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To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence and late recurrence following curative surgery.A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence.Among the 473 GC patients, 119 had early recurrence (2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and TNM stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed with late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors.PIK3CA amplifications were more common in diffuse-type GC with early recurrence, while ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients.

BACKGROUND The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients. METHODS A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV. RESULTS Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient's survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001). CONCLUSION Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.

Patients with hepatocellular carcinoma (HCC) and with a single tumor2 cm in size are classified as having Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC. We aimed to investigate the role of the albumin-bilirubin (ALBI) grade in predicting outcomes in patients with BCLC stage 0 HCC.We retrospectively enrolled patients with BCLC stage 0 HCC in Taipei Veterans General Hospital from 2007 to 2015. Prognostic factors were analyzed using a Cox proportional hazards model and propensity score matching (PSM) analysis.There were 420 patients enrolled, including 207 with ALBI grade 1, and 213 with ALBI grade 2 or 3. After a median follow-up of 60.0 months (interquartile range, 37.2-84.6 months), 179 patients died. The cumulative 5-year overall survival (OS) rates were 80.6% in patients with ALBI grade 1 and 53.7% in those with ALBI grade 2 or 3, respectively (p0.001). Multivariate analysis showed that age65 years, negative hepatitis B surface in serum, creatinine1.0 mg/dL, platelet count ≤105/mm3, tumor size1.5 cm, nonsurgical resection (SR) therapy, and higher ALBI grade were independent risk factors related to poor OS. Patients who underwent SR had a better OS and recurrence-free survival than those who received radiofrequency ablation, which was confirmed by a multivariate analysis and PSM analysis.The ALBI grade can determine OS for patients with BCLC stage 0 HCC. SR can also provide a better outcome than nonsurgical treatment.

Background Mucinous gastric carcinoma (MGC) is rare and often associated with an advanced stage. The clinicopathological features and prognosis of MGC and non-MGC (NMGC) are controversial. Methods In total, 2637 gastric cancer (GC) patients receiving curative surgery were enrolled. The clinicopathological features and genetic alterations were compared between patients with MGC and NMGC. Results Among the 2637 GC patients, 92 (3.5%) had MGC. After propensity score matching, compared to patients with NMGC, patients with MGC had more poorly differentiated tumors, medullary stromal reaction-type tumors, tumors with infiltrating Ming's classification, diffuse-type tumors, more abnormal preoperative serum carbohydrate antigen 19-9 levels, and more advanced T categories. After propensity score matching, there were no significant differences between MGC and NMGC regarding the initial recurrence patterns, 5-year overall survival (OS), and disease-free survival (DFS) rates. Multivariate analysis demonstrated that the MGC cell type is not an independent prognostic factor of OS and DFS. No significant differences in microsatellite instability status, Epstein-Barr virus infection, Helicobacter pylori infection, or genetic mutations were observed between MGC and NMGC. The expression of programmed death-ligand 1 (PD-L1) was significantly higher in MGC than that in NMGC. MGC was diagnosed at a more advanced stage compared with NMGC. Conclusion MGC itself was not an independent prognostic factor of worse survival. MGC was correlated with higher PD-L1 expression than NMGC, which may have a clinical impact on the treatment of MGC in the future.

BACKGROUND Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P

Background Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. Methods The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. Results A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. Conclusion DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation.

Surgery is the main treatment for curing gastric cancer. Early diagnosis provides an excellent survival outcome via an improved detection of early gastric cancer and an improved resection rate. The extent of lymphadenectomy surgery has been under debate for a long time. In East Asian countries, especially Japan, Korea, and Taiwan, gastrectomy with D2 dissection is routinely performed. By contrast, in most Western countries, gastrectomy with D1 dissection is performed, due to lower mortality and morbidity. Recently, acceptance of D2 surgery has increased in Western countries because: (1) modified D2 lymphadenectomy (preservation of pancreas and spleen) improves operative morbidity and mortality; (2) Western surgeons can be trained to performed D2 lymph node dissection on Western patients safely; and (3) D2 resection decreases locoregional recurrence and prolongs survival. Current guidelines in the United States and Europe suggest modified D2 dissection is recommended, but needs to be performed by high-volume centers with experienced surgeons. Adjuvant or perioperative chemotherapy should be prescribed for gastric cancer with Stage II or III disease, due to its marked benefits of reducing disease recurrence and increasing long-term survival. Patients with inoperable advanced gastric cancer should receive chemotherapy to improve their survival and quality of life if an acceptable performance status can be achieved. Targeted therapy with trastuzumab should be considered in patients with HER-2/neu overexpression who have a higher response rate and a longer survival.

Complete Response to the Combination of Pembrolizumab and Sorafenib for Metastatic Hepatocellular Carcinoma: A Case Report

A phase 1 study was conducted to assess the safety and immunologic response induced by direct injection of autologous immature dendritic cells (DCs) into tumor under radiotherapy in advanced hepatoma patients. Patients with advanced/metastatic stage hepatoma not suitable for surgery or transarterial embolization were enrolled. Groups of patients received two vaccinations. Each vaccination consisted of intratumoral injections of autologous immature DCs in four dose cohorts of 5 x 10(6), 1.5 x 10(7), 3 x 10(7), and 5 x 10(7) cells 2 days after a single fraction of conformal radiotherapy of 8 Gy. The second vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed two cycles of vaccination. The treatment was well tolerated at any of the dose levels. Six patients had mild transient fever (grade 1-2) with chill reactions, three patients developed grade 1 fatigue, and one patient developed mild myalgia and arthralgia after DC injections. There was no evidence of clinically manifested autoimmune disease. There were two partial responses and four minor responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was found in three patients. Ten patients had completed immunologic response evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune response was evident in eight patients examined by cytokine release assay and in seven patients by ELISPOT assay. Six patients showed an increased NK cell cytotoxic activity after vaccination. These data suggest that the combination of intratumoral injection of DCs and conformal radiotherapy is safe and can induce tumor-specific and innate immunity.

BACKGROUND/OBJECTIVE The survival benefit of treatment for unresectable hepatocellular carcinoma (HCC) with transcatheter arterial chemoembolization (TACE) combined with sorafenib remains uncertain. We compared the survival of patients treated with TACE and sorafenib with that of patients treated with TACE alone. METHODS This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC (START) trial. All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group. They were randomly matched 1:1 by age, sex, Child-Pugh score, tumor size, tumor number, and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period (control group). Patient survival [cumulative incidence and hazard ratio (HR)] of the 2 groups were analyzed and compared. RESULTS The baseline characteristics of the 36 patients in each group were similar. Tumor response rates were significantly better in the TACE and sorafenib group (P

Fluorouracil and platinum are considered the standard treatment options for advanced gastric cancer. Docetaxel is also an effective agent and it shows no cross-resistance with fluorouracil and platinum. The combination treatment of docetaxel with fluorouracil and platinum has been explored, but it demonstrated intolerable toxicities. An alternative approach in the first-line treatment of gastric adenocarcinoma may be to use these agents sequentially. We aimed to evaluate the activity and safety profile of sequential chemotherapy with capecitabine plus oxaliplatin, followed by docetaxel plus capecitabine in the first-line treatment of unresectable gastric cancer.We conducted a phase II study of sequential first-line chemotherapy in advanced gastric cancer. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (capecitabine 1000 mg/m bid on days 1-10 and oxaliplatin 85 mg/m on day 1, every 2 weeks), followed by 4 cycles of docetaxel plus capecitabine (docetaxel 30 mg/m on days 1 and 8, capecitabine 825 mg/m bid on days 1-14, every 3 weeks). The primary end-point was the objective response rate.Fifty-one patients were enrolled: median age, 63 years; male/female: 37/14. The main grade 3 to 4 toxicities were a decreased absolute neutrophil count (25.4%), diarrhea (9.8%), and hand-foot syndrome (15.7%). The objective response rate was 61.7%. The median progression-free survival and overall survival were 8.6 and 11.0 months, respectively. Six patients (11.8%) received surgery after chemotherapy and 5 are still disease-free.This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy.

To date, there have been few reports investigating the relationship between tuberculosis (TB) and gastric cancer. We conducted a nationwide population-based matched cohort study using data retrieved from Taiwan's National Health Insurance Research Database to determine the incidence of and risk factors for TB in patients diagnosed with gastric cancer. From 2000 to 2011, we identified 36,972 gastric cancer patients and normal subjects from the general population matched for age, sex, and comorbidities at a 1:1 ratio. The data were analyzed using Cox proportional hazards models. Compared with the matched cohort, gastric cancer patients exhibited a higher risk for TB (adjusted hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.65–3.05, P

The major issue in selecting patients for transarterial chemoembolization (TACE) lies in determining the optimal number of TACE sessions that may benefit patients before switching to other therapies. This is often a subjective decision not based on any standardized protocol. The ART (Assessment for Retreatment with Transarterial chemoembolization) score was recently developed to determine patients who may benefit from multiple sessions of TACE for treatment of hepatocellular carcinoma. The primary aim of the study was to validate the ART score in a Taiwanese cohort. The secondary aims were to evaluate overall survival and clinical determinants of improved survival in patients treated with multiple TACE sessions. The ART score, clinical characteristics, and outcomes of 82 patients with hepatocellular carcinoma who received multiple TACE sessions at Taipei Veterans General Hospital from September 2007 to July 2013 were analyzed. Among the 82 patients evaluated, 69.5% (n = 57) had an ART score of 0 to 1.5 and 34.1% (n = 25) had a score of ≥2.5. The median overall survival was 23.1 months and the overall mortality rate was 62.2% (n = 51). The ART score was not associated with survival (P = 0.58). Multivariate Cox regression analysis revealed that tumor size >7.2 cm (hazard ratio 4.44, P 25%, and lack of radiological response to TACE were independently associated with shorter survival after TACE therapy.

Supplemental Digital Content is available in the text, The prognostic implication of Barcelona Clinic Liver Cancer (BCLC) substages in Asian patients with hepatocellular carcinoma (HCC) is still obscure. The aim to this study is to compare the prognoses among HCC patients in different substages of the BCLC stage 0 and A. We enrolled 1265 treatment-naive HCC patients with BCLC stage 0 or A from 2007 to 2014. Factors in terms of prognoses were analyzed by multivariate analysis. There were 184, 446, 271, 92, and 272 patients in substage 0, A1, A2, A3, and A4, respectively. After a median follow-up period of 21.0 months, patients in stages 0 and A1 had comparable prognoses (P = 0.136). Both of them had significantly higher overall survival rates than those in stages A2–A4 (all P 20 ng/mL (HR 1.863), tumor size >3 cm (HR 1.542), BCLC stage A2–A4 (HR 1.488), and treatment modality. Surgical resection had the highest overall survival rate followed by radiofrequency ablation (RFA) (HR 1.598), transarterial chemoembolization (HR 2.224), and other treatments (HR 3.707). Verus patients receiving RFA, those who underwent resection had a higher overall survival rate and lower recurrence rate especially in BCLC stages A2–A4. The BCLC-staging system provided good prognostic stratification for early-stage HCC. Patients with a single tumor >2 cm but without portal hypertension or jaundice had similar prognosis to those in BCLC stage 0. Curative therapies—especially hepatic resection—are suggested in early-stage HCC.

Malignant gastric outlet obstruction is a late complication of intraabdominal malignancy. Self-expandable metallic stent placement has been a safe palliative treatment to relieve obstructive symptoms. We aimed to assess the efficacy and safety of metallic stents in our patients and analyzed the clinical outcome of different brands. Seventy-one patients with inoperable gastric outlet obstruction receiving WallFlex enteral stents (WallFlex group) or Bonastents (Bonastent group) since April 2010 were analyzed retrospectively. The overall technical and clinical success rates of stent placement were 100% and 93%, respectively. The baseline characteristics and clinical outcomes including procedure-related complications, restenosis, and reintervention rates were comparable between the 2 groups. However, the Bonastent group had a higher rate of stent fracture than the WallFlex group (13.3% vs 0%, P = 0.03). The mean duration of overall stent patency was 132.7 days. The mean duration of survival was 181.9 days. Resumption of regular diet or low residual diet at day 7 after stent insertion predicted stent patency (hazard ratio [HR]: 0.28, P = 0.01). Cancer with gastric origin (HR: 0.25, P = 0.045) and poststent chemotherapy (HR: 0.38, P = 0.006) predicted lower mortality; however, peritoneal carcinomatosis (HR: 3.09, P = 0.04) correlated with higher mortality. Metallic stent placement is a safe and effective method for relieving gastric outlet obstruction. Except higher rate of stent fracture in the Bonastent group, there is no significant difference in clinical outcomes between the Bonastent group and the WallFlex group.

The objective of this work is to compare the outcomes between the Child–Pugh score 5 (A5 group) and Child–Pugh score 6 (A6 group) in patients with hepatocellular carcinoma (HCC). Whether HCC patients with A5 and A6 groups have different prognoses is still obscure. We enrolled 2462 consecutive treatment-naive HCC patients from 2007 to 2012. Among them, 1486 patients had Child–Pugh grade A, including 1016 in the A5 group and 470 in the A6 group. Factors in the prognoses were analyzed by multivariate analysis. Compared with those in the A6 group, patients in the A5 group were younger, had higher proportions of tumors within the Milan criteria, and more of them underwent curative therapies. The cumulative survival rates at 5 years were 51.3% and 37.1% for patients in the A5 and A6 groups, respectively (P 45 U/L, α-fetoprotein >20 ng/mL, multinodularity, tumor size >3 cm, vascular invasion, and noncurative therapies, but not the Child–Pugh numeric score. The Child–Pugh numeric score had a significant prognostic effect only in patients who had tumors beyond the Milan criteria and received noncurative therapies. HCC patients with A5 group had a better overall survival rate than those with A6 group due to the early tumor stage and higher rate of receiving curative treatments. Tumor factors and treatment modalities were more important than the Child–Pugh numeric score.

Complication of endoscopic variceal injection sclerotherapy for esophageal variceal hemorrhage is not unusual. However, sclerotherapy complicated panophthalmitis was never reported before. We report such an unusual complication and discuss its possible mechanism and treatment.