A sutureless overlapped anastomosis technique using linear staplers with reinforced bioabsorbable material in robotic right colectomy with intracorporeal anastomosis.

AIM: Creation of an overlapped anastomosis using handsewn sutures for common enterotomy is very popular in robotic right colectomy (RRC) with intracorpareal anastomosis (IA). The aim of this study is to present a simple method for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in RRC with IA. METHOD: The distal ileum and proximal colon were put in overlapping positions. Enterotomies were created 2 cm proximal to the ileal stump and 8 cm distal to the colonic stump on the antimesenteric side. Subsequently, a 60 mm linear stapler with a reinforced bioabsorbable material was inserted into each lumen and fired. Finally, the bowel was elevated while holding the bioabsorbable material, and the common enterotomy was grasped with the robotic instrument in the middle and closed using a linear stapler with a reinforced bioabsorbable material. RESULTS: This technique was applied to 10 patients with tumours of the caecum, ascending colon, or transverse colon. The median operating time, anastomosis construction time, blood loss, and postoperative stay were 281 min (range 228-459 min), 12 min (range 11-17 min), 10 mL (range 0-110 mL), and 10 days (range 8-15 days), respectively. No adverse intraoperative events were observed. Postoperatively, one patient developed chylous ascites, but there were no other complications. CONCLUSION: The simple technique for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in robotic right colectomy with intracorporeal anastomosis appears to be safe and feasible.

The 1-year outcomes after pancreaticogastrostomy using vertical versus horizontal mattress suturing for gastric wrapping.

PURPOSE: To investigate the differences in nutritional status 1 year after pancreaticogastrostomy (PG) using vertical suturing (VS) vs. twin square horizontal mattress (HMS) suturing in patients undergoing pancreaticoduodenectomy (PD). METHODS: The subjects of this study were 134 patients who underwent PD, followed by PG, which was closed by VS in 52 and by HMS in 82. We evaluated the peri- and postoperative factors, nutritional parameters, diameter of the remnant main pancreatic duct, and glucose intolerance 1 year postoperatively. RESULTS: Forty-five (87%) patients from the VS group and 75 (91%) patients from the HMS group survived for more than 1 year. The incidences of intraabdominal abscess and pancreatic fistula were significantly lower in the HMS group than in the VS group (19.2% vs. 6.6% and19.2% vs. 2.6%, respectively). There were no significant changes in the total protein, serum albumin, and HbA1c levels 1 year postoperatively. The postoperative expansion ratio of the main pancreatic duct diameter was significantly smaller in the HMS group than in the VS group. The strongest risk factor for body weight loss 1 year postoperatively was a non-soft pancreas texture. CONCLUSION: HMS was superior to VS for preventing early postoperative complications and did not affect pancreatic function.

[A Case of an Elderly Frail Patient with Unresectable Colorectal Cancer Controlled by Trifluridine/Tipiracil with Bevacizumab Therapy as a First-Line Treatment].

Although the effectiveness of trifluridine/tipiracil(TFTD)with bevacizumab for unresectable colorectal cancer that was refractory to previous standard chemotherapy was reported, its effectiveness as a first-line treatment, especially for elderly frail patients, is unclear. An 85-year-old woman complaining of anorexia was diagnosed with unresectable sigmoid colon cancer with multiple metastases. Her general status was very poor, and her performance status(PS)was 4. We first performed laparoscopic transverse colostomy. As her general status gradually improved, we administered TFTD with bevacizumab as a first-line treatment based on the patient's strong request for chemotherapy. The patient underwent this regimen in the outpatient clinic for 9 months(9 courses). Although the size of the liver metastases increased, lung metastases and abdominal disseminations were under control and her PS became 0. She has been taking mFOLFOX6 with bevacizumab (80%)as a second-line treatment. TFTD with bevacizumab treatment was safe and efficacious as a first-line treatment for a frail elderly patient with unresectable colorectal cancer.

Regulation of aberrantly expressed SERPINH1 by antitumor miR-148a-5p inhibits cancer cell aggressiveness in gastric cancer.

RNA-sequencing-based microRNA (miRNA) expression signatures have revealed that miR-148a-5p (the passenger strand of the miR-148a-duplex) is downregulated in various kinds of cancer tissues. Analysis of The Cancer Genome Atlas (TCGA) database showed that low expression of miR-148a-5p was predictive of a lower survival rate (p = 0.041) in patients with gastric cancer (GC). Downregulation of miR-148a-5p was confirmed in GC clinical specimens, and its ectopic expression attenuated GC cell proliferation. Our search for miRNA target genes identified a total of 18 oncogenic targets of miR-148a-5p in GC cells. Among these targets, high expression levels of six genes (THBS2, P4HA3, SERPINH1, CDH11, BCAT1, and KCNG3) were closely associated with a poor prognosis (10-year survival rates) in GC patients (p < 0.05) according to TCGA database analyses. Furthermore, we focused on SERPINH1 as a chaperone protein involved in collagen folding in humans. Aberrant expression of SERPINH1 (mRNA and protein levels) was confirmed in GC clinical specimens. Knockdown assays of SERPINH1 using siRNAs resulted in inhibition of the aggressive phenotype of GC cells. Exploring the molecular networks controlled by miRNAs (including miRNA passenger strands) will broaden our understanding of the molecular pathogenesis of GC.

RNA sequencing-based microRNA expression signature in esophageal squamous cell carcinoma: oncogenic targets by antitumor miR-143-5p and miR-143-3p regulation.

Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs were candidates for antitumor miRNAs in ESCC cells. Analysis of the signature revealed that several passenger strands of miRNAs were significantly downregulated in ESCC, e.g., miR-28-3p, miR-30a-3p, miR-30c-3p, miR-133a-3p, miR-139-3p, miR-143-5p, and miR-145-3p. Recent studies indicate that some passenger strands of miRNAs closely involved in cancer pathogenesis. In this study, we focused on both strands of pre-miR-143, and investigated their antitumor roles and target oncogenes in ESCC. Ectopic expression of miR-143-5p and miR-143-3p significantly attenuated malignant phenotypes (e.g., proliferation, migration, and invasive abilities) in ESCC cell lines. We revealed that six genes (HN1, HMGA2, NETO2, STMN1, TCF3, and MET) were putative targets of miR-143-5p regulation, and one gene (KRT80) was a putative target of miR-143-3p regulation in ESCC cells. Our ESCC miRNA signature and analysis strategy provided important insights into the molecular pathogenesis of ESCC.

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer.

OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.

Visual enhancement pattern during the delayed phase of enhanced CT as an independent prognostic factor in stage IV pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has substantial heterogeneity in biophysical features and in outcomes of patients. Identifying reliable pretreatment imaging biomarkers for PDAC with distant metastases (stage IV) is a key imperative. Our objective was to determine whether visual tumor enhancement pattern on enhanced computed tomography (CT) can be used as a prognostic factor in stage IV PDAC treated with chemotherapy. METHODS: This is a retrospective cohort study of 133 patients with stage IV PDAC who underwent multiphasic enhanced CT before systemic chemotherapy. The enhancement pattern of PDAC was qualitatively categorized as hypoattenuation, isoattenuation, or hyperattenuation on each of the pancreatic, portal venous, and delayed phases. The effects of clinical prognostic factors and the visual tumor enhancement pattern on progression-free survival (PFS) and overall survival (OS) were assessed in univariate and multivariate analyses using Cox proportional hazards models. RESULTS: On univariate analysis, the number of metastatic organs and the visual tumor enhancement pattern during the delayed phase were significantly associated with PFS (p = 0.003 and < 0.001, respectively) and OS (p = 0.005 and < 0.001, respectively). Multivariate analysis identified the number of metastatic organs (PFS, p = 0.021; OS, p = 0.041) and visual tumor enhancement pattern during the delayed phase (PFS, p < 0.001; OS, p < 0.001) as independent predictors of PFS and OS. CONCLUSION: Visual enhancement pattern of PDAC on delayed phase enhanced CT appears to be associated with outcomes and could be a useful prognostic factor in stage IV PDAC, despite the need to add the delayed phase to CT protocol for pancreatic disease.

Lung recurrence and its therapeutic strategy in patients with pancreatic cancer.

BACKGROUND: /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion. METHODS: We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A. RESULTS: The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUVmax of the primary pancreatic tumor. CONCLUSIONS: Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUVmax of the primary pancreatic tumor.

Extracellular volume fraction determined by equilibrium contrast-enhanced dual-energy CT as a prognostic factor in patients with stage IV pancreatic ductal adenocarcinoma.

OBJECTIVES: To evaluate the feasibility of equilibrium contrast-enhanced dual-energy CT (DECT), as compared with single-energy CT (SECT) and to calculate extracellular volume (ECV) fraction to predict the survival outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with distant metastases (stage IV) treated with chemotherapy. METHODS: The study cohort included a total of 66 patients with stage IV PDAC who underwent DECT before systemic chemotherapy between July 2014 and March 2017. Unenhanced and 120-kVp equivalent images during the equilibrium phase were used to calculate tumor SECT-derived ECV fractions, and iodine density images were obtained from equilibrium-phase DECT for DECT-derived ECV fractions. Correlations between SECT- and DECT-derived ECV fractions were identified using the Pearson correlation coefficient and Bland-Altman analysis. The effects of clinical prognostic factors and tumor SECT- and DECT-derived ECV fractions on progression-free survival (PFS) and overall survival (OS) were assessed by univariate and multivariate analyses using Cox proportional hazards models. RESULTS: The correlation between SECT- and DECT-derived ECV fractions was strong (r = 0.965; p < 0.001). The Bland-Altman plot between SECT- and DECT-derived ECV fractions showed a small bias (- 3.4%). Increasing tumor SECT- and DECT-derived ECV fractions were associated with a positive effect on PFS (SECT, p = 0.002; DECT, p = 0.007) and OS (DECT, p = 0.014; DECT, p = 0.015). Only tumor DECT-derived ECV fraction was an independent predictor of PFS (p = 0.018) and OS (p = 0.022) in patients with stage IV PDAC treated with chemotherapy on multivariate analysis. CONCLUSIONS: The ECV fraction determined by equilibrium contrast-enhanced DECT can potentially predict the survival of patients with stage IV PDAC treated with chemotherapy. KEY POINTS: • Extracellular volume fraction of stage IV pancreatic ductal adenocarcinoma determined by dual-energy CT was strongly correlated to that with single-energy CT (r = 0.965, p < 0.001). • Tumor extracellular volume fraction was an independent predictor of progression-free survival (p = 0.018) and overall survival (p = 0.022). • Extracellular volume fraction determined by dual-energy CT could be a useful imaging biomarker to predict the survival of patients with stage IV pancreatic ductal adenocarcinoma treated with chemotherapy.

Evaluation of postoperative quality of life by PGSAS-45 following local gastrectomy based on the sentinel lymph node concept in early gastric cancer.

BACKGROUND: The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. METHODS: We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) (n = 44) and laparoscopic local resection (LLR) (n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. RESULTS: In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months (P = 0.006) and esophageal reflux and residual gastritis at 12 months (P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months (P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months (P = 0.041 and P = 0.007, respectively). CONCLUSIONS: CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.

Upgraded bidirectional approach video-assisted neck surgery (BAVANS) using a rigid endoscope with variable viewing direction for advanced endoscopic lymph node dissection in thyroid cancer patients.

In 2011, we developed bidirectional approach video-assisted neck surgery (BAVANS) for endoscopic thyroid cancer surgery. BAVANS combines two different approach pathways at 180 degrees to the cervical lesion for endoscopic thyroidectomy and complete cervical lymphadenectomy. We reported previously that the cranio-caudal approach is extremely useful for endoscopic complete lymph node dissection around the trachea. In 2014, we upgraded the initial BAVANS for better maneuverability and quality of lymph node dissection. A new high-tech rigid endoscope with a variable viewing direction (EndoCAMeleon™), has enabled us to reduce the camera port in the anterior neck while keeping the easy maneuverability and the same quality of central lymph node dissection (LND) as with the initial BAVANS. Endoscopic thyroid cancer surgery is now evolving concurrently with new visual technology.

[A Case of Colon Cancer with Tumor Embolism in the Superior Mesenteric Vein Disappearing after Chemotherapy].

A woman in her 50s received a detailed examination for her abdominal pain. CT indicated intestinal wall thickening of the ascending colon, lymphadenopathy, and tumor embolism in the superior mesenteric vein. Colonoscopy revealed type 2 tumor in the hepatic flexure of the colon, and she was diagnosed as having moderately differentiated adenocarcinoma by biopsy specimen. She received 12 courses of FOLFOXIRI plus BV therapy after ileostomy. As the tumor embolism disappeared and the primary lesion shrank after chemotherapy, right hemicolectomy and lymph node dissection were performed. Six months after surgery, she has had no recurrent disease. This case suggests that FOLFOXIRI plus BV therapy could be an effective treatment for right colon cancer with tumor embolism.

Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8.

Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) were significantly downregulated in cancer tissues. Our functional assays revealed that miR-130b-5p significantly blocked the malignant abilities of PDAC cell lines (PANC-1 and SW1990), e.g., cancer cell proliferation, migration, and invasion. A total of 103 genes were identified as possible oncogenic targets by miR-130b-5p regulation in PDAC cells based on genome-wide gene expression analysis and in silico database search. Among the possible targets, high expression of 9 genes (EPS8, ZWINT, SMC4, LDHA, GJB2, ZCCHC24, TOP2A, ANLN, and ADCY3) predicted a significantly poorer prognosis of PDAC patients (5-year overall survival, p < 0.001). Furthermore, we focused on EPS8 because its expression had the greatest impact on patient prognosis (overall survival, p < 0.0001). Overexpression of EPS8 was detected in PDAC clinical specimens. Knockdown assays with siEPS8 showed that its overexpression enhanced cancer cell proliferation, migration, and invasion. Analysis of downstream RNA networks regulated by EPS8 indicated that MET, HMGA2, FERMT1, RARRES3, PTK2, MAD2L1, and FLI1 were closely involved in PDAC pathogenesis. Genes regulated by antitumor miR-130b-5p were closely involved in PDAC molecular pathogenesis. Our approach, discovery of antitumor miRNAs and their target RNAs, will contribute to exploring the causes of this malignant disease.

Significance of 18F-Fluorodeoxyglucose (FDG) Uptake in Response to Chemoradiotherapy for Pancreatic Cancer.

BACKGROUND: A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). METHODS: Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. RESULTS: Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUVmax) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUVmax was independently associated with tumor response rate on multivariate analysis. In the low SUVmax group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUVmax group. CONCLUSIONS: FDG-PET SUVmax was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUVmax tumor.

Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses. However, the clinical significance of the combination of these markers is unclear. This study aimed to investigate the NLR and PLR in patients with advanced gastric cancer treated with chemotherapy and assess the clinical utility of a new blood score combining the NLR and PLR (NLR-PLR score) as a predictor of tumor response and prognosis. METHODS: We retrospectively analyzed 175 patients with gastric cancer receiving chemotherapy or chemoradiotherapy. These patients were categorized into progressive disease (PD) and non-PD groups according to tumor response. The NLR and PLR before treatment were examined, and the cut-off values were determined. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (> 2.461) and high PLR (> 248.4); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. RESULTS: With regard to tumor response, 64 and 111 patients had PD and non-PD, respectively. The NLR-PLR score was significantly higher in patients with PD than in those with non-PD (p = 0.0009). The prognosis was significantly poorer in patients with a higher NLR-PLR score than in those with a lower NLR-PLR score (p <  0.0001). Multivariate analysis demonstrated that the NLR-PLR score was an independent prognostic factor for prediction of overall survival (p = 0.0392). CONCLUSION: Low-cost stratification according to the NLR-PLR score might be a promising approach for predicting tumor response and prognosis in patients with advanced gastric cancer.

Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy.

OBJECTIVES: To assess whether extracellular volume (ECV) fraction with equilibrium contrast-enhanced multidetector computed tomography (MDCT) predicts outcomes for unresectable pancreatic adenocarcinoma patients treated with chemotherapy METHODS: Sixty-seven patients (42 men, 25 women; mean age, 67.5 years; range, 45-83 years) with histologically confirmed surgically unresectable pancreatic adenocarcinoma underwent contrast-enhanced MDCT before systemic chemotherapy. Tumour contrast enhancement (CE) and ECV fraction were calculated using region-of-interest measurement within the pancreatic adenocarcinoma and aorta on unenhanced and equilibrium phase-enhanced CT. The effect on survival variables including age, sex, tumour location, tumour size, TNM stage, carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), tumour CE and tumour ECV fraction was determined on univariate and multivariate analyses using Cox proportional hazards regression model. RESULTS: Median overall survival was 10.5 months. On univariate analysis, elevated serum CA19-9 (hazard ratio (HR), 1.00; p = 0.006) and CEA (HR, 1.02; p = 0.011) levels were found to be associated with a negative effect on overall survival. Increasing tumour CE (HR, 0.98; p < 0.001) and ECV fraction (HR, 0.97; p = 0.001) were associated with a positive effect. Multivariate analysis revealed that only tumour ECV fraction was an independent predictor of overall survival (HR, 0.97; p = 0.012). CONCLUSIONS: ECV fraction with equilibrium contrast-enhanced MDCT could be a useful imaging biomarker for predicting patient survival after chemotherapy for unresectable pancreatic adenocarcinoma. KEY POINTS: • Tumour aggressiveness and response to therapy are influenced by the extravascular extracellular space. • Extracellular volume (ECV) fraction can be quantified with equilibrium contrast-enhanced CT. • Patients with higher tumour ECV fraction had better prognosis after chemotherapy.

Radial incision and cutting method using a transanal approach for treatment of anastomotic strictures following rectal cancer surgery: a case report.

BACKGROUND: Development of an anastomotic stricture following rectal cancer surgery is not uncommon. Such strictures are usually managed by manual or instrumental dilatation techniques that are often insufficiently effective, as evidenced by the high recurrence rate. Various surgical procedures using minimally invasive approaches have also been reported. One of these procedures, endoscopic radial incision and cutting (RIC), has been extensively reported. However, RIC by transanal minimally invasive surgery (TAMIS) is yet to be reported. We here report a novel application of TAMIS for performing RIC for anastomotic rectal stenosis. CASE PRESENTATION: A 67-year-old man had suffered from constipation for 6 years after undergoing low anterior resection for stage II rectal cancer 7 years ago. Colonoscopy showed a 1-cm diameter stricture in the lower rectum. Balloon dilatation was performed many times because of repeated recurrences. Thus, surgical management was considered and the stricture was successfully excised via a RIC method using a TAMIS approach. Postoperatively, the patient had minimal leakage that resolved with conservative treatment. CONCLUSIONS: A RIC method using a TAMIS approach is an effective minimally invasive means of managing anastomotic strictures following rectal cancer surgery.

Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer.

Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer.

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation.

We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre-miR-148a (miR-148a-5p: the passenger strand and miR-148a-3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR-148a-5p and miR-148a-3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre-miR-148a had tumor-suppressive roles in PDAC cells. In silico database and genome-wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR-148a-5p targets (PHLDA2, LPCAT2 and AP1S3) and miR-148a-3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre-miR-148a (miR-148-5p) is a new concept in cancer research. Novel approaches that identify tumor-suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.

Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3.

Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.