[A case of resected synchronous hepatocellular and cholangiolocellular carcinoma in the background of resolved hepatitis B virus infection].

An 85-year-old male patient was referred to our hospital for further examination of a liver tumor. Imaging examination revealed a 90-mm tumor in segment 4/8 and 30-mm tumor in segment 6 of the liver. Histopathological examination revealed that the tumor in segment 4/8 was cholangiolocellular carcinoma (CLC) and the tumor in segment 6 was hepatocellular carcinoma (HCC). This case shows that although the frequency of CLC is very low, recent studies have indicated the novel knowledge of CLC. Herein, we report a surgical case of CLC and HCC in the background of resolved hepatitis B virus infection.

Esophageal Carcinosarcoma that Was Diagnosed as a Granulocyte-colony Stimulating Factor and Interleukin-6-producing Tumor with a Tumor Fever.

A 51-year-old man visited our hospital with a main complaint of precordial pain, difficulty swallowing, and pyrexia. The patient was diagnosed with esophageal carcinosarcoma, based on the characteristic morphology noted on upper gastrointestinal endoscopy and histology tests, and he underwent surgical treatment. His preoperative blood granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) levels were high, and the surgical specimens were positive in both immunohistochemical tests; therefore, he was diagnosed with a G-CSF- and IL-6-producing tumor. When pyrexia is seen as a paraneoplastic symptom, it is important to consider and investigate the possibility of a cytokine-producing tumor.

Randomized crossover trial comparing EUS-guided fine-needle aspiration with EUS-guided fine-needle biopsy for gastric subepithelial tumors.

AIM: The purpose of this study is to compare the diagnostic yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided fine-needle biopsy (EUS-FNB) for gastric subepithelial tumors (SET). METHODS: Patients diagnosed SET derived from fourth layer of the stomach were prospectively enrolled and randomly assigned to undergo both EUS-FNA using standard needle and EUS-FNB using a core biopsy needle alternatively to the same lesion a total of four times per session. The specimen was carefully examined for the presence of a macroscopic visible core, appearing as threadlike yellowish or bloody pieces of tissue and blinded histocytologic analyses were conducted. For spindle cell lesions by hematoxylin and eosin staining (H&E) on histologic evaluation, immunohistochemical staining was performed in all cases to confirm the pathological diagnosis. RESULTS: A total of 23 patients were enrolled and underwent paired EUS-FNA and -FNB sampling. The diagnostic rate due to immunohistochemical staining was 73.9% and 91.3%, respectively (P = .120). The rate of obtaining specimens with a macroscopic yellowish core and only a bloody core among the tissue specimens were respectively 43.5% and 52.2% for EUS-FNA and 69.6% and 30.4% for EUS-FNB. The diagnostic rate for a yellowish core (84.6%) and a bloody core (84.2%, P = .971) did not differ significantly. CONCLUSION: Both techniques were equivalently safe and successful in terms of a high diagnostic yield for gastric SET. And the tissue that can be immunohistochemically stained is present even in the specimens that appear to be a macroscopically bloody core.

Therapeutic peroral direct cholangioscopy using a single balloon enteroscope in patients with Roux-en-Y anastomosis (with videos).

BACKGROUND: Peroral cholangioscopic lithotripsy is a useful procedure in patients with a normal gastrointestinal anatomy who have difficult-to-treat stones. We evaluated the usefulness of peroral direct cholangioscopy (PDCS) using single-balloon enteroscope (SBE) in patients with difficult-to-treat stones who had undergone Roux-en-Y reconstruction. METHODS: Among 118 patients (169 sessions) who underwent SBE-assisted endoscopic retrograde cholangiopancreatography to treat biliary stones after Roux-en-Y reconstruction, patients in whom it was difficult to remove biliary stones via a transpapillary or transanastomotic approach and difficult to switch to ultra-slim endoscope, were retrospectively enrolled. The biliary insertion success rate, procedure success rate, procedure time, and procedural complications were assessed. The SBE was inserted into the bile-duct, first using a free-hand technique, second using a guide wire, and third using the large balloon anchoring and deflation (LBAD) technique. RESULTS: A total of 11 patients (14 sessions) were enrolled in this study. The biliary insertion success rate was 100%. Bile-duct insertion was performed using a free-hand technique in 4 sessions, a guide wire in 3 sessions (rendezvous technique, 2 sessions), and the LBAD technique in 7 sessions. The procedure success rate was 86% in first session, and 100% in second session. The median procedure time was 81 min (range 49-137). The median procedure time in the bile-duct was 21.5 min (range 6-60). Mild pancreatitis occurred as a complication in one patient. The median follow-up was 528 days (range 282-764). No patient had stone recurrence. CONCLUSIONS: PDCS using SBE is a useful procedure in patients with Roux-en-Y reconstruction. The LBAD technique is an useful technique of inserting SBE into the bile-duct.

Endoscopic ultrasonography diagnosis of subepithelial lesions.

Using endoscopic ultrasonography (EUS), it is practicable to diagnose subepithelial lesions (SEL) with originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma, and cyst have characteristic features; therefore, there is no need for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Ectopic pancreas and glomus tumors, which originate from the third and fourth layers, are frequently seen in the antrum. However, ectopic pancreas located in the fundus or body is large and originates from the third and fourth layers (thickening of fourth layer). Each subepithelial lesion has characteristic findings. However, imaging differentiation of tumors originating from the fourth layer is very difficult, even if contrast echo is used. Therefore, EUS-FNA should be done in these tumors, but the diagnostic yield for small lesions is not sufficient for clinical demands. Generally, those tumors, including small ones, should be first followed up in 6 months, then yearly follow up in cases of no significant change in size and features. When those tumors become larger than 1-2 cm, EUS-FNA is recommended. Furthermore, unusual SEL and SEL with malignant findings such as nodular, heterogeneous, anechoic area, and ulceration indicate EUS-FNA. Cap-attached forward-viewing echoendoscope is very helpful for EUS-FNA of small SEL.

Pancreatic Fistula Extending into the Thigh Caused by the Rupture of an Intraductal Papillary Mucinous Adenoma of the Pancreas.

We herein report the first case of a pancreatic fistula extending into the thigh caused by the rupture of an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. An 80-year-old man was suspected to have necrotizing fasciitis because of right femoral pain. Computed tomography showed fluid retention from the pancreatic head to the right iliopsoas muscle and an IPMN at the pancreatic head. The findings of endoscopic retrograde pancreatography led to the suspicion of a minor leak and a pancreatic stent was placed. The patient died due to an uncontrollable infection. A pathological autopsy showed a pancreatic fistula extending into the thigh that had been caused by the rupture of the IPMN.

Clinical implications of doubling time of gastrointestinal submucosal tumors.

AIM: To evaluate the efficacy of doubling time (DT) of gastrointestinal submucosal tumors (GIST). METHODS: From April 1987 through November 2012, a total of 323 patients were given a final histopathological diagnosis of GISTs on surgical resection or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in Kitasato University East Hospital or Kitasato University Hospital. We studied 53 of these patients (34 with resected tumors and 19 with unresected tumors) whose tumors could be measured on EUS on at least two successive occasions. The histopathological diagnosis was GIST in 34 patients, leiomyoma in 5, schwannoma in 3, ectopic pancreas in 1, hamartoma in 1, cyst in 1, Brunner's adenoma in 1, and spindle-cell tumor in 7. We retrospectively calculated the DT of GISTs on the basis of the time course of EUS findings to estimate the growth rate of such tumors. RESULTS: The DT was 17.2 mo for GIST, as compared with 231.2 mo for leiomyoma, 104.7 mo for schwannoma, 274.9 mo for ectopic pancreas, 61.2 mo for hamartoma, 49.0 mo for cyst, and 134.7 mo for Brunner's adenoma. The GISTs were divided into risk classes on the basis of tumor diameters and mitotic figures (Fletcher's classification). The classification was extremely low risk or low risk in 28 patients, intermediate risk in 3, and high risk in 3. DT of GIST according to risk was 24.0 mo for extremely low-risk plus low-risk GIST, 17.1 mo for intermediate-risk GIST, and 3.9 mo for high-risk GIST. DT of GIST was significantly shorter than that of leiomyoma plus schwannoma (P < 0.05), and DT of high-risk GIST was significantly shorter than that of extremely low-risk plus low-risk GIST (P < 0.05). CONCLUSION: For GIST, a higher risk grade was associated with a significantly shorter DT. Small SMTs should initially be followed up within 6 mo after detection.

A case of thrombus of the descending aorta successfully diagnosed on preoperative endoscopic ultrasonography.

A 45-year-old woman presented with left lower abdominal pain. A plain CT scan showed a slightly high-density, cord-like structure extending from the level of the diaphragm of the descending aorta to the superior mesenteric artery. Transgastric endoscopic ultrasonography (EUS) revealed a floating mass, smoothly attaching to the aortic intima and depicted as a hyperechoic region containing a mixture of hyperechoic and hypoechoic areas. EUS elastography revealed that the body of the mass consisted of medium soft tissue, with hard tissue at its base. On histopathological examination after surgery, the mass was found to consist mainly of fibrin, with no atypical cells. EUS examination should be used for the differential diagnosis between thrombi and tumors in the aorta.

A Case Series: Outcomes of Endoscopic Biliary Self-Expandable Metal Stent for Malignant Biliary Obstruction with Surgically Altered Anatomy.

BACKGROUND: Few studies have reported the outcomes of self-expandable metal stent (SEMS) placement for malignant biliary obstruction in patients with surgically altered anatomy. AIMS: To evaluate the outcomes of biliary metal stent placement with the use of a short-type single-balloon enteroscope (working length, 1520 mm; channel diameter, 3.2 mm) in such patients. METHODS: We retrospectively studied 13 malignant biliary obstructions treated by SEMS placement. Technical success rate, functional success rate, time to recurrent biliary obstruction (RBO), and complications were evaluated. RESULTS: Technical success rate was 100 % (13/13), functional success rate was 92 % (12/13), and the median time to RBO was 247 days (95 % CI 205.6-285.5). Complications comprised mild pancreatitis in one patient. Uncovered SEMSs were placed in three obstructions, partially covered SEMS in five obstructions, and fully covered SEMSs in five obstructions. Three stents occluded (two ingrowths and one mucosal hyperplasia), and one symptomatic distal stent migration occurred after more than 30 days from placement. CONCLUSIONS: A short-type single-balloon enteroscope was useful for the placement of various SEMS in this patient population with satisfactory outcomes.

A Patient with Pancreatic Castleman's Disease Arising around the Main Pancreatic Duct.

Castleman's disease of the pancreas is extremely rare. To the best of our knowledge, Castleman's disease arising around the main pancreatic duct has not been previously reported. The patient was a 74-year-old man. Abdominal ultrasonography performed at a health check-up revealed a dilated main pancreatic duct. Pancreatic cancer was strongly suspected on various imaging studies. However, the results of a cytological examination of the pancreatic juice were negative for malignancy. The patient did not want to undergo a histological diagnosis by endoscopic ultrasound-guided fine-needle aspiration, thus pylorus-preserving pancreatoduodenectomy was performed. Pancreatic Castleman's disease arising around the main pancreatic was diagnosed by the histopathological examination.

Innovations and techniques for balloon-enteroscope-assisted endoscopic retrograde cholangiopancreatography in patients with altered gastrointestinal anatomy.

Endoscopic retrograde cholangiopancreatography (ERCP) remains challenging in patients who have undergone surgical reconstruction of the intestine. Recently, many studies have reported that balloon-enteroscope-assisted ERCP (BEA-ERCP) is a safe and effective procedure. However, further improvements in outcomes and the development of simplified procedures are required. Percutaneous treatment, Laparoscopy-assisted ERCP, endoscopic ultrasound-guided anterograde intervention, and open surgery are effective treatments. However, treatment should be noninvasive, effective, and safe. We believe that these procedures should be performed only in difficult-to-treat patients because of many potential complications. BEA-ERCP still requires high expertise-level techniques and is far from a routinely performed procedure. Various techniques have been proposed to facilitate scope insertion (insertion with percutaneous transhepatic biliary drainage (PTBD) rendezvous technique, Short type single-balloon enteroscopes with passive bending section, Intraluminal injection of indigo carmine, CO2 inflation guidance), cannulation (PTBD or percutaneous transgallbladder drainage rendezvous technique, Dilation using screw drill, Rendezvous technique combining DBE with a cholangioscope, endoscopic ultrasound-guided rendezvous technique), and treatment (overtube-assisted technique, Short type balloon enteroscopes) during BEA-ERCP. The use of these techniques may allow treatment to be performed by BEA-ERCP in many patients. A standard procedure for ERCP yet to be established for patients with a reconstructed intestine. At present, BEA-ERCP is considered the safest and most effective procedure and is therefore likely to be recommended as first-line treatment. In this article, we discuss the current status of BEA-ERCP in patients with surgically altered gastrointestinal anatomy.

Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer.

AIM: To evaluate the dose-limiting toxicities (DLTs) and determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer. METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine (mg/m(2)), cisplatin (mg/m(2)), and S-1 (mg/m(2) per day) were as follows: level -1, 800/20/60; level 0, 800/25/60; level 1, 1000/25/60; and level 2, 1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15, and S-1 was administered orally twice daily on days 1 to 7 and days 15 to 21, every 4 wk. RESULTS: Twelve patients were enrolled, and level 0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs (grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1. We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase II study. CONCLUSION: The RD was defined as gemcitabine 1000 mg/m(2) (days 1, 15), cisplatin 25 mg/m(2) (days 1, 15), and S-1 80 mg/m(2) per day (days 1-7, 15-21), every 4 weeks. A phase II study is planned to evaluate the effectiveness of combination chemotherapy with gemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.

Passive-bending, short-type single-balloon enteroscope for endoscopic retrograde cholangiopancreatography in Roux-en-Y anastomosis patients.

AIM: To evaluate short-type-single-balloon enteroscope (SBE) with passive-bending, high-force transmission functions for endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anastomosis. METHODS: Short-type SBE with this technology (SIF-Y0004-V01; working length, 1520 mm; channel diameter, 3.2 mm) was used to perform 50 ERCP procedures in 37 patients with Roux-en-Y anastomosis. The rate of reaching the blind end, time required to reach the blind end, diagnostic and therapeutic success rates, and procedure time and complications were studied retrospectively and compared with the results of 34 sessions of ERCP performed using a short-type SBE without this technology (SIF-Y0004; working length, 1520 mm; channel diameter, 3.2 mm) in 25 patients. RESULTS: The rate of reaching the blind end was 90% with SIF-Y0004-V01 and 91% with SIF-Y0004 (P = 0.59). The median time required to reach the papilla was significantly shorter with SIF-Y0004-V01 than with SIF-Y0004 (16 min vs 24 min, P = 0.04). The diagnostic success rate was 93% with SIF-Y0004-V01 and 84% with SIF-Y0004 (P = 0.17). The therapeutic success rate was 95% with SIF-Y0004-V01 and 96% with SIF-Y0004 (P = 0.68). The median procedure time was 40 min with SIF-Y0004-V01 and 36 min with SIF-Y0004 (P = 0.50). The incidence of hyperamylasemia was 6.0% in the SIF-Y0004-V01 group and 14.7% in the SIF-Y0004 group (P = 0.723). The incidence of pancreatitis was 0% in the SIF-Y0004-V01 group and 5.9% in the SIF-Y0004 group (P > 0.999). The incidence of gastrointestinal perforation was 2.0% (1/50) in the SIF-Y0004-V01 group and 2.9% (1/34) in the SIF-Y0004 group (P > 0.999). CONCLUSION: SIF-Y0004-V01 is useful for ERCP in patients with Roux-en-Y anastomosis and may reduce the time required to reach the blind end.