Distal esophageal spasm with multiple esophageal diverticula successfully treated by peroral endoscopic myotomy

Distal esophageal spasm (DES) is a primary esophageal motility disorder. We encountered a rare case of DES accompanied by multiple esophageal diverticula. A 72-year-old woman complained of prolonged dysphagia and chest pain. A barium esophagogram showed multiple esophageal diverticula and significant contraction of the lower esophagus just above the cardia. Esophagogastroduodenoscopy revealed a corkscrew-like appearance, with spiral contractions and diverticula. High-resolution manometry revealed that the integrated relaxation pressure was normal; premature contractions were observed in ≥20% of the swallowing wave; the distal contractile integral was normal. She was diagnosed with DES according to the Chicago classification v 3.0. As smooth muscle relaxants were not effective, we decided to perform peroral endoscopic myotomy (POEM) to eliminate persistent esophageal contraction. After POEM treatment, her symptoms were markedly improved, and the Eckardt score significantly decreased from 11 points to 1. An esophagogram after POEM showed that barium flowed promptly into the stomach. The multiple esophageal diverticula were considered to be the result of false pulsion diverticulosis caused by excessive internal esophageal pressure, and this represented the most severe form of DES. POEM could be a new curative strategy for the most severe DES cases with multiple diverticula.     

Serum concentrations of l‐kynurenine predict clinical outcomes of patients with peripheral T‐cell lymphoma,not otherwise specified

Indoleamine 2,3‐dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l ‐tryptophan. The activity of indoleamine 2,3‐dioxygenase can be estimated by measuring serum l ‐kynurenine concentrations. Here, we aimed to determine the role of l ‐kynurenine as a prognostic factor for peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL‐NOS according to the World Health Organization classification and treated with 6?8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l ‐kynurenine concentrations in serum samples collected at admission were measured using high‐performance liquid chromatography. The median serum concentration of l ‐kynurenine was 3.28 (range 0.92–8.16) μM. The l ‐kynurenine cutoff was set at 3.07 μM using receiver operating characteristics curves. The complete remission rates of patients with l ‐kynurenine <3.07 and ≥3.07 μM were 69% and 51%, respectively. The 5‐year overall survival (OS) rates for patients with l ‐kynurenine <3.07 and ≥3.07 μM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T‐cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l ‐kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l ‐kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL‐NOS. Copyright © 2016 John Wiley & Sons, Ltd.     

A salvage chemotherapy of R‐P‐IMVP16/CBDCA consisting of rituximab,methylprednisolone, ifosfamide,methotrexate, etoposide,and carboplatin for patients with diffuse large B cell lymphoma who had previously received R‐CHOP therapy as first‐line chemotherapy

We have reported the efficacy of the salvage chemotherapy P‐IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P‐IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R‐CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m² on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m² for 5 days (from day 3 to day 7), methotrexate 30 mg/m² on day 5 and day 12, etoposide 80 mg/m² for 3 days (from day 3 to day 5), and carboplatin 300 mg/m² on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2‐year overall survival rate was 55.3%. The 2‐year progression free survival rate was 34.7%. The 2‐year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p < 0.0001). One patient died because of sepsis related to the treatment regimen. Non‐hematological adverse effects were mild and tolerable. The R‐P‐IMVP‐16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.     

Adipose-Derived Stem Cells Ameliorate Experimental Murine Colitis via TSP-1-Dependent Activation of Latent TGF-β

Background

Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease.

Methods

Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally. Tregs and CD103⁺ dendritic cells were analyzed in the mesenteric lymph nodes (MLNs), spleen, and colonic lamina propria (CLP). Activation of latent TGF-β by ASCs was analyzed in vitro using ELISA. siRNA technology was used to create ASCs in which TSP-1 or integrinαv was knocked down in order to investigate the involvement of these proteins in the activation of latent TGF-β. In addition, TSP-1-knockdown ASCs were administered to mice with colitis to assess their clinical efficacy in vivo.

Results

Systemic administration of ASCs significantly lessened the clinical and histopathological severity of colitis. ASCs were distributed throughout the lymphatic system in the MLNs and spleen. Tregs were increased in the MLNs and CLP, but CD103⁺ dendritic cells were not significantly altered. The ASCs activated latent TGF-β. TSP-1 knockdown impaired TGF-β activation in vitro and abrogated the therapeutic effects of the ASCs in vivo. Furthermore, Tregs were not increased in the MLNs and CLP from mice treated with TSP-1-knockdown ASCs.

Conclusions

These results demonstrate that ASCs induce Tregs by activating latent TGF-β via TSP-1, independent of CD103⁺ dendritic cell induction.

     

Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients

Journal of Gastroenterology - The effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this...     

Clinical impact of endoscopy position detecting unit(UPD-3) for a non-sedated colonoscopy

AIM:To evaluate whether an endoscopy position detecting unit(UPD-3) can improve cecal intubation rates, cecal intubation times and visual analog scale(VAS) pain scores, regardless of the colonoscopist's level of experience.METHODS:A total of 260 patients(170 men and 90women)who underwent a colonoscopy were divided into the UPD-3-guided group or the conventional group(no UPD-3 guidance).Colonoscopies were performed by experts(experience of more than 1000colonoscopies)or trainees(experience of less than 100colonoscopies).Cecal intubation rates,cecal intubation times,insertion methods(straight insertion:shortening the colonic fold through the bending technique;roping insertion:right turn shortening technique)and patient discomfort were assessed.Patient discomfort during the endoscope insertion was scored by the VAS that was divided into 6 degrees of pain.RESULTS:The cecum intubation rates,cecal intubation times,number of cecal intubations that were performed in15 min and insertion methods were not significantly different between the conventional group and the UPD-3-guided group.The number of patients who experienced pain during the insertion was markedly less in the UPD-3-guided group than in the conventional group.Univariate and multivariate analysis showed that the following factors were associated with lower VAS pain scores during endoscope insertion:insertion method(straight insertion)and UPD-3guidance in the trainee group.For the experts group,univariate analysis showed that only the insertion method(straight insertion)was associated with lower VAS pain scores.CONCLUSION:Although UPD-3 guidance did not shorten intubation times,it resulted in less patient painduring endoscope insertion compared with conventional endoscopy for the procedures performed by trainees.     

Preliminary study of photodynamic diagnosis using 5-aminolevulinic acid in gastric and colorectal tumors

AIM: To investigate the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) to detect gastric/colorectal tumors.METHODS: This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection. Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013. Selection criteria included age 20-80 years, either sex, and provision of informed consent. Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules (SBI ALApromo Co., Tokyo, Japan). Administration of 5-ALA was followed by endoscopic resection of gastric or colorectal tumors, and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope (SAFE-3000 and EB-1970AK, respectively; Pentax, Tokyo, Japan). The primary endpoint was the presence of fluorescence in tumors. Endoscopic, macroscopic, and histopathologic findings of tumors were assessed. We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA, namely, hematocytopenia, liver dysfunction, hypotension, nausea, and photosensitivity.RESULTS: We enrolled 10 patients (7 men, 3 women) (n = 13 lesions: 10 gastric/3 colorectal tumors). Fluorescence was detected in 7/13 (53.8%) lesions. No significant differences in sex (male: 55.6% vs female: 50.5%, P = 1.00), age (67.1 ± 1.9 years vs 65.0 ± 2.0 years, P = 0.45), tumor color (reddish: 60.0% vs discolored: 33.3%, P = 0.56), tumor diameter (15.0 ± 2.1 mm vs 14.2 ± 2.3 mm, P = 0.80), macroscopic type (protruded: 70.0% vs depressed 0%, P = 0.07), histologic type (differentiated type: 58.3% vs 0%, P = 0.46), invasion depth (mucosal layer: 55.6% vs submucosal layer: 33.3%, P = 1.00), lymphatic invasion (present: 33.3% vs absent: 50.0%, P = 1.00), venous invasion (present: 0% vs absent: 54.5%, P = 1.00) or procedure time of endoscopic resection (36.3 ± 8.3 min vs 36.7 ± 9.0 min, P = 0.98) were observed between the patients with and without fluorescence. Fluorescence detection rate tended to be high for elevated lesions. Liver dysfunction developed in 4/10 (40.0%) patients. The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels, which spontaneously improved in the patients. None of the patients developed photosensitivity.CONCLUSION: Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers.     

Complications and Outcome of Free Flap Transfers for Oral and Maxillofacial Reconstruction: Analysis of 213 Cases

Microvascular free flap transfers have become a preferred reconstructive technique; however, rare complications may still prove devastating. This study reviewed 213 consecutive freetissue transfers in order to assess the incidence and causes of complications in patients undergoing microvascular free flap reconstruction in the oral and maxillofacial region. In most cases, reconstruction was undertaken after resection of a malignant tumor. The flap donor sites were the radial forearm (n=111), rectus abdominis (n=88), scapula (n=13), and latissimus dorsi (n=1). The superior thyroid artery and the external jugular vein were commonly used as recipient vessels for anastomosis. The overall flap success rate was 99%. There were 7 cases of postoperative vascular thrombosis (6 venous and 1 arterial), constituting 3.3% of the entire series. Five flaps were salvaged, representing a 71.4% successful salvage rate in cases of vascular complications. Most of the successful salvage attempts were made within 24 hours of the end of the initial operation, and the successful salvage rate for re-exploration was 100%. Finally, the total flap loss rate was 0.9% and the partial flap loss rate was 2.3%. We conclude that early re-exploration should be the first choice for management of vascular compromised flaps. Complications at the donor site occurred in 17 cases (8.0%), the most common complication of which was partial skin graft loss after harvesting a radial forearm flap (n=10; 9.0%). Recipient and donor site morbidity was limited and considered acceptable.