Multicenter epidemiological survey of pneumatosis intestinalis in Japan.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome. METHODS: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion. RESULTS: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425). DISCUSSION: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis.

A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome with Recurrent Olfactory Neuroblastoma.

A 40-year-old woman who had a history of recurrent olfactory neuroblastoma presented with full moon face, central obesity, buffalo hump, impaired glucose tolerance and bilateral cervical lymph node swelling. Laboratory tests showed morbidly elevated levels of adrenocorticotropic hormone (ACTH) and cortisol, which were not suppressed by high-dose (8 mg) dexamethasone. Biopsies of the enlarged cervical lymph nodes revealed ACTH-positive metastatic olfactory neuroblastoma, and ectopic ACTH syndrome was diagnosed. Metyrapone was used to suppress cortisol production and resulted in decreased levels of ACTH and cortisol. Bilateral cervical tumor resection further reduced the ACTH and cortisol levels, accompanied by a reduction in the metyrapone dosage. Cushing's syndrome was alleviated through ACTH-producing tumor removal.

Assessing hypoglycemia frequency using flash glucose monitoring in older Japanese patients with type 2 diabetes receiving oral hypoglycemic agents.

AIM: It is important to consider hypoglycemia for glycemic control in elderly patients with type 2 diabetes. Continuous blood glucose monitoring system is an effective method to investigate blood glucose fluctuation. This study examined hypoglycemia frequency using continuous blood glucose monitoring system in older patients with type 2 diabetes. METHODS: A total of 70 patients with type 2 diabetes aged >65 years, receiving oral treatment only and having a glycated hemoglobin (HbA1c) level of <8% were enrolled. Flash glucose monitoring system was used for the device. Patients were classified into three groups according to the type of medicine administered, in addition to other oral hypoglycemics, and were compared: (i) those taking sulfonylureas (SU); (ii) those taking glinides; and (iii) those who did not take either SU or glinides. RESULTS: There was a significant positive correlation between the coefficient of variation and hypoglycemic frequency in all the patients, and a significant negative correlation between HbA1c and hypoglycemia in those receiving SU. When hypoglycemia was defined as glucose levels <54 mg/dL and <70 mg/dL, the cut-off HbA1c values for developing hypoglycemia were 6.3% and 6.7%, sensitivity was 75.0% and 76.2%, and specificity was 90.9% and 77.6%, respectively. CONCLUSIONS: In older patients with type 2 diabetes receiving SU, hypoglycemic frequency increases with decreases in HbA1c level. In particular, in patients with HbA1c levels of <6.3% receiving SU, it is necessary to consider medication modification. Geriatr Gerontol Int 2019; 19: 1030-1035.

Eradication therapy for Helicobacter pylori infection improves nutrition status in Japanese hemodialysis patients: a pilot study.

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild-moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal atrophy.

[A Case of Rupture of Esophageal Varices during a Course of CAPOX with Bevacizumab Therapy for Sigmoid Colon Cancer with Multiple Liver Metastases].

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan.

The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).

[Reduced-intensity umbilical cord blood transplantation for adult patients with fulminant aplastic anemia].

Allogeneic hematopoietic stem cell transplantation is recommended as a curative treatment option for fulminant aplastic anemia with no neutrophil despite the administration of granulocyte-colony stimulating factor. In the absence of an HLA-matched donor, unrelated cord blood transplantation (UCBT) is a treatment option that can be performed quickly. However, the optimal conditioning regimen of UCBT is yet to be established. We report two cases of fulminant aplastic anemia in adult patients who received UCBT. The first patient was a 52-year-old woman and the second was a 26-year-old man, both of whom received a conditioning regimen of total body irradiation (TBI; 2-4 Gy), fludarabine (Flu; 120 mg/kg), and cyclophosphamide (CY; 100 mg/kg) before UCBT. Short-term methotrexate and tacrolimus were used for prophylaxis of acute graft-versus-host disease (GVHD). Engraftments were achieved on days 26 and 19, and they exhibited complete donor chimerism by days 28 and 34. There was no evidence of acute GVHD, and therefore, the immunosuppressant drugs were discontinued. Reduced-intensity UCBT using a low-dose TBI/Flu/CY conditioning regimen could be an effective treatment option for fulminant aplastic anemia in the absence of a suitable donor.

Clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma.

The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule-containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May-Giemsa staining. The patients were classified into two groups, the granule-containing myeloma (GM) and nongranule-containing myeloma (non-GM) groups, depending on the proportion of myeloma cells that contained granules (cut-off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non-GM group (t-test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow-up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non-GM group; 4-year OS of the GM and non-GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule-containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

Optimal management for patients not meeting the inclusion criteria after endoscopic submucosal dissection for gastric cancer.

BACKGROUND: The necessity of additional gastrectomy for patients not meeting the inclusion criteria after endoscopic submu cosal dissection (ESD) is controversial. The aim of this study was to elucidate the risk factors for lymph node metastasis (LNM) and residual cancer (RC) in patients not meeting the inclusion criteria after ESD and to determine additional treatment strategies. METHODS: Of 1443 gastric cancer patients who underwent ESD between 2004 and 2013, 167 patients diagnosed as having a lesion not meeting the inclusion criteria after ESD were retrospectively analyzed. Of the 167 cases, 100 cases underwent additional gastrectomy, and 67 cases were observed without surgery. RESULTS: Overall, 9.0 % (9/100) and 9.0 % (9/100) of patients not meeting the inclusion criteria after ESD presented with LNM and RC, respectively, but neither was observed in 83 patients (83.0 %). Multivariate analysis revealed that lymphovascular involvement (LVI) (OR 38.38; 95 % CI 1.94-761.43, p = 0.017) and undifferentiated type (OR 45.58; 95 % CI 2.88-720.94, p = 0.007) were independent risk factors for LNM, and positive horizontal margin was an independent risk factor for RC (OR 9.48; 95 % CI 1.72-52.13, p = 0.010). In differentiated types without LVI, no cases had LNM (0/38) in the additional gastrectomy group, and there was no lymph node or distant recurrence (0/39) in the observation group. CONCLUSIONS: Additional treatment is necessary for patients with LVI, undifferentiated type, and positive horizontal margin. Careful follow-up may be acceptable for patients with the differentiated type without LVI, especially for the elderly or patients with severe comorbidities.

Human T-cell Lymphotropic Virus Type-1 (HTLV-1)-associated Bronchioloalveolar Disorder Presenting with Mosaic Perfusion.

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a specific state with chronic and progressive respiratory symptoms caused by bronchiolar or alveolar disorder characterized by smoldering adult T-cell leukemia or the HTLV-I carrier state. We herein report a rare case of HABA with an initial presentation of mosaic perfusion in the lung. The diagnosis was made according to the results of a flow cytometry analysis of the bronchoalveolar lavage fluid and pathological findings. Clinicians must be careful to recognize that mosaic perfusion may be a radiological finding of HABA.

Pulmonary Nocardia nova infection after allogeneic hematopoietic stem cell transplantation.

We herein report the case of a 68-year-old man with a history of allogeneic hematopoietic stem cell transplantation for acute myelocytic leukemia in whom graft-versus-host disease (GVHD) developed in the gastrointestinal tract and liver five months after transplantation. In that same period, chest computed tomography showed infiltration in both upper lungs. We performed bronchoscopy to clarify the GVHD and pulmonary infection. Nocardia nova was identified in the bronchoalveolar lavage fluid, and we diagnosed the patient as having pulmonary nocardiosis. Because the differential diagnosis is important for the medical management of GVHD and pulmonary infection, performing bronchoscopy is essential for making an appropriate and rapid diagnosis.

[A case of paralytic ileus associated with varicella zoster virus infection].

A 79-year-old woman with a history of pyothorax was admitted with a 4-day history of abdominal distension. Physical examination revealed marked abdominal distention, absent bowel sounds, and a vesicular rash over the left Th8-10 dermatome. Abdominal radiography showed gaseous distension of the colon and ileum. Colonoscopy excluded any obstructive process of the colon. Laboratory findings yielded positive results for serum IgM and IgG against the varicella zoster virus (VZV) . Paralytic ileus associated with the VZV was therefore diagnosed. The ileus improved after conservative treatment with intravenous acyclovir. Although shingles is frequently encountered, it is a rare cause of paralytic ileus. In the future, the VZV should be considered as one of the causes of paralytic ileus, and complete resolution can be achieved with conservative management.

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

[A case of primary biliary cirrhosis with systemic lymph node enlargement].

A 40's woman was hospitalized with cervical lymph node enlargement. Laboratory examinations showed elevated serum bile duct enzymes and the presence of anti-mitochondrial antibody. Abdominal ultrasonography and computed tomography showed enlargement of not only perihepatic lymph nodes, but also axillary and cervical lymph nodes. FDG-PET showed intense uptake concordant with these lymph nodes. We performed endoscopic ultrasonographic fine-needle aspiration biopsy of a perihepatic lymph node, but detected no malignant cells. We then performed liver biopsy, and obtained a histological diagnosed primary biliary cirrhosis. Systemic lymph nodes decreased together with serum bile duct enzyme levels during treatment with ursodeoxycholic acid.

[A case of autoimmune pancreatitis with multifocal mass lesions].

We present a case of a 73-year-old man with multifocal autoimmune pancreatitis (AIP) in the pancreatic head and tail, and who had undergone sigmoidectomy and rectectomy 28 months before presenting to our department. Upon presentation, his serum IgG4 level was elevated at 267mg/dl, but tumor marker levels were within normal ranges. CT and MRI showed two localized pancreatic masses with delayed enhancement, but endoscopic retrograde pancreatography revealed neither stenosis nor dilatation of the main pancreatic duct. FDG-PET examination showed intense uptake in regions concordant with both tumors. The possibility of atypical AIP was a concern, but malignant tumor could not be clinically or radiologically excluded. Endoscopic ultrasonographic fine-needle aspiration biopsy was performed, but no malignant cells were detected. The patient underwent subsequent distal pancreatectomy. Histological evaluation of the tumors showed the presence of many IgG4-positive plasma cells without any evidence of malignancy.

Cancer of unknown primary site: a review of 28 cases and the efficacy of cisplatin/docetaxel therapy at a single institute in Japan.

We evaluated the efficacy and toxicity of cisplatin/docetaxel (CDDP/TXT) chemotherapy and identified prognostic factors in Japanese patients with cancer of unknown primary site (CUP). Twenty-eight consecutive patients seen at a single institute were reviewed retrospectively. Sixteen patients were treated with TXT 80 mg/m2, followed by CDDP 75 mg/m2. The overall response rate to CDDP/TXT treatment was 62.5%, with a median survival time (MST) of 22.7 months. Common adverse reactions were myelosuppression and hyponatremia. The MST of all 28 patients with CUP was 8.3 months, and the 1-year overall survival rate was 45.6%. Univariate analysis identified 5 prognostic factors:performance status, liver involvement, bone involvement, pleural involvement, and lymph node involvement. In conclusion, CDDP/TXT chemotherapy is effective with tolerable toxicity in patients with CUP. Japanese patients with CUP might be chemosensitive and may survive longer.

A case of mesenteric lymphadenitis with long-acting symptom, showing marked response to corticosteroid.

A 17-year-old girl who had right lower abdominal pain with multiple swelling of lymph nodes in the ileocecal region and she was admitted to a neighboring hospital. Since there was no improvement of condition with antibiotic resistance, we were consulted. Lymph node biopsy under laparoscopy demonstrated nonspecific findings. She then developed erythema nodosum, suggesting the presence of autoimmune etiology. Treatment with systemic corticosteroid resulted in symptomatic improvement. Mesenteric lymphadenitis like this case is rare.