Sonographic findings in two cases of lymphangioma of the mesocolon in adults.

Lymphangioma of the mesocolon is very rare. We report two cases of surgically resected and histologically proven mesocolic lymphangioma in adults. In both cases, ultrasound revealed a large cystic mass with multiple thin septa in the lower abdomen. A peculiar finding was the large craniocaudal sliding movement of the mass synchronized with the patient's respiration, which was a clue to the diagnosis of mesenteric lymphangioma. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:78-81, 2018.

Successful Treatment with 5-fluorouracil and Levofolinate Calcium in Advanced Gastric Cancer Patient with Disseminated Intravascular Coagulation.

A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.

Modified administration schedule of docetaxel, cisplatin, and fluorouracil for advanced or recurrent gastric cancer with gastrointestinal stenosis.

PURPOSE: To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF)in patients with advanced gastric cancer with gastrointestinal stenosis in clinical practice. METHODS: In the chemotherapy-naïve patients who had metastatic or recurrent histologically confirmed gastric cancer, docetaxel(40mg/m2), levofolinate(200mg/m / / / 2), fluorouracil(400mg/m2)on day 1, fluorouracil 1,000 mg/m2d-2 days intravenous continuous in fusion beginning on day 1, and cisplatin(40mg/m2)on day 3 was administered every 2 weeks. RESULTS: Six patients received mDCF therapy. In 5 patients with measurable disease, the overall response rate was 86%. Median progression-free survival was 310 days and median overall survival was 599 days. Symptom improvement after the first cycle of mDCF was obtained in all patients. Grade 3 or 4 leukopenia and neutropenia were observed in 2(33%)and 6(100%)patients, respectively. There were no treatment-related deaths. CONCLUSION: mDCF seems to be active against metastatic and recurrent gastric cancer with gastrointestinal stenosis. Further study is needed to confirm the efficacy and safety of mDCF regimen.

Spontaneous Resolution of Strangulated Small Bowel Obstruction in a Patient With Intestinal Tuberculosis After Starting Anti-tuberculosis Drugs: A Case Report.

Intestinal tuberculosis can cause strangulated small bowel obstruction. Strangulated small bowel obstruction usually requires surgery. We report a case of a patient with intestinal tuberculosis, who developed a spontaneously resolving strangulated small bowel obstruction after the commencement of anti-tuberculosis drugs. A 72-year-old woman presented with abdominal pain and ascites was noticed on abdominal ultrasonography. Contrast-enhanced computed tomography (CT) revealed a 50-mm tumor in the ileocecal region that was darkly contrasted, along with peritoneal thickening and ascites. A malignant tumor and carcinomatous peritonitis were suspected. Colonoscopy showed an ulcerative lesion in the terminal ileum, and the acid-fast bacillus culture was positive; therefore, the patient was diagnosed with intestinal tuberculosis and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. After commencing treatment, improvement in peritoneal thickening and ascites was confirmed using abdominal ultrasonography; therefore, we concluded that the ascites was due to tuberculous peritonitis. Six weeks after the initiation of treatment, the patient visited our facility with complaints of abdominal pain. Contrast-enhanced CT revealed unenhanced small intestinal walls, and a diagnosis of strangulated small bowel obstruction was made; however, her symptoms improved naturally. Strangulated small bowel obstruction was presumed to be due to the presence of bands as anti-tuberculosis therapy could promote fibrosis. In this case, abdominal ultrasonography was useful in the evaluation of the effects of treatment.

A case of intussusception caused by cecal duplication after COVID-19.

Coronavirus disease 2019 (COVID-19) was thought to have respiratory symptoms as the main manifestation, but it has become clear that extrapulmonary symptoms such as gastrointestinal disorders also occur. There are several reports of intussusception associated with COVID-19 in children, but these are rare in adults. In this report, we present a case of cystic intestinal duplication that enlarged during the course of COVID-19 treatment and resulted in intussusception. Right hemicolectomy was performed for intussusception due to the cystic lesion. To the best of our knowledge, this is the first resected case of intussusception due to alimentary tract duplication after COVID-19 infection.

A case of gastric cancer with delayed onset of tumor reduction effect by nivolumab therapy.

Immune checkpoint inhibitors may have different clinical effects compared with conventional anticancer drugs. An 85-year-old male received chemotherapy for recurrent gastric cancer. As liver metastasis progressed, nivolumab was introduced as a fourth line treatment. Progression of liver metastasis in size was observed in CT after 3 courses of nivolumab therapy. Nivolumab treatment was discontinued, because the general condition of the patient also worsened. However, his general condition improved as hepatobiliary enzyme levels, inflammatory response, and tumor markers improved. Liver metastasis was shrinking on the image, so we resumed nivolumab therapy. To the authors' knowledge, this is the first case of pseudoprogression undergoing immunotherapy for gastric cancer. In this case, the antitumor effect was exhibited in a delayed manner and the tumor shrinkage was obtained.

Effect of donor age on function of isolated human islets.

This study intended to evaluate the impact of donor age on the function of isolated islets. Analysis of human islets from cadaveric donors (age 16-70 years) was performed using glucose-stimulated insulin release (GSIR) (n = 93), islet ATP content (n = 27), diabetic nude mouse bioassay (n = 72), and the insulin secretory function after single-donor clinical islet allotransplantation (n = 7). The GSIR index was significantly higher in younger donors (age < or =40 years) than in older donors and negatively correlated with the donor age (r = -0.535). Islet ATP was higher in younger donors (115.7 +/- 17.7 vs. 75.7 +/- 6.6 pmol/microg DNA). The diabetes reversal rate of mice with 2,000 IE was significantly higher in younger donors (96 vs. 68%). C-peptide increment to glucose during intravenous glucose tolerance test at days 90-120 after clinical transplantation showed negative correlation with donor age (r = -0.872) and positive correlation with the islet mass (r = 0.832). On the other hand, acute insulin response to arginine only showed correlation with the islet mass and not with donor age. These results show that insulin secretory response to glucose deteriorates with increasing age and that it may be related to changes in ATP generation in beta-cells.

Preoperative evaluation of irreversible bowel ischemia in obturator hernia.

BACKGROUND/AIMS: Obturator hernia presenting in elderly women accompanies a high rate of bowel resection because of strangulation. Open laparotomy is usually indicated in general anesthesia. However, minimal invasive approaches would be advantageous unless resection is necessary. We aimed to determine clinical and radiological criteria for the selection of these patients. METHODOLOGY: Preoperative clinical data from 23 cases and known signs of ischemia on CT examination were retrospectively compared to operative findings. RESULTS: Identification of patients having necrotic bowel was not possible by any clinical parameter or their combination. Patients with necrosis had longer history of symptoms, but acute onset less than 24 h does not exclude the need of resection (negative predictive value 83%). Impaired contrast enhancement was frequently seen on CTs independently from the onset of symptoms suggesting early vascular compromise (sensitivity 80%, specificity 22%), but not helping the differentiation. Signs of ischemia (bowel wall thickening and/or ascites) were present in every resected case while both were absent in 69% of patients having viable bowel. CONCLUSIONS: Absence of ischemic signs on nonenhanced CT may allow safe and more accurate selection of patients for minimal invasive surgery than any clinical or anamnestic parameter in obturator hernia.

Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure.

Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting requires transplantation of a sufficient number of islets, usually requiring two or more donors. During the isolation process and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. Here, we have mapped the major intracellular stress-signaling pathways that may mediate human islet loss during isolation and following cytokine attack. We found that the isolation procedure potently recruits two pathways consisting of |mitogen-activated protein kinase kinase (MKK)7 --> Jun NH(2)-terminal kinase (JNK)/p38 --> c-fos| and the |nuclear factor-kappaB (NF-kappaB) --> iNOS| module. Cytokines activate the |NF-kappaB --> iNOS| and |MKK4/MKK3/6 --> JNK/p38| pathways without recruitment of c-fos. Culturing the islets for 48 h after isolation allows for the activated pathways to return to background levels, with expression of MKK7 becoming undetectable. These data indicate that isolation and cytokines recruit different death pathways. Therefore, strategies might be rationally developed to avoid possible synergistic activation of these pathways in mediating islet loss during isolation and following grafting.

Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.

CONTEXT: Islet allografts from 2 to 4 donors can reverse type 1 diabetes. However, for islet transplants to become a widespread clinical reality, diabetes reversal must be achieved with a single donor to reduce risks and costs and increase the availability of transplantation. OBJECTIVE: To assess the safety of a single-donor, marginal-dose islet transplant protocol using potent induction immunotherapy and less diabetogenic maintenance immunosuppression in recipients with type 1 diabetes. A secondary objective was to assess the proportion of islet transplant recipients who achieve insulin independence in the first year after single-donor islet transplantation. DESIGN, SETTING, AND PARTICIPANTS: Prospective, 1-year follow-up trial conducted July 2001 to August 2003 at a single US center and enrolling 8 women with type 1 diabetes accompanied by recurrent hypoglycemia unawareness or advanced secondary complications. INTERVENTIONS: Study participants underwent a primary islet allotransplant with 7271 (SD, 1035) islet equivalents/kg prepared from a single cadaver donor pancreas. Induction immunosuppression was with antithymocyte globulin, daclizumab, and etanercept. Maintenance immunosuppression consisted of mycophenolate mofetil, sirolimus, and no or low-dose tacrolimus. MAIN OUTCOME MEASURES: Safety (assessed by monitoring the severity and duration of adverse events) and efficacy (assessed by studying the recipients' insulin requirements, C-peptide levels, oral and intravenous glucose tolerance results, intravenous arginine stimulation responses, glycosylated hemoglobin levels, and hypoglycemic episodes) associated with the study transplant protocol. RESULTS: There were no serious, unexpected, or procedure- or immunosuppression-related adverse events. All 8 recipients achieved insulin independence and freedom from hypoglycemia. Five remained insulin-independent for longer than 1 year. Graft failure in 3 recipients was preceded by subtherapeutic sirolimus exposure in the absence of measurable tacrolimus trough levels. CONCLUSIONS: The tested transplant protocol restored insulin independence and protected against hypoglycemia after single-donor, marginal-dose islet transplantation in 8 of 8 recipients. These results may be related to improved islet engraftment secondary to peritransplant administration of antithymocyte globulin and etanercept. These findings may have implications for the ongoing transition of islet transplantation from clinical investigation to routine clinical care.

Improved islet yield and function with ductal injection of University of Wisconsin solution before pancreas preservation.

BACKGROUND: Ensuring sufficient islet yield from preserved pancreases is a critical step in clinical islet transplantation. The aim of this study was to investigate whether pancreatic ductal injection, performed at procurement, using a small volume of preservation solution before cold storage (ductal preservation method) would improve islet yield and function from rat pancreases preserved for 6 and 24 hr. MATERIALS AND METHODS: Islets were isolated from Lewis rats. Pancreases were classified into five groups: fresh (group 1); preserved for 6 hr in University of Wisconsin solution without and with ductal preservation (groups 2 and 3); and preserved for 24 hr in University of Wisconsin solution without and with ductal preservation (groups 4 and 5). We assessed islet yield, function, and viability of pancreatic ductal cells. RESULTS: Islet yields per pancreas in groups 1 to 5 were 2010+/-774, 674+/-450, 1418+/-528, 527+/-263, and 1655+/-618 (islet equivalent) (+/-SD), respectively. Stimulation indices in groups 1 to 5 were 11.97+/-3.17, 6.48+/-4.04, 12.44+/-5.65, 2.56+/-2.03, and 5.55+/-2.71. Functional success rates in groups 1 to 5 were 100%, 0%, 100%, 0%, and 66.7%. Percentages of nonviable pancreatic duct cells in groups 1 to 5 were 3.8+/-2.7%, 59.7+/-4.4%, 19.5+/-7.3%, 64.7+/-4.5%, and 17.2+/-2.6%. In all experiments, the differences were significant between the groups without versus the groups with ductal preservation (P<0.05, group 2 vs. group 3 and group 4 vs. group 5). CONCLUSIONS: Ductal preservation improved islet yield and function after 6 and 24 hr of preservation. Well-preserved pancreatic ducts maintained good distribution of collagenase solution.

Improvement in islet yield from obese donors for human islet transplants.

BACKGROUND: The feasibility of human islet transplantations has been firmly established. To increase the number of islet transplants, the suitability of pancreases from organ donors considered inappropriate for pancreas transplantations must be evaluated. METHODS: We isolated islets from 114 human cadaver donor pancreases by the automated Ricordi method, followed by purification using continuous-density gradients. We divided the pancreases into two groups by donor body mass index (BMI)--group 1: n=51, BMI of 30 or more; group 2: n=63, BMI of less than 30. We compared the results of human islet isolation, in vitro potency assays, and a nude mouse bioassay. RESULTS: In group 1 (vs. group 2), we found a significantly higher mean pancreas weight (109.5+/-30.7 vs. 90.6+/-24.0 g; P=0.0002); higher mean islet equivalents/pancreas, after digestion (442,565+/-238,741 vs. 289,860+/-158,995; P<0.0001) and after purification (319,129+/-164,002 vs. 215,753+/-126,089; P=0.0002); and a higher islet isolation success rate--defined as isolations yielding more than 300,000 islet equivalents/pancreas, with purities of more than 50% (37.3% [19 of 51 pancreases] vs. 15.9% [10 of 63]; P=0.009). Our in vitro potency assays and bioassay uncovered no differences between the two groups. Notably, all except one of the donor BMIs for the successful isolations in group 2 exceeded 26; the mean donor BMI for the successful isolations (27.3+/-3.0, n=10) was significantly higher than for the unsuccessful isolations (24.8+/-3.3, n=53) (P=0.03). CONCLUSIONS: Pancreases from both overweight (BMI > or = 26 but <30) and obese (BMI > or = 30) cadaver donors are suitable for islet isolation and transplantations. Their use could increase the size of the islet donor pool.

Caspase-3 inhibitor prevents apoptosis of human islets immediately after isolation and improves islet graft function.

OBJECTIVES: Apoptosis appears in islets after isolation, and it has a detrimental effect on the islet function. To improve the outcome of clinical islet transplantation, it is crucial to protect islets from apoptosis. The aim of this study was to determine whether a caspase-3 inhibitor (Z-DEVD-FMK) added to culture media protects islets from apoptosis and to compare the effects of fetal bovine serum (FBS) with human serum albumin (HSA) as a protein supplement in culture. METHODS: Isolated human islets were cultured under 4 different conditions: 0.5% HSA (control), 0.5% HSA + 25 micromol/L Z-DEVD-FMK, 0.5% HSA + 100 micromol/L Z-DEVD-FMK and 10% FBS for 2 days. Next, 1000 IEQ islets precultured with 0.5% HSA and with or without 100 micromol/L Z-DEVD-FMK were transplanted to diabetic nude mice. RESULTS: The islet yields were higher in Z-DEVD-FMK-treated groups, and the inhibitor prevented apoptosis dose dependently. The yield and insulin release were higher in FBS-treated group than in the control group, but FBS did not affect apoptosis. All 6 mice transplanted with islets pretreated with Z-DEVD-FMK, and 3 of 8 mice with control islets became normoglycemic posttransplantation. CONCLUSION: Z-DEVD-FMK prevented apoptosis of isolated human islets and improved its function. FBS (10%) improved the islet yield and insulin secretion more than 0.5% HSA.

Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody.

We sought to determine whether or not optimizing pancreas preservation, islet processing, and induction immunosuppression would facilitate sustained diabetes reversal after single-donor islet transplants. Islets were isolated from two-layer preserved pancreata, purified, cultured for 2 days; and transplanted into six C-peptide-negative, nonuremic, type 1 diabetic patients with hypoglycemia unawareness. Induction immunosuppression, which began 2 days pretransplant, included the Fc receptor nonbinding humanized anti-CD3 monoclonal antibody hOKT3gamma1 (Ala-Ala) and sirolimus. Immunosuppression was maintained with sirolimus and reduced-dose tacrolimus. Of our six recipients, four achieved and maintained insulin independence with normal HbA1c levels and freedom from hypoglycemia; one had partial islet graft function; and one lost islet graft function 2 weeks post-transplant. The four insulin-independent patients showed prolonged CD4+ T-cell lymphocytopenia; inverted CD4:CD8 ratios; and increases in the percentage of CD4+CD25+ T cells. These cells suppressed the in-vitro proliferative response to donor cells and, to a lesser extent, to third-party cells. Severe adverse events were limited to a transient rash in one recipient and to temporary neutropenia in three. Our preliminary results thus suggest that a combination of maximized viable islet yield, pretransplant islet culture, and preemptive immunosuppression can result in successful single-donor islet transplants.