Predictive factors for fundoplication following esophageal atresia repair.

BACKGROUND: One of the most frequent complications after repair of esophageal atresia (EA) is gastroesophageal reflux disease (GERD). Although GERD-associated EA is known to often require anti-reflux surgery, the predicting factors remain unclear. We retrospectively analyzed EA in our institution. METHODS: Of 65 children with EA treated in our hospital from 1995 to 2018, 45 with Gross C type EA, followed for over 1 year, were enrolled in this study. The patients were divided into fundoplication and non-fundoplication groups and compared in terms of their clinical features. RESULTS: The fundoplication and non-fundoplication groups included 13 and 32 cases, respectively. On univariate analysis, gestational age, body weight, prenatal diagnosis, polyhydramnios, re-do surgery, and gap length of the esophagus differed significantly between the groups (P < 0.05). CONCLUSION: Early delivery, low body weight, and a long gap length are, are considered to be risk factors for fundoplication. However, the present study further showed that prenatal diagnosis and polyhydramnios were also significant contributing factors. The presence of a prenatal diagnosis and polyhydramnios may induce preterm delivery, therefore, cases of polyhydramnios due to suspected EA should be managed to prevent early delivery. Better understanding of the postnatal course after surgery is required, especially for prenatal diagnosis cases.

Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model.

PURPOSE: Mouse IgG anti-disialoganglioside GD2 antibody-secreting mouse mesenchymal stem cells (anti-GD2-MSCs) were developed, and their anti-tumor effects were validated in an in vivo neuroblastoma mouse model. METHODS: Anti-GD2 antibody constructs were generated, incorporating FLAG-tagged single-chain fragment variables against GD2 fused to a linker sequence, and a fragment of a stationary portion was changed from human IgG to mouse IgG and GFP protein. The construct was lentivirally introduced into mouse MSCs. A syngeneic mouse model was established through the subcutaneous transplantation of a tumor tissue fragment from a TH-MYCN transgenic mouse, and the homing effects of anti-GD2-MSCs were validated by In vivo imaging system imaging. The syngeneic model was divided into three groups according to topical injection materials: anti-GD2-MSCs with IL-2, IL-2, and PBS. The tumors were removed, and natural killer (NK) cells were counted. RESULTS: Anti-GD2-MSCs showed homing effects in syngeneic models. The growth rate of subcutaneous tumors was significantly suppressed by anti-GD2-MSCs with IL-2 (p < 0.05). Subcutaneous tumor immunostaining showed an increased NK cell infiltration in the same group (p < 0.01). CONCLUSION: Anti-GD2-MSCs using mouse IgG showed a homing effect and significant tumor growth suppression in syngeneic models. Anti-GD2-MSC-based cellular immunotherapy could be a novel therapeutic strategy for intractable neuroblastoma.

[A Case of Cancerous Meningitis in Juvenile Onset Gastric Cancer].

A 30-year-old woman was diagnosed with advanced gastric cancer(MUL, Circ, Type 4, por1+2, T4a, N3a, M1[LYM, P1, CY1, H0], Stage Ⅳ)on delivery. Because of unresectable, she underwent chemotherapy(first-line: S-1 plus CDDP, secondline: PTX plus Rmab, and third-line: Nmab); approximately 10 months later, she started complaining of headache. We performed a close examination, because she also developed resistance to chemotherapy. Contrast-enhanced magnetic resonance imaging of the brain revealed intense and diffuse enhancement on the brain surface, leading to the suspicion of meningeal carcinomatosis. However, hydrocephalus did not occur. She was given steroids to alleviate symptoms, but this treatment did not effective. We used neither intrathecal chemotherapy nor radiation therapy. Her symptoms gradually worsened, and she died approximately 4 weeks after the diagnosis of meningeal carcinomatosis. Meningeal carcinomatosis resulting from gastric cancer is very rare and is often difficult to diagnose. Even though this type of disease is diagnosed correctly, rapid disease progression makes the treatment difficult; therefore, patients with this type of disease have a terribly poor prognosis in daily clinical practice.

[A Study of 15 Patients with Colorectal Cancer Perforation, Kyoto Chubu Medical Center].

In colorectal cancer perforation, selecting the appropriate surgical operation while considering the patient's life and radical treatment is important. We divided 15 patients who underwent surgical intervention at our department into 2 groups, namely, free and covering perforation groups, and conducted a retrospective analysis. In the comparison between the 2 groups (free vs covering), there were 11 vs 4 cases with similar morphology, 2 vs 0 cases of perioperative death, and 3 vs 0 cases of recurrence, respectively. For the 2 groups(free vs covering), the SOFA score was 1.72 vs 1.0, postoperative chemotherapy enforcement rate was 55%vs 75%, start time was 59.4 days vs 40.3 days, and postoperative PMX implementation was 6 vs 0, respectively. All cases of recurrence and perioperative deaths were from the free perforation group. In free perforation, patients have a high risk of sepsis before surgery, and postoperative chemotherapy cannot be performed smoothly and completed. This leads to an increase in the relapse rate. It is important to select the appropriate operative method for curability and to perform postoperative chemotherapy without delay, especially in covering perforation.

Development of anti-GD2 Antibody-producing Mesenchymal Stem Cells as Cellular Immunotherapy.

BACKGROUND/AIM: Using the tyrosine hydroxylase (TH)-MYCN mouse neuroblastoma (NB) model, we have previously reported the accumulation of mouse mesenchymal stem cells (mMSCs) on tumors in vivo and the antitumor effect of mMSCs transfected with a small molecule (IFN-ß) expression gene. In this study, we have developed novel MSCs secreting anti-disialoganglioside GD2 antibody (anti-GD2-MSCs) and evaluated their antitumor effects in vitro. MATERIALS AND METHODS: We generated an anti-GD2 antibody construct (14.G2a-Fcx2-GFP) incorporating FLAG-tagged single-chain fragment variable against GD2 fused to a linker sequence, a fragment of the constant portion of human IgG1, and GFP protein. The construct was lentivirally transduced into mMSCs and the transduction efficiency was assessed by GFP expression. The secretion of FLAG-tagged anti-GD2 antibody was detected by Western blotting using anti-FLAG antibody. Antibody binding capacity was confirmed by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was evaluated using human NB cells and human natural killer (NK) cells to assess whether the antitumor activity was enhanced in the presence of the produced antibodies. RESULTS: The transduction efficiency of anti-GD2-MSCs was more than 90%. anti-GD2-MSCs secreted antibodies extracellularly and these antibodies had high affinity to GD2-expressing human NB cells. ADCC assays showed that the addition of antibodies secreted from anti-GD2-MSCs significantly increased the cytotoxic activity of NK cells against NB cells. CONCLUSION: Newly developed anti-GD2-MSCs produced functional antibodies that have affinity to the GD2 antigen on NB cells and can induce ADCC-mediated cytotoxicity. Anti-GD2-MSCs based cellular immunotherapy has the potential to be a novel therapeutic option for intractable NB.

Is pneumoperitoneum necessary for single-incision laparoscopy-assisted appendectomy for pediatric appendicitis?

INTRODUCTION: Several studies have reported the treatment of pediatric appendicitis with single-incision laparoscopy-assisted appendectomy using a muscle hook without pneumoperitoneum to lift the abdominal wall. However, very few studies have investigated the advantages of this procedure. We examined the utility of this procedure in our department. METHODS: This study included 33 children with appendicitis who underwent single-incision laparoscopy-assisted appendectomy at our hospital from April 2011 to March 2018. Patients were divided into two groups depending on whether they underwent the procedure with pneumoperitoneum: the no pneumoperitoneum group (n = 12) and the pneumoperitoneum group (n = 21). The clinicopathological factors and surgical costs were compared between the two groups. RESULTS: In the pneumoperitoneum group, the procedure was initiated in four patients by lifting the abdominal wall but was changed to include a pneumoperitoneum because of difficulty. There were no significant differences between the two groups with regard to age, sex, or pathological severity. CT revealed a significant difference in the distance from the appendicular root to the umbilicus between the groups. There was a significant difference in the operative duration, but not in estimated blood loss or length of postoperative hospital stay. Complications were observed in one patient in each group. There was a significant difference in cost between the two groups. CONCLUSIONS: Single-incision laparoscopy-assisted appendectomy without pneumoperitoneum is less expensive because certain supplies and CO2 are not required. Because there were no differences in the length of postoperative hospital stay or complications, this procedure may be safe in cases that are expected to be mild.

Early Neuropathy Related to Oxaliplatin Treatment in Advanced and Recurrent Colorectal Cancer.

BACKGROUND/AIM: Chemotherapy dose adjustments in colorectal cancer are usually based on body surface area (BSA). The goal of this study was to investigate patients with nutritional disorder who developed early peripheral neuropathy due to inappropriate dose adjustment of oxaliplatin. PATIENTS AND METHODS: The study subjects were 88 patients with advanced or recurrent colorectal cancer who underwent chemotherapy with oxaliplatin. The psoas muscle area (PMA) was used as a nutritional index. Mild (grades 0-1, MN group) and severe (grades 2-3, SN group) peripheral neuropathy was defined using neurotoxicity criteria of Debiopharm. RESULTS: Severe peripheral neuropathy developed in 29 patients (33.0%). The total oxaliplatin dose/PMA was significantly higher for the SN group (107.6±8.5 mg/cm2) and compared with the MN group (53.8±6.0 mg/cm2) in univariate (p<0.0001) and multivariate (p=0.012) analyses. CONCLUSION: In order to prevent peripheral neuropathy from chemotherapy for colorectal cancer, dose adjustment of oxaliplatin should be based on PMA, in addition to BSA.