Risk factors for catheter-related bloodstream infections in patients with intestinal failure undergoing home parenteral nutrition: a single-center study.

PURPOSE: The incidence and risk factors of catheter-related bloodstream infections (CRBSI) in patients with intestinal failure (IF) have not been established, partly because catheter management methods vary from different facilities. This study aimed to identify the risk factors and incidence rate of CRBSIs in patients with IF who were given prophylactic treatment. METHODS: Sixteen patients with IF who required home parenteral nutrition were enrolled in this study. Prophylactic management of CRBSI included monthly ethanol lock therapy and standardized infection prevention education. The outcomes included the incidence and risk factors of CRBSI. RESULTS: The median incidence rate of CRBSI was 1.2 per 1000 catheter days. Univariate analysis showed that the risk of developing CRBSI was significantly associated with short bowel syndrome (< 30 cm) (p = 0.016). Other relevant findings included a significant negative correlation between serum albumin and CRBSI rate (r = - 0.505, p = 0.046), and past history of mixed bacterial infections was significantly associated with increased CRBSI rate (p = 0.013). CONCLUSION: CRBSIs can still develop despite undergoing prophylactic management. Risk factors for CRBSI include the residual intestinal length, nutritional status, and susceptibility to certain microorganisms.

Pediatric intestinal rehabilitation.

PURPOSE OF REVIEW: The intestinal rehabilitation program (IRP) is a comprehensive treatment strategy that employs various approaches implemented by multidisciplinary teams to treat intestinal failure in children. This program has shown promising results, such as reducing complications and improving prognosis and quality of life (QOL). In this review, we discuss the current status of this program and relevant topics. RECENT FINDINGS: IRP includes the prevention and treatment of various complications such as intestinal failure associated liver disease, catheter-related bloodstream infection or sepsis, and venous thromboembolism. In addition, treatment strategies such as glucagon-like peptide-2 analogs, surgical interventions, and intestinal transplantation have evolved over time and have contributed to improved outcomes. In addition, the scope and regions for IRP activities have expanded. SUMMARY: IRP improves the prognosis and QOL of children with intestinal failure. The development of new drugs, surgical methods, and treatment strategies is expected to improve the current and future status of pediatric patients with intestinal failure. Furthermore, international institutions must collaborate, share knowledge, conduct joint research, and establish patient registries to advance IRP progress.

Intraoperative Placement of an Absorbable Spacer Prior to Radiation Therapy for a Malignant Peripheral Nerve Sheath Tumor.

A 7-year-6-month-old female was diagnosed with a pelvic malignant peripheral nerve sheath tumor and lymph node metastases. Tumorectomy was performed after four cycles of chemotherapy. A 33-mm cystic lesion was observed around the left iliac muscle after three cycles of postoperative chemotherapy, and proton beam therapy (PBT) was recommended. She was referred for absorbable spacer (AS) placement. The left ovarian appendage (OA) was resected due to the direct tumor infiltration. The right OA was fixed to the uterosacral ligament. The AS was fixed to the lateral pelvis. The PBT (70.3 Gy relative biological effectiveness) was performed successfully with the AS, and she also had the reproducing possibility due to prevention of severe irradiation damage of the right OA. AS eliminated the surgical removal of spacers and enabled us high-dose PBT for residual tumor without severe irradiation damage including infertility.

Intestinal Transplantation at a Single Institution in Japan.

BACKGROUND: This study aimed to compare the clinical outcomes of intestinal transplantation (ITX) between 2 groups by using medications for induction treatment and assess the utility of the current protocol. METHODS: From 2003 to 2020, 11 patients underwent ITX. Recipients were classified into 2 groups: group IL-2Ra (interleukin-2 receptor antagonist therapy, n = 6) and ATG (rabbit antithymocyte globulin therapy, n = 5). We conducted a retrospective review of patient and graft survival rates and the postoperative course. RESULTS: The 1-, 5-, and 10-year patient and graft survival rates of the 11 primary grafts in the 11 recipients were 100%, 88.9%, 62.2% and 90.0%, 78.8%, 56.3%, respectively. The median duration of follow-up for the IL-2Ra and ATG groups was 197.3 and 87.3 months, respectively. The 1-, 5-, and 10-year patient survival rates were 100%, 83.3%, 50% and 100%, 100%, 100% for the IL-2Ra and ATG groups, respectively (P = .25) and 83.3%, 66.7%, 33.3% and 100%, 100%, 100% for graft survival in the IL-2Ra and ATG groups, respectively (P = .08). The incidence of moderate and severe acute rejection was 100% and 20% in the IL-2Ra and ATG groups, respectively (P = .02). The 1- and 5-year moderate and severe rejection-free survival rates were 33.3%, 0% and 80%, 80% in the IL-2Ra and ATG groups, respectively (P = .04). CONCLUSIONS: ATG significantly suppressed moderate and severe acute rejection compared with IL-2Ra, thereby showing better short- and mid-term rejection-free survival rates. Additional clinical experience is needed to determine the optimal regimen for the management of ITX recipients.

Longterm Outcome of Liver Transplantation for Congenital Extrahepatic Portosystemic Shunt.

Liver transplantation (LT) is often viewed as the last resort for the treatment of congenital extrahepatic portosystemic shunt (CEPS) due to advancement of imaging and interventional radiology techniques. However, some patients still require LT, and criteria for LT are yet to be determined. We conducted a national survey of patients undergoing LT for CEPS between June 1998 and August 2018 and evaluated the clinical data and outcomes with a review of previously reported patients from the English-language medical literature. A total of 26 patients underwent LT in Japan at a median age of 5.2 years old. The most common indications for LT were persistent hyperammonemia (54%) and liver mass (50%), followed by pulmonary complications (38%). Pulmonary complications in all patients, including intrapulmonary shunt and pulmonary hypertension (PH), were improved after LT. Regarding the 29 previously reported patients in the English-language literature, a liver nodule (49%), including hepatoblastoma and hepatocellular carcinoma, was the most common indication for LT, followed by pulmonary complications (34%). A total of 25 (96%) patients in our survey and 26 (90%) patients in the literature review were alive with a median follow-up period of 9.5 and 1.6 years, respectively. Although LT has a limited role in management of CEPS, our study indicated that LT was safe as an alternative treatment for select patients with malignant tumor or pulmonary complications and those with complications related to new portosystemic collateral vessels after shunt closure, such as PH or hepatopulmonary syndrome.

GITR controls intestinal inflammation by suppressing IL-15-dependent NK cell activity.

Glucocorticoid-induced TNFR family related gene (GITR) is a member of the TNFR superfamily that is expressed on cells of the immune system. Although the protective and pathogenic roles of GITR in T cell immunity are well characterized, the role of GITR in innate immunity in the intestinal tissues has not been well clarified. In this study, using a dextran sulfate sodium (DSS)-induced colitis model in mice, we found that GITR-deficiency rendered mice more susceptible to acute intestinal inflammation and that a significantly higher number of activated natural killer (NK) cells was accumulated in the colonic lamina propria of Gitr-/- mice as compared to wild-type mice. Additionally, Rag2-/- Gitr-/- mice, which lack T cells but have NK cells, also displayed more severe colonic inflammation than Rag2-/- mice. In contrast, an anti-GITR agonistic antibody significantly alleviated colitis in Rag2-/- mice. Engagement of GITR inhibited IL-15-mediated activating signaling events in NK cells, which include cell activation and proliferation, and production of cytokines and cytotoxic granules. Taken together, our results provide the first evidence that GITR negatively controls intestinal inflammation through NK cell functions.

Treatment of classic-type Hirschsprung's disease: rectoplasty with posterior triangular colonic flap versus transanal endorectal pull-through with rectoanal myotomy.

PURPOSE: Our institution employs rectoplasty with a posterior triangular colonic flap (RPTCF) for classic-type Hirschsprung's disease. Recently, we employed a modified Soave procedure: transanal endorectal pull-through with rectoanal myotomy (TEPTRAM). In both procedures, the internal sphincter muscle is completely divided vertically at the 6 o'clock position. Unlike RPTCF, TEPTRAM does not require abdominal manipulation. We aimed to verify the usefulness of TEPTRAM. METHODS: 64 patients with classic-type Hirschsprung's disease who underwent surgery between 1970 and 2017 were divided into group R (RPTCF, 47 cases) and group T (TEPTRAM, 17 cases). We compared the defecation function of the groups. RESULTS: No patient showed fecal incontinence (R: 0/41, T: 0/10, ns). Three patients (6%) in group R and four (24%) in group T developed postoperative enterocolitis (P = 0.16). Three patients (10%) in group R and one (20%) in group T needed an enema (P = 0.36). CONCLUSION: There was no adverse effect of rectoanal myotomy; incontinence was not observed in either procedure. Although there was no significant difference, the incidences of enterocolitis and constipation were slightly higher in group T, perhaps because of the residual muscle cuff; therefore, it is necessary to provide best care with attention to constipation immediately after surgery.

Using 99mTc-DTPA galactosyl human serum albumin liver scintigraphy as a prognostic indicator in jaundice-free patients with biliary atresia.

BACKGROUND: We evaluated the clinical significance of follow-up data, including 99mTc-DTPA galactosyl human serum albumin (99mTc-GSA) liver scintigraphy data, as prognostic indicators for jaundice-free patients with biliary atresia (BA). METHODS: Of 87 patients who underwent Kasai portoenterostomy (KP) between 1991 and 2012, 45 jaundice-free patients aged 1-2 years underwent 99mTc-GSA scintigraphy and were classified into 2 groups: those who survived with a native liver (Group A, n = 34) and those who required liver transplantation (LTx) (Group B, n = 11). We compared 99mTc-GSA scintigraphy data (HH15, LHL15, and HH15/LHL15 [H/L15]) and liver function test (LFT) results between the groups. The patients underwent a second 99mTc-GSA scintigraphy at approximately 5 years of age. RESULTS: All patients survived. HH15, H/L15, total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, and alanine transaminase levels were higher in Group B than in Group A (p<0.05). Total and direct bilirubin levels were associated with H/L15 (p<0.05). There were no significant changes in results between the first and second 99mTc-GSA scintigraphy in Group A. CONCLUSIONS: Mid- and long-term prognoses may be predicted using 99mTc-GSA scintigraphy data and LFTs in patients aged 1-2 years. We recommend regular monitoring of postoperative data following KP, even in jaundice-free patients. LEVEL OF EVIDENCE: III.

Technical standardization of Kasai portoenterostomy for biliary atresia.

BACKGROUND: The purpose of this study was to assess the clinical outcome of patients treated with the current technique of Kasai procedure compared with that of those treated with previous procedures. METHODS: We retrospectively assessed the outcomes of 256 patients with biliary atresia who underwent Kasai portoenterostomy at our hospital between 1972 and 2014. Patients were divided into four groups: group 1 (1972-1981, double Roux-en Y, n=91), group 2 (1982-1991, Suruga II, n=80), group 3 (1992-2000, double-valve Roux-en Y, n=46), and group 4 (2001-2014, total removal of the extrahepatic biliary remnants at hepatic capsule and Roux-en Y reconstruction with a spur valve, n=39). Clinical outcomes were compared between the four groups. RESULTS: In groups 1, 2, 3, and 4, the rate of jaundice clearance was 65.9%, 77.5%, 63.0%, and 87.2%, respectively; incidence of early cholangitis was 60.4%, 53.8%, 37.0%, and 23.1%, respectively; requirement for redo Kasai surgery was 15.4%, 37.5%, 17.4%, and 5.1%, respectively; 10-year native liver survival rate was 53.8%, 60.1%, 44.1%, and 73.7%, respectively; and 10-year overall survival rate was 55.0%, 72.3%, 86.7%, and 97.3%, respectively. CONCLUSION: The standardized Kasai procedure was associated with favorable outcomes. Long-term outcomes remain to be evaluated. LEVEL OF EVIDENCE: Case-control/treatment study, level III.

Analysis of the prognostic factors of long-term native liver survival in survivors of biliary atresia.

PURPOSE: Long-term survivors of biliary atresia (BA) sometimes experience liver dysfunction. We evaluated the prognostic factors for long-term native liver survival (NLS) in BA patients after the Kasai procedure. METHODS: This study included 67 patients with jaundice disappearance after the Kasai procedure performed between 1972 and 1995, and NLS for over 10 years. We retrospectively evaluated the clinical parameters, including the type of BA, age at the Kasai procedure, medical conditions, and treatments. The adjusted odds ratios (aOR) were obtained for 20-year NLS using logistic regression analysis. RESULTS: The median age of the patients at the Kasai procedure was 63 days. Of the 67 study patients, 62 patients (92.5 %) had jaundice-free NLS at the age of 20 years, 4 patients died before the age of 20 years from liver failure, and 1 patient underwent living related liver transplantation. The presence of gastro-esophageal varices requiring endoscopic injection sclerotherapy was a significant factor (aOR 33.8; p = 0.0033), while hypersplenism and cholangitis were not identified as significant factors. CONCLUSIONS: The existence of symptomatic portal hypertension would influence long-term NLS in BA patients after the Kasai procedure. In such patients, accurate evaluation of hepatic function and adequate treatment for sequelae are needed.

Mediastinal tumor resection via open or video-assisted surgery in 31 pediatric cases: Experiences at a single institution.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been increasingly used for the diagnosis and treatment of thoracic diseases. Pediatric mediastinal tumors are often difficult to resect because of their proximity to important organs. For this reason, VATS is not established as a standard surgical approach for such tumors. We compared the efficacy and safety of mediastinal tumor resection in children using open thoracotomy (OT) and VATS. METHODS: A total of 31 children underwent mediastinal tumor resection (21 by VATS and 10 by OT). These nonrandomized approaches were retrospectively compared for incidence of operative complications, morbidity, and mortality. RESULTS: Tumor sizes and operation times were similar between groups. However, the VATS group required significantly fewer blood transfusions and shorter durations of thoracic drainage and hospital stays (p<0.05). Complications greater than grade 2 on the Clavien-Dindo classification occurred in four patients treated by VATS and OT. No delayed effects were noted in the survivors of either group. A patient with clear cell sarcoma of the kidney who underwent OT relapsed and died. CONCLUSION: Although complication rates were similar between the two approaches, VATS was suggested as less invasive because of fewer blood transfusions required, and shorter thoracic drainage and hospital stay durations.

Postnatal management of prenatally diagnosed biliary cystic malformation.

PURPOSE: Recent advances in ultrasonography have increased prenatal diagnosis of biliary atresia (BA) and choledochal cyst (CC). These conditions are not easy to distinguish before or just after birth. This study investigated diagnostic and therapeutic problems in prenatal diagnosis of BA and CC. METHODS: We retrospectively studied clinical characteristics and progression of hepatobiliary cysts in 10 patients (4 cases of BA, 6 cases of CC) from the time of diagnosis. Chronological changes in cyst size and gallbladder morphology were assessed and measured sequentially by ultrasonography. RESULTS: Three cases of BA were type I cyst and 1 case was type III-d. All cases of CC were type Ia. Cyst size decreased between birth and surgery in BA but increased in CC. The gallbladder appeared atrophic in BA. There was no significant difference in gestational age or cyst size at prenatal diagnosis, changes in cyst size between birth and surgery, and degree of liver fibrosis. CONCLUSIONS: BA should be suspected if cyst size decreases before and after birth and the gallbladder atrophies after birth. Cholangiography is the only reliable method to differentiate BA from CC. Neonatal surgery is indicated for CC with icterus and liver dysfunction.

OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4⁺ T cells.

T-cell homeostasis preserves the numbers, the diversity and functional competence of different T-cell subsets that are required for adaptive immunity. Naïve CD4(+) T (TN ) cells are maintained in the periphery via the common γ-chain family cytokine IL-7 and weak antigenic signals. However, it is not clear how memory CD4(+) T-cell subsets are maintained in the periphery and which factors are responsible for the maintenance. To examine the homeostatic mechanisms, CFSE-labeled CD4(+) CD44(high) CD62L(low) effector memory T (TEM ) cells were transferred into sublethally-irradiated syngeneic C57BL/6 mice, and the systemic cell proliferative responses, which can be divided distinctively into fast and slow proliferations, were assessed by CFSE dye dilution. We found that the fast homeostatic proliferation of TEM cells was strictly regulated by both antigen and OX40 costimulatory signals and that the slow proliferation was dependent on IL-7. The simultaneous blockade of both OX40 and IL-7 signaling completely inhibited the both fast and slow proliferation. The antigen- and OX40-dependent fast proliferation preferentially expanded IL-17-producing helper T cells (Th17 cells). Thus, OX40 and IL-7 play synergistic, but distinct roles in the homeostatic proliferation of CD4(+) TEM cells.

Liver transplantation following the Kasai procedure in treatment of biliary atresia: a single institution analysis.

PURPOSE: This study aimed to assess outcomes of liver transplantation (LTx) in patients with biliary atresia (BA). METHODS: The Kasai procedure was performed for 358 patients at Tohoku University Hospital between January 1955 and December 2013; 64 (17.9%) required LTx. These 64 patients were divided into 4 groups according to their age at the time of transplantation: Group 1, aged <2 years (n = 27); Group 2, aged 2-9 years (n = 16); Group 3, aged 10-19 years (n = 11); and Group 4, aged ≥20 years (n = 10). Clinical parameters were evaluated retrospectively. RESULTS: Both living-donor (n = 57) and deceased-donor (n = 7) LTx were performed. Indications were irreversible jaundice (n = 53), intractable cholangitis (n = 3), hepatopulmonary syndrome (n = 6), portopulmonary hypertension (n = 1), and intestinal bleeding (n = 1). Jaundice occurred more frequently in Groups 1 and 2 than in Groups 3 and 4 (p = 0.031). Survival rates were 81.5, 100, 90.9, and 80% in Groups 1, 2, 3, and 4, respectively. CONCLUSION: Although the overall LTx survival rate was satisfactory, some adult recipients experienced LTx-related difficulty. Close follow-up, meticulous assessment of physical and social conditions, presence of a multidisciplinary support system, and appropriate time course for LTx are all essential factors in the treatment of BA.

Life-threatening risk factors and the role of intestinal transplantation in patients with intestinal failure.

PURPOSE: We elucidated the life-threatening risk factors for intestinal failure (IF) and characterized the role of intestinal transplantation (ITx) in affected patients. METHODS: We conducted a retrospective review of 38 patients with short bowel (SB) and 19 with motility disorders (MD). The SB patients were divided into three categories according to the length of their residual small bowel and the presence of the ileocecal valve. The four disease subcategories were grouped into two categories: low-risk category (mild and moderated SB) and high-risk category (extensive SB and MD). The age at the introduction of parenteral nutrition (PN) was <1 year in 50 patients (infant group, IG) and 1-15 years in 7 patients (pediatric group, PG). RESULTS: Enteral autonomy was rarely achieved in the high-risk category (p < 0.0001). IG was associated with a higher incidence of developing intestinal failure-associated liver disease (IFALD) (p = 0.004). Eight patients died, due to IFALD in four, sepsis in three and acute heart failure in one. Twenty-eight patients (49 %) are currently alive without PN, including four after ITx. CONCLUSION: The treatment of high-risk IF is still challenging. Inclusion of ITx in appropriate timing, along with aggressive medical, nutritional and surgical management, may reduce advanced morbidity and mortality of high-risk IF.

[Current status and future perspective of clinical intestinal transplantation].

Results of intestinal transplant are improving in recent years and intestinal transplantation has been established as a therapeutic option for patients with intestinal failure associated with serious parenteral nutrition (PN) -related complications. According to the latest results from the Intestinal Transplant Registry (ITR), reported at the 11th International Small Bowel Transplantation Symposium held in Bologna, Italy in September 2009, the number of transplants was increasing every year and annually rose to 220 transplants per year. Recently one-year graft survival rates achieved more than 80% and most of current survivors had stopped parenteral nutrition and resumed normal daily activities. As of September 2010, 20 intestinal transplants have been performed for 18 patients with intestinal failure in Japan. Eleven living-related segmental intestinal transplants (including 1 combined liver-intestine transplant) were performed, whereas six patients have received intestinal grafts from cadaveric donors. Fourteen of 18 patients are currently alive after transplant. This article reviews current status and future perspective in management of intestinal failure and clinical intestinal transplantation on the basis of our experience and recent publications.

Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma.

We report a case of perivascular epithelioid cell tumor (PEComa) with an SFPQ/PSF-TFE3 gene fusion in a 14-year-old girl treated for adrenal neuroblastoma for 4 years. Imaging studies revealed a tumor in the wall of the sigmoid colon, which was radiologically different from the neuroblastoma, together with several inguinal and cervical lymph node metastases of the neuroblastoma. Microscopically, the tumor in the sigmoid colon showed sheet-like growth of epithelioid cells with abundant clear cytoplasm and round nuclei, which were separated by thin fibrovascular septa. These epithelioid cells were immunohistochemically positive for vimentin, gp100 (detected with monoclonal antibody HMB-45), and TFE3, and the tumor was diagnosed as PEComa. In a fluorescence in situ hybridization assay using an in-house probe for TFE3, the tumor cells showed split signals, indicating a rearrangement of TFE3. Molecular cloning using 5' rapid amplification of complementary DNA ends and subsequent reverse transcription-polymerase chain reaction revealed an SFPQ/PSF-TFE3 gene fusion. To the best of our knowledge, this is the second reported case of metachronous PEComa subsequent to a primary tumor, and the first report confirming an SFPQ/PSF-TFE3 gene fusion in PEComa.

Long-term outcome of children with biliary atresia who were not transplanted after the Kasai operation: >20-year experience at a children's hospital.

OBJECTIVE: Sequential strategies combining the Kasai operation as a first-line treatment and liver transplantation as a second-line option, if necessary, have been accepted for patients with biliary atresia (BA). To understand the role of the Kasai operation in the treatment of BA, it is necessary to analyze the long-term outcome of the operation alone and to evaluate the present status of survivors retaining their native livers. MATERIALS AND METHODS: A retrospective chart review was carried out for a group of 80 patients who had undergone the Kasai operation between 1970 and 1986 at the Kanagawa Children's Medical Center. RESULTS: The 5-, 10-, and 20-year survival rates of patients with their native livers were 63%, 54%, and 44%, respectively. The survival rates varied significantly depending on the type of BA, age at initial Kasai operation, era of surgery, and surgical method. By age 20, nearly half of the adult survivors had already developed liver cirrhosis and its sequelae. Episodes of cholangitis and gastrointestinal bleeding occurred after 20 years of age in 37% and 17% of the adult patients, respectively, and 20% of the adult patients died of liver failure or underwent living-related partial liver transplantation in their 20s. Five female patients gave birth to a total of 9 children, and 1 male patient fathered a child. CONCLUSIONS: Although increasing numbers of patients with BA survive 20 years or more after the Kasai operation, meticulous lifelong postoperative care should be continued for the survivors because of the possibility of hepatic deterioration.

[Aspergillosis of masticator space including mandibular bone responding to itraconazole treatment in a diabetic adult: case report].

Aspergillosis of the bone is rare and resistant to treatment. We report a case of Aspergillus infection of the masticator space including mandibular bone in a diabetic adult. After extraction of a posterior tooth, the patient began to suffer from facial pain. The pain worsened in spite of antibiotic treatment. The results of serum tests and biopsy showed an invasive aspergillosis of the left masticator space including the mandibular bone six months after the onset. Although invasive aspergillosis can be fatal, the infection in our case responded to itraconazole treatment. Even in diabetes mellitus, invasive aspergillosis may occur after surgical interventions such as tooth extraction.