Vascular access management of hemodialysis patients at the bedside using point-of-care ultrasound.

When vascular access (VA) for hemodialysis is established using an autologous fistula or synthetic graft, repeated damage from needle insertion at each dialysis session can lead to thrombosis, resulting in vascular stenosis or occlusion that can cause poor blood removal, elevated venous pressure, and other impairments of blood flow. Compact, high-performance ultrasound devices have been developed in recent years. Such devices are used for point-of-care ultrasound (POCUS), which has been used on many occasions for emergency evaluation in the dialysis room and is becoming an important tool in VA management. POCUS provides a wealth of imaging information, such as needle position, whether the needle is inside or outside the blood vessel, and lesion position, width, and depth. This allows clinicians to detect VA problems early and take suitable measures, such as changing the cannulation site, thereby avoiding the need for unnecessary and highly invasive angiography or surgical procedures.

[A Case of Primary Breast Cancer and Gastric Cancer Metastasis to the Skin-Usefulness of Immunohistochemistry in Differentiating Primary Breast Cancer from Metastatic Breast Cancer].

We herein report the case of a 76-year-old female patient who had undergone gastrectomy for advanced gastric cancer (histologically tubular adenocarcinoma)before 5 months, presenting with abdominal skin tumor. A skin biopsy revealed tubular adenocarcinoma. Positron emission tomography-computed tomographic scanning detected right breast tumor. A partial mastectomy of the right breast and local resection of abdominal skin tumor were performed and both tumors depicted similar histology of tubular adenocarcinoma in routine pathological examination. Immunohistochemically, positive for CDX2 and MUC5AC in previously resected gastric cancer and skin tumor tissues, whereas negative for both antigens in breast cancer. Thus, the final pathological diagnosis demonstrated skin metastasis originating from gastric cancer and primary breast cancer(invasive ductal carcinoma)histologically mimicking gastric cancer. We emphasize difficulties in diagnosis of this situation and that immunohistochemistry is helpful to distinguish primary breast cancer from gastric cancer metastasizing to the breast.

[Postoperative Recurrence of Pancreatic Cancer Successfully Treated with the Gemcitabine plus Oxaliplatin Regimen Resulting in Long-Term Survival-ACase Report].

A 38-year-old woman who presented with complaints of back pain was diagnosed with cancer of the pancreatic body. Since invasion of the celiac artery/superior mesenteric artery was suspected, she was referred to our department for chemotherapy. She received 4 courses of gemcitabine plus S-1(GS), and she underwent distal pancreatectomy with en bloc celiac axis resection/portal vein resection/reconstruction using a left renal vein graft(OP-CAR). Histopathological examination of the resected specimen revealed a positive margin(R1). She received 11 courses of GS as postoperative adjuvant chemotherapy. She developed marked abdominal distension due to metastatic ovarian enlargement, and bilateral salpingo-oophorectomy was performed. The intraoperative findings revealed multiple peritoneal dissemination. Peritoneocentesis was performed, and the patient was started on gemcitabine plus oxaliplatin(GEMOX)for control of the ascites. This treatment was followed by a rapid decrease in the size of the ascites and resolution of the symptoms of stenosis. The serum tumor marker levels decreased over the following 18months. She received a total of 35 courses of GEMOX. This patient showed long-term survival after the start of treatment: she survived for 5 years and 11 months after the initial examination and for 5 years and 6 months after the surgery. Our experience in this case suggests that GEMOX could be a useful treatment option to improve prognosis.

An in vitro evaluation of the influence of neonatal endotracheal tube diameter and length on the work of breathing.

BACKGROUND: Neonates, particularly premature babies, are often managed with endotracheal intubation and subsequent mechanical ventilation to maintain adequate pulmonary gas exchange. There is no consensus on the standard length of endotracheal tube. Although a short tube reduces resistance and respiratory dead space, it is believed to increase the risk of accidental extubation. There are not entirely coherent data regarding the effect of endotracheal tube length on work of breathing in infants. AIM: The aim of this study was to evaluate the impact of neonatal endotracheal tube diameter and length on the work of breathing using an infant in vitro lung model. METHOD: We assessed the work of breathing index and mechanical ventilation settings with various endotracheal tube diameters and lengths using the JTR100 in vitro infant lung model. The basic parameters of the model were breathing frequency of 20 per minutes, inspiratory-expiratory ratio of 1:3, and positive end-expiratory pressure of 5 cmH2 O. In addition, the diaphragm driving pressure to maintain the set tidal volume was measured as the work of breathing index. The JTR100 was connected to the Babylog 8000plus through the endotracheal tube. Finally, we monitored the peak inspiratory pressure generated during assist-control volume guarantee mode with a targeted tidal volume of 10-30 mL. RESULTS: The diaphragm driving pressure using a 2.0-mm inner diameter tube was twice as high as that using a 4.0-mm inner diameter tube. To maintain the targeted tidal volume, a shorter tube reduced both the diaphragm driving pressure and ventilator-generated peak inspiratory pressure. The difference in the generated peak inspiratory pressure between the shortest and longest tubes was 5 cmH2 O. CONCLUSION: In our infant lung model, a shorter tube resulted in a lower work of breathing and lower ventilator-generated peak inspiratory pressure.

Acotiamide hydrochloride hydrate added to combination treatment with an α-blocker and a cholinergic drug improved the QOL of women with acute urinary retention: case series.

Acute urinary retention is the most common urological emergency. To resolve this emergency, urethral catheterization is performed. If the procedure fails and permanent transurethral catheterization is required, the patient's quality of life is significantly affected. Therefore, catheter-free treatment is the ideal goal of therapy for patients with acute urinary retention. Especially, for women, placement of a catheter poses a cosmetic problem. Therefore, the aim of this study was to treat female patients who had already received urapidil/distigmine bromide with acotiamide. Acotiamide was administered at a dose of 100 mg three times daily for 2 weeks, and the outcome of trial without catheter was evaluated. Only female patients were enrolled for this study. Treatment proved successful and all patients become catheter free.

[Severe Therapy-Related Pancytopenia Caused by UFT and LV in a Patient with Ascending Colon Cancer].

We report a case of a 79-year-old man who developed severe therapy-related pancytopenia from tegafur uracil(UFT)and Leucovorin(LV)as adjuvant chemotherapy for ascending colon cancer. Laparoscopic right hemicolectomy resection was performed for the ascending colon cancer. Pathohistological analysis revealed that the ascending colon tumor was moderately differentiated tubular adenocarcinoma(T3, N1, M0, and Stage III a). Postoperative adjuvant chemotherapy with UFT and LV was administered. After 2 courses of chemotherapies, severe thrombocytopenia(Grade 4)and neutropenia(Grade 4)were noted. Platelet and granulocyte-colony stimulating factor(G-CSF)were transfused. Furthermore, red blood cell transfusions were given for anemia(Grade 3). Dihydropyrimidine dehydrogenase(DPD)deficiency was suspected as the cause of the pancytopenia, and the ratio of dihydrouracil(DHU)and uracil(URA)was measured. However, the result was negative for DPD deficiency. Bone marrowaspiration revealed that therapy-related leukemia(TRL)and therapy-related myelodysplastic syndrome(T-MDS)were not the causes of the pancytopenia either. A total of 230 units of platelet transfusions and 20 units of red blood cell transfusions have been given for 32 weeks, and the patient currently requires routine blood transfusions. Fortunately, infection and bleeding never occurred. Subsequently, the patient should be monitored carefully.

[Long-Term Survivors after Resection for Primary Pancreatic Carcinoma Stage IV].

We discuss the prognosis of cases of Stage IV pancreatic carcinoma with distant metastases(7th Edition of General Rules for the Study of Pancreatic Cancer, Japan Pancreas Society)for which any treatment was performed at our hospital. Fiftythree patients were radiographically or pathologically diagnosed as having Stage IV pancreatic carcinoma with definite prognosis, and received treatments, includingsurg ery or chemotherapy, at our department. Twenty-two cases showed more metastases, and celiac artery or superior mesenteric artery invasion was suspected in 28 cases. The 5-year survival rate of all 53 cases was 3.8%, and the median survival time(MST)was 6.2 months. The MST in the palliative surgery cases was 6.7 months, and that in the cases given best supportive care(BSC)was only 1.9 months. There were no 2-year survivors in the group given chemotherapy without any other treatments and in the group given BSC alone, while the longest survival time and MST were 66.9 and 31.3 months(p<0.001), respectively, in the 10 patients treated by primary tumor resection. There was only 1 patient who showed relapse-free survival. Primary site resection and chemotherapy over 4 cycles was revealed as an independent prognostic factor by multivariable analysis. Patients with Stage IV pancreatic carcinoma have a poor prognosis. However, the possibility of achievingimproved prognosis was noted with combined-modality therapy, including aggressive resection in limited cases showinga good response to chemotherapy or cases in whom preoperative metastasis assessment was difficult.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Transnasal inner drainage: an option for managing anastomotic leakage after esophagectomy.

PURPOSE: Anastomotic leakage, a serious complication of esophagectomy, continues to contribute to high surgery-related mortality. Management of anastomotic leakage has become a serious concern for surgeons. This study aimed to evaluate the utility of transnasal inner drainage using a Salem Sump tube for anastomotic leakage after esophagectomy. METHODS: We inserted a Salem Sump tube into the esophagus through one nostril. By using a 0.035-inch guide wire under fluoroscopic guidance, we advanced this drainage tube into the abscess through the site of the anastomotic leakage. We also used upper endoscopy if necessary. RESULTS: We performed transnasal inner drainage in five patients with anastomotic leakage after esophagectomy. The average interval from the operation to diagnosis of anastomotic leakage was 7.8 days (median: 7, range: 3-18 days). The average duration of drainage was 15.8 days (median: 16, range: 11-21 days). No patients required additional surgical treatment and there was no operative mortality. No stricture was observed during the follow-up period. CONCLUSIONS: Transnasal inner drainage is successful, and may decrease the duration of drainage and reduce surgery-related mortality caused by anastomotic leakage. Additionally, this technique enables treatment of abscesses that cannot be managed by percutaneous drainage because of their locations, and can be safely undertaken in most institutions. Transnasal inner drainage is a safe, useful, inexpensive, and minimally invasive method, which may be an option for management of post-esophagectomy anastomotic leakage.

Invalidation of Diphyllobothrium hottai (Cestoda: Diphyllobothriidae) based on morphological and molecular phylogenetic analyses.

Diphyllobothrium hottai Yazaki, Fukumoto & Abe, 1988 was described based on the morphology of adult worms recovered from golden hamsters that had been experimentally infected with plerocercoids obtained from Japanese surf smelts (Hypomesus pretiosus japonicus) and olive rainbow smelts (Osmerus eperlanus mordax). Although D. hottai was considered to be distinct from Diphyllobothrium ditremum (Creplin, 1825), their taxonomic relationship requires further clarification. In our study, D. hottai and D. ditremum obtained from hamsters experimentally infected with plerocercoids isolated from Japanese surf smelts were compared using morphological and molecular methods. The criterion usually used to differentiate between D. hottai and D. ditremum is the difference in the angle between the long axis of the cirrus sac and that of the seminal vesicle. However, we found variation of the angle within the same individual and, one specimen showed both of the different angles that were supposedly unique to each of the species. Furthermore, phylogenetic analysis of the complete sequences of the mitochondrial cytochrome c oxidase subunit 1 and cytochrome b genes revealed that both species were genetically indistinguishable. Therefore, D. hottai is considered to be a junior synonym of D. ditremum.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Expression of Sex Determining Region Y-Box 2 and Pancreatic and Duodenal Homeobox 1 in Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The World Health Organization 2010 classification divides pancreatic neuroendocrine tumors (p-NETs) entity to well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC) by Ki-67 index. The aim of this study is elucidate the pathophysiology and tumor biology of p-NETs. METHODS: We assessed the expression of transcription factors sex determining region Y-box 2 (SOX2) and pancreatic and duodenal homeobox 1 (Pdx1)) essential for the normal fetal development of pancreatic neuroendocrine cells in 46 surgically resected p-NETs by immunohistochemistry. The relationship of expression levels of these factors and clinicopathological factors were analyzed. RESULTS: SOX2 was positive in 6 p-NETs (13.0%). Five of 7 NEC patients showed positive for SOX2. SOX2 was highly (sensitivity 71%) and specifically (specificity 97%) expressed in NEC. Patients with SOX2 positive p-NET showed the significantly shorter disease-free and overall survival than patients with SOX2 negative p-NET. High Pdx1 expression was seen in 25 p-NET patients (54.3%). None of the NEC patients showed high Pdx1 expression. There was a significant reverse correlation between SOX2 and Pdx1 expression. CONCLUSIONS: The expression patterns of SOX2 and Pdx1 highly correlated with prognosis of p-NETs. These expression patterns may represent the biological and pathophysiological difference of p-NETs and indicate the origin of tumor.

A pilot study of acotiamide hydrochloride hydrate in patients with detrusor underactivity.

AIM: To investigate the clinical efficacy of acotiamide hydrochloride hydrate in patients with detrusor underactivity. METHODS: We measured the post-void residual urinary volume in 19 patients with underactive bladders. All these patients had been under treatment with distigmine bromide and were prescribed acotiamide hydrochloride hydrate at a dose of 100 mg three times daily for 2 weeks. RESULTS: Compared with the post-void residual urinary volume value at baseline (161.4±90.0 mL) a statistically significant reduction was observed at the end of treatment (116.3±63.1 mL) (P=0.006). The drug was generally well tolerated by the majority of patients. CONCLUSION: Maybe, acotiamide hydrochloride hydrate showed clinical efficacy in patients with underactive bladders and may, therefore, be used alternatively in patients who do not respond sufficiently to distigmine bromide.

[Effect of tolvaptan on ascites due to malignancy].

Ascites accompanying a malignancy is often refractory to conventional treatment with saline diuretics, making it difficult to control. We administered a new diuretic, Tolvaptan, to 10 individuals with malignancy and heart failure accompanied by ascites, which was refractory to saline diuretics, and assessed its efficacy and adverse events. We observed a significant reduction in abdominal distension following 2 weeks of Tolvaptan administration. However, we also observed significant increases in serum potassium, urea nitrogen, and creatinine levels, but no serious adverse events. This suggests that Tolvaptan may also be effective as treatment for ascites.

[Two Cases of Pancreatic Neuroendocrine Tumor with Liver Metastases Successfully Treated with Multidisciplinary Therapy including Multiple Surgical Resections].

UNLABELLED: We report 2 cases of pancreatic neuroendocrine tumor with liver metastases successfully treated with multidisciplinary therapy, including multiple surgical resections. Case 1: A 63-year-old man underwent distal pancreatectomy and portal vein resection for a pancreatic body tumor. Histological analysis revealed the tumor was a pancreatic neuroendocrine tumor (p-NET), classified as NET G2. His metachronous liver metastases were treated with lateral sectionectomy and 2 rounds of transcatheter arterial chemoembolization (TACE). He is being treated with everolimus for para-aortic lymph node metastases and is alive 90 months after the primary operation. Case 2: A 64-year-old man underwent distal gastrectomy for a duodenal ulcer and distal pancreatectomy for a pancreatic tumor. The histological diagnosis was gastrinoma classified as NET G2. Hepatectomy (segmentectomy of segment 8 and partial hepatectomy) was performed twice for metachronous liver metastases. Everolimus has been administered for liver and para-aortic lymph node metastases, and the patient is alive 108 months after the primary operation. CONCLUSION: Multidisciplinary treatment should be considered for patients with p-NETs with multiple metastases.

Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation.

BACKGROUND: Mizoribine (MZR) was approved in 1984 in Japan for the suppression of rejection in renal transplantation with an approved administration dosage of 1-3 mg/kg/day. The action of MZR resembles that of mycophenolate mofetil (MMF), but MZR dosing is markedly lower than that of MMF. To examine whether higher dosing of MZR could obtain efficacy similar to MMF in renal transplantation, we conducted a comparative study of MZR and MMF using a high daily dose of MZR. METHODS: A prospective, randomized comparative study of MZR versus MMF using tacrolimus (FK) and steroids as the base was conducted in 35 patients who had undergone living-donor renal transplantation (ABO-incompatible patients were not included) at 8 institutions in Japan between July 2005 and June 2007. Starting doses were 12 mg/kg/day for MZR and 2 g/day for MMF. Dosages of FK and steroids were set according to the protocol of each institution. RESULTS: Patient and graft survival rate at 1 year after transplantation was 100 % in each group, with no significant difference in rejection rate apparent between groups. Adverse events found in both groups were characteristic, frequently involving infection and digestive organ disorder in the MMF group and elevated uric acid levels in the MZR group. CONCLUSIONS: Based on these results, MZR and MMF are considered almost equivalent in terms of efficacy and safety.

Monoclonal antibodies against large oval aggregates of Aß1-42.

Abnormal cerebral accumulation of amyloid beta protein(1-42) (Aß(1-42)) is one of the hallmarks of Alzheimer's disease (AD). Aß(1-42) aggregates exist in two distinct forms: fibrils that are composed of highly ordered ß-sheets and amorphous aggregates that differ in size and toxicity. Here, we generated large oval aggregates (LOA) 369 ± 81 nm and 224 ± 92 nm in size on their major and minor axes, respectively, as measured by tapping-mode atomic force microscopy. LOA were produced by slow rotation of high concentrations (0.22 mM, 1.0 mg/mL) of Aß(1-42) for 16 h at 37°C in the presence of 2.2 mM Aß(16-20), which prevents the fibril formation, and purified with 0.22-µm filters. Analysis with thioflavin T showed that LOA have little ß-sheet structure on their surfaces. Monoclonal antibodies that react with LOA, but not the fibril forms, were screened from 960 mouse hybridoma cell lines, and seven antibodies consisting of four IgG and three IgM antibodies were obtained. Four IgG monoclonal antibodies showed cross-reactivity of <10% against the monomer and fibril forms and amorphous aggregates that passed through 0.22-µm filters. Among the four antibodies, the antibody that was designated as 31-2 exhibited the highest reactivity against LOA and showed the lowest reactivity against the fibril forms. On the basis of these results, a unique epitope on the surface of LOA was suggested. The 31-2 antibody may be useful for future basic research and therapeutic applications for AD.

[Case of anti-glomerular basement membrane antibody nephritis in a patient who was able to withdraw from dialysis and gave birth twice but underwent living renal transplantation due to progression to end-stage renal failure 15 years after onset].

A 34-year-old woman with suspected rapidly progressive glomerulonephritis had been admitted to our hospital in March 1993 at the age of 19 years. Renal biopsy revealed cellular crescent formation in 24 of 26 glomeruli. Serum examination was positive for anti-glomerular basement membrane (GBM) antibody, while pulmonary hemorrhage was absent. Based on these findings, she was diagnosed with anti-GBM antibody nephritis, and treated with corticosteroid pulse therapy and double filtration plasmapheresis (DFPP) in addition to hemodialysis (HD). HD was withdrawn within 2 months. Wishing to have a baby, she had delivery in 1997 and 2000. Subsequently, her renal function gradually decreased, and she underwent an ABO-incompatible living-donor kidney transplant, with her husband as the donor, in March 2008. She has been making good progress after transplantation. Anti-GBM antibody nephritis has a poor prognosis, but renal function was maintained for 15 years in this patient, who responded well to the initial treatment. The underlying disease rarely recurs if transplantation is performed after the patient has become negative for anti-GBM antibody, anti-GBM antibody nephritis therefore seems to be a good indication for treating patients with renal transplantation.

A novel phosphorylated glycoprotein in the shell matrix of the oyster Crassostrea nippona.

We found a novel 52 kDa matrix glycoprotein MPP1 in the shell of Crassostrea nippona that was unusually acidic and heavily phosphorylated. Deduced from the nucleotide sequence of 1.9 kb cDNA, which is likely to encode MPP1 with high probability, the primary structure of this protein shows a modular structure characterized by repeat sequences rich in Asp, Ser and Gly. The most remarkable of these is the DE-rich sequence, in which continuous repeats of Asp are interrupted by a single Cys residue. Disulfide-dependent MPP1 polymers occurring in the form of multimeric insoluble gels are estimated to contain repetitive locations of the anionic molecules of phosphates and acidic amino acids, particularly Asp. Thus, MPP1 and its polymers possess characteristic features of a charged molecule for oyster biomineralization, namely accumulation and trapping of Ca2+. In addition, MPP1 is the first organic matrix component considered to be expressed in both the foliated and prismatic layers of the molluscan shell microstructure. In vitro crystallization assays demonstrate the induction of tabular crystals with a completely different morphology from those formed spontaneously, indicating that MPP1 and its polymers are potentially the agent that controls crystal growth and shell microstructure.