Low preoperative hemoglobin A1c level is a predictor of perioperative infectious complications after esophagectomy: A retrospective, single-center study.

This retrospective, single-center study aimed to evaluate the impact of blood glucose (BG) markers on perioperative complications after esophagectomy in a cohort of 176 patients. Study analyses included the correlation of daily maximum BG level and hemoglobin A1c (HbA1c) with clinicopathological factors. Maximum BG levels were significantly higher on postoperative day (POD) 0 than on PODs 2, 3, 5, and 7 (p < 0.05). Additionally, maximum BG levels on PODs 1, 2, and 7 were significantly higher in patients with preoperative HbA1c levels of ≥ 5.6% than in those with preoperative HbA1c levels of < 5.6% (p < 0.05 for all). The rates of any complications and infectious complications were higher in patients with preoperative HbA1c levels of < 5.6% than in those with preoperative HbA1c levels of ≥ 5.6% (p < 0.05 for both). A preoperative HbA1c level of < 5.6% was a significant predictor of infectious complications after esophagectomy by logistic regression analysis (p < 0.05). Maximum BG level after esophagectomy remained high in patients with high preoperative HbA1c levels, whereas a normal HbA1c level was an independent risk factor for infectious complications.

A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa.

BACKGROUND: The development of immunohistochemical staining has revealed that gastric adenocarcinoma with the gastric phenotype can be divided into the foveolar, fundic gland, and pyloric gland phenotypes. Gastric adenocarcinoma of the pyloric gland type is difficult to diagnose using biopsy because of its low atypia and rarity. Herein, we describe a case of gastric adenocarcinoma of the pyloric gland type that was diagnosed immunohistochemically after endoscopic resection. CASE PRESENTATION: A 67-year-old man was referred to our hospital for the diagnosis and treatment of a 30-mm elevated lesion on the lesser curvature side of the middle of the gastric body. Although four biopsies were performed, it was difficult to determine whether the lesion was benign or malignant. Therefore, endoscopic submucosal dissection was performed, and the presence of tumor cells infiltrating the submucosa with venous invasions was identified. Immunohistochemical staining revealed that the tumor cells were positive for MUC5AC and MUC6 and negative for Pepsinogen I and H + /K + -ATPase. From the above findings, he was diagnosed as having gastric adenocarcinoma with pyloric gland type. The patient underwent a laparoscopic distal gastrectomy and was discharged without any adverse events. CONCLUSIONS: Gastric adenocarcinoma of the pyloric gland type is a rare disease, and endoscopic resection can serve as a viable diagnostic option for this condition when it is difficult to diagnose using biopsy. Immunohistochemical pathology images can aid in the diagnosis of gastric adenocarcinoma of the pyloric gland type.

Induction of Kallikrein-Related Peptidase 13 and TET2/3 by Anticancer Drugs and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma After Preoperative Treatment.

BACKGROUND: Preoperative chemotherapy/chemoradiotherapy has been generally considered for the treatment of esophageal squamous cell carcinoma (ESCC) to improve prognosis. We examined the effects of anticancer drugs on the expression of kallikrein-related peptidase 13 (KLK13), a potential ESCC prognostic marker, and its clinical relevance in patients who received chemotherapy/chemoradiotherapy for ESCC. METHODS: Overall, 105 patients with ESCC who received chemotherapy or chemoradiotherapy before esophagectomy were enrolled. The expression of KLK13 in biopsy samples obtained before chemotherapy/chemoradiotherapy and resected ESCC tumors was assessed by immunohistochemical staining. The effects of 5-fluorouracil (5-FU) and/or cisplatin (CDDP) exposure on the expressions of KLK13 and ten-eleven translocation dioxygenases (TET) in ESCC cells were examined by reverse transcription-polymerase chain reaction. RESULTS: Immunohistochemical staining of paired ESCC specimens before (biopsy samples) and after (resected specimens) chemotherapy/chemoradiotherapy demonstrated a change in KLK13 expression. KLK13 and TET2/3 transcriptions were induced when human ESCC cell lines were treated with 5-FU and/or CDDP. Among patients with KLK13-negative status before chemotherapy/chemoradiotherapy, those with KLK13-positive resected tumors had a significantly poorer prognosis than those with KLK13-negative resected tumors (p = 0.0477). By using tumor cells isolated from ESCC biopsy tissues obtained before chemotherapy/chemoradiotherapy, we established a primary culture system and detected the induction of KLK13 expression by anticancer drugs. CONCLUSIONS: Preoperative treatments alter KLK13 expression in ESCC. The conversion of KLK13 expression from a negative status in biopsy samples to a positive status in resected tumor samples is a predictor of poor prognosis. KLK13 status is a potential marker for decision making to avoid harmful chemotherapy/chemoradiotherapy in patients with ESCC.

Refractory gastrocutaneous fistula treated by two-stage surgery: a case report.

BACKGROUND: Gastrocutaneous fistulas are a rare complication of enterocutaneous fistulas and can be caused by intestinal injury, infection, and anastomotic leakage. They are typically treated conservatively or endoscopically; however, for large or difficult-to-treat gastrocutaneous fistulas, surgical intervention is required. Herein, we present a case of a huge gastrocutaneous fistula that was successfully treated with a two-stage surgery performed using open abdomen management. CASE PRESENTATION: A 61-year-old man with a perforated gastric ulcer underwent omental filling as an emergency surgery. Post-operative leakage led the development of a 10-cm gastrocutaneous fistula. He was transferred to our hospital for the treatment of gastrocutaneous fistula. Furthermore, nutritional therapy was administered for dehydration, electrolyte abnormalities, metabolic acidosis, and acute kidney injury due to the high-output nature of the fistula. Moreover, owing to the intraperitoneal severe adhesion and poor nutritional status, two-stage surgery was planned. In the first stage, extensive dissection of the adhesions, distal gastrectomy reconstruction with Roux-en-Y anastomosis, and jejunostomy were performed. Furthermore, open abdomen management was conducted to check for the presence of unexpected complications due to extensive dissection of the adhesion and anastomotic leakage. Subsequently, in the second stage of the surgery, abdominal closure was performed on the 9th day after gastrectomy. CONCLUSION: Open abdomen management may be effective for huge gastrocutaneous fistulas with extensive adhesions that require surgical intervention.

Usefulness of indocyanine green fluorescence-guided small intestinal bleeding site identification in small bowel resection: a report of two cases and literature review.

Small bowel bleeding that does not respond to conservative therapy requires surgical resection. However, identifying the bleeding sites intraoperatively is challenging. Indocyanine green (ICG) fluorescence imaging improves diagnosis of small bowel bleeding and surgical decision-making by visualizing blood flow. Herein, we reported two cases of small bowel bleeding that were successfully treated by using ICG to identify the bleeding sites and determine the extent of small bowel resection. The patients were a 46-year-old and a 75-year-old woman, both of whom presented with melena. Contrast-enhanced computed tomography and arteriography confirmed small bowel bleeding, and rebleeding occurred in both patients after transcatheter arterial embolization. Emergent surgeries were performed, and intraoperative selective angiography with ICG injections was conducted to identify obscure bleeding sites. ICG fluorescence identified all bleeding sites in both cases, and small bowel resections were successfully performed. The postoperative courses were uneventful, and both patients had a favorable postoperative course without recurrence of bleeding. ICG fluorescence imaging can safely identify the sites of intestinal bleeding and determine the appropriate extent of bowel resection.

Gastric cancer with a giant lymph node metastasis: a case report and review of the literature.

A 78-year-old man presented with a large abdominal mass detected by ultrasonography during a regular checkup. Even if the mass was > 10 cm in diameter, he was asymptomatic. Computed tomography detected an oval-shaped mass, with a maximum diameter of 12 cm, adjacent to the greater curvature of the stomach. Esophagogastroduodenoscopy revealed a 20 mm slightly depressed (type 0-IIc) lesion on the posterior wall of the gastric antrum, which was confirmed to be adenocarcinoma. Three cycles of combination chemotherapy with S-1 and oxaliplatin were administered as neoadjuvant chemotherapy. After neoadjuvant chemotherapy, the patient underwent distal gastrectomy, and a histopathological study identified the 12 cm giant mass as a lymph node metastasis. The postoperative course was uneventful, and thus far, the patient has completed adjuvant chemotherapy without relapse. Cases of gastric cancer with a giant lymph node metastasis are extremely rare. In this study, we report the present case and review the previous literature.

False-positive 123I-metaiodobenzylguanidine scintigraphy in a patient with a gastrointestinal stromal tumor presenting as a left adrenal incidentaloma.

Summary: A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. On computed tomography scan, the mass appeared to localize within the tip of the lateral limb of the left adrenal gland, and between the left adrenal gland and the posterior wall of the stomach. The plasma corticotropin and cortisol concentrations and the 24-h urine fractionated metanephrine levels were normal. 123I-metaiodobenzylguanidine scintigraphy showed tumor avidity consistent with a hormonally inactive pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal computed tomography postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a gastrointestinal stromal tumor. Clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathological analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Learning points: Anatomic structures and tumors that develop in neighboring tissues to the adrenal glands may be confused with primary adrenal tumors. 123I- metaiodobenzylguanidine (MIBG) scintigraphy is specific for diagnosing pheochromocytomas and paragangliomas; however, it has been reported that 123I-MIBG may accumulate in neuroendocrine tumors as well as other tumors. Clinicians should recognize the limitations of imaging studies and the uncertainty of an imaging-based preoperative diagnosis.

Hemothorax due to a ruptured esophageal gastrointestinal stromal tumor: case report.

BACKGROUND: Esophageal gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal interstitium, and comprise less than 0.7% of all GISTs. The presentation of esophageal GIST is relatively benign, commonly characterized by symptoms of dysphagia and gastrointestinal bleed. On the contrary, it is highly unusual for these tumors to present as surgical emergencies. CASE PRESENTATION: Here, we describe a case of hemothorax secondary to the rupture of a massive (19 cm) esophageal GIST in a 79-year-old male. The patient presented with mild back pain, vomiting, and hypotension. A CT scan revealed significant mediastinal enlargement and left hemothorax. We conducted an emergency thoracotomy which revealed a 19 × 15 × 7 cm ruptured esophageal tumor that was bleeding profusely into the left thoracic cavity. Piecemeal resection without esophagectomy was performed to achieve hemostasis. Pathological evaluation of resected tissue confirmed the diagnosis of GIST. The patient was provided adjuvant imatinib therapy and remains progression-free at the 10-month follow-up. CONCLUSIONS: To the best of our knowledge, this is the first reported case of life-threatening hemothorax caused by a ruptured esophageal GIST. Findings from this case may aid in the diagnosis and management of these rare tumors.

Bowel perfusion demonstrated using indocyanine green fluorescence imaging in two cases of strangulated ileus.

We report the use of indocyanine green (ICG) fluorescence for intraoperative diagnosis in two cases of strangulated ileus. We successfully preserved the bowel and avoided postoperative complications by detecting adequate perfusion and no necrosis in the intestine's strangulated regions. In the first case, enhanced computed tomography (CT) revealed a closed loop intestine, which showed poor contrast, and we performed laparotomy with ICG fluorescence. In the second case, the CT scan revealed bowel obstruction without ascites. We conservatively treated the patient with the insertion of a long tube. The patient's condition did not improve, and we performed laparotomy using ICG fluorescence. In both of these cases, the visual observation during laparotomy showed that the ileum had dark-red discoloration. We demonstrated perfusion and preserved the ileum by injecting 2.5 mg of ICG intravenously; fluorescence was observed in the dark-red ileum using the PINPOINT system (Novadaq, Kalamazoo, MI, US). Both patients recovered successfully after the surgery with no adverse events. Our data suggest that ICG fluorescence imaging can be one of the decision-making modalities in patients with strangulated ileus.

Proposal of new treatment algorithm for gastric cancer liver metastases: Up-front surgery or conversion surgery?

Hepatectomy for gastric cancer liver metastases (GCLM) has a 5-year survival rate of 9-42%; however, indications for hepatectomy remain unclear. Many researchers have reported prognostic factors for GCLM after hepatectomy, but surgical indications vary according to the literature. Furthermore, the indication for optimal candidates for neoadjuvant chemotherapy and intensive chemotherapy is also unclear. To understand the indications for surgery and chemotherapy intended for hepatectomy for GCLM, a new treatment algorithm was created based on previously reported evidence from the viewpoint of hepatic surgeons.

Computed tomography-guided lymphangiography from the para-aortic lymph node: a useful approach for chylothorax after esophagectomy.

BACKGROUND: Chylothorax is a relatively rare complication of esophagectomy but can lead to fatal conditions. The aim of this report was to present a case of lymphangiography from the para-aortic lymph node (PALN) under computed tomography (CT) guidance, which could be an alternative modality to ultrasound sonography from the groin. CASE PRESENTATION: A 58-year-old man was diagnosed as having postoperative chylothorax after esophagectomy following neoadjuvant chemotherapy. As the pleural effusion did not improve, intranodal lipiodol lymphangiography from the inguinal lymph node was performed but was unsuccessful. Therefore, CT-guided lymphangiography from the left PALN was performed, and the pleural effusion drainage significantly disappeared. CONCLUSIONS: CT-guided lipiodol lymphangiography from the PALN for chylothorax after esophagectomy was safe and thus can be considered an alternative treatment option to ultrasonography-guided intranodal lymphangiography. The flexible use of CT and ultrasonography for lymphangiography may improve the treatment outcomes of chylothorax after esophagectomy.

Infection control of COVID-19 in operating theaters in a designated hospital for specified infectious diseases in Japan.

At the beginning of the COVID-19 pandemic in 2020, many hospitals around the world recommended stopping elective surgery as a precaution to stop the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The number of elective surgeries was reduced in Japan due to several waves of the pandemic. This work describes the management of COVID-19 and actual polymerase chain reaction (PCR) screening in operating theaters at the National Center for Global Health and Medicine (NCGM), a designated hospital for specified infectious diseases in Japan. The following three steps for COVID-19 infection control were taken to maintain the operating theater: i) Do not bring COVID-19 into the operating theater, ii) Infection control for all medical staff, and iii) Surgical management of surgical patients with COVID-19. We introduced checklists for surgical patients, simulations of surgery on infected patients, screening PCR tests for all surgical patients, and use of a negative pressure room for infective or suspected cases. We determined the flow and timing of surgery for patients with COVID-19. However, many aspects of COVID-19 infection control measures in the operating theater are still unclear. Therefore, infection control measures require further advances in the future to manage new infections.

Right-sided Bochdalek hernia in an adult with hepatic malformation and intestinal malrotation.

BACKGROUND: Bochdalek hernia is a common congenital diaphragmatic defect that usually manifests with cardiopulmonary insufficiency in neonates. It is very rare in adults, and symptomatic cases are mostly left-sided. Diaphragmatic defects generally warrant immediate surgical intervention to reduce the risk of incarceration or strangulation of the displaced viscera. CASE PRESENTATION: A 47-year-old woman presented with dyspnea on exertion. Computed tomography revealed that a large part of the intestinal loop with superior mesenteric vessels and the right kidney were displaced into the right thoracic cavity. Preoperative three-dimensional (3D) simulation software visualized detailed anatomy of displaced viscera and the precise location and size of the diaphragmatic defect. She underwent elective surgery after concomitant pulmonary hypertension was stabilized preoperatively. The laparotomic approach was adopted. Malformation of the liver and the presence of intestinal malrotation were confirmed during the operation. The distal part of the duodenum, jejunum, ileum, colon, and right kidney were reduced into the abdominal cavity consecutively. A large-sized oval defect was closed with monofilament polypropylene mesh. No complications occurred postoperatively. CONCLUSION: Symptomatic right-sided Bochdalek hernia in adults is exceedingly rare and is frequently accompanied by various visceral anomalies. Accurate diagnosis and appropriate surgical repair are crucial to prevent possible incarceration or strangulation. The preoperative 3D simulation provided comprehensive information on anatomy and concomitant anomalies and helped surgeons plan the operation meticulously and perform procedures safely.

Prolonged survival of a patient with aortogastric fistula treated with combined surgery and endovascular stent placement: A case report.

INTRODUCTION: Aortogastric tube fistula is a rare and fatal complication of esophagectomy. The treatment for aortogastric tube fistula with active infection is challenging, wherein a contamination around the fistula can cause a high risk of aneurysm and recurrence of bleeding, even if large amount of bleeding is controlled immediately. PRESENTATION OF CASE: We present a case of a 54-year-old male patient who underwent lower esophagectomy for esophageal squamous cell carcinoma 22 years ago. He developed aortogastric tube fistula on postoperative day 46. The patient underwent two surgeries and stenting for aortogastric tube fistula and pseudoaneurysm between days 46 and 120 following the first surgery, and digestive reconstruction was performed 6 months after the first surgery. Computed tomography and esophagogastroduodenoscopy were performed periodically, and the postoperative course was uneventful for 22 years. However, the patient died from pneumonia at the age of 76 years. Autopsy findings revealed no recurrence of esophageal cancer, anastomotic complications, or stent issues. The fistula between the aorta and gastric tube was closed with a stent and connective tissue. Intrathoracic findings revealed that the cause of death was severe bilateral pneumonia. DISCUSSION: Immediate hemodynamics stabilization and interval infection control enabled successful disease management. CONCLUSION: Tenting for aneurysm was performed under aseptic conditions, and the patient did not experience recurrence of esophageal cancer and stent issues, which contributed to the long-term survival of 22 years.

Current status of doublet combinations of platinum and fluoropyrimidines using oxaliplatin for advanced gastric cancer.

The most common treatment for advanced gastric cancer (AGC) is systemic chemotherapy. The standard treatment for advanced gastric cancer differs worldwide. In Japan, two phase III clinical trials demonstrated the non-inferiority of S-1 compared with 5-fluorouracil (5-FU) and superiority of cisplatin plus S-1 (CS), compared with S-1, with respect to overall survival (SPIRITS trial). Oxaliplatin (L-OHP) has a favorable toxicity profile compared with cisplatin; hence, a phase III clinical trial (G-SOX trial) demonstrated the progression-free survival (PFS) and overall survival in CS was 5.4 and 13.1 months and those in SOX was 5.5 and 14.1 months, respectively. Serious adverse events were more frequently seen in CS than in SOX. So, SOX is as effective as CS for advanced gastric cancer with favorable safety profile. After the publication of this G-SOX trial, the combination of oral or intravenous 5-FU and various doses of L-OHP have been reported. And FOLFOX6 regimen (FOLFOX: a combination of 1-LV and FU with L-OHP) was approved for the treatment of AGC in Japan in 2017. FOLFOX was promising for patients with severe peritoneal metastasis from AGC, because the FOLFOX regimen does not require hydration and does not include oral agents. This review summarizes the efficacy and safety of doublet combinations of platinum and fluoropyrimidines using L-OHP for advanced gastric cancer.

Efficacy of cell proliferation imaging with 4DST PET/CT for predicting the prognosis of patients with esophageal cancer: a comparison study with FDG PET/CT.

PURPOSE: 4'-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer used for cell proliferation imaging. The aim of this study was to evaluate the prediction of prognosis with pretreatment 4DST PET/CT compared to fluorodeoxyglucose (FDG) PET/CT in patients with esophageal cancer. METHODS: In this prospective study, we analyzed 46 patients (68.2 ± 10.0 years old) with pathologically proven esophageal squamous cell cancer who underwent pretreatment 4DST and FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion proliferation (TLP) were measured for FDG and 4DST PET. The study endpoints were progression-free survival (PFS) and overall survival (OS). Patients' clinical backgrounds, including age, histological type, clinical stage, and surgical treatment, were adjusted using the Cox proportional-hazards model. RESULTS: In the follow-up period (median 18.8 (interquartile range: 10.1-29.0) months), 26 and 19 patients showed disease progression and cancer-related death, respectively. After adjusting for clinical variables, only the 4DST parameters (SUVmax (p = 0.001) and TLP (p = 0.022)) were statistically significant for predicting PFS. FDG MTV (p = 0.031), 4DST SUVmax (p = 0.022), and TLP (p = 0.023) were statistically significant for predicting OS. Of the PET parameters, 4DST SUVmax yielded the highest adjusted hazard ratio for both PFS (4.88, 95% confidence intervals (CI): 1.83-12.97) and OS (4.19, 95% CI: 1.23-14.20). CONCLUSION: Higher accumulation of 4DST in the primary tumor may lead to shorter OS and PFS. 4DST PET/CT is useful for predicting prognosis and may outperform FDG PET/CT.

Expression Status of Serine Protease 27: A Prognostic Marker for Esophageal Squamous Cell Carcinoma Treated with Preoperative Chemotherapy/Chemoradiotherapy.

BACKGROUND: A previous study conducted a transcriptome analysis of paired normal and esophageal squamous cell carcinoma (ESCC) tissue samples. The results showed that the expression of serine protease 27 (PRSS27) was perturbed in tumor samples. Hence, this retrospective study aimed to validate the prognostic significance of PRSS27 in patients with preoperative treatment for ESCC. METHODS: We enrolled 86 patients who received preoperative treatment before esophagectomy for ESCC. The expression of PRSS27 in resected ESCC and biopsy tissue samples obtained before preoperative treatment was evaluated via immunostaining, and its relationship with clinicopathological features and prognosis was analyzed. RESULTS: In normal esophageal mucosa tissue samples, PRSS27 was expressed in the cytoplasm of spinous cells in the suprabasal layer and basal cells in the basal layer. Of 64 resected ESCC tissue samples, 35 (54.7%) expressed PRSS27 and 29 (45.3%) did not. Moreover, ectopic nuclear expression of PRSS27 was observed. Based on multivariate analysis, PRSS27 expression in resected tumor samples was a predictor of poor prognosis. In cases in which PRSS27 expression was observed in biopsy samples, patients with PRSS27-negative resected tumors had a better postoperative prognosis than those with PRSS27-positive resected tumors. CONCLUSIONS: PRSS27 expression in resected ESCC tissue samples is a poor prognostic factor in ESCC patients with preoperative treatment. Furthermore, conversion of PRSS27 expression from positive in biopsy samples to negative in resected tumor samples is a predictor of good prognosis in these patients. Hence, PRSS27 status is an effective tool for decision making regarding adjuvant treatment in ESCC patients.

Surgical strategies for treatment of clinical T4 esophageal cancer in Japan.

Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued. However, salvage operation has been selected as a therapeutic option for recurrent or residual tumors after dCRT. There is weak evidence for not recommending surgery for cStage IVa ESCC exhibiting residual disease following dCRT. It has been reported that during salvage surgery the only prognostic factor that is thought to be performed is complete resection (R0), but at the same time, salvage esophagectomy increases the incidence of postoperative complications and mortality. The phase II chemoselection study by Yokota T et al. in Japan showed that multidisciplinary treatment initiated by induction therapy, in which docetaxel is added to cisplatin and 5-fluorouracil, resulted in a good prognosis in the short term. In this review, we discuss the surgical strategy and future of unresectable clinical T4 (cT4) ESCC.

Occupational exposure of platinum-based anti-cancer drugs: five-year monitoring of hair and environmental samples in a single hospital.

BACKGROUND: Occupational exposure to chemotherapeutic agents in hospitals is a critical issue. Here, we focused on occupational exposure to platinum-based anti-cancer drugs (PDs) by evaluating platinum concentrations in hair and environmental workplace samples to monitor the risk among workers. METHODS: Hospital workers who dealt with or without PDs, patients treated with PDs, and non-medical office workers outside the hospital donated hair samples and completed a questionnaire regarding their history of handling PDs, including any incidents. Hair samples were collected and surface wipe sampling was performed in July 2010 and April 2015, before and after moving to a new building and introducing a revised safety program in August 2010. Samples were analyzed by inductively coupled plasma-mass spectrometry. RESULTS: Platinum concentrations in hair from PDs-handling workers was significantly higher than in non-PDs-handling workers (P = 0.045), although 50 times lower than that from PDs-treated patients. Platinum concentrations in the hospital environment had decreased at the second survey 5 years later but had not changed significantly in the hair samples from hospital workers. CONCLUSION: Platinum concentrations in hair are likely dependent on the frequency of handling PDs. Reduced environmental contamination from PDs did not influence platinum levels in hospital workers' hair. Continuous monitoring by measuring platinum concentrations in the environment and in hair would provide information regarding these issues.

Glutathione S-transferase omega 2 regulates cell growth and the expression of E-cadherin via post-transcriptional down-regulation of ß-catenin in human esophageal squamous cells.

Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and ß-catenin at the cell-cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of ß-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.