Transhiatal bilateral thoracic duct ligation for duplicated thoracic duct injury after esophagectomy: a case report.

BACKGROUND: The treatment of duplicated thoracic ducts (TDs) injury after esophagectomy generally requires a bilateral transthoracic approach. We present the cases of two patients with postoperative chylothorax who underwent transhiatal bilateral TD ligation for duplicated TDs. CASE PRESENTATION: Two patients diagnosed with chylothorax after esophagectomy performed for thoracic esophageal cancer underwent transhiatal TD ligation. Although supradiaphragmatic mass ligation was performed on the fat tissue of the right side of the aorta containing the TD, chyle leakage persisted. To tackle this, the fat tissue of the left side of the aorta was ligated, after which the chyle leakage stopped. CONCLUSION: Compared to the conventional transthoracic approach, the transhiatal approach enables the ligation of both left- and right-sided TD in a single surgical operation, without the need to change the patient's posture. This approach may be appropriate for the treatment of chylothorax after esophagectomy, considering the possibility of duplicated TDs.

Posterior Cervical Intramuscular Schwannoma Within the Trapezius Muscle: A Case Report.

Schwannomas are benign soft tissue tumors derived from the Schwann cells of the peripheral nerves. An intramuscular schwannoma arising within the trapezius muscle in the posterior neck is rare. We report a case of a 31-year-old woman with an intramuscular schwannoma in the trapezius muscle. A painless and smooth-surfaced mass from 10 years ago was evident on palpation in the right posterior neck. Ultrasonography revealed an oval mass with clear borders and slight internal blood flow. No continuous hypoechoic lesions were noted at the tip of the mass. Magnetic resonance imaging of the neck revealed a mass in the right posterior cervical trapezius muscle with isointensity on T1-weighted imaging and heterointensity on T2-weighted imaging. Based on these findings, a schwannoma was suspected. Ultrasonography guided fine needle aspiration cytology revealed no significant findings. During surgery, a white-colored, encapsulated-tumor mass was found in the trapezius muscle. Histopathologically, hypocellular and hypercellular areas of fusiform cells were conspicuous, and nuclear palisading was observed in a part of the hypercellular region, confirming the diagnosis of schwannoma. To our knowledge, this is an extremely rare report of an intramuscular schwannoma within the trapezius muscle; herein, we report its clinical, radiological, and pathological features.

Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer (VOICE trial).

PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1-14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. RESULTS: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6-19.5), and median TTF was 12.3 months (95% CI, 10.3-14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CONCLUSION: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. TRIAL REGISTRATION: UMIN ID: 000,005,732, date of registration: June 7, 2011.  https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695.

[A Case of Colon Cancer with DPD Deficiency That Showed Severe Myelosuppression by CapeOX Adjuvant Chemotherapy after Colon Resection].

A 57-year-old female patient received ileocecal colon resection because of colon cancer. Pathological findings showed pSSN2M0(pStage III b). After surgery, CapeOX was administered as an adjuvant chemotherapy. On day 13 of CapeOX treatment, severe oral mucositis and Grade 4 myelosuppression appeared, and the CapeOX treatment was immediately stopped. However, these adverse effects continued for 19 days, and she gradually recovered. The severe myelosuppression was caused bydeficiencyof DPD, which is a keyenzy me that metabolizes 5-FU. While DPD deficiencyis veryrare, we need to consider that 5-FU causes severe adverse events in patients with DPD deficiency.

Diagnostic accuracy of diffusion-weighted whole-body imaging with background body signal suppression/T2-weighted image fusion for the detection of abdominal solid cancer.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

[Long-Term Successful Management of Recurrent Rectal Cancer in the Predialysis State with FOLFIRI Chemotherapy].

A 71-year-old man with predialysis terminal renal insufficiency experienced peritoneal dissemination 1.5 years after low anterior resection for advanced rectal cancer. He received FOLFIRI therapy (70% dose); he achieved partial response (PR) under computed tomography and stable disease (SD) was maintained over a long term. Although Grade 3 myelosuppression was occasionally noted, he was treated with FOLFIRI for 2 years without other severe complications and without requiring the initiation of hemodialysis. After the initiation of hemodialysis, FOLFIRI treatment was continued for 1 year until progressive disease (PD). He received mFOLFOX6 as second-line therapy for 6 months, followed by LV-5-FU and a molecular targeting agent. These treatments prolonged his survival for 1 year and 8 months. FOLFIRI can be administered as an effective first-line therapy even for patients with predialysis terminal renal impairment without major renal damage. FOLFOX and molecular targeting agents should be made available and prolonged survival can be expected for advanced colorectal cancer patients with terminal renal disease after the initiation of hemodialysis.

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion and positron emission tomography/computed tomography of upper gastrointestinal cancers.

PURPOSE: Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. METHODS: Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. RESULTS: Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. CONCLUSIONS: DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.

Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant.

Generation of functional and vascularized organs from human induced pluripotent stem cells (iPSCs) will facilitate our understanding of human developmental biology and disease modeling, hopefully offering a drug-screening platform and providing novel therapies against end-stage organ failure. Here we describe a protocol for the in vitro generation of a 3D liver bud from human iPSC cultures and the monitoring of further hepatic maturation after transplantation at various ectopic sites. iPSC-derived specified hepatic cells are dissociated and suspended with endothelial cells and mesenchymal stem cells. These mixed cells are then plated onto a presolidified matrix, and they form a 3D spherical tissue mass termed a liver bud (iPSC-LB) in 1-2 d. To facilitate additional maturation, 4-d-old iPSC-LBs are transplanted in the immunodeficient mouse. Live imaging has identified functional blood perfusion into the preformed human vascular networks. Functional analyses show the appearance of multiple hepatic functions in a chronological manner in vivo.

Vascularized and functional human liver from an iPSC-derived organ bud transplant.

A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.

[Successful management using laparoscopic splenectomy for splenomegaly and thrombocytopenia caused by oxaliplatin-based chemotherapy for advanced rectal cancer].

We report a case of advanced rectal cancer treated with chemotherapy, for which laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old man suffered from advanced rectal cancer with multiple lung metastases. He underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly and thrombocytopenia. Laparoscopic splenectomy produced and increased the thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating thrombocytopenia, and allowed the continuation of chemotherapy.

Imaging studies of intraductal tubulopapillary neoplasms of the pancreas: 2-tone duct sign and cork-of-wine-bottle sign as indicators of intraductal tumor growth.

OBJECTIVE: The objective of this study was to describe the imaging findings for intraductal tubulopapillary neoplasms of the pancreas. METHODS: Eleven pancreatic tumors pathologically confirmed as intraductal tubulopapillary neoplasm were retrospectively collected. The dynamic contrast-enhanced computed tomography (CT), magnetic resonance (MR) imaging including MR cholangiopancreatography (MRCP), ultrasound, and endoscopic retrograde cholangiopancreatography (ERCP) results were reviewed. The 2-tone duct sign and cork-of-wine-bottle sign were reviewed as indicators of intraductal tumor growth on CT/MR and MRCP/ERCP images, respectively. RESULTS: A 2-tone duct sign was noted on the dynamic CT images (7/10, 70%) and on the MR imaging (5/8, 63%). The distal main pancreatic duct was dilated in all the patients except one, who had a branch duct lesion. A cork-of-wine-bottle sign was observed on the MRCP image (3/8, 38%) and on the ERCP image (3/6, 50%). CONCLUSIONS: Intraductal tubulopapillary neoplasms are rare tumors showing characteristic imaging findings such as the 2-tone duct sign and the cork-of-wine-bottle sign that represent their intraductal growth.

Role of diffusion-weighted magnetic resonance imaging in the differential diagnosis of focal hepatic lesions.

AIM: To evaluate the utility of diffusion-weighted imaging (DWI) in screening and differential diagnosis of benign and malignant focal hepatic lesions. METHODS: Magnetic resonance imaging (MRI) examinations were performed using the Signa Excite Xl Twin Speed 1.5T system (GE Healthcare, Milwaukee, WI, USA). Seventy patients who had undergone MRI of the liver [29 hepatocellular carcinomas (HCC), four cholangiocarcinomas, 34 metastatic liver cancers, 10 hemangiomas, and eight cysts] between April 2004 and August 2008 were retrospectively evaluated. Visualization of lesions, relative contrast ratio (RCR), and apparent diffusion coefficient (ADC) were compared between benign and malignant lesions on DWI. Superparamagnetic iron oxide (SPIO) was administered to 59 patients, and RCR was compared pre- and post-administration. RESULTS: DWI showed higher contrast between malignant lesions (especially in multiple small metastatic cancers) and surrounding liver parenchyma than did contrast-enhanced computed tomography. ADCs (mean +/- SD x 10(-3) mm(2)/s) were significantly lower (P < 0.05) in malignant lesions (HCC: 1.31 +/- 0.28 and liver metastasis: 1.11 +/- 0.22) and were significantly higher in benign lesions (hemangioma: 1.84 +/- 0.37 and cyst: 2.61 +/- 0.45) than in the surrounding hepatic tissues. RCR between malignant lesions and surrounding hepatic tissues significantly improved after SPIO administration, but RCRs in benign lesions were not improved. CONCLUSION: DWI is a simple and sensitive method for screening focal hepatic lesions and is useful for differential diagnosis.

Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms.

We have encountered cases of unusual intraductal pancreatic neoplasms with predominant tubulopapillary growth. We collected data on 10 similar cases of "intraductal tubulopapillary neoplasms (ITPNs)" and analyzed their clinicopathologic and molecular features. Tumor specimens were obtained from 5 men and 5 women with a mean age of 58 years. ITPNs were solid and nodular tumors obstructing dilated pancreatic ducts and did not contain any visible mucin. The tumor cells formed tubulopapillae and contained little cytoplasmic mucin. The tumors exhibited uniform high-grade atypia. Necrotic foci were frequently observed, and invasion was observed in some cases. The ITPNs were immunohistochemically positive for cytokeratin 7 and/or cytokeratin 19 and negative for trypsin, MUC2, MUC5AC, and fascin. Molecular studies revealed abnormal expressions of TP53 and SMAD4 in 1 case, but aberrant expression of beta-catenin was not observed. No mutations in KRAS and BRAF were observed in the 8 cases that were examined. Eight patients are alive without recurrence, 1 patient died of liver metastases, and 1 patient is alive but had a recurrence and underwent additional pancreatectomy. The mitotic count and Ki-67 labeling index were significantly associated with invasion. All the features of ITPN were distinct from those of other known intraductal pancreatic neoplasms, including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and the intraductal variant of acinar cell carcinoma. Intraductal tubular carcinomas showed several features that were similar to those of ITPN, except for the tubulopapillary growth pattern. In conclusion, ITPNs can be considered to represent a new disease entity encompassing intraductal tubular carcinoma as a morphologic variant.

Hepatic hilar resection for hilar cholangiocarcinoma based on a reclassification.

Major hepatic resection for hilar cholangiocarcinoma is reportedly closely associated with severe postoperative complications. We performed a new limited resection that included total resection of the caudate lobe and anterior segment (ventral region of the right paramedian sector), and bile duct resection with hepaticojejunostomy in 3 patients with hilar cholangiocarcinoma that had not infiltrated the hepatic artery or portal vein. In all 3 patients, curative surgical resections were obtained and no serious complications were encountered. This new limited resection based on a reclassification of the liver may offer an effective procedure in limited patients with hilar cholangiocarcinoma.

Intersegmental arterial communication between the medial and left lateral segments of the liver.

BACKGROUND/AIMS: Although the interlobar arterial collateral of the liver has been thoroughly analyzed, few reports have described the intersegmental arterial collateral between the medial and left lateral segments. METHODS: The hepatic arterial system of the left liver was evaluated using 12 latex resin cast specimens in which latex resin was injected into the left hepatic artery after ligation of the right hepatic artery. RESULTS: In all 12 livers, an intersegmental collateral between the medial and left lateral segments was detected. These collaterals were extrahepatically located in the umbilical plate and gave rise to branches traveling to the bile duct of the left liver. CONCLUSIONS: The present study showed that the communicating arcade between the middle and left lateral hepatic arteries was consistently present in the umbilical plate and played an important role not only in the intersegmental arterial collateral system of the left liver but also in the blood supply to the bile ducts.

Extrahepatic control of the middle hepatic vein with inflow control by pedicle clamping in major liver surgery.

Surgical techniques commonly used for controlling bleeding during major liver surgery are hepatic inflow occlusion (Pringle maneuver) or total hepatic vascular exclusion (THVE), which are effective procedures of diminishing intraoperative blood loss. However, it is difficult to control retrograde bleeding from the hepatic veins using Pringle maneuver and some patients do not tolerate hemodynamic changes caused by THVE. We isolated the left and middle hepatic veins separately using Arantius' ligament approach to these hepatic veins, and extrahepatic control of the relevant to the liver segment to be resected hepatic veins with inflow control by Glissonian pedicle clamping was successfully performed.

Ventral pancreatectomy associated with segmental duodenectomy including the major papilla.

During embryonic development, the head of the pancreas comprises ventral and dorsal primordia. The embryological fusion plane between the ventral and dorsal primordia reportedly separates the adult pancreas into the ventral and dorsal pancreas. The duct of Wirsung drains the ventral pancreas and terminates in the major papilla, while the duct of Santorini drains the dorsal pancreas and terminates in the minor papilla. However, complete resection of the ventral pancreas is difficult and impractical because the lower bile duct is buried in ventral pancreatic parenchyma and resection may lead to postoperative ischemic necrosis of the duodenum, particularly around the major papilla. We have therefore performed ventral pancreatectomy associated with segmental duodenectomy including the major papilla in 3 cases with intraductal papillary mucinous neoplasm that involved only the duct of Wirsung.

Two-staged hepato-pancreatoduodenectomy and interventional pancreaticojejunostomy.

Two-staged pancreatoduodenectomy, including exteriorization of the pancreatic juice and second-look pancreaticojejunostomy, has been recommended for high-risk patients to avoid pancreatic leakage, which often causes intra-abdominal hemorrhage. We present a new technique of interventional pancreaticojejunostomy under both fluoroscopy and endoscopy without second-look laparotomy. A 77-year-old woman with local recurrence and liver metastasis from colon cancer underwent hepato-pancreatoduodenectomy with the external drainage of pancreatic juice via the pancreatic duct tube without pancreaticojejunostomy. Two months later, the jejunum was punctured with the insertion of a 5-F needle-knife into the pancreatic fistula during endoscopic observation of jejunal lumen, followed by the insertion of two 0.35-inch guidewires into the jejunum and the pancreatic fistula. Finally, a 10-Fr stenting tube was placed between the jejunum and the pancreatic fistula. No complications developed.

Characterization and genetic analysis in the newly established human bile duct cancer cell lines.

Bile duct carcinoma patients generally have a poor prognosis. Understanding this cancer at the biological, genetic, molecular, and cellular level in ways relevant to clinical management is essential for developing effective preventive and therapeutic regimens. However, the currently established bile duct cancer cell lines are still insufficient for the research required to attain such an improved understanding. The aim of this study was to establish and characterize human bile duct cancer cell lines. We examined the growth characteristics and colony-forming ability of the established cell lines in terms of their cell cycle parameters and expression of tumor markers (CEA, CA19-9, MUC-1 and c-kit) and oncogene (c-erbB2) by flow cytometry. Comparative genomic hybridization (CGH) was performed to detect changes in the gene copy numbers. Human origin of the cell lines was confirmed by chromosomal analysis. We have established 3 cell lines and designated them as TGBC-47, TGBC-51, and TBCN-6 and the population doubling times of the three cell lines were 28, 38 and 94 h, respectively. The cells maintained differentiation characteristics of the original tumors. Two cell lines formed colonies in the colony forming assays; all three-cell lines expressed CEA, CA19-9, MUC-1 and c-erbB2 and showed chromosomal aneuploidy. CGH analysis demonstrated gains in various chromosomal regions, including 1q, 5p, 6p, 7q and 8q in two cell lines, and the loss in 17p in three cell lines. These newly established cell lines might serve as useful models for studying the advanced molecular tumor biology of bile duct cancer. Furthermore, they may assist translational research in the development of new effective molecular targeting chemoradiotherapy regimens. These chromosomal aberrations and imbalances provide some starting points for the molecular analysis of genomic regions and genes involved in bile duct carcinogenesis.

Refractory proctosigmoiditis probably caused by inferior mesenteric vein ligation at sigmoidectomy.

A case of refractory proctosigmoiditis is reported in a 65-year-old female post-sigmoidectomy patient. She had bloody diarrhea and abdominal pain 2 years after sigmoidectomy, in which the inferior mesenteric vein was ligated close to the inferior mesenteric artery root during the lymph node dissection, while the inferior mesenteric artery trunk and the last branch of the sigmoid arteries was preserved. The biopsied specimen obtained by a fiber optic colonoscopy was diagnosed as proctitis. Antidiarrheals, 5-aminosalicylic acid and steroid enemas showed only limited therapeutic effects. An angiography revealed a mild degree of rectal artery dilatation and tiny venous angiogenesis detected on the delayed phase images. Because the inferior mesenteric vein had been ligated, collateral veins developed to drain the blood on the distal side of the anastomosis to bilateral internal iliac veins. The venous blood of the descending colon (oral side of anastomosis) drained to left colic vein. The cause of rectosigmoiditis was considered to be venous congestion due to the inferior mesenteric vein ligation. A rectosigmoidectomy with reanastomosis using a double-stapling technique was performed, and the patient was discharged without symptoms.