Peritoneal Lavage Tumor DNA as a Novel Biomarker for Predicting Peritoneal Recurrence in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study aimed to develop a new biomarker, defined as peritoneal lavage tumor DNA (ptDNA), using DNAs extracted from peritoneal lavage samples from patients with PDAC. METHODS: Samples were collected intraoperatively from 89 PDAC patients who underwent pancreatectomy between 2012 and 2017. Droplet digital polymerase chain reaction (PCR) was used to measure ptDNA for detection of KRAS mutations. The ptDNA status and clinical characteristics were retrospectively evaluated. RESULTS: Positive ptDNA was found in 41 patients, including all 9 patients positive for CY (CY+) and 32 patients negative for CY (CY-). The mutant allele frequency was significantly higher in the CY+ patients than in the CY- patients. The disease-free survival (DFS) and overall survival (OS) were significantly poorer in the high-ptDNA group than in the low-ptDNA group (median DFS, 11.0 vs. 18.8 months; p = 0.007; median OS, 28.7 vs not reached; p = 0.001). The survival curves of DFS and OS in the CY+ group were almost equal to those in the CY- and high-ptDNA group. In a multivariable analysis, ptDNA was an independent predictive factor for DFS (p = 0.025) and OS (p = 0.047). The estimated cumulative incidence of peritoneal recurrence was 45.5% in the high-ptDNA group. The ptDNA biomarker had a much higher sensitivity for peritoneal recurrence than CY, whereas CY had higher specificity. CONCLUSIONS: As a promising biomarker, ptDNA may predict poor prognosis and peritoneal recurrence in PDAC, resolving the controversy surrounding CY.

Preoperative six-minute walk distance as a predictor of postoperative complication in patients with esophageal cancer.

Surgery for esophageal cancer is associated with high morbidity and mortality. Reduced pulmonary functions and exercise capacity are known as risk factors for complications after esophagectomy. The 6-minute walk distance (6MWD) measured by the 6-minute walk test (6MWT) is a simple field test that can be used to evaluate the functional exercise capacity of patients who undergo thoracic surgery. The aim of this study was to evaluate the association of the preoperative 6MWD with postoperative complications in patients with esophageal cancer. Records of a total of 111 patients who underwent thoracic surgery followed by postoperative rehabilitation from January 2013 to December 2015 were retrospectively reviewed. Data of patients who experienced Clavien-Dindo grade II or severer (grade ≥ II) complications were compared with those who experienced grade ≤I complications. The 6MWD was significantly correlated with age, serum albumin concentration, hemoglobin concentration, and hand grip strength. A total of 42 patients experienced grade ≥II. The 6MWD of patients with grade ≥ II complications was significantly shorter than that of those with grade ≤I complications. In receiver operating characteristic analysis, 6MWD ≤ 454 m was a threshold for predicting grade ≥II complications with 71.0% sensitivity and 54.8% specificity. The incidence of grade ≥II complications led to delayed ambulation and longer stays in hospital. In the multiple regression analysis, the preoperative risk factors for incidence of grade ≥II complications included lower levels of preoperative 6MWD and % of the predicted value of forced expiratory volume in 1 second. Our results indicate that the 6MWT is useful to assess preoperative physical status in patients with esophageal cancer.

Identification of a serum-based miRNA signature for response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the standard of care for resectable esophageal squamous cell carcinoma (ESCC) which is one of the most lethal cancers, to improve resectability and prognosis. On this basis, to provide individually optimized therapy for ESCC, a minimally-invasive biomarker for response to NAC is strongly desired. This study aimed to identify the miRNA signature in serum specimens taken from ESCC patients undergoing NAC through genome-wide microarray technology. METHODS: Comprehensive miRNA-expression profiles of serum specimens from ESCC patients before initial treatment were analyzed using microarray. A qPCR assay was performed to test the robustness of identified serum-based miRNA signature for discriminating response to NAC with serum specimens taken from 100 ESCC cases undergoing NAC. RESULTS: We prioritized 62 miRNAs differentially expressed between responders and non-responders (absolute log2 fold change > 1.0, corresponding P < 0.05) and from the 62 miRNAs, we selected the miR-23a-5p, miR-193b-5p, and miR-873-3p, which were highly expressed in non-responders. Following qPCR analysis indicated the expression of miR-193b-5p and miR-873-3p in serum specimens were significantly higher in non-responders among three selected miRNAs (P = 0.004 and 0.001, respectively). Subsequently, we developed 2-miR-model (miR-193b-5p and miR-873-3p), 3-miR-model, and 2-miR + lymphatic invasion (ly) model based on logistic regression analysis, which achieved the better area under the receiver operating characteristic curves than those of single miRNAs as 2-miR-model, 0.70 (95% CI 0.57 to 0.82); 3-miR-model, 0.70 (95% CI 0.57 to 0.83); and 2-miR + ly, 0.73 (95% CI 0.60-0.86), respectively. Furthermore, we compared the detective power of the combined model: 2-miR + ly for discriminating non-responders to NAC, to other pretreatment clinical features. Consequently, 2-miR + ly model was superior to serum SCC antigen with great significance (P = 0.01) and to ly, and clinical T stage with marginal significance (P = 0.18, 0.07, respectively). CONCLUSIONS: Collectively, we demonstrated that the potential of a multi-miRNA biomarker for identifying NAC response in ESCC is realistic, and can be used in the clinic with the further validation.

Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer.

OBJECTIVE: To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). BACKGROUND: Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. METHODS: We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. RESULTS: Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. CONCLUSIONS: SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.

Clinical Impact of Neoadjuvant Therapy on Nutritional Status in Pancreatic Cancer.

BACKGROUND: The association between neoadjuvant therapy (NAT) and nutritional status in pancreatic cancer (PC) is unknown. OBJECTIVE: The aim of this study was to assess the impact of NAT on nutritional status. METHODS: Overall, 161 patients who underwent pancreatoduodenectomy for PC between August 2010 and March 2017 were enrolled and were divided into two groups: the neoadjuvant group (NAG; n = 67) and the control group (CG; n = 94). Based on relative dose intensity (RDI), patients in the NAG group were further divided into RDI ≥ 80% (n = 39) and RDI < 80% (n = 19). Changes in nutritional index, inflammatory index, and inflammation-based prognostic scores during NAT and the perioperative period were assessed. RESULTS: Retinol-binding protein, prealbumin, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutrition index significantly worsened in the NAG after NAT (p = 0.007, p = 0.03, p = 0.04, p = 0.007, and p = 0.004, respectively). The recovery of rapid turnover proteins after postoperative day 5 was significantly worse in the NAG compared with the CG (p < 0.05), but tended to be more prompt in the RDI ≥ 80% group among the NAG. There was no significant difference in the incidence of postoperative complications, length of hospital stay, and time to postoperative adjuvant therapy between the NAG and the CG. CONCLUSIONS: NAT for PC could aggravate nutritional status and hamper its postoperative recovery. Furthermore, malnutrition might decrease tolerance of NAT. These findings suggest the importance of nutritional support for patients with NAT in PC.

FAM46C Serves as a Predictor of Hepatic Recurrence in Patients with Resectable Gastric Cancer.

BACKGROUND: Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy. METHODS: A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome. RESULTS: Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence. CONCLUSIONS: Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.

Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer.

BACKGROUND: Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). METHODS: Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. RESULTS: Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). CONCLUSIONS: The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma.

BACKGROUND: Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker. METHODS: We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection. RESULTS: GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences. CONCLUSIONS: Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.

Usefulness of preoperative estimated glomerular filtration rate to predict complications after curative gastrectomy in patients with clinical T2-4 gastric cancer.

BACKGROUND: Gastrectomy with systemic lymphadenectomy is the standard of care for resectable gastric cancer (GC), but it is sometimes associated with postoperative morbidity. Predicting complications is therefore an essential part of risk management in clinical practice. The renal function is routinely evaluated before surgery by blood examinations to determine dose of medication and infusion. However, the value of various parameters of renal function in prediction of postoperative complications remain unclear. METHODS: We included 315 patients who underwent curative D2 gastrectomy for clinical T2-T4 GC without preoperative treatment, and evaluated the correlation between the incidence of postoperative complications and the indicators of renal function. RESULTS: Forty-three patients experienced clinically relevant postoperative complications. Estimated glomerular filtration rate (eGFR) showed a higher area under the curve for predicting complications compared with urea nitrogen, creatinine, and creatinine clearance. The optimal eGFR cutoff value was 63.2 ml/min/1.73 m2, and eGFR < 63.2 was an independent risk factor for postoperative complications in multivariable analysis (odds ratio 4.67; 95 % confidence interval 2.16-10.5; p < 0.001). Particularly, the incidence of anastomotic leakage was significantly higher in patients with eGFR < 63.2 than those with eGFR ≥ 63.2 (9.4 % vs. 3.5 %). eGFR < 63.2 was also associated with a higher incidence of postoperative complications independent of age, body mass index, operative procedure, and clinical disease stage. Postoperative hospital stay was significantly longer in the eGFR < 63.2 group. CONCLUSIONS: Preoperative eGFR is a simple and useful predictor for complications after gastrectomy in patients with GC and may improve clinical care and the process of obtaining informed consent.

Epigenetic suppression of the immunoregulator MZB1 is associated with the malignant phenotype of gastric cancer.

Prediction of tumor recurrence after curative resection is critical for determining the prognosis of patients with gastric cancer (GC). The initiation and progression of GC are associated with inappropriate immune responses caused by chronic inflammation of the gastric mucosa. To identify immunoregulatory molecules involved in GC progression, GC cell lines and 200 pairs of tumor and normal tissues from patients with GC were analyzed for gene expression, amplification and methylation as well as function of a differentially expressed gene. The transcriptome analysis revealed that marginal zone B and B1 cell specific protein (MZB1) was expressed at significantly decreased levels in primary GC tissues when compared with the corresponding normal gastric mucosa. PCR array analysis exploring genes expressed cooperatively with MZB1 revealed that differential expression of MZB1 mRNA in GC cell lines correlated positively with the levels of the mRNAs encoding estrogen receptor 1 and desumoylating isopeptidase 1. Hypermethylation of the MZB1 promoter was frequent in cell lines with decreased levels of MZB1 mRNA. siRNA-mediated knockdown of MZB1 significantly increased proliferation, invasion and migration of GC cell lines. Low MZB1 expression was an independent prognostic factor for recurrence after curative gastrectomy and was associated significantly with increased hematogenous recurrence. MZB1 acts as a suppressor of GC. Low MZB1 expression in the primary GC tissue is predictive of recurrence after curative resection.

The Prognostic Relevance of Subcarinal Lymph Node Dissection in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The objective of this study was to evaluate the prognostic relevance of subcarinal lymph node dissection in patients with esophageal squamous cell carcinoma (ESCC) and to identify a subset of patients in whom subcarinal lymph node dissection can be omitted. METHODS: We retrospectively analyzed 342 consecutive patients with thoracic ESCC who underwent R0 subtotal esophagectomy. All patients underwent subcarinal lymph node dissection. The efficacy index (frequency of metastasis to a particular lymph node station multiplied by the 5-year disease-specific survival rate of patients with metastasis to the station) was calculated for the subcarinal lymph node station, and the prognostic impact of dissecting this station was estimated with reference to the main tumor location. Independent predictive factors for pathological subcarinal lymph node metastasis were analyzed using a proportional hazards model. RESULTS: The overall frequency of metastasis to the subcarinal lymph nodes was 7.0 % (2.4, 8.9, and 5.8 % in patients with upper, middle, and lower thoracic ESCC, respectively). The efficacy index for the middle thoracic esophagus was 2.9, and that for the upper and lower thoracic esophagus was 0.0. The 5-year disease-free survival rate was significantly lower in patients with pathological subcarinal lymph node metastasis than those without (23.1 vs. 67.5 %, respectively; log-rank p < 0.0001). In multivariate analysis, clinical T stage (T2-T4) was the independent predictive factor for pathological subcarinal lymph node metastasis (p = 0.021). CONCLUSIONS: Subcarinal lymph node dissection might have little value in patients with upper and lower thoracic ESCC and could be omitted, especially for superficial carcinoma.

Tumor Infiltrative Pattern Predicts Sites of Recurrence After Curative Gastrectomy for Stages 2 and 3 Gastric Cancer.

BACKGROUND: In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. METHODS: The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. RESULTS: Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. CONCLUSIONS: Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC.

Short-term outcomes after conventional transthoracic esophagectomy.

In our department, we have attempted to reduce the incidence of complications of conventional esophagectomy. The objective of this retrospective study was to report the short-term outcomes of esophagectomy. We reviewed 138 consecutive patients who had undergone subtotal esophagectomy by combined laparotomy via a 12-cm upper abdominal vertical incision combined with right anterior muscle-sparing thoracotomy from August 2010 to August 2014. Most of the cervical para-esophageal lymph node dissection was completed within the thoracic cavity. We performed three-field dissection in patients with tumors in the upper or middle third of the esophagus with clinical lymph node metastases in the superior mediastinum; the others underwent two-field dissection. We performed neck anastomoses in patients undergoing three-field dissection and thoracic anastomoses in those undergoing two-field dissection. Effective postoperative pain management was achieved with a combination of epidural anesthesia and paravertebral block. Postoperative rehabilitation was instituted for early ambulation and recovery. Enteral nutrition via a duodenal feeding tube was administered from postoperative day 2. Median hospital stay after surgery was 15 days (range, 10-129). Rates for both 30-day and in-hospital mortality were 0%. Morbidity rate for all Clavien-Dindo grades was 41.3%, whereas the morbidity rate for Clavien-Dindo grades III and IV was 7.2%. Anastomotic leakage developed in two patients (1.4%), recurrent laryngeal nerve palsy in 11 (8.0%), and pneumonia in nine (6.5%). Good short-term outcomes, especially regarding anastomotic leaks, were achieved by consistent improvements in surgical techniques, optimization of several operative procedures, and appropriate perioperative management.

Method of bilateral pleural drainage by single Blake drain after esophagectomy.

BACKGROUND: Clinicians often encounter left pleural effusion after esophagectomy, which sometimes necessitates thoracentesis. We have introduced a new drainage method, bilateral pleural drainage by single Blake drain (BDSD), which we have been using since April 2013. This study aims to evaluate the performance of the BDSD. METHODS: The BDSD method employs a 15-F Blake drain inserted from the right thoracic cavity to the left thoracic cavity across the posterior mediastinum. The conventional drain (CD) group consisted of 50 patients with a 19-F Blake drain placed in the right thoracic cavity during the period from April 2012 to March 2013. The BDSD group consisted of 54 patients treated from April 2013 to June 2014. RESULTS: The amount of total drainage in the BDSD group was significantly higher than that in the CD group (P < 0.0001). The rates of left pleural effusion and left lower lobe atelectasis in the BDSD group were significantly lower than those in the CD group (P < 0.0001 and P < 0.0001, respectively). No patients developed a left pleural effusion necessitating thoracentesis drainage in the BDSD group. CONCLUSIONS: Compared with the conventional method, BDSD was able to evacuate bilateral pleural effusion more effectively, and the incidences of left pleural effusion and left atelectasis were lower. This method is therefore clinically useful after esophagectomy.

Feeding duodenostomy decreases the incidence of mechanical obstruction after radical esophageal cancer surgery.

BACKGROUND: Nutritional support influences the outcome of gastroenterological surgery, and enteral nutrition effectively mitigates postoperative complications in highly invasive surgery such as resection of esophageal cancer. However, feeding via jejunostomy can cause complications including mechanical obstruction, which could be life threatening. From 2009, we began enteral feeding via duodenostomy to reduce the likelihood of complications. In this study, we compared duodenostomy with the conventional jejunostomy feeding, mainly looking at the catheter-related complications. METHODS: The database records of 378 patients with esophageal cancer who underwent radical esophagectomy with retrosternal or posterior mediastinal gastric tube reconstruction in our department from January 1998 to December 2012 were examined. Of the 378 patients, 111 underwent feeding via duodenostomy (FD) and 267 underwent feeding via jejunostomy (FJ), and their records were reviewed for the following catheter-related complications: site infection, dislodgement, peritonitis, and mechanical obstruction. RESULTS: Mechanical obstruction occurred in 12 patients in the FJ group but none in the FD group (4.5 % vs. 0 %, P = 0.023). Of the 12 cases, 7 (58.3 %) required surgery of which 2 had bowel resection due to strangulated mechanical obstruction. Catheter site infection was seen in 14 cases in the FJ group, of which 2 (14.2 %) had peritonitis following catheter dislocation, while only one case of site infection was seen in the FD group (5.2 % vs. 0.9 %, P = 0.078). CONCLUSIONS: Feeding via duodenectomy could be the procedure of choice since neither mechanical obstruction nor relaparotomy was seen during enteral feeding through this technique.

Epithelial to mesenchymal transition correlates with tumor budding and predicts prognosis in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Epithelial to mesenchymal transition (EMT) is considered to play an important role in cancer invasion. Tumor budding is a prognostic factor in esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore the correlation between EMT and tumor budding. METHODS: Surgical specimens from 78 cases of ESCC resected without preoperative treatment between 2001 and 2013 were enrolled in the study. The mRNA expressions of E-cadherin and vimentin were measured in cancerous tissues using real-time PCR, and each tumor was classified into either epithelial or mesenchymal group. Tumor budding was evaluated in H&E-stained slides and divided into two groups; low-grade budding (<3) and high-grade budding (≥3). RESULTS: The 5-year survival rate in the epithelial group was significantly higher than that in the mesenchymal group (62.0% vs. 31.5%, P = 0.021). Survival rate of patients in the low-grade budding group was significantly higher than that of patients in the high-grade budding group (75.1% vs. 25.9%, P < 0.001). High-grade tumor budding was significantly associated with the mesenchymal group (P = 0.009). CONCLUSION: EMT was found to occur in ESCC and was significantly associated with tumor budding. Tumor budding was identified as a significant independent prognostic factor among the current population of ESCC.

Effect of landiolol hydrochloride on tachyarrhythmia after esophagectomy.

BACKGROUND/AIMS: The objective of this study was to evaluate the efficacy and safety of landiolol hydrochloride, a newly developed ultra-short-acting ß1-selective blocker, for postoperative tachyarrhythmia after esophagectomy. METHODOLOGY: In total 231 patients underwent transthoracic esophagectomy at the Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine from 2007 to 2012. Twenty-four patients who were treated with either landiolol hydrochloride (n = 11) or conventional agents (combination of calcium channel blocker and digitalis preparation; control group, n = 13) for postoperative tachyarrhythmia after transthoracic esophagectomy were retrospectively analyzed. Tachyarrhythmia was defined as a heart rate of >120 bpm or atrial fibrillation. Hemodynamic changes, conversion rates, and adverse events were evaluated. RESULTS: The reduction in the heart rate at 1 h after medication was seen significantly more frequent in the landiolol group than in the control group. The time to conversion to sinus rhythm was also significantly shorter in the landiolol group. There were no significant differences between the two groups in blood pressure either before or after the medication. One patient in the landiolol group showed hypotension and bradycardia, without serious consequences. CONCLUSIONS: Landiolol hydrochloride can be effectively and safely used in patients who develop tachyarrhythmia after esophagectomy.

No-touch isolation technique in emergency pancreaticoduodenectomy for neoplastic hemorrhage: Two case reports and review of literature.

BACKGROUND: Emergency pancreaticoduodenectomy (EPD) is a rare event for complex periampullary etiology. Increased intraoperative blood loss is correlated with poor postoperative outcomes. CASE SUMMARY: Two patients underwent EPD using a no-touch isolation technique, in which all arteries supplying the pancreatic head region were ligated and divided before manipulation of the pancreatic head and duodenum. The operative times were 220 and 239 min, and the blood loss was 70 and 270 g, respectively. The patients were discharged on the 14th and 10th postoperative day, respectively. Thirty-two patients underwent EPD for the treatment of neoplastic bleeding. The mean operative time was 361.6 min, and the mean blood loss was 747.3 g. The complication rate was 37.5%. The in-hospital mortality rate was 9.38%. CONCLUSION: The no-touch isolation technique is feasible, safe, and effective for reducing intraoperative blood loss in EPD.

Perioperative and prognostic implication of albumin-bilirubin-TNM score in Child-Pugh class A hepatocellular carcinoma.

BACKGROUND AND AIM: A reliable classification for predicting postoperative prognosis and perioperative risk of hepatocellular carcinoma (HCC) patients is required to make a precise decision for HCC treatment. In the present study, we assessed the perioperative and prognostic importance of indocyanine green (ICG) testing, tumor-node-metastasis (TNM) stage, albumin-bilirubin (ALBI) grade, and ALBI-TNM (ALBI-T) score using consecutive resected HCC cases. METHODS: Between 1998 and 2011, 273 consecutive patients who underwent primary and curative hepatectomy for HCC were identified. Among these 273 cases, 235 Child-Pugh class A patients were enrolled in the present study. RESULTS: Correlation analysis showed that the value of linear predictor for ALBI grade was significantly correlated with ICG 15-minute retention rates (r = 0.51, P < 0.0001). Survival analysis for both recurrence-free survival (RFS) and overall survival (OS) showed there were significant differences between the two groups stratified by stage or ALBI-T score (stage, RFS: P = 0.01, OS: P = 0.003; ALBI-T, RFS: P < 0.0001, OS: P < 0.0001). In addition, Cox proportional hazard model identified ALBI-T score was a significant predictor for both RFS and OS (RFS, P = 0.001; OS, P = 0.004). Furthermore, ALBI-T score could predict perioperative risk in hepatectomy such as longer operation time and excessive intraoperative blood loss. CONCLUSIONS: This study showed a robust association of ALBI-T score with postoperative HCC patient survival and perioperative risk in hepatectomy. ALBI-T score can be used as a simple and powerful tool for assessing HCC patients with further study.

Phase II study of chemoradiotherapy combined with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic ductal adenocarcinoma (NUPAT 05 Trial): study protocol for a single arm phase II study.

The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.