different nutritional interventions via a traditional network meta-analysis (NMA) and component network meta-analysis (cNMA). EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched to identify the RCTs. The evaluated nutritional interventions comprised standard postoperative enteral nutrition by feeding tube (Postop-SEN), preoperative enteral feeding (Preop-EN), postoperative immunonutrients (Postop-IM), preoperative oral immunonutrient supplement (Preop-IM), and postoperative total parenteral nutrition (TPN). The primary outcomes were general, infectious, and noninfectious complications; postoperative pancreatic fistula (POPF); and delayed gastric emptying (DGE). The secondary outcomes were mortality and length of hospital stay (LOS). The NMA and cNMA were conducted with a frequentist approach. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Two primary outcomes, infectious complications and POPF, were positively influenced by nutritional interventions. Preop-EN plus Postop-SEN (OR 0.11; 95% CI 0.02~0.72), Preop-IM (OR 0.22; 95% CI 0.08~0.62), and Preop-IM plus Postop-IM (OR 0.11; 95% CI 0.03~0.37) were all demonstrated to be associated with a decrease in infectious complications. Postop-TPN (OR 0.37; 95% CI 0.19~0.71) and Preop-IM plus Postop-IM (OR 0.21; 95% CI 0.06~0.77) were clinically beneficial for the prevention of POPF. While enteral feeding and TPN may decrease infectious complications and POPF, respectively, Preop-IM plus Postop-IM may provide the best clinical benefit for patients undergoing PD, as this approach decreases the incidence of both the aforementioned adverse effects.

Background International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. Methods This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. Results Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X-ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. Conclusion This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.

Background Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A retrospective study was conducted to evaluate the postoperative prognostic predictors of HCC focusing on sex differences. Methods We enrolled 516 consecutive adult patients with HCC (118 women, 398 men), who received surgical resection between January 2000 and December 2007, and were followed-up for >10 years. Clinical and laboratory data together with postoperative outcomes were reviewed. Results At baseline, female patients had a higher anti-hepatitis C virus antibody prevalence (P = 0.002); lower hepatitis B virus surface antigen prevalence (P = 0.006); less microvascular invasion (P = 0.019); and lower alpha-fetoprotein (P = 0.023), bilirubin (P = 0.002), and alanine transaminase (P = 0.001) levels. Overall, there were no significant sex differences in terms of intrahepatic recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS). However, subgroup analysis showed that women had favorable RFS (P = 0.019) and MFS (P = 0.034) in patients with alpha-fetoprotein ≤ 35 ng/mL, independent of other clinical variables (adjusted P = 0.008 and 0.043, respectively). Additionally, men had favorable OS in patients with prothrombin time (international normalized ratio [INR])

Summary: Background: Determining the survival outcome for gastric cancer patients with metastases to more than 15 regional lymph nodes is difficult. This study aims to develop a lymph node metastatic ratio (LNR)-based prognostic model to predict the survival outcome after D2 surgery in such patient groups. Methods: Our study retrospectively enrolled 139 gastric cancer patients with metastases to more than 15 regional lymph nodes who underwent D2 surgery between 2007 and 2014. Clinicopathologic variables to predict overall survival (OS) using multivariate Cox regression were selected to create a prognostic model. Results: The prognostic model for predicting OS was developed based on five independent factors, namely, T-classification (T2 or T3 vs. T4), LNR (

BackgroundEverolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR).Case PresentationA 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up–related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation.ConclusionA literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.

Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR), group 2 (G2), pT4b with PR, group 3 (G3), positive duodenal margins without Whipple’s operation, and group 4 (G4), cT4b with Whipple’s operation. Demographics, clinicopathological features, and outcomes were compared between G1 and G2 and G3 and G4. G2 patients were more likely to have perineural invasion than G1 patients (80.6% vs. 50%, p &lt, 0.001). G4 patients had higher lymph node yield (40.8 vs. 31.3, p = 0.002), lower nodal status (p = 0.029), lower lymph node ratios (0.20 vs. 0.48, p &lt, 0.0001) and higher complication rates (45.2% vs. 26.3%, p = 0.047) than G3 patients. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly longer in G1 than in G2 (28.1% vs. 9.3%, p = 0.003, 32% vs. 13%, p = 0.004, respectively). The 5-year survival rates did not differ between G4 and G3 (DFS: 14% vs. 14.4%, p = 0.384, OS: 12.6% vs. 16.4%, p = 0.321, respectively). In conclusion, patients with T4b lesion who underwent PR had poorer survival than those who underwent resection of other adjacent organs. Further Whipple’s operation did not improve survival in pT3–pT4 GC with positive duodenal margins.

Percutaneous cholecystostomy (PC) has become an important procedure for the treatment of acute cholecystitis (AC). PC is currently applied for patients who cannot undergo immediate laparoscopic cholecystectomy. However, the management following PC has not been well-reviewed. The efficacy of PC tubes has already been indicated, and compared to complications of other invasive biliary procedures, complications related to PC are rare. Following the resolution of AC, patients who can tolerate anesthesia and the surgical risk should undergo interval cholecystectomy to reduce the recurrence of biliary events. For patients unfit for surgery, whether owing to comorbidities, anesthesia risks, or surgical risks, expectant management may be applied; however, a high incidence of recurrence has been noted. In addition, several interesting issues, such as the indications for cholangiography via the PC tube, removal or maintenance of the PC catheter before definitive treatment, and timing of elective surgery, are all discussed in this review, and a relevant decision-making flowchart is proposed. PC is an effective and safe intervention, whether as expectant treatment or bridge therapy to definitive surgery. High-level evidence of post-PC care is still necessary to modify current practices.

Traditionally, surgical residency training is more focused on obtaining surgical skills through a well-established coaching system worldwide. However, constant advances in medical science require surgeons to learn not only surgical skills but also the ability of scientific research to improve clinical practice and future professional development. The study aims to emphasize that professional education in terms of scientific research is also significant for surgical residency training. All residents who had been recruited in a medical center for the surgery residency program between years 2006 and 2015 were evaluated in the study. Generally, every resident is assigned to a mentor since the first year of residency. Then, the mentor would help the resident qualify a 2-step evaluation in terms of scientific research during the residency training program. A total of 193 residents were evaluated in the study. All of them had completed the first step regarding oral presentation of their designated research, and the majority of residents obtained 80 to 90 points that were rated by referees. Overall, 102 residents (52.8%) had completed the second step with the publication of a research manuscript. The percentage of residents who had fulfilled the criteria of this 2-step assessment ranged from 35.3% to 81.8% by year. The continuing education for surgical residents should not be limited in coaching clinical practice. Scientific research is also essential for current surgical residency training, and a formal mentorship program may be beneficial for the future professional development of surgical residents. However, the success of the 2-step evaluation could possibly depend on the career choices of the residents instead of the mentorship program.

Studies have shown the anticancer effects of metformin in vitro. However, whether metformin can prevent cancer recurrence or prolong survival in patients with gastric cancer (GC) and diabetes mellitus (DM) post-gastrectomy remains unknown. We evaluated the beneficial effects of metformin in patients with GC and DM post-gastrectomy. We recruited 2400 patients with GC (1749 without DM, 651 with DM) who underwent surgery between 1997 and 2010. Patients with DM were stratified into metformin (group 1) and non-metformin (group 2) users. Their clinicopathological data were recorded prospectively, and demographics, recurrence-free survival (RFS), and cancer-specific survival (CSS) were compared. Tumour recurrence risk and cause of death were analysed between groups 1 and 2 among patients with DM stratified by tumour stage. We also compared RFS and overall survival among patients with and without DM. Tumour recurrence occurred in 201 patients with GC: 57 (25%) in group 1 and 144 (37%) in group 2. After adjusting for confounders, metformin significantly prolonged CSS (hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.38&ndash, 0.77) in patients with stage I&ndash, III GC and DM. In subgroup analysis, metformin users with stage III GC and DM had significantly prolonged CSS compared to non-metformin users (HR = 0.45, 95% CI = 0.30&ndash, 0.68), with an insignificant difference in patients with stage I&ndash, II GC. Adjusted HRs for RFS and CSS were significantly lower in patients with stage I&ndash, III GC and DM than those in patients without DM (0.67 (95% CI = 0.54&ndash, 0.92) and 0.62 (95% CI = 0.50&ndash, 0.77), respectively), with an insignificant difference in patients with stage I GC. Metformin significantly reduces tumour recurrence risk and improves CSS in patients with stage III GC and DM post-gastrectomy. Further prospective studies may confirm the efficacy of metformin as an adjunctive treatment for advanced GC postoperatively.

The physiological roles and clinical impacts of the differences between visceral fat (VF) and subcutaneous fat (SF) are unclear. The present study aimed to compare the miRNA signatures between visceral fat (VF) and subcutaneous fat (SF) and study their influences on outcomes of bariatric surgery. To study the microRNA signatures of the VF and SF in obesity, we performed paired microRNA arrays of the adipose tissues from 20 bariatric surgery patients. The microRNA analysis identified miR-122 as the most significant signature between VF and SF. The tissue distribution, functions, and influences on adipogensis of miR-122 were analysed by Northern blotting, microRNA mimics and inhibitors, and whole-genome microarray analysis. The outcomes of body weight changes after bariatric surgery were analysed and correlated with the miR-122 abundances. Northern blotting confirmed that miR-122 was highly expressed in VF and SF. Bioinformatics analysis of the microarray revealed that proliferator activator receptor-γ (PPAR-γ) signalling was critically affected by miR-122. The modulation of PPAR-γ by miR-122 was confirmed in murine adipocytes and human adipose tissues. Furthermore, the differentiation of preadipocytes was significantly influenced by miR-122. In obese patients receiving bariatric surgery, the ratio of VF and SF miR-122 abundance correlated with 6-month and 1-year % excess body weight loss. Our findings indicate that miR-122 is highly expressed in adipose tissue. The abundance of miR-122 affects PPAR-γ signalling and adipocytes differentiation in vitro and human adipose tissues. Higher miR-122 in VF may be associated with greater body weight loss after bariatric surgery.

Aim: Whether the obesity prevention by chemicals or surgeries in already obese patients is the better choice remains controversial. We aimed to compare the effect of orally silibinin-loaded nanocarriers and Roux-en-Y gastric bypass surgery on hepatic fibrosis in high-fat feeding-induced obese rats. Methodology: The developed nanocarriers included self-emulsifying drug delivery system (SNEDDS) and nanostructured lipid carriers (NLC). Results: A significant decrease in collagen production and lipid droplet formation was observed upon nanosystem and bariatric surgery than the rats treated with silibinin control suspension. Stage 3 fibrosis was present in 33% of the obese rats. This percentage could be minimized to 0% by SNEDDS and NLC. Following oral administration, SNEDDS and NLC resulted in 3.5- and 2.9-fold increase, respectively, in bioavailability compared with the reference suspension. Conclusion: Nanomedicine prevention provided a comparable efficiency to ameliorate liver steatosis as Roux-en-Y gastric bypass due to the improvement of silibinin dissolution and gastrointestinal permeation.

Summary: Background: Given the global increase in aging populations and cancer incidence, understanding the influence of age on postoperative outcome after cancer surgery is imperative. This study aimed to evaluate the impact of age on survival outcome in solid cancer patients receiving curative surgery. Methods: A total of 37,288 patients receiving curative surgeries for solid cancers between 2007 and 2012 at four affiliated Chang Gung Memorial Hospital were included in the study. All patients were categorized into age groups by decades for survival analysis. Results: The percentages of patient populations aged

Background/purpose: To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site. Methods: Patients with clinically suspected NET and NET of unknown primary site were eligible. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard. Results: Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants. Conclusion: Our data confirm the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients. Keywords: 68Ga-DOTATOC, 18F-FDG, Neuroendocrine tumors, PET/CT

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values

Summary Objective Pancreatic ductal adenocarcinoma is one of the most malignant types of cancer. This study evaluated the 3-year and 5-year surgical outcomes associated with the cancer and determined whether statistically identified factors can be used to predict survival. Methods This retrospective review was conducted from 1995 to 2010. Patients who had resectable pancreatic ductal adenocarcinoma and received surgical treatment were included. Cases of hospital mortality were excluded. The relationships between several clinicopathological factors and the survival rate were analyzed. Results A total of 223 patients were included in this study. The 3-year and 5-year survival rates were 21.4% and 10.1%, respectively, and the median survival was 16.1 months. Tumor size, N status, and resection margins were independent predictive factors for 3-year survival. Tumor size independently predicted 5-year survival. Conclusion Tumor size is the most important independent prognostic factor for 3-year and 5-year survival. Lymph node status and the resection margins also independently affected the 3-year survival. These patient outcomes might be improved by early diagnosis and radical resection. Future studies should focus on the tumor biology of this aggressive cancer.

Background: Obesity has become a healthcare burden in Taiwan and the rest of Asia. Laparoscopic Roux-en-Y gastric bypass (LRYGB) provides good weight loss outcome, and improves comorbidity as well as quality of life. We present our experience of the learning curve for LRYGB in a low-volume bariatric unit. Methods: From March 2009 to August 2011, 60 consecutive patients who underwent LRYGB were included. They were separated into two groups, with the first 30 cases in Group 1 and the remaining 30 cases in Group 2. Indicators for evaluating the learning curve for LRYGB included surgical time, rate of conversion to open surgery, surgical and total complication rates, length of hospital stay, mortality, and postoperative weight loss. Results: There were no significant differences in demographic measurements between the two groups. In Group 1, the median surgical time was 120 minutes and in Group 2 it was 80 minutes (p

Background: Stage III gastric cancer is characterized by locally advanced disease with varying anatomic extent as measured by the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. There are no prognostic factors specifically identified in patients with stage III gastric cancer following extended lymph node dissection (D2) surgery. Materials and Methods: From 2007 to 2014, 534 patients with stage III gastric cancer underwent radical gastrectomy and D2 dissection at the Chang Gung Memorial Hospital. Patients' characteristics and the impact of adjuvant chemotherapy were analyzed using univariate and multivariate analyses to identify variables associated with overall survival (OS) and disease-free survival (DFS). Results: There were 320 deaths (60.0%) and 284 recurrences (53.2%) by the end of the study. The median OS and DFS were 30.7 months (95% confidence interval [CI]: 27.5-33.9) and 26.4 months (95% CI: 21.2-31.6), respectively. The multivariate analysis identified 7 variables that were independent prognostic factors both for OS and DFS including ratio of metastatic lymph nodes to total resection lymph nodes, carcinoembryonic antigen level, Eastern Cooperative Oncology Group performance status, gastrectomy method, vascular invasion, surgical margin, and adjuvant chemotherapy. Patients with stage IIIA-IIIC disease who received adjuvant chemotherapy had better OS and DFS outcomes than those who did not. Conclusions: Our study identified several independent prognostic factors that might help determine the appropriate counseling patients following surgical treatment. D2 surgery alone was inadequate to achieve long-term survival. As the only correctable independent prognostic factor, postoperative adjuvant chemotherapy should be recommended for eligible patients with stage III gastric cancer.

Background: Gastric signet ring cell carcinoma (SRCC) is a histologic variant characterized by abundant intracytoplasmic mucin. Although it has been recognized that gastric adenocarcinoma harboring this feature has poorer prognosis, prognostic stratification within gastric SRCCs themselves has not been clearly defined. N-acetylgalactosaminyltransferase14 (GALNT14) genotype has been associated to poorer treatment outcome in mucinous type colorectal cancer. Here we incorporated clinicopathological factors and GALNT14 genotype to stratify prognosis of advanced gastric SRCC. Methods: Totally 347 gastric SRCC patients were retrospectively enrolled for GALNT14 genotyping. Clinicopathological factors were included for prognosis stratification. Results: Of the 347 patients, 341 underwent radical-intent gastrectomy and 6 received palliative gastrectomy. Kaplan-Meier analysis for overall survival indicated that Tumor-Node-Metastasis staging could only stratify the patients into three prognosis-distinguishable groups: group-1 (stage IA); group-2 (stage IB/IIA) and group-3 (the remaining Tumor-Node-Metastasis stages combined). Multivariate Cox-proportional hazard models for group-3 patients revealed GALNT14 “TT” genotype (P = 0.0482). Tumor size (P = 0.0009), node status (P 0 (P = 0.0013), lymphatic invasion (P = 0.021), vascular invasion (P = 0.0076) and perineural invasion (P = 0.0161). Accordingly, a scoring system was established capable of stratifying advanced gastric SRCC patients into three distinguishable prognostic subgroups. Conclusions: Gastric SRCC could be stratified into different prognostic subgroups by combining clinicopathological factors and GALNT14 genotype.

Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an effective targeted therapy. Here, we assessed the therapeutic efficacy of regorafenib in CCA, as well as elucidated its underlying mechanism. We first demonstrated that regorafenib not only inhibited growth but also induced apoptosis in human CCA cells. Subsequently, we used in silico approaches to identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an important role in activating NF-κB, as a potential target of regorafenib. Overexpression of Elk-1, but not Ets-1, in HuCCT1 cells markedly reduced their sensitivity to regorafenib, which might be attributed to a significant increase in MALT1 levels. Our results further demonstrated that this drug drastically inhibited MALT1 expression by suppressing the Raf/Erk/Elk-1 pathway. The efficacy of regorafenib in decreasing in vivo CCA growth was confirmed in animal models. Regorafenib efficacy was observed in two MALT1-positive CCA patients who failed to respond to several other lines of therapy. Finally, MALT1 was also identified as an independent poor prognostic factor for patients with intrahepatic CCA. In conclusion, our study identified MALT1 to be a downstream mediator of the Raf/Erk/Elk-1 pathway and suggested that MALT1 may be a new therapeutic target for successful treatment of CCA by regorafenib.

MicroRNA-196a (miRNA-196a) is associated with the development of gastric cancer and metastasis. Intestinal metaplasia and low- or high-grade dysplasia are considered to be precursors of intestinal type gastric cancer. Accordingly, we investigated the expression of plasma miRNA-196a as an early detection biomarker in precancerous gastric lesions and early cancer (pT1a/b), which is otherwise treated with endoscopic submucosal dissection. Our data showed that levels of circulating (plasma) miRNA-196a were higher in patients with precancerous lesions/early gastric adenocarcinoma than in healthy controls. The area under the receiver operating characteristic curve (AUC) for healthy controls vs. intestinal metaplasia was 0.9736; healthy controls vs. low-grade/high-grade dysplasia 0.9495; and healthy controls vs. early gastric cancer 0.9318. These results indicate that circulating miRNA-196a is a novel biomarker for detection of early gastric cancer and its precursor.

Introduction Information on primary small intestinal lymphoma is more limited than for gastric lymphoma because most of the previous studies did not focus on the former. Few prognostic indicators in primary intestinal lymphoma have been reliably established because of limited patient numbers and variations in criteria for patient selection. In this study, we retrospectively reviewed the clinical and pathological characteristics of small intestinal lymphoma cases from our hospital, to determine prognostic factors and to clarify the effect of surgical resection on prognosis. Methods Eighty-two patients were enrolled in this retrospective study between January 1997 and December 2012. Patients were divided into two groups based on whether or not they underwent surgical management. Gross resection was defined as complete removal of the primary lesion(s), as confirmed by the naked eye. Combined therapy refers to concurrent surgery and chemotherapy. The clinicopathological characteristics and long-term outcomes of patients were analyzed and compared between the two groups. Results Most of the patients had abdominal pain (75.6%), and some had loss of body weight (29.3%) and bowel perforation (22.0%). Sixty-two patients (75.6%) underwent surgical management. Patients in the surgery group presented with fewer B symptoms (fever, night sweats, and weight loss; P = 0.035) but more bulky disease (P = 0.009). The ileocecal region was the most common site of solitary involvement (34.1%). The most common reason for surgery was for tumor-related complications (61.3%). Seven patients (11.3%) developed major complications of surgery, but these were not related to the indication, timing, or type of surgery. Only major surgical complications were statistically significant in relation to early mortality (P = 0.004). The estimated 5-year progression-free survival (PFS) was 35.1% and 5-year overall survival (OS) was 43.2%. Univariate analysis revealed that patients in the surgery group had improved 5-year PFS (P = 0.028). T-cell lymphoma, involvement of multiple gastrointestinal regions and extranodal involvement, higher scores for International Prognostic Index (IPI), more advanced Ann Arbor stage, lactate dehydrogenase (LDH) levels above 215 U/L, and management without combined therapy were prognostic for shorter PFS and OS in univariate analyses. Individuals who received R0 resection or gross resection had improved 5-year PFS and OS. Cox regression analysis demonstrated that primary T-cell lymphoma was an independent negative prognostic factor for both OS and PFS. Conclusion Combined therapy is an independent prognostic factor for long-term survival in small intestinal lymphoma. Gross resection is recommended in patients with small intestinal lymphoma and leads to improved PFS without significantly increasing the risk of complications. Emergency surgery does not lead to poor prognosis. However, caution is warranted in the management of all patients, because of the high risk of post-operative complications and potential for early mortality.

Near-infrared (NIR) fluorescence cholangiography by systemic administration of indocyanine green (ICG) enhances the visualization of the biliary tree anatomy. However, the simultaneous enhancement of liver parenchyma can disturb the visualization of critical details. We herein proposed a new technique of NIR cholecystocholangiography by intragallbladder ICG injection to increase the safety during laparoscopic cholecystectomy. A total of 46 patients scheduled for laparoscopic cholecystectomy for symptomatic lithiasis (n = 21) or cholecystitis (n = 25) were enrolled. A fluorescence cholangiography by direct gallbladder injection of ICG was performed in all cases. Of them, the ICG was injected through a previously placed percutaneous transhepatic gallbladder drainage catheter (n = 18) or by intraoperative, percutaneous needle puncture of the gallbladder (n = 28). Visualization of biliary structures, including the cystic duct (CD), the common bile and hepatic ducts (CBD and CHD), the gallbladder neck, and the Hartmann’s pouch (HP), was performed using White Light (served as control modality) and by NIR enhancement. Cholecystocholangiography provided a significantly higher rate of visualization of the CD in case of cholecystitis with mild adhesions, and an improved visualization of the HP, CBD, and CHD in case of severe inflammation, when compared to White Light observation. There were no benefits of NIR in case of non-inflamed lithiasis. Clinical translation of NIR cholecystocholangiography has been successful with a noise-free visualization of biliary anatomy. It can be considered in difficult cases to increase the safety of laparoscopic cholecystectomy.

Perforated gastric cancer (PGC) is a rare condition of gastric cancer (GC). In this study, we sought to assess the outcome of PGC from the aspects of both acute care surgery and surgical oncology at a single institute, Chang Gung Memorial Hospital (CGMH).From 1997 to 2013, 6864 patients were diagnosed with GC and 2738 were diagnosed with gastroduodenal perforation at CGMH. In total, 29 patients with PGC were identified. Immediate surgical and long-term oncologic outcomes were evaluated after an appropriate matching process was performed.The immediate surgical outcome of PGC, i.e., the hospital mortality rate within 30 d after surgery, did not significantly differ from that of non-cancer related gastroduodenal perforation. The long-term oncologic outcome, with matching by age, gender, year of surgery and AJCC 7th stage grouping, also did not significantly differ from that of GC without perforation.Aggressive surgical treatment, including an initial emergency procedure for containing peritonitis and radical surgery for GC, may benefit PGC patients in terms of both the immediate and oncologic outcomes.

Background The purpose of this study was to test the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting recurrence risk of major salivary gland carcinoma in an Asian cohort. Methods We retrospectively enrolled 149 patients who had undergone intended curative resections for major salivary gland carcinoma between 2007 and 2012. The performance of the MSKCC nomogram and the American Joint Committee on Cancer (AJCC) seventh staging system in predicting recurrence risk was compared. Results The MSKCC nomogram and the AJCC staging system both accurately predicted the 5-year recurrence probabilities, with the concordance index (c-index = 0.82; 95% confidence interval [CI], 0.75–0.89 vs c-index, 0.77; 95% CI, 0.68–0.87; p = .45) in patients with major salivary gland carcinomas after curative surgeries. Comparing to the actual observed events, the calibration plot indicated that the MSKCC nomogram accurately estimated the recurrence in low-risk groups but tended to overestimate in high-risk groups. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the prediction was very good for patients with AJCC stages I and II disease (c-index = 0.92 and 0.90, respectively) and modest for those of AJCC stages III and IVa (c-index = 0.51 and 0.62, respectively). Conclusion The MSKCC nomogram and the AJCC staging system each had its value in predicting recurrence of major salivary gland cancers. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the MSKCC nomogram was more accurate in predicting recurrence risks in those patients with AJCC stage I and II diseases than those with late-stage diseases. © 2017 Wiley Periodicals, Inc. Head Neck 39: 860–867, 2017

The positive expression of human epidermal growth factor receptor 2 (HER-2) is phenotypically associated with differentiated gastric cancer (GC) and is a prognostic factor for resectable GC. The aim of this study was to explore the clinical significance of vascular endothelial growth factor (VEGF), protein kinase B, and p38 mitogen-activated protein kinase (MAPK) regarding outcome in patients with HER-2 positive GC, and to analyze the relationship between these molecules and clinicopathologic parameters.Between January 2001 and December 2012, radical-intent gastrectomy specimens from GC patients were evaluated for HER-2 expression by immunohistochemistry (IHC); and with HER-2 expression levels of 2+ were further subjected to fluorescence in situ hybridization analysis. HER-2 positivity was defined by a HER-2 3+ score on IHC or a HER-2 2+ score on IHC and HER-2 amplification by fluorescence in situ hybridization. The expression of VEGF, phosphorylated protein kinase B, and phosphorylated p38 MAPK in HER-2 positive specimens was scored using IHC.Fifty-four patients with HER-2 positive stage I-III GCs were identified. Univariate analysis of prognostic factors showed that tumor differentiation, the presence of vascular invasion, and overexpression of p-p38 MAPK, and VEGF significantly affected prognosis. Multivariate analysis identified vascular invasion (hazard ratio = 2.704; 95% confidence interval = 1.074-7.088; P 0.033) and the overexpression of VEGF (hazard ratio = 2.760; 95% confidence interval = 1.083-6.753; P 0.035) to be independent prognostic predictors of HER-2 positive GC.VEGF overexpression and the presence of vascular invasion were independent poor prognostic factors for HER-2 positive GCs.

Background and Objectives: The standard treatment for carcinomas of the ampulla of Vater (CAV) is surgical resection. Nevertheless, recurrence is observed in half of the patients within five years after cancer surgery. In this study, we aimed to identify predictive factors and develop a nomogram capable of predicting the risk of recurrence in post-resection CAV patients. Methods: Our study cohort was composed of two hundred and twelve patients who had undergone radical surgery for CAV between 2000 and 2012. Clinicopathological variables predictive of recurrence were identified using univariate analysis. A Cox proportional hazards model was used to select the predictive factors used for the nomogram. Results: The 5-year overall survival, cancer-specific survival and disease-free survival rates were 44.3%, 51.1%, and 42.8%, respectively. The five most predictive variables for tumor recurrence were chosen to develop the nomogram. The nomogram had a highly predictive performance, with a bootstrap-corrected concordance index of 0.72 (95% confidence interval, 0.67-0.79). Furthermore, the performance of the nomogram was found to be better than the American Joint Committee on Cancer (AJCC) staging system due to better homogeneity, higher ability of discrimination and higher risk stratification of the model. Conclusions: We developed a predictive nomogram for estimating tumor relapse probability in CAV patients after radical surgery. This nomogram might be more informative than the AJCC staging system and may allow for better estimation of the probability of relapse after surgical resections.

Background and Aim Epstein–Barr virus (EBV) is suggested to actively utilize its ebv-microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. A systemic profiling of ebv-miRNAs expressed in EBV-associated gastric carcinoma (EBVa GC) helps understand its epigenetic regulation of carcinogenesis. Methods A total of 1039 patients with gastric cancer were screened for EBVa GC using EBV-encoded RNAs in situ hybridization. A comprehensive profiling of ebv-miRNAs expressed in EBVa GC was constructed using stem-loop quantitative polymerase chain reaction. Functional assay of specific ebv-miRNA was conducted. Expression of epithelial-to-mesenchymal transition (EMT) markers among EBVa GC and non-EBVa GC was compared. Results The prevalence of EBVa GC was 5.0% (52 out of 1039) in our series. The most abundant ebv-miRNAs of EBVa GC were Bart4, followed by Bart11, Bart2, Bart6, Bart9, and Bart18, in the decreasing order. Of them, Bart9 exhibited the same seed sequence as to hsa miR-200a and miR-141. Expression of E-cadherin of EBV-positive SNU-719 was increased after BART9 knockdown. Depleting endogenous Bart9 of SNU-719 induced a surged expression of miR-200a and miR-141, accompanied by decreased proliferative and invasive ability. Expression of mesenchymal markers in EBVa GC was increased compared with those of non-EBVa GC, albeit the two cohorts exhibited a comparable long-term survival. Conclusions We constructed a comprehensive profiling of ebv-miRNAs in EBVa GC. BART9 plays an important role during carcinogenesis through EMT. Inherent mesenchymal phenotype of EBVa GC represents a unique virus-induced morphology and microenvironment rather than being able to predict the prognosis.

Pancreatic body or tail cancer with invasion to major vessels, including the common hepatic artery and the celiac artery, was previously considered to be unresectable. However, an increasing number of surgeons have aggressively adopted distal pancreatectomy, splenectomy, and celiac axis resection (DP-CAR) in this scenario to attempt curative resection, thus improving long-term survival. In this paper, we present the case of a 45-year-old man with pancreatic body cancer invading the celiac axis who underwent DP-CAR with negative margins (R0) and subsequently exhibited an uneventful postoperative course. We also reviewed literature, which unequivocally demonstrates a comparable oncological outcome between pancreatic body or tail cancer with and without celiac artery resection. To the best of our knowledge, our study is the first documented case in which DP-CAR was successfully performed in Taiwan.

Approximately, 50% of all gastric cancer patients are aged70 y. Although curative surgery is the treatment of choice, many geriatric patients die of surgical complications. Therefore, we aimed to evaluate the impact of radical surgery on the survival outcome of geriatric patients with resectable gastric cancers.About 488 patients diagnosed with resectable gastric cancers, aged ≥70 y, between January 2007 and December 2012 at Chang Gung Memorial Hospital (CGMH) Linkou branch were included in this study. Using univariate and multivariate analyses, possible prognostic variables for survival outcome were assessed in 445 patients (91.2%) treated with radical surgery (operation [OP] group) and 43 (8.8%) receiving conservative treatment (non-OP group). The impact of radical surgery on survival outcomes was evaluated according to CGMH scores.On multivariate analysis, surgical resection with subtotal gastrectomy and CGMH score were the only independent prognostic factors for both overall and cancer-specific survival. The median survival time was 43 mo for the entire cohort. The OP group had significantly better survival outcome than the non-OP group (median survival, 50.3 versus 16.2 mo, P 0.001). The median survival times for patients with CGMH scores ≤20 were 64.1 and 20.0 mo (P 0.002) and those for patients with CGMH scores20 were 13.8 and 10.4 mo (P = 0.18) in the OP and non-OP groups, respectively.Surgical resection and CGMH score are independent prognostic factors for overall and cancer-specific survival; the CGMH score might be a prognostic indicator of surgical outcome in geriatric patients with resectable gastric cancers.

Background Percutaneous cholecystostomy (PC) followed by definitive cholecystectomy is an alternative treatment for acute cholecystitis (AC). We retrospectively investigated the impact of PC tube removal before definitive cholecystectomy on surgical outcomes. Methods From 2012 to 2017, 942 AC patients underwent PC at a single institute. Eligible patients were selected according to inclusion criteria. Demographic data, clinical and laboratory parameters, and treatment outcomes were extracted from medical records. Categorization of patients and subsequent subgroup analysis were based on cholangiography. Results The rate of emergent cholecystectomy in the PC tube removal group was higher than that in the PC tube preserved group (OR = 2.969, 95% CI 1.334-6.612, P = 0.008). In subgroup analysis of patients with patent bile flow under cholangiography, the rate of emergent cholecystectomy was higher in the PC tube removal group (OR = 3.173, 95% CI 1.182-8.523, P = 0.022), though the incidence of complications was higher in the PC tube preserved group (P = 0.012). In addition, routine preoperative cholangiography had no clinical impact on surgical outcome. Conclusion Percutaneous cholecystostomy tube can be removed before subsequent LC to avoid postoperative complications, though removal of the PC tube is associated with an increased likelihood of emergent cholecystectomy.

Purpose The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for fluorouracil-based adjuvant chemotherapy in colorectal cancer has been a paradigm shift. However, whether this applies to gastric cancer is questionable. Furthermore, we herein investigated whether and how autophagy plays a role in MSI-relevant chemoresistance. Materials and Methods A total of 929 patients with deficient MMR (dMMR) and proficient MMR (pMMR) gastric cancers who underwent curative-intent gastrectomy were enrolled. We compared clinicopathological variables and survival among dMMR and pMMR cohorts and tested the responses of MSI-high and microsatellite stable (MSS) gastric cancer cell lines to 5-fluorouracil (5-FU) with or without chloroquine, an autophagy inhibitor. Results We identified an 8.9% prevalence of dMMR cases (83 out of 929) in our cohort. This was associated with old age, tumor site at the distal stomach, an intestinal phenotype, fewer nodal metastasis, and early pathological stages. MMR was an independent prognostic factor after multivariate adjustment. Overall survival (OS) of dMMR patients was better than that of the pMMR patients but was only applicable to stage III patients. There was no difference in OS between dMMR patients treated with or without adjuvant chemotherapy, although the latter showed more medical morbidities. The MSI-high gastric cancer cell lines, versus the MSS counterparts, displayed increased resistance to 5-FU and increased autophagy. Interestingly, autophagy inhibition abrogated the chemoresistance. Conclusion Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. Implications for Practice The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor for gastric cancer. Standard fluorouracil-based adjuvant chemotherapy did not work for deficient MMR cases, and was likely worse. Instead, strategies like autophagy inhibition and/or immune checkpoint inhibition should be taken into consideration in the future.

Chromosomal instability (CIN) of gastric cancer is correlated with distinct outcomes. This study aimed to investigate the role of computed tomography (CT) imaging traits in predicting the CIN status of gastric cancer. We screened 443 patients in the Cancer Genome Atlas gastric cancer cohort to filter 40 patients with complete CT imaging and genomic data as the training cohort. CT imaging traits were subjected to logistic regression to select independent predictors for the CIN status. For the validation cohort, we prospectively enrolled 18 gastric cancer patients for CT and tumor genomic analysis. The imaging predictors were tested in the validation cohort using receiver operating characteristic curve (ROC) analysis. Thirty patients (75%) in the training cohort and 9 patients (50%) in the validation cohort had CIN subtype gastric cancers. Smaller tumor diameter (p = 0.017) and acute tumor transition angle (p = 0.045) independently predict CIN status in the training cohort. In the validation cohort, acute tumor transition angle demonstrated the highest accuracy, sensitivity, and specificity of 88.9%, 88.9%, and 88.9%, respectively, and areas under ROC curve of 0.89. In conclusion, this pilot study showed acute tumor transition angle on CT images may predict the CIN status of gastric cancer.

BACKGROUND: Hilar cholangiocarcinoma accounts for 60% of cholangiocarcinomas from an anatomic point of view, followed by 30% of extrahepatic and 10% of intrahepatic. Curative resection represents the only hope for cure; however, more than 60% patients diagnosed of hilar cholangiocarcinoma were deemed unresectable, many with insufficient future liver remnant (FLR). We present a case underwent hepatico-pancreaticoduodenectomy (HPD) who had received neoadjuvant chemotherapy while waiting for an optimal hypertrophy of FLR after percutaneous transhepatic portal vein embolization (PTPE). METHODS: A 64-year-old female presented with acute cholecystitis associated with jaundice and underwent cholecystectomy plus choledocholithotomy in August 2018. The specimen yielded adenocarcinoma at the cystic duct stump and she was referred to our hospital. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) demonstrated a Klatskin cancer, Bismuth type IV, with downward horizontal extension. The planned surgery was extended right HPD. However, FLR was only 19% (segment 2 and 3), thus PTPE targeting right portal branches was performed. RESULTS: Stemming from unexpected longer time period needed to achieve an optimal FLR, gemcitabine plus oxaliplatin chemotherapy was administered. She underwent an extended right HPD with left portal vein reconstruction in October 2018 not until FLR came to 38% after 12 weeks span. She was discharged uneventfully at postoperative day 21. CONCLUSIONS: We recommend that neoadjuvant chemotherapy should be employed to buy time while awaiting an optimal FLR whenever regeneration rate of FLR following PTPE is slow.

Percutaneous transhepatic portal vein embolization (PTE) has been regarded an indispensable armamentarium for extended liver surgery such as extended right (or left) hepatectomy and hepatopancreatoduodenectomy (HPD) for perihilar cholangiocarcinoma. Before PTPE, we set up appropriately one or more percutaneous transhepatic biliary drains (PTBD) to reach a minimally jaundiced status. We prefer to have (extended) right hepatectomy for Bismuth 1, 2, 3a and 4 subtypes; and (extended) left hepatectomy for Bismuth 3b. Accordingly, PTPE against V5-8 and CV1 is most desirable. The elapsed time period between PTPE and hepatectomy varies remarkably, ranging from 6–14 weeks, whenever the future liver remnant approaches >35% of whole liver or >0.7% of body weight, based on computed tomography-based volumetry. We heavily rely on (indocyanine green) ICG 15’ retention test and those who display >10% of ICG 15’ tests are considered contraindicated for major hepatectomy in our practice.

Chun-Nan Yeh,1 Ren-Chin Wu,2 Chi-Tung Cheng,1 Chun-Yi Tsai,1 Yau-Ren Chang,1 Ta-Sen Yeh,1 Tsung-Han Wu,1 Wei-Chen Lee,1 Kun-Chun Chiang3 1Department of Surgery, Liver Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan; 2Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan; 3General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan Background: More than 500,000 people suffered from hepatocelluar carcinoma (HCC) annually and the relative incidence to mortality rate indicates its unfavorable prognosis. Several studies have proved that heme-oxygenase-1 (HO-1) is indirectly engaged in the invasion and the metastasis of some types of malignancies, including breast cancer, prostate cancer, and lung cancer. The role of HO-1 in hepatitis B virus (HBV)-related HCC is still not clarified.Materials and methods: The Western blot, doubling time, cell cycle analysis, migration assay, invasion assay, gene transfection, xenograft animal model, immunohistochemistry staining, and clinical validation study were applied in this study.Results: HO-1 overexpression not only decreased the growth but also inhibited the migration and invasion in human HBV-HCC cells (Hep-3B vs PLC/PRF/5 ). The inhibitory effect on growth, migration, and invasion is further demonstrated by the overexpression of HO-1 in Hep-3B cell by transfection study. Furthermore, HO-1 decreasing the growth of HBV-HCC was confirmed in animal study. The clinical validation illustrated that higher HO1 expression was also associated with favorable disease-free survival of HBV-HCC patients who underwent hepatectomy.Conclusions: We identified HO-1 as a favorable prognostic factor for HBV-HCC patients who underwent hepatectomy. Keywords: HO-1, HBV, HCC, hepatectomy

Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative treatment for acute cholecystitis (AC). We aimed to understand the natural course of AC in patients treated with PTGBD but without later definitive treatments, such as laparoscopic cholecystectomy. This was a retrospective study of the period from June 2010 to December 2016, during which time 2371 patients were diagnosed with AC and 625 received PTGBD treatment. Among the 625 patients, 237 received no definitive treatment. A biliary event after the initial AC episode was the outcome of interest. In addition, the competing risk of death unrelated to biliary causes was present in the cohort. Therefore, a competing risk model was applied for analysis. The cumulative incidence of biliary events was 29.8% with a median of 4.27 months, while the competing event, i.e., death unrelated to a biliary event, was noted in 14.9% of patients with a median 23.54 months. The risk factors of biliary events were prolonged PTGBD indwelling and an abnormal PTGBD cholangiogram. The risk factors of death unrelated to a biliary event included a high Charlson comorbidity index and the initial AC severity. Definitive cholecystectomy is still recommended for patients undergoing PTGBD treatment due to the high incidence of later biliary events. A thorough preoperative evaluation is necessary for those patients before elective cholecystectomy because of the inferior life expectancy and physical status.

Background Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. Methods A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. Results Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. Conclusion Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.

// Bo-Ru Lai 1, * , Yu-Tung Wu 1, * , Yung-Chia Kuo 2 , Hung-Chih Hsu 2 , Jen-Shi Chen 2 , Tse-Ching Chen 3 , Ren-Chin Wu 3 , Cheng-Tang Chiu 4 , Chun-Nan Yeh 1 , Ta-Sen Yeh 1 1 Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan 2 Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan 3 Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan 4 Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan * These authors have contributed equally to this work Correspondence to: Ta-Sen Yeh, email: tsy471027@adm.cgmh.org.tw Keywords: GIST, second primary cancer, cancer driver gene, c kit, colorectal cancer Received: June 08, 2016 Accepted: September 17, 2016 Published: October 28, 2016 ABSTRACT The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction.