A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency.

BACKGROUND: The application of laparoscopic procedures in the liver surgery has been growing. We herein present the first case of a pediatric patient who underwent living donor liver transplantation (LDLT) using a hybrid procedure with hand-assisted laparoscopic mobilization of the liver, subsequent explantation of the diseased liver, and implantation of the graft under direct vision. METHODS: A 12-year-old girl with citrin deficiency was scheduled for LDLT with a left lobe graft. After making an 8-cm upper midline incision, a 5-mm trocar was placed at the umbilicus and the right upper abdomen. Mobilization of the right liver lobe was performed using a hand-assisted laparoscopic surgery (HALS) procedure. After the extension of the midline incision, short hepatic vein dissection, encircling the right hepatic vein and hepatic hilum dissection was performed. Explantation of the liver and subsequent implantation of the liver graft were conducted under direct vision. RESULTS: Since the operation, her normal activities of daily life have been maintained with a normal liver function. Subsequently, her secondary sexual characteristics have recovered without any wound-related complications. CONCLUSIONS: A hybrid LDLT procedure was feasible for a pediatric patient. This procedure's benefits are considered meaningful for pediatric patients as it does not disrupt the rectus muscles or nerves and achieves cosmesis.

[A CASE OF CONGENITAL UNILATERAL ABSENCE OF THE VAS DEFERENS WITH SUSPECTED IPSILATERAL RENAL AGENESIS].

A 5-month-old boy was referred to our department to examine poor development of external genitalia. The patient was diagnosed with micropenis and bilateral impalpable testes, and testosterone replacement therapy was recommended. The testes remained impalpable at 14 months of age; therefore, laparoscopy was performed to explore intra-abdominal testes. The patient was incidentally diagnosed with congenital unilateral absence of the right vas deferens. A renal sonography performed after the operation revealed a high possibility of right renal agenesis. Congenital absence of the vas deferens is associated with a high probability of renal anomalies. It is, therefore, essential to pay careful attention to renal dysfunction.

Downstaging and Histological Effects Might Be Reliable Predictors of the Efficacy of DOC+CDDP+5-FU (DCF) as Neoadjuvant Therapy for Stage III or Borderline Resectable Esophageal Cancer: a Single Institute Experience.

PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.

S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

Efficacy and Safety of Modified FOLFOXIRI+α in the Treatment of Advanced and Recurrent Colorectal Cancer: A Single-center Experience.

Objective In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab) +FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab) +FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+α (mFOLFOXIRI+α) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+α. Methods Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment. Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+α (Bmab: 10, Pmab: 1, alone: 1). Results The median PFS in the mFOLFOXIRI+α and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+α and OTHERS groups was 66.7% and 31.3%, respectively (p=0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+α and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+α developed grade ≥3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+α treatment. Conclusion Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+α was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden.

IVC angioplasty using an autologous vascular graft for IVC stenosis due to metallic stent in a pediatric liver transplant.

A 12-year-old girl underwent LDLT using a left lobe graft for hepatic dysfunction associated with citrin deficiency. A continuous anastomosis suture technique was performed between the recipient's IVC and the donor's left hepatic vein. At age 14, the patient developed intractable ascites. Venography of the IVC and hepatic vein showed twisted-shape stenosis of the hepatic vein-IVC anastomosis with intravascular pressure gradient, probably due to the enlarged transplanted liver, for which a metallic stent was placed. The ascites disappeared, and the patient was making satisfactory progress eight months after surgery. However, nine months after surgery, the ascites appeared again with edema in the lower extremities. Since the stent that had been inserted was suspected of hampering the outflow of the graft liver and IVC, it was decided to conduct stent removal and IVC angioplasty. After intravascular exploration, the stent was removed. Angioplasty was performed. An autologous vascular graft patch was designed to be wedge-shaped to fit the incised part of the IVC, and it was sutured with 5-0 non-absorbable surgical sutures using a continuous suture technique. No postoperative complications or perioperative graft dysfunction were observed. The ascites decreased markedly, and the edema in the lower extremities disappeared. Thus, we were able to successfully perform IVC angioplasty using an autologous vascular graft patch in a patient who developed IVC stenosis after stenting. This procedure is one of the most effective treatment options, especially for pediatric patients requiring long-term vascular patency.

Standardized hybrid living donor hemihepatectomy in adult-to-adult living donor liver transplantation.

The aim of this study was to analyze the outcomes of the most updated version and largest group of our standardized hybrid (laparoscopic mobilization and hepatectomy through midline incision) living donor (LD) hemihepatectomy compared with those from a conventional laparotomy in adult-to-adult living donor liver transplantation (LDLT). Of 237 adult-to-adult LDLTs from August 1997 to March 2017, 110 LDs underwent the hybrid procedure. Preoperative and operative factors were analyzed and compared with conventional laparotomy (n = 126). The median duration of laparoscopic usage was 26 minutes in the hybrid group. Although there was improvement in applying this procedure over time from the beginning of the series of cases studied, blood loss and operative duration were still smaller and shorter in the hybrid group. There was no significant difference between the groups in the incidence of postoperative complications greater than or equal to Clavien-Dindo class III. There was no difference in recipient outcome between the groups. Our standardized procedure of hybrid LD hepatectomy is applicable and safe for all types of LD hepatectomies, and it enables the benefit of both the laparoscopic and the open approach in a transplant center without a laparoscopic expert. Liver Transplantation 24 363-368 2018 AASLD.

Histological study of the elongated esophagus in a rat model.

BACKGROUND: Esophageal elongation by traction suture is used in pediatric patients to manage long-gap esophageal atresia (EA). There was no histological evidence of the esophageal elongation. Here, we sought to clarify the histologic effects of traction on the esophagus by using a rat EA model simulating Foker's method. MATERIALS AND METHODS: Rats were randomly assigned into three groups (n = 5 each). The traction group underwent daily stretching of the distal segment of the esophagus. The nontraction group underwent a sham operation, and the normal group served as controls. Seven days after the operation, the distal segments of the esophagus were removed. The length and thickness were measured, and samples were stained with Ki-67, nNOS, and S-100. RESULTS: The whole length of the esophagus in the traction group was significantly longer than that in the nontraction group (P < 0.01). The thickness of esophageal mucosa and muscle tended to become thin by traction, but not significantly. The Ki-67-positive ratio of mucosa and muscle was significantly higher in the traction group (P < 0.05). There were no significant differences in Ki-67 between two segments (cardia-middle and middle-stump) in any group. Auerbach's plexus was identified at all sites of elongated esophagus by nNOS and S-100 staining. CONCLUSIONS: By traction, the esophagus was elongated uniformly and cell proliferation activity was promoted in all parts of the elongated esophagus in the rat EA model.

Expression of alpha smooth muscle actin in living donor liver transplant recipients.

Recently, there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression. Herein, we focused on activated hepatic stellate cells expressing alpha smooth muscle actin (α-SMA) to understand the correlation between immunosuppressant medication and liver fibrosis. The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy. The number of α-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy. In addition, the α-SMA-positive area evaluated using the WinRooF image processing software program continued to increase over time in three adult transplanted patients with liver fibrosis, and the α-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases, according to a retrospective review. Therefore, α-SMA could be a useful marker for the detection of early stage fibrosis.

A modified Foker's technique for long gap esophageal atresia.

External traction using the Foker's technique enables elongation in the esophageal segments within days, and allows the primary repair of the long gap. This article presents our modified Foker's technique which was easily applicable for long-gap esophageal atresia.

Papillary carcinoma with extensive squamous metaplasia arising from thyroglossal duct cyst in an 11-year-old girl: significance of differentiation from squamous cell carcinoma: a case report.

We report a case of papillary carcinoma (PC) with extensive squamous metaplasia arising from a thyroglossal duct cyst (TDC) that required differential diagnosis from squamous cell carcinoma (SCC). An 11-year-old Japanese girl presented with a 9-month history of an anterior-midline neck mass that was clinically diagnosed as TDC. Open neck biopsy revealed nested proliferation of atypical squamous cells within the cystic structures, and SCC arising from TDC was initially suspected. Further examination, however, including immunohistochemistry, revealed the tumor to be of thyroid cell origin. The patient underwent wide local resection of the thyroglossal duct carcinoma by Sistrunk procedure and cervical lymph node dissection. Microscopically, the diagnosis was of PC with extensive squamous metaplasia and metastasis to the medial submandibular lymph node. Distinction of squamous metaplasia in PC from SCC is sometimes difficult, but has a significant effect on postoperative management.

Hemi-hepatectomy in pediatric patients using two-surgeon technique and a liver hanging maneuver.

AIM: To evaluate the efficacy of the two-surgeon technique with the liver hanging maneuver (LHM) for hepatectomies in pediatric patients with hepatoblastoma. METHODS: Three pediatric patients with hepatoblastoma were enrolled in this study. Two underwent right hemi-hepatectomies and one underwent a left hemi-hepatectomy using the two-surgeon technique by means of saline-linked electric cautery (SLC) and the Cavitron Ultrasonic Surgical Aspirator (CUSA; Valleylab, Boulder, CO) and the LHM. RESULTS: The mean operative time during the parenchymal transections was 50 min and the mean blood loss was 235 g. There was no bile leakage from the cut surface after surgery. No macroscopic or microscopic-positive margins were observed in the hepatic transections. CONCLUSION: The two-surgeon technique using SLC and CUSA with the LHM is applicable to even pediatric patients with hepatoblastoma.

Prediction and management of a low-lying costal arch which restricts the operative working space during laparoscopic cholecystectomy.

BACKGROUND/PURPOSE: Laparoscopic cholecystectomy is difficult to perform in patients with a low-lying costal arch that entirely covers the liver. We conducted this study to clarify the factors related to a low-lying costal arch and establish countermeasures to circumvent this characteristic. METHODS: The study included 103 consecutive patients who underwent a laparoscopic cholecystectomy. The possible clinical factors associated with a low-lying costal arch restricting the operative working space were analyzed. The position of the liver against the costal arch and the presumed surgical visual angle for laparoscopic cholecystectomy, comprising the hepatic porta, umbilicus, and costal arch, were estimated with abdominal multidetector computed tomography (MDCT). RESULTS: Seven (7%) patients had a low-lying costal arch presenting an inadequate exposure of Calot's triangle and restricted instrument mobility during laparoscopic cholecystectomy, and three patients required conversion to a laparotomy. A low-lying costal arch was significantly associated with advanced age, shorter stature, lighter body weight, coexisting kyphoscoliosis, gallbladder pathology, laparotomy conversion, and most of all, the liver edge lying above the costal arch and a narrow surgical visual angle upon MDCT. Of the seven patients with a critical low-lying costal arch, four underwent a successful laparoscopic cholecystectomy, this being done by lifting the right costal arch to create a workable surgical field; the rib-lifting procedure was planned as part of the scheduled procedure in the other three patients because the preoperative MDCT examination indicated a poor working space for a laparoscopic cholecystectomy. CONCLUSIONS: A low-lying costal arch is a substantial risk factor for conversion to a laparotomy when performing a laparoscopic cholecystectomy. However, the operative difficulty related to a low-lying costal arch can be predicted by using preoperative MDCT images and can be managed with proper planning and the appropriate use of the rib-lifting technique.

Endoscopic balloon dilatation for congenital membranous stenosis in the jejunum in an infant.

INTRODUCTION: As endoscopic equipment and instruments have improved, the indications for endoscopic treatment have also been extended. This report presents an applicable procedure of endoscopic balloon dilatation for an infant patient with congenital membranous stenosis in the jejunum. METHODS: We used a 9-mm flexible endoscope and a through-the-scope multidiameter balloon catheter in the endoscopic treatment. RESULTS: Dilatation was performed for dilatation diameters 10, 12, and 15 mm each for 2 min. After carrying out balloon dilatation, the endoscope could be smoothly inserted through the opening. CONCLUSION: In upper jejunal stenosis, endoscopic balloon dilatation was minimally invasive and effective as a treatment modality.

Anatomy-specific pancreatic stump management to reduce the risk of pancreatic fistula after pancreatic head resection.

BACKGROUND: The anatomical status of the pancreatic remnant after a pancreatic head resection varies greatly among patients. The aim of the present study was to improve management of the pancreatic remnant for reducing pancreatic fistula after pancreatic head resection. METHODS: Ninety-five consecutive patients who underwent an end-to-side, duct-to-mucosa pancreaticojejunostomy after pancreatic head resection were included in the study. To approximate the pancreatic stump to the jejunum, the transfixing and interrupted suture techniques were used in 51 and 44 patients, respectively. We modified the interrupted suture technique according to the anatomical status of the pancreatic remnant, i.e., the shape of the pancreatic stump and the location of the pancreatic duct. RESULTS: There was no operative mortality in this study. Overall, 14 patients (15%) developed a clinically relevant pancreatic fistula. Certain anatomical features, including a small pancreatic duct, a soft, nonfibrotic pancreatic gland, and a pancreatic duct adjacent to the posterior cut edge, were significantly associated with pancreatic fistula. The fistula rate in the interrupted suture group was 7%, lower than that (22%) in the transfixing suture group (P = 0.036), and it was not influenced by pancreatic anatomy. Multivariate analysis identified a nonfibrotic pancreas (versus fibrotic pancreas; odds ratio [OR] 12.58, 95% CI 1.2-23.9; P = 0.001), a soft pancreas (versus hard pancreas; OR 4.67, CI 1.2-51.1; P = 0.006), and the transfixing suture technique (versus interrupted suture technique; OR 9.91, CI 1.7-57.5; P = 0.003) as significant predictors of clinically relevant pancreatic fistula. CONCLUSIONS: Pancreatic anastomosis modified according to the pancreatic anatomy is effective in reducing the risk of pancreatic fistula formation with end-to-side, duct-to-mucosa pancreaticojejunostomy after pancreatic head resection.

Chemopreventative effect of an inducible nitric oxide synthase inhibitor, ONO-1714, on inflammation-associated biliary carcinogenesis in hamsters.

The present study was designed to investigate whether an inducible nitric oxide synthase (iNOS)-specific inhibitor, ONO-1714 [(1S, 5S, 6R, 7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0] heptane], could prevent inflammation-associated biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters underwent choledochojejunostomy and then received subcutaneous injections of the chemical carcinogen N-nitrosobis(2-oxopropyl)amine every 2 weeks at a dose of 10 mg/kg body wt, starting 4 weeks after surgery and continuing for 18 weeks. The hamsters were divided into two groups according to their oral intake of either a standard pelleted diet containing ONO-1714 at 100 p.p.m. for 18 weeks (ONO group, n = 15) or an ordinary diet alone (control group, n = 15). The animals were killed 22 weeks after surgery, and the development of biliary tumors was examined histologically. The presence and degree of cholangitis, cell kinetic status of the biliary epithelium and iNOS expression were evaluated. Intrahepatic biliary adenomas developed in all control animals, whereas they developed in only seven (47%) hamsters treated with ONO-1714 (P < 0.05). Intrahepatic biliary carcinomas were present in 13 (87%) hamsters in the control group and in only 6 (40%) hamsters in the ONO groups (P < 0.05). Histological and immunohistochemical examinations demonstrated a significant decrease in the degree of cholangitis, biliary epithelial cell kinetics and the expression of iNOS in the biliary epithelium in the ONO group in comparison with the control (P < 0.05). These results indicate that ONO-1714 represses N-nitrosobis(2-oxopropyl)amine-induced biliary carcinogenesis in bilioenterostomized hamsters and inhibits iNOS expression in the biliary epithelium. ONO-1714 may therefore be a promising agent for the prevention of biliary carcinoma in various inflammation-associated biliary disorders.

Intraductal papillary mucinous neoplasm of the pancreas with a bifid pancreatic duct.

A bifid pancreatic duct presenting a major bifurcation in the main pancreatic duct is one of the anatomical variations of the pancreatic ducts. We encountered a 71-year-old female with a 5-cm-diameter branch duct intraductal papillary mucinous neoplasm of the pancreas in whom preoperative endoscopic retrograde pancreatography demonstrated an anomalous bifurcation of the main pancreatic duct at the body of the pancreas. We performed a distal pancreatectomy, instead of a middle pancreatectomy, with a cutting line at the downstream pancreas to the duct bifurcation point. Intraoperative ultrasonography was useful to confirm the exact location of the pancreatic duct bifurcation as well as the tumor extension. The procedure resulted in a favorable outcome without any postoperative complications. Although a bifid pancreatic duct is an unusual anomalous condition, this case should alert surgeons to be aware of such anatomical variants when performing pancreatic resection, otherwise, incurable pancreatic complications may occur postoperatively.

Multifocal branch-duct pancreatic intraductal papillary mucinous neoplasms.

The appropriate management for patients with multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas involving the entire pancreatic gland remains unclear. We present a 66-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for a branch-duct intraductal papillary mucinous carcinoma demonstrating a grape-like multilocular cyst, 35 mm in diameter, in the head of the pancreas along with numerous number of small branch-duct IPMNs in the whole pancreas. Histologically, the multifocal cystic lesions were lined by a single row of columnar mucin-containing epithelial cells without atypia. The patient has been doing well without any recurrence during 9-year follow-up after surgery. Surgical removal of the prominent lesions suspicious of malignancy and a close observation of the remaining lesions in the remnant pancreas may be a reasonable treatment plan for patients with multifocal branch-duct IPMNs involving the entire pancreatic gland.