Cell-cell contact-dependent secretion of large-extracellular vesicles from EFNBhigh cancer cells accelerates peritoneal dissemination.

BACKGROUND: Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown. METHODS: Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1CreERT2-tdTnu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry. RESULTS: In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-ß1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events. CONCLUSIONS: EFNBhigh cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination.

FoxD1 expression identifies a distinct subset of hepatic stellate cells involved in liver fibrosis.

Hepatic stellate cells (HSCs) are pericytes of the liver responsible for liver fibrosis and cirrhosis, which are the end stages of chronic liver diseases. TGF-ß activates HSCs, leading to the differentiation of myofibroblasts in the process of liver fibrosis. While the heterogeneity of HSCs is appreciated in the fibrotic liver, it remains elusive which HSC subsets mainly contribute to fibrosis. Here, we show that the expression of the pericyte marker FoxD1 specifically marks a subset of HSCs in FoxD1-fate tracer mice. HSCs fate-mapped by FoxD1 were preferentially localized in the portal and peripheral areas of both the homeostatic and fibrotic liver induced by carbon tetrachloride. Furthermore, the deletion of Cbfß, which is necessary for TGF-ß signaling, in FoxD1-expressing cells ameliorated liver fibrosis. Thus, we identified an HSC subset that preferentially responds to liver injuries.

Investigation of operative outcomes of thoracoscopic esophagectomy after triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for advanced esophageal squamous cell carcinoma.

BACKGROUND: Preoperative chemotherapy with cisplatin and 5-fluorouracil (CF) has become the standard treatment for resectable stage II/III thoracic esophageal carcinoma in Japan. Recently, preoperative triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) has been reported to be effective for locally advanced esophageal cancer. Thoracoscopic esophagectomy (TE) has been increasingly accepted worldwide for the treatment of esophageal cancer. We conducted a retrospective study to evaluate the safety and outcomes of TE after DCF therapy for patients with advanced esophageal cancer. METHODS: The medical records of 63 consecutive patients with esophageal squamous cell carcinoma who underwent thoracoscopic surgery after chemotherapy were reviewed. Thirty-four patients received neoadjuvant chemotherapy with CF, and 29 received DCF as first-line chemotherapy. RESULTS: The clinical T stage was significantly higher in the DCF group than in the CF group (p < 0.0001), including 17 patients with T4. Lymph node metastasis was more frequent in the DCF group (p = 0.0005), and the clinical stage of the tumor was significantly higher in the DCF group than in the CF group (p = 0.0001). No significant difference existed between the two groups in operation time for the thoracic procedure (DCF 277.2 min vs. CF 302 min). Blood loss during the thoracic procedure was less in the DCF group than in the CF group (DCF 46.9 mL vs. CF 88.8 mL; p = 0.0056). No significant differences existed between the two groups in postoperative morbidity (DCF 34.5% vs. CF 47%) or mortality (DCF 0% vs. CF 2.9%) rates. CONCLUSIONS: Our study suggests that TE after DCF therapy for advanced esophageal cancer is as safe as TE after CF therapy.

Thoracoscopic esophagectomy with total meso-esophageal excision reduces regional lymph node recurrence.

PURPOSE: We investigated the operative outcomes of thoracoscopic esophagectomy (TE) in the prone position, using the concept of total meso-esophageal excision for esophageal cancer. METHODS: The medical records of 140 consecutive patients with esophageal cancer who underwent radical esophagectomy by TE were reviewed retrospectively, and operative outcomes were compared between patients treated before (non-meso-esophagus; non-ME group) and after (ME group) the introduction of total meso-esophageal excision (ME). RESULTS: There were no significant differences between the groups in postoperative morbidity (non-ME group vs. ME group, 28.3% vs. 41.4%, p = 0.119), 30-day mortality (non-ME group vs. ME group, 0% vs. 1.1%; p = 0.433), and in-hospital mortality (non-ME group vs. ME group, 1.9% vs. 0%, p = 0.199). Although overall survival and relapse-free survival did not differ significantly between the groups, the overall recurrence rate was significantly lower in the ME group than the non-ME group (non-ME group vs. ME group, 43.4% vs. 23%, p = 0.011). In particular, the rate of regional lymph node recurrence in the mediastinum was lower in the ME group (non-ME group vs. ME group, 11.3% vs. 2.3%; p = 0.026). CONCLUSIONS: Our results suggest that the ME procedure might be one of the procedures that reduce regional lymph node recurrence in the mediastinum without any deterioration in short-term outcomes.

Outcomes of esophagectomy after chemotherapy with biweekly docetaxel plus cisplatin and fluorouracil for advanced esophageal cancer: a retrospective cohort analysis.

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy can cause severe adverse events, including neutropenia and febrile neutropenia. The feasibility of DCF therapy is a concern, particularly for elderly patients, patients with moderate organ disorders, and patients suffering from malnutrition caused by dysphagia or insufficient oral intake. We introduced a biweekly DCF therapy (bDCF) for the purpose of reducing severe adverse events for these fragile patients. This study investigated the feasibility and outcome of an esophagectomy after bDCF therapy for patients with advanced esophageal squamous cell carcinoma. METHODS: Fifty-nine patients with esophageal carcinoma underwent an esophagectomy after DCF or bDCF therapy as primary chemotherapy. DCF was administered to 37 patients in the DCF group, whereas bDCF was administered to 22 patients in the bDCF group. RESULTS: Patients in the bDCF group were significantly older than those in the DCF group (p = 0.016). Heart and pulmonary comorbidities were significantly more common in the bDCF than in the DCF group (p < 0.001 and p = 0.039, respectively). Grade 3 or 4 neutropenia was less frequent in the bDCF than in the DCF group (40.9 vs. 81.1%, p = 0.002). Anorexia was more frequent in the DCF group than in the bDCF group (18.9 vs. 0%, p = 0.030). The clinical response rate of the bDCF group was significantly higher than that of the DCF group (86.4 vs. 62.2%, p = 0.047). There was no significant between-group difference in the postoperative morbidity rate (bDCF 45.5% vs. DCF 32.4%) or in the histological therapeutic effect. CONCLUSION: The results demonstrate that primary bDCF therapy for high-risk patients with advanced esophageal cancer is feasible and safe in both chemotherapeutic and perioperative periods without a reduction in the efficacy of DCF therapy.

Effectiveness of intervention with a perioperative multidisciplinary support team for radical esophagectomy.

PURPOSE: We aimed to evaluate the effectiveness of intervention by a perioperative multidisciplinary support team for radical esophagectomy for esophageal cancer. METHODS: We retrospectively reviewed 85 consecutive patients with esophageal cancer who underwent radical esophagectomy via right thoracotomy or thoracoscopic surgery with gastric tube reconstruction. Twenty-one patients were enrolled in the non-intervention group (group N) from May 2011 to September 2012, 31 patients in the perioperative rehabilitation group (group R) from October 2012 to April 2014, and 33 patients in the multidisciplinary support team group (group S) from May 2014 to September 2015. RESULTS: Morbidity rates were 38, 45.2, and 42.4% for groups N, R, and S, respectively. Although there were no significant differences in the incidence of pneumonia among the groups, the durations of fever and C-reactive protein positivity were shorter in group S. Moreover, postoperative oral intake commenced earlier [5.9 (5-8) days] and postoperative hospital stay was shorter [19.6 (13-29) days] for group S. CONCLUSIONS: The intervention by a perioperative multidisciplinary support team for radical esophagectomy was effective in preventing the progression and prolongation of pneumonia as well as earlier ambulation, oral feeding, and shortening of postoperative hospitalization.

[Fluorescence-Imaging of Nerves - A Novel Trial of Intraoperative Nerve-Preservation].

Nerve-preservation technique during surgery is important. Intraoperative nerve injury often causes permanent palsy or numbness and/or neurogenic functional disorders. To evade such intraoperative nerve injuries, we proposed a novel manner to specifically visualize peripheral nerve fibers. Low-toxic agents clinically available, amphotericin B(AmB)or fluorescein isothiocyanate(FITC)were used as neuro-indicators. In in vitro, we used Schwann cells as nerve models to basically confirm these agents effectively functioned as neural markers. In in vivo, we examined whether this novel method was clinically applicable. The Schwann cells reacted with AmB or FITC emitted blue or yellow-green fluorescence in a dark environment. The rat nerve models also fluorescently glimmered in blue-tone when each agent was given. These data suggested that we could clinically discriminate nerve fibers from the surrounding tissues. Our fluorescent-imaging methods warrant further studies for clinical applications.

[A Case of Para-Aortic Lymph Node Metastasis of Rectal Cancer Successfully Treated Using Multidisciplinary Therapy].

A 66-year-old man diagnosed with rectal cancer underwent high anterior resection and received adjuvant chemotherapy (UFT plus UZEL). One year after the surgery, lung and para-aortic lymph node(PLN)metastases were identified. We chose mFOLFOX6 for first-line chemotherapy. After 7 courses, we changed the regimen to sLV5FU2 because of Grade 3 neuropathy. After 5 courses, to treat progressive disease(PD), we changed the regimen to FOLFIRI. Then, the patient had stable disease (SD), and surgical excision was performed for both lung and lymph node recurrence without adjuvant chemotherapy. Six years after the excision, a CT scan revealed PLNagain. We chose FOLFIRI plus cetuximab. After 9 courses, the lymph nodes decreased in size and there was no other recurrence; thus we performed resection. However, a third PLNrecurrence was identified 20 months after the resection. Chemotherapy has continued for 47 courses, and he has maintained SD for more than 2 years.

Laparoendoscopic single site adrenalectomy: initial results of cosmetic satisfaction and the potential for postoperative pain reduction.

BACKGROUND: Recent reports have suggested that laparoendoscopic single site (LESS) surgery is technically feasible. The aim of this study was to describe our initial experience with LESS adrenalectomy for benign adrenal tumors, focusing the attention about cosmetic satisfaction and reduction of postoperative pain. METHODS: Medical records of consecutive patients undergoing LESS adrenalectomy were analyzed. All procedures were performed through a single multichannel port. Demographic and operative data were assessed. A visual analog scale (VAS) was used with a 10-point scale for an objective assessment of incisional pain and incisional cosmesis. RESULTS: Between January 2010 and July 2012, 14 consecutive patients with benign adrenal tumors underwent LESS adrenalectomies. Of the planned LESS adrenalectomies, 12 (86%) were completed with a single-port, whereas two required an additional port placement. Mean operating time was 128.1 ± 31.5 min and mean blood loss 10.5 ± 12.1 ml. Mean pain scores using the VAS on postoperative days 1, 3, and 14 were 2.3, 1.0, and 0.3 points, respectively. The rate of analgesic use was also lower within 12 hours after surgery (14%). The patient was highly satisfied with the single small wound procedure, and mean cosmesis scores of postoperative days 3 and 14 were 9.4 and 9.8 points, respectively. The postoperative course was uneventful with no morbidity within one month of follow-up. CONCLUSIONS: LESS adrenalectomy is a safe and technically feasible procedure for patients with benign adrenal tumors, and offers cosmetic benefit and the potential for postoperative pain reduction. However, surgeons with lack of experience as LESS surgery should be comprehended that the assistance of the needlescopic instrument does not compromise the cosmetic outcomes for difficult cases and the obese patients may not always be suitable candidates for pure LESS technique.

Early experience with single-incision laparoscopic Nissen fundoplication for gastroesophageal reflux disease in patients with mental retardation via a gastrostomy site incision: report of five cases.

Single-incision laparoscopic fundoplication for gastroesophageal reflux disease is not widespread because of its technical difficulty. On the other hand, patients with gastroesophageal reflux frequently also have mental retardation and eating disorders. We have been performing single-incision laparoscopic fundoplication via a gastrostomy site incision since October 2009 for these patients. The treated patients were 4 males and 1 female. A small skin incision was made on the gastrostomy site and a SILS port was placed. Under pneumoperitoneum, a single-incision laparoscopic Nissen fundoplication and gastrostomy were performed with a flexible scope, conventional instruments, and high-dexterity instruments. The pneumoperitoneal time was 115-180 min and blood loss was 1-15 ml. There were no intra- or postoperative complications. The hospital stay was under 8 days for all patients. Using this procedure, the incidence of postoperative intestinal obstruction was very low. The results indicate this procedure can be used as a standard operation for these patients in the future.

Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury.

OBJECTIVES: The usefulness of omega-3 lipid emulsions has been extensively studied. The objectives of the present study were to examine the effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury and the underlying mechanism. METHODS: A total of 66 rats were divided into three dietary groups (lipid-free, soybean oil, and fish oil groups). Each animal was administered total parenteral nutrition for 3 days, followed by induction of intestinal ischemia for 100 min. Animals subjected to sham surgery served as the controls. Intestinal tissue and blood were harvested 6 and 12 h after the surgery, then, assessment of the histological damage score, plasma-related parameters, and statistical evaluation were performed. RESULTS: The histological damage score in the intestinal tissues was significantly lower in the fish oil group than in the soybean oil group (P = 0.0121). The late-phase urinary level of 8-hydroxy-2-deoxyguanosine was also significantly lower in the fish oil group as compared with that in the other groups (P = 0.0267). Furthermore, the plasma level of high-mobility group box 1 protein was also significantly lower in the fish oil group as compared with that in the lipid-free group (P = 0.0398). CONCLUSION: It appeared that intravenous administration of an omega-3 lipid emulsion prior to ischemia-reperfusion injury reduced the oxidative stress and severity of tissue damage. Modification of membrane fatty acids may serve as the mechanism underlying this reduction of tissue damage.

[Usefulness of esophageal stenting for esophagorespiratory fistula with esophageal cancer].

We evaluated the outcome of esophageal stenting for esophagorespiratory fistula in patients with advanced esophageal cancer. Six patients with such fistula underwent esophageal stenting at our department from January 2000 to May 2012. Intraoral ingestion improved in all patients. Cough decreased immediately after stenting in 3 patients, and pneumonia detected by chest radiography improved within 1 week in 2 patients. Ventilation was weaned 2 days after stenting in 1 patient. The median survival duration after stenting was 31 days, and the cause of death was cancer in all patients. The following background factors were identified at the time of death: bleeding(n=3), mediastinitis(n=1), and pneumonia(n=1). Esophageal stenting, which should always be performed with the informed consent of the patient, improves respiratory symptoms, intraoral ingestion, and quality of life. Therefore, it is one of the best palliative therapies for patients with esophagorespiratory fistula associated with advanced esophageal cancer.

[Surgical strategy and treatment for pediatric surgical diseases accompanied with congenital heart diseases].

Advances in perinatal care in recent years have resulted in improved outcomes in both pediatric diseases treated surgically and congenital heart disease. However, aggressive surgical treatment is sometimes not performed because of a lack of knowledge of cardiac and pediatric surgeons. Lives may be saved if current pediatric surgical and pediatric cardiovascular surgical skills are combined. In complicated cases, a medical team is formed in our institution consisting of representatives of various departments, and the best treatment strategy tailored for individual patients is determined. We have treated 17 patients under this system, and 12 including 2 patients who had both severe pediatric diseases requiring surgery and congenital heart disease survived without major complications. Two patients died due to intestinal ischemia after cardiac surgery. To improve the survival rate of complicated cases, early detection or prevention of intestinal ischemia is required.

Safety of thoracoscopic esophagectomy after induction chemotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

INTRODUCTION: Recent studies have reported that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) is an effective treatment for unresectable, locally advanced esophageal cancer. The aim of this study was to investigate the safety and feasibility of thoracoscopic esophagectomy (TE) after DCF for initially unresectable esophageal squamous cell carcinoma (ESCC). METHODS: Twenty-three patients with initially unresectable T4 thoracic ESCC underwent TE after induction DCF. RESULTS: The neighboring organs with tumors were the tracheobronchus in nine patients, thoracic aorta in 13, and pericardium and diaphragm in three each (concurrent overlapping invasion occurred in five patients). The mean total operation time was 556.3 ± 107.2 minutes, and the mean time of the thoracic procedure was 258.9 ± 83.9 minutes. The mean total blood loss was 166.2 ± 117.8 mL, and the loss during the thoracic procedure was 33.5 ± 24.6 mL. All patients achieved complete R0 resection under TE. No conversions to open thoracotomy were performed. The postoperative morbidity rate was 34.8%. The postoperative hospital stay was 24.3 (range, 13-38) days. Five patients had recurrence: four had distant metastasis (lung, two; liver, three; and one with overlap), and one had mediastinal lymph node recurrence. No local recurrence was noted at the site of the primary T4 tumor. CONCLUSIONS: TE was safely performed in 23 patients after DCF therapy for locally advanced unresectable ESCC. Induction DCF, followed by TE, could be an alternative treatment for unresectable T4 ESCC.

[A novel formulation of cisplatin (CDDP)].

The study aimed to assess our newly devised CDDP delivery system designed to provide targeting potential and a sustained release of the anticancer agent. Seventy percent deacetylated chitin was applied as a drug carrier. We prepared two different types of systems with two different procedures: namely, system A with direct method and system B with indirect method. The targeting property of the system was evaluated ex vivo with measuring adhesive force between each system and human colonic mucosa. The release behavior of the CDDP from the system was examined in vitro. The anticancer activities of the released CDDP were also examined in vitro using human gastric cancer cell line, MKN-45. Each system was a viscose elastic solution. The adhesive forces of the novel systems were stronger at 37 degrees C than that of 25 degrees C. Each system provided a sustained release of CDDP. The released CDDP demonstrated effective growth suppression activity against the MKN-45 cancer cells. The novel systems basically showed a favorable targeting function and a sustained release of CDDP, which effectively provided a growth inhibition potential against human cancer cell line. Our newly devised CDDP delivery systems are promising as a novel approach to cancer chemotherapy.

Evaluation of the need for routine feeding jejunostomy for enteral nutrition after esophagectomy.

BACKGROUND: Previous studies have shown that enteral nutrition (EN) helps reduce severe postoperative complications after esophagectomy. However, the incidence of jejunostomy-related complications is approximately 30%. We evaluated the operative outcomes in patients who did not receive EN via feeding jejunostomy after esophagectomy. METHODS: We retrospectively reviewed 76 consecutive patients with esophageal cancer who received radical esophagectomy. Operative outcomes were compared between 33 patients who received postoperative EN via feeding jejunostomy (group A; from May 2014 to September 2015) and 43 patients who did not receive EN via feeding jejunostomy (group B; from September 2015 to December 2017). RESULTS: The American Society of Anesthesiologists performance status score of the patients in group B was significantly higher than that of patients in group A (P=0.002). The postoperative morbidity rate was comparable between the two groups (group A, 30.3% vs. group B, 44.2%, P=0.217). No significant between-group differences were observed in the incidence of infectious complications, postoperative hospital stay, readmission within 30 days after discharge, or pneumonia after discharge within 6 months. The incidence of bowel obstruction was significantly higher in group A than in group B (group A, 9.1% vs. group B, 0%, P=0.044). Two patients in group B required nutritional support via total parenteral nutrition due to bilateral vocal cord palsy or pneumonia. CONCLUSIONS: Jejunostomy-related bowel obstruction in the patients with feeding jejunostomy was significantly higher than that in the patients without jejunostomy. There was no increase in postoperative complications (including pneumonia) in the patients who did not receive EN via feeding jejunostomy. Our results suggest that routine feeding jejunostomy may not be necessary for all patients undergoing esophagectomy.

Giant gastrointestinal stromal tumor of the mediastinum associated with an esophageal hiatal hernia and chest discomfort: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) grow relatively slowly and without specific symptoms; therefore, they are typically incidental findings. We report a rare gastric GIST in the mediastinum associated with chest discomfort and an esophageal hiatal hernia. CASE PRESENTATION: An 81-year-old woman with chest discomfort was admitted to the hospital, where barium esophagography showed a sliding esophageal hiatal hernia and a tumor of the lower esophagus and gastric wall. Esophagogastroscopy confirmed the presence of a huge submucosal tumor that extended from the lower esophagus to the gastric fundus. According to computed tomography, the mediastinal mass measured 12.7 cm and had heterogeneous low-density areas. A submucosal gastric tumor, which we suspected to be a GIST, was diagnosed in association with an esophageal hiatal hernia. Using thoracolaparotomy, we performed a total gastrectomy, a lower esophagectomy, and a Roux-en-Y reconstruction with the jejunum. The presumptive diagnosis was confirmed through immunohistochemical examination; immunostaining yielded results positive for CD34 and c-kit. The patient was discharged from the hospital 13 days after surgery with no complications and remained disease-free at follow-up 24 months after surgery. CONCLUSIONS: GIST should be considered in the differential diagnosis of tumors growing in the mediastinum.

Successful repair using innominate vein flap, pericardial flap and thymus pedicle flap for tracheo-innominate artery fistula.

Tracheo-innominate artery fistula (TIF) is a rare but frequently fatal complication after tracheostomy. Without operation, the mortality is nearly 100% because of acute massive tracheal hemorrhage. Although the survival rate is extremely low, survival is possible only when an immediate operation is performed. Many surgeons have chosen ligation or resection of the innominate artery because repair with blood flow maintained in the innominate artery carries a high risk of postoperative fatal recurrent bleeding. We report on a successful surgical management of one case by patch closure with an innominate vein flap, wrapping of the innominate artery with a pericardial flap, and interposition of a thymus pedicle flap between the innominate artery and the trachea. Our surgical procedure is effective in maintaining the patency of the innominate artery preventing neurological deficits, and in preventing postoperative recurrent bleeding.

Laparoscopic repair of parahiatal hernia after esophagectomy: a case report.

BACKGROUND: Diaphragmatic hernia is a potential complication of esophagectomy, which usually occurs as a hiatal hernia and more frequently after minimally invasive esophagectomy. Parahiatal hernia is a rare form of diaphragmatic hernia, and to the best of our knowledge, parahiatal hernia after esophagectomy has not been previously reported. Here, we report a case of parahiatal hernia after esophagectomy that was successfully managed laparoscopically. CASE PRESENTATION: A 73-year-old man underwent thoracoscopic esophagectomy for esophageal cancer with gastric tube reconstruction via the posterior mediastinum. Postoperative morbidity was ileus, which required conservative treatment, and intestinal obstruction for which operation with laparotomy was necessary. He was admitted with abdominal pain and vomiting at 15 months after esophagectomy. Abdominal X-ray revealed colon gas in the intrathoracic space. A barium enema examination showed a transverse colon incarcerated in the intrathoracic space. The patient was preoperatively diagnosed with hiatal hernia after esophagectomy, and laparoscopic hernia repair was performed. During the surgery, the hiatus was found to be intact, and the defect was clearly separated from the left crus of the diaphragm. Parahiatal hernia was the operative diagnosis. The incarcerated colon was repositioned in the abdominal cavity, and the defect was repaired using a composite mesh. CONCLUSIONS: Laparoscopic surgery was found to be effective for the diagnosis and repair of parahiatal hernia.

Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development.

Tylosis is an inherited disorder characterized by abnormal palmoplantar skin thickening and a highly elevated risk of esophageal squamous cell carcinoma (ESCC). Analyses of tylosis in families have localized the responsible gene locus to a region of chromosome 17q25.1. Frequent loss of heterozygosity (LOH) in 17q25.1 was also observed in the sporadic form of ESCC. A putative tumor suppressor gene for ESCC may exist at this locus. We investigated the expression patterns of genes on 17q25.1 in tumor and corresponding normal tissues from patients with sporadic ESCC using RNA sequence analysis. For candidate genes, quantitative real-time reverse transcription-PCR (qRT-PCR), direct sequence, LOH and methylation analyses were performed using 93 clinical ESCC samples and 10 cell lines. A significant downregulation of ST6GALNAC1 was demonstrated in ESCC tissues compared to its expression in normal tissues by qRT-PCR (n=93, p<0.0001). Frequent LOH (17/27, 62.9%) and hyper­methylation in ST6GALNAC1 were also observed in all cell lines. Our results indicated that ST6GALNAC1 was downregulated in sporadic ESCC via hyper-methylation and LOH, and it may be a candidate responsible gene for ESCC. Furthermore, recent studies suggest that multiple genes on chromosome 17q25 are involved in ESCC development.