Disseminated Carcinomatosis of Bone Marrow as the Initial Presentation of Intrahepatic Cholangiocarcinoma without Jaundice: An Autopsy Case Report.

Disseminated carcinomatosis of the bone marrow (DCBM) is often accompanied by disseminated intravascular coagulation (DIC) and has a poor prognosis. DCBM develops most frequently in gastric cancer and is rarely associated with intrahepatic cholangiocarcinoma. A 41-year-old man was incidentally found to have DIC on his regular visit for ulcerative colitis and was diagnosed with DCBM with intrahepatic cholangiocarcinoma. He received intensive care, including chemotherapy, but died suddenly from hyperkalemia, possibly due to tumor lysis syndrome (TLS). The autopsy showed the periductal infiltrating type of intrahepatic cholangiocarcinoma and tumor necrosis, possibly due to chemotherapy, indicating the effectiveness of chemotherapy for DCBM with intrahepatic cholangiocarcinoma.

Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

BACKGROUND: Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). METHODS: A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. RESULTS: Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. CONCLUSIONS: Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

A case of granulocyte-colony stimulating factor-producing hepatocellular carcinoma confirmed by immunohistochemistry.

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/microL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.

A comparison of outcomes of endoscopic submucosal dissection (ESD) For early gastric neoplasms between high-volume and low-volume centers: multi-center retrospective questionnaire study conducted by the Nagano ESD Study Group.

OBJECTIVE: Outcomes of endoscopic submucosal dissection (ESD) for early gastric neoplasms at low-volume centers have been unknown, because all previous reports have studied in advanced single centers. The aim of this study was to compare ESD outcomes between high- and low-volume centers. METHODS: A retrospective questionnaire survey was conducted and 30 centers (96.8%) responded. The complete en-bloc resection rate (CERR) and the incidence of complications were analyzed. Early gastric cancer (EGC) was divided into three categories on the basis of pathological diagnosis-standard indication (SI), expanded indication (EI) and out-of-indication (OI). RESULTS: A total of 703 early gastric neoplasms (586 EGCs, 117 gastric adenomas) were treated with ESD from January to December 2005. The institutions that treated more than 30 cases a year were classified as high-volume centers, and those with less than 30 cases, low-volume centers. In SI, the CERRs at high- and low-volume centers were 92.1% and 91.1%, in EI, CERRs were 86.2% and 82.6% and in OI, CERRs were 80.3% and 88.0%. The perforation rates at high- and low-volume centers were 3.6% and 4.7%. The intra-operative bleeding rates at high- and low-volume centers were 0.26% and 0%, while the delayed bleeding rates were 0% and 0.63%. CONCLUSION: There were no significant difference in the outcomes of ESD for early gastric neoplasms between high- and low volume centers.

Usefulness of double balloon enteroscopy and video capsule endoscopy for the diagnosis and management of primary follicular lymphoma of the gastrointestinal tract in its early stages.

AIM: The aim of this study is to evaluate the usefulness of double balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in patients with primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. Furthermore, we estimate the effectiveness of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) including rituximab for them. METHODS: Thirteen consecutive patients who were diagnosed of having FL in the duodenum between July 2005 and September 2008 were studied. All patients were given the conventional staging examinations, including total enteroscopy using DBE and/or VCE procedures. Chemotherapy was performed after written informed consent. Response assessment was performed every 6-12 months. The median follow-up period was 30.2 months. RESULTS: FL was diagnosed in each patient as low grade (grade 1, n = 7; 2, n = 6) and, in all but 4 patients, localized lymphoma (stage I, n = 8; II(1), n = 1; II(2), n = 4). DBE revealed multifocal lesions in the jejunum in 10 of the patients, and in the ileum in 6. VCE showed similar findings in the jejunum in the recent 2 patients. Eleven of 13 patients finally received chemotherapy, and all of them achieved complete regression. They showed no evidence of recurrence after that. CONCLUSION: Total examination of the small intestine using DBE should be performed before treatment to choose a suitable treatment procedure for primary FL of the GI tract. On the other hand, VCE is useful for screening and following the small intestine in the patients with it. Chemotherapy is effective to achieve complete regression of primary FL of the GI tract.

Impairment of changes in the diameter of the pancreatic portion of the superior mesenteric vein: an ultrasonographic sign of chronic pancreatitis or fibrosis.

OBJECTIVE: A new ultrasonographic technique for detecting parenchymal stiffness of the pancreas is proposed. This technique measures changes in the diameter of the origin of the superior mesenteric vein (SMV) induced by deep inspiration. The origin of the SMV has extensive attachments to the pancreatic parenchyma; therefore, both physiologic enlargement and shrinkage of the venous lumen cannot occur without changes in the shape of the surrounding parenchyma. Therefore, increased parenchymal stiffness due to chronic pancreatitis (CP) may result in impaired changes in the venous diameter. To confirm this hypothesis, patients with CP and those with a normal pancreas were examined in this study. METHODS: Twelve patients in each group were examined. Images of the origin of the SMV were obtained with a commercial ultrasound system. The smallest diameter of the SMV was measured during normal breathing. The patients were then asked to take a deep breath to increase the portal blood pressure followed immediately by the same measurements as performed during normal breathing, and the ratio of the change was calculated. RESULTS: In the normal group, the diameter of the SMV changed by 79.5% +/- 43.8% (mean +/- SD), whereas a change of 1.4% +/- 7.3% was observed in the CP group. The difference between the two groups was statistically significant (P < .0001). CONCLUSIONS: The physiologic change in the diameter of the origin of the SMV enhanced by deep inspiration may reflect the stiffness of the pancreatic parenchyma. Therefore, detection of an impaired diameter change may be useful for screening of CP.

Primitive neuroectodermal tumor as a differential diagnosis of CD56-positive tumors in adults.

A 33-year-old Japanese man was referred to our hospital after a huge intrapelvic tumor with bilateral hydronephrosis was found following persistent lumbago. Natural killer/T-cell lymphoma was suspected due to positive immunostaining for CD56, but CHOP therapy was ineffective. Re-evaluation of the tumor cells showed that they were positive for CD99, neuron-specific enolase, and synaptophysin and had a t(11 ; 22) (q24 ; q12) translocation, leading to the revised diagnosis of primitive neuroectodermal tumor (PNET). Systemic chemotherapies and radiation therapy were added to surgical resection, and no recurrence has been detected for 3 years. Taken together, PNET may be considered in adult patients with CD56-positive tumors.

Granulocyte-colony stimulating factor-producing pancreatic adenosquamous carcinoma showing aggressive clinical course.

Herein, we encountered an 89-year-old woman with pancreatic cancer who presented with fever without infective focus, leukocytosis of 45,860 /microL, and elevation of serum granulocyte-colony stimulating factor (G-CSF). The patient could not receive any curative therapy due to an extremely aggressive clinical course. Specimens taken at necropsy revealed an adenosquamous carcinoma positive for G-CSF by immunohistochemistry; it was only the second reported case to date. She was finally diagnosed with G-CSF-producing pancreatic cancer. In light of the above, clinicians should consider the presence of G-CSF-producing tumors, including pancreatic cancer, when presented with patients showing leukocytosis of unknown origin and fever without infective focus.

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection.

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.

Gastric MALT lymphomas are divided into three groups based on responsiveness to Helicobacter Pylori eradication and detection of API2-MALT1 fusion.

Gastric MALT lymphoma shows unique features including regression by Helicobacter pylori eradication and API2-MALT1 fusion. We performed a molecular and clinicopathologic study for 115 cases. All eradication-responsive cases were devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative for H. pylori infection were nonresponsive to the eradication. Consequently, gastric MALT lymphomas were divided into three groups: Eradication-responsive and fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n = 21). Group A tumors were characterized by low clinical stage and superficial gastric wall involvement, and group C tumors by low H. pylori infection rate, advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed exclusively low-grade histology. Group B tumors, which have not been well recognized, frequently showed nodal involvement, deep gastric wall involvement, and advanced clinical stage, and sometimes an increased large cell component. A multivariate discriminant analysis revealed that responsiveness to the eradication could be predicted accurately by negative API2-MALT1 fusion, positive H. pylori infection, low clinical stage, and superficial gastric wall invasion, the former being the most important factor for the prediction. This 3-group categorization may be helpful for a comprehensive understanding of gastric MALT lymphoma.

Successful treatment with corticosteroid in a case of Behçet's syndrome with multiple esophageal ulcerations.

A 59-year-old woman was diagnosed with incomplete type Behçet's syndrome in 1994. The patient was hospitalized with pharyngitis and fever in August 2000, and was treated using non-steroidal anti-inflammatory drugs (NSAIDs). Symptoms improved and she was discharged. After only 3 weeks, she reported swallowing disturbance due to retrosternal pain. Esophagoscopy revealed multiple shallow oval ulcerations in the middle esophagus. Colonoscopy revealed aphthous lesions in the rectum. Prednisolone (0.5 mg/kg) was initiated for treatment of esophageal involvement. Symptoms gradually improved and subsequent esophagoscopy revealed complete healing of esophageal ulcerations.

Small cell carcinoma of the esophagus with reference to alternating multiagent chemotherapy: report of two cases.

We herein report the findings of two patients with small cell carcinoma of the esophagus (SCEC) who were treated with alternating chemotherapy using cisplatin and etoposide (PVP), and cyclophosphamide, adriamycin or epirubicin, and vincristine (CAV). Patient 1 was a 61-year-old woman with SCEC. Her serum level of pro-gastrin-releasing peptide (Pro-GRP) was elevated (79.8 pg/ml; normal range <46.0 pg/ml). The patient underwent an esophagectomy following PVP/CAV-therapy. Six months later her serum level of Pro-GRP became elevated, and multiple metastases to the liver and lung were detected. Two courses of PVP/CAV-therapy were performed, and these metastatic foci almost completely disappeared. The serum level of Pro-GRP was in the normal range. One year after surgery, multiple brain metastases and recurrence of liver metastases were detected, then the serum level of Pro-GRP became re-elevated. Two courses of PVP/CEV-therapy were performed, and the metastases to the brain and liver decreased in size. However, the brain metastases relapsed, and the patient died 21 months after the diagnosis. Patient 2 was treated with two courses of preoperative PVP/CAV-therapy; however, the patient died of multiple liver metastases 17 months after the diagnosis. In six previously documented patients and the two present patients who were treated with PVP/CAV-therapy, the primary or metastatic foci of SCEC decreased in size, and the mean survival of the patients was 19 months. In conclusion, PVP/CAV alternating chemotherapy is beneficial for prolonging the survival of SCEC patients; however, new chemotherapeutic modalities are still needed to further improve the prognosis of SCEC patients. Furthermore, the level of serum Pro-GRP in patients with SCEC may be both a diagnostic marker and a therapeutic monitor.