Endoscopic Submucosal Dissection Using EndoTrac, a Novel Traction Device.

BACKGROUND: Endoscopic submucosal dissection (ESD) is recognized as a minimally invasive and curative treatment for superficial gastrointestinal (GI) cancers. However, ESD is still challenging and time-consuming with a high risk of adverse events such as bleeding and perforation. Various traction methods have been explored for maintaining good visualization of the submucosal layer during ESD. We developed a novel traction device (the EndoTrac) which can easily tie the thread and has the ability to change the towing direction. The aim of this study is to evaluate safety and feasibility of ESD using the EndoTrac for GI neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 44 patients (45 lesions) with esophageal, gastric, duodenal, and colorectal neoplasms who had undergone ESD using the EndoTrac device between June 2018 and May 2019. Primary outcome measures were preparation time, procedural success using the EndoTrac device, and ease of ability to change towing direction. RESULTS: Mean preparation time was 2 (2-5) min in esophagus, 3 (1-5) min in stomach, 6 (5-9) min in duodenum, and 4 (2-8) min in colorectum. The procedural success rate was 100% (8/8) in esophagus, 100% (21/21) in stomach, 100% (4/4) in duodenum, and 100% (12/12) in colorectum. The rate of successful towing to both proximal and distal sides was 100% (8/8) in esophagus, 100% (21/21) in stomach, 0% (0/4) in duodenum, and 100% (12/12) in colorectum. CONCLUSIONS: Use of the EndoTrac device appears to be a feasible approach to ESD for GI neoplasms.

Peranal endoscopic myectomy (PAEM) for rectal lesions with severe fibrosis and exhibiting the muscle-retracting sign.

BACKGROUND: Although endoscopic submucosal dissection has enabled complete tumor resection and accurate pathological assessment in a manner that is less invasive than surgery, the complete resection of lesions with severe fibrosis in the submucosal layer and exhibiting the muscle-retracting sign is often difficult. We have devised a new method, peranal endoscopic myectomy (PAEM), for rectal lesions with severe fibrosis, in which dissection is performed between the inner circular and outer longitudinal muscles, and have examined the usefulness and safety of this new technique. METHODS: All of the patients who underwent PAEM in our hospital and affiliated hospitals between July 2015 and June 2017 were retrospectively reviewed. RESULTS: 10 rectal lesions were treated with PAEM. En bloc resection with a negative vertical margin was achieved in eight patients (80 %), whose lesions were mucosal (n = 2), shallow submucosal (n = 1), deep submucosal (n = 4), and muscle invasive (n = 1). The clinical course of all patients after PAEM was favorable. In patients who underwent additional surgery, anus preservation was achieved on the basis of the pathological results from PAEM. CONCLUSIONS: PAEM for lesions with severe fibrosis exhibiting the muscle-retracting sign appears to be both safe and useful.

Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses.

We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type.

Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1.

AIM: To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells. METHODS: In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H2O2. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4). The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The expression of tight junction (TJ) proteins was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. RESULTS: Without H2O2 treatment, fucoidan significantly increased the TER compared to control (P < 0.05), indicating a direct enhancement of intestinal epithelial barrier function. Next, H2O2 disrupted the epithelial barrier function in a time-dependent manner. Fucoidan prevented the H2O2-induced destruction in a dose-dependent manner. Fucoidan significantly decreased H2O2-induced FD4 flux (P < 0.01), indicating the prevention of disruption in paracellular permeability. RT-PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and occludin and that H2O2 reduced the mRNA expression of these TJ proteins. Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin. Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface. H2O2 disrupted the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the expression of claudin-1. CONCLUSION: Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis.

AIM: To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M. tuberculosis) for the diagnosis of intestinal tuberculosis (TB). METHODS: We retrospectively identified 10 patients (4 males and 6 females; mean age = 65.1 ± 13.6 years) with intestinal TB. Clinical characteristics, including age, gender, underlying disease, and symptoms were obtained. Chest radiograph and laboratory tests, including sputum Ziehl-Neelsen (ZN) staining, M. tuberculosis culture, and sputum polymerase chain reaction (PCR) for tubercle bacilli DNA, as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT), were examined. Colonoscopic records recorded on the basis of Sato's classification were also reviewed, in addition to data from intestinal biopsies examined for histopathological findings, including hematoxylin and eosin staining, and ZN staining, as well as M. tuberculosis culture, and PCR for tubercle bacilli DNA. For the present study, archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M. tuberculosis complex. These sections were also stained with the pan-macrophage marker CD68 antibody. RESULTS: From the clinical data, we found that no patients were immunocompromised, and that the main symptoms were diarrhea and weight loss. Three patients displayed active pulmonary TB, six patients (60%) had a positive TST, and 4 patients (40%) had a positive QFT. Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules), all of which were located in the right hemicolon and/or terminal ileum. Seven patients (70%) had concomitant healed lesions in the ileocecal area. No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples, and both M. tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples. The histopathological data revealed that tuberculous granulomas were present in 4 cases (40%). IHC staining in archived FFPE samples with anti-M. tuberculosis monoclonal antibody revealed positive findings in 4 patients (40%); the same patients in which granulomas were detected by hematoxylin and eosin staining. M. tuberculosis antigens were found to be mostly intracellular, granular in pattern, and primarily located in the CD68(+) macrophages of the granulomas. CONCLUSION: IHC staining with a monoclonal antibody to M. tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

Endoscopic and histopathological features of gastrointestinal amyloidosis.

Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, multiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory disorders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudo-obstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.

Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection.

AIM: To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis (S. stercoralis) hyperinfection. METHODS: Over a period of 23 years (1984-2006), we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively. RESULTS: Twenty-four (96%) of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 (HTLV-1) infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 (92%) patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative (Endoscopic severity score: 4.86 +/- 2.47 vs 2.71 +/- 1.38, P < 0.05). CONCLUSION: Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.

Low prevalence of human T cell lymphotropic virus type 1 infection in patients with gastric cancer.

BACKGROUND AND AIM: There have been few studies on the association between human T cell lymphotropic virus type 1 (HTLV-1) infection and cancer risk. It is still controversial whether or not HTLV-1 infection affects the incidence of several cancers. With this background, we aimed to evaluate the relationship between HTLV-1 infection and the occurrence of several types of cancers. METHODS: Subjects were 699 patients with cancer aged 50 years and older diagnosed between 1991 and 2004 at the Department of Medicine and Therapeutics, Ryukyu University Hospital, Okinawa, Japan, and 1365 control patients without cancer. The association between HTLV-1 infection and cancer (biliary tract, pancreatic, esophageal, gastric, colorectal, liver, and lung cancers) was analyzed by logistic regression analysis adjusted for age and sex. RESULTS: The infection rate of HTLV-1 in patients with gastric cancer was significantly lower than in controls (P = 0.01, adjusted odds ratio 0.46). The infection rate of HTLV-1 was not associated with increased or decreased risk of cancers other than gastric cancer. CONCLUSION: Our study indicated that the prevalence of HTLV-1 infection in patients with gastric cancer appears to be significantly lower than that in control patients.

[Recurrent esophageal cancer with complete response to TS-1 chemotherapy].

An 80-year-old man was admitted to our hospital for treatment of recurrent esophageal cancer in December, 2004. He was diagnosed as having esophageal cancer of stage IVa (T2N4M0) in October, 2002, and he received chemoradiotherapy (nedaplatin (CDGP)/5-fluorouracil (5-FU) total 6 course+60 Gy). Afterwards, lymph nodes recurred, and two courses of CDGP/vindesine were given. Then, the primary lesion showed a complete response (CR), and lymph nodes a partial response (PR). In December, 2004, paraesophageal lymph nodes were enlarged to the size of 7 cm. On admission, because of renal disturbance and dementia with advanced age, we chose chemotherapy with TS-1 (100 mg/body/day, three weeks of administration, then two weeks of withdrawal). He had adverse effects of hematotoxicity of grade 3, and non-hematotoxicity of grade 1. He received 6 courses of this regimen and eventually showed CR. Serum SCC was decreased from 4.7 ng/mL to 0.9 ng/mL. At present,the lesions have not recurred during the follow-up for 18 months.

[A case of primary malignant lymphoma of the duodenum successfully treated with dose escalating chemotherapy].

A 65-year-old woman with diabetes mellitus was hospitalized for heart failure and anemia in August 2001, and recovered with conservative treatment. An endoscopic examination revealed an ulcerative mass located in the duodenal bulb to the 2nd portion. Abdominal CT scan demonstrated tumor involvement in the pancreas head. The diagnosis of a diffuse large B-cell lymphoma, clinical stage IIE, was made by endoscopic biopsy. Although surgical resection of the localized intestinal tumor would have been a common choice for initial treatment, polychemotherapy was selected; the patient had diabetes mellitus and preferred polychemotherapy to surgical operation. Because of bulky intestinal mass, transmural disease and sensitive histological type, standard-dose chemotherapy was considered to include a high risk of intestinal perforation. We performed dose-escalating chemotherapy: A half dose of THP-COP (pirarubicin, cyclophosphamide, vincristine) was given at the start in October 2001, 60% THP-COP as the next cycle, 80% THP-COP as the 3rd cycle and thereafter. Without serious complications of the intestine, she received a total of 6 cycles of chemotherapy and subsequent involved field radiation. There has been no evidence of recurrence of disease 14 months from the start of chemotherapy. When conditions make surgical treatment difficult, dose-escalating chemotherapy in a treatment cycle may be considered as an alternative.