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A parahiatal hernia (PH) is a rare diaphragmatic hernia (DH) adjacent to but separated from the esophageal hiatus. The surgical repair for PH needs primary suture closure or complicated hernioplasty and the addition of an anti-reflux procedure. This report describes a case of PH with a symptomatic esophageal hiatal hernia managed using three-dimensional (3D) laparoscopy. A 65-year-old woman with back pain and breathlessness was referred to our hospital for a DH. Computed tomography showed a diaphragmatic defect on the left side of the esophageal hiatus. Upper gastrointestinal endoscopy and 24-hour esophageal impedance-pH monitoring showed a symptomatic esophageal hiatal hernia. Laparoscopic repair for both hernias was performed using 3D laparoscopy. The DH orifice was located in the left crus of the diaphragm, and it was separated from the esophageal hiatus. These findings showed that this DH was a PH. The PH was repaired with primary suturing, and a hiatoplasty was performed. Toupet fundoplication was performed with a 270° posterior wrap of the gastric fornix. The patient has remained asymptomatic a year after surgery without any complications. 3D laparoscopy provides significant advantages in surgeries requiring precise suturing. PH repairs require complex procedures, including mesh repair or suturing. Approximately 44 % of PH cases also necessitate fundoplication. 3D laparoscopy was useful for the present case. A rare PH and a symptomatic type 1 hiatal hernia were repaired with 3D laparoscopy, which is helpful for PH treatment in cases requiring complicated procedures. • A parahiatal hernia is a diaphragmatic hernia adjacent to but separated from the esophageal hiatus. • Parahiatal hernias need to be repaired with primary suture closure or complicated hernioplasty using a mesh and adding an anti-reflux procedure. • In 44% of past cases, anti-reflux surgery was performed in cases of symptomatic reflux or a complicated hiatal hernia with reflux. • 3D laparoscopy provides particular benefits for operation time in surgeries that included sutures. • A rare parahiatal hernia and a symptomatic type 1 hiatal hernia were repaired with 3D laparoscopy, which is helpful for PH treatment in cases requiring complicated procedures. [ABSTRACT FROM AUTHOR]

Background: Evaluation of the blood supply to gastric conduits is critically important to avoid complications after esophagectomy. We began visual evaluation of blood flow using indocyanine green (ICG) fluorescent imaging in July 2015, to reduce reconstructive complications. In this study, we aimed to statistically verify the efficacy of blood flow evaluation using our simplified ICG method.Study Design: A total of 285 consecutive patients who underwent esophagectomy and gastric conduit reconstruction were reviewed and divided into 2 groups: before and after introduction of ICG evaluation. The entire cohort and 68 patient pairs after propensity score matching (PS-M) were evaluated for clinical outcomes and the effect of visualized evaluation on reducing the risk of complication.Results: The leakage rate in the ICG group was significantly lower than in the non-ICG group for each severity grade, both in the entire cohort (285 subjects) and after PS-M; the rates of other major complications, including recurrent laryngeal nerve palsy and pneumonia, were not different. The duration of postoperative ICU stay was approximately 1 day shorter in the ICG group than in the non-ICG group in the entire cohort, and approximately 2 days shorter after PS-M. Visualized evaluation of blood flow with ICG methods significantly reduced the rate of anastomotic complications of all Clavien-Dindo (CD) grades. Odds ratios for ICG evaluation decreased with CD grade (0.3419 for CD ≥ 1; 0.241 for CD ≥ 2; and 0.2153 for CD ≥ 3).Conclusions: Objective evaluation of blood supply to the reconstructed conduit using ICG fluorescent imaging reduces the risk and degree of anastomotic complication. [ABSTRACT FROM AUTHOR]

Summary: Gastrointestinal stromal tumors often express gene mutations to c-KIT and platelet-derived growth factor receptor-α, both of which result in constitutive activations of their signaling pathways that are quite essential for the proliferation and survival of tumor cells in most clinical gastrointestinal stromal tumors. Targeting these molecules provides a dramatic improvement to therapeutic strategy. To identify a new therapeutic target for gastrointestinal stromal tumor treatment, we focused on focal adhesion kinase, which is reported to be an up-regulated gene in clinical gastrointestinal stromal tumors, because so far no one has examined its expression status at the protein level. In this study, Western blot analysis revealed that all 10 of the examined gastrointestinal stromal tumor tissues strongly expressed focal adhesion kinase protein and that phosphorylated focal adhesion kinase was detected in 9 of them. Next, we assessed the expression status of focal adhesion kinase and phosphorylated focal adhesion kinase in 51 cases of gastrointestinal stromal tumor by immunohistochemistry. Positive stainings for focal adhesion kinase and phosphorylated focal adhesion kinase were confirmed in 44 (86.3%) and in 40 cases (78.4%) of the 51 gastrointestinal stromal tumors, respectively. We further found that the focal adhesion kinase–positive staining rate became higher along with the increased status of malignant behavior. Moreover, when the 51 gastrointestinal stromal tumors were divided into 2 groups based upon their focal adhesion kinase expression status, the 5-year overall survival of patients in the focal adhesion kinase–positive group (66.5%) was significantly poorer than that in the focal adhesion kinase–negative group (100%). These results indicate that the up-regulation of focal adhesion kinase protein may also contribute to the tumor progression of gastrointestinal stromal tumors and that focal adhesion kinase is a potential target for gastrointestinal stromal tumor treatment. [Copyright &y& Elsevier]

Background & Aims: Esophageal squamous cell carcinoma (ESCC) is known to be a highly angiogenic tumor. Here, we investigated the role of the stromal fibroblasts in the ESCC-induced angiogenic response using a novel 3-dimensional model. Methods: A novel assay was developed where cocultures of ESCC and esophageal fibroblasts induced human microvascular endothelial cell (HMVEC) vascular network formation in a 3-dimensional collagen gel. Biochemical studies showed that the ESCC-induced activation of the fibroblasts was required to induce vascular network formation via a transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF)-dependent pathway. Results: Conditioned media from a panel of 4 ESCC lines transdifferentiated normal esophageal fibroblasts into myofibroblasts via TGF-β signaling. The presence of fibroblasts was essential for efficient HMVEC network formation, and the addition of ESCC cells to these cultures greatly enhanced the angiogenic process. The role of TGF-β in this process was shown by the complete inhibition of network formation following TGF-β inhibitor treatment. Finally, we showed that ESCC-derived TGF-β regulates angiogenesis through the release of VEGF from the fibroblasts and that the VEGF release was blocked following TGF-β inhibition. Conclusions: This study shows the essential role of fibroblasts in the ESCC angiogenic-induced response and suggests that the pharmacologic targeting of the TGF-β signaling axis could be of therapeutic benefit in this deadly disease. [Copyright &y& Elsevier]

OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor–mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments. A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Of the 13 patients, 7, 3 and 3 patients were treated with 1010, 1011 and 1012 virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53–91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8+ cells and increased PD-L1 expression. Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. [Display omitted] • Our study showed the tolerability of repeated endoscopic injection of OBP-301. • OBP-301 and radiotherapy sensitises each other with the bidirectional synergism. • The objective response rate is higher than that expected from radiotherapy alone. • This less invasive combination therapy is useful in patients with oesophageal cancer. • OBP-301 received a SAKIGAKE and an orphan drug designation for oesophageal cancer. [ABSTRACT FROM AUTHOR]

Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. However, its functional role in cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) and its clinical significance remains unclear. Herein, we systematically analyzed a large cohort of 627 colorectal cancer (CRC) specimens, and investigated the expression pattern of ADAR1 and its biological significance on the antizyme inhibitor 1 (AZIN1) RNA editing levels. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues vs. normal mucosa, and these findings correlated with the increased expression of mesenchymal markers, Vimentin (ρ = 0.44) and Fibroblast activation protein (ρ = 0.38). Intriguingly, ADAR1 expression was specifically upregulated in both cancer cells and fibroblasts from cancerous lesions. Conditioned medium from cancer cells led to induction of ADAR1 expression and activation of AZIN1 RNA editing in fibroblasts (p < 0.05). Additionally, edited AZIN1 enhanced the invasive potential of fibroblasts. In conclusion, we provide novel evidence that hyper-editing of AZIN1 enhances the invasive potential of CAFs within the TME in colon and is an important predictor of tumor invasiveness in CRC. [ABSTRACT FROM AUTHOR]