Effectiveness of concomitant enteral nutrition therapy and infliximab for maintenance treatment of Crohn's disease in adults.

BACKGROUND: One of the problems associated with infliximab (IFX) treatment for Crohn's disease (CD) is loss of response during maintenance therapy. AIMS: The aim of this multicenter, retrospective, cohort study was to determine whether enteral nutrition (EN) added to the IFX therapy regimen is effective for maintaining remission in adult CD patients. METHODS: Patients with CD who had started IFX therapy between April 2003 and March 2008 at any one of the seven participating medical centers and who met the following inclusion criteria were enrolled in the study: remission after triple infusions of IFX followed by IFX maintenance therapy every 8 weeks, and follow-up data available for ≥ 1 year. Remission was defined as a C-reactive protein (CRP) level of <0.3 mg/dL, and recurrence was defined as an increase in CRP to ≥ 1.5 mg/dL or shortening of the IFX interval. Patients were classified by EN dosage into two groups (EN group and non-EN group). The cumulative remission period and related factors were analyzed. RESULTS: Of the 102 adult CD patients who met the inclusion criteria, 45 were in the EN group and 57 were in the non-EN group. The cumulative remission rate was significantly higher in the EN group than in the non-EN group (P = 0.009). Multivariate analysis revealed that EN was the only suppressive factor for disease recurrence (P = 0.01). CONCLUSIONS: The results demonstrate that among this CD patient cohort, EN combined with IFX maintenance treatment was clinically useful for maintaining remission.

Clinicopathological analysis of hematological disorders in tube-fed patients with copper deficiency.

OBJECT: Anemia and leukopenia caused by copper deficiency are well-documented consequences of long-term total parenteral nutrition. We measured the serum copper levels of bed-ridden patients receiving enteral feeding, and evaluated optical and ultrastructural features of bone marrow before and after copper supplementation. PATIENTS AND METHODS: Serum samples were obtained from 15 bed-ridden elderly patients receiving tube feeding (TF) and 10 age-matched bed-ridden patients who took food orally (CO), and the copper ceruloplasmin concentration of each sample was measured. Bone marrow samples were obtained from patients who exhibited copper deficiency and leukopenia and/or anemia before and after the copper supplementation, for use in light and electron microscopic analysis. RESULTS: The tube-fed patients had significantly lower mean serum copper and ceruloplasmin concentrations than the control patients. Seven of the 15 tube-fed patients had reduced serum copper concentrations and leukopenia. Six of those 7 patients also had anemia. Copper sulfate was administered to those 7 patients by enteral tube; their copper concentration, anemia and leukopenia improved within 1 month after they were administered copper sulfate. In the bone marrow examination before copper supplementation, light microscopy showed cytoplasmic vacuolization in both myeloid and erythroid precursors, and electron microscopy showed electron-dense deposits in mitochondria and cytoplasm of erythroid and myeloid cells. After copper supplementation, these pathological changes disappeared. CONCLUSIONS: Bicytopenia is likely to occur in tube-fed patients with copper deficiency. Copper deficiency appears to be associated with cytoplasmic vacuolization and electron-dense deposits in mitochondria in erythroid and myeloid cells.

[Two cases of mesenteric panniculitis].

Two patients with mesenteric panniculitis are presented. In the first patient, a provisional diagnosis of ileus was made, based on the clinical features and imaging data. Laparotomic findings showed that the ileum was bound tightly by a fibrous strip and dilated, with thickened and swollen mesentery. Incision of the fibrous strip was performed, and the clinical symptoms were improved. The second patient was strongly suspected to have mesenteric panniculitis, from characteristic features on abdominal computed tomography and barium enema. Conservative therapy was effective in this case. We emphasize the variety of clinical courses in mesenteric panniculitis, requiring selection of the most suitable treatment.

Recent insights into digestive motility in functional dyspepsia.

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.

Heat-directed suicide gene therapy mediated by heat shock protein promoter for gastric cancer.

The prognosis of patients with metastatic gastric cancer, particularly peritoneal carcinomatosis, remains poor despite intensive interventions. Gene therapy and hyperthermia can be promising strategies for such advanced disease. The study was conducted to explore the possible effective therapeutic approach of suicide gene therapy with herpes simplex virus thymidine kinase (HSV-tk) in combination with hyperthermia for advanced gastric cancer. The heat shock protein (hsp) 70B gene promoter-oriented HSV-tk (HSP-tk)/ganciclovir (GCV) system directed by heat shock was developed. Hsp promoter activity under the control of heating was assessed by dual luciferase assay in gastric cancer cell lines and implanted tumors of nude mice. In vitro cytotoxic assay was performed using the HSP-tk/GCV delivered by the hemagglutinating virus of Japan (HVJ) liposome, with or without heating. Mice with subcutaneously xenografted tumors and peritoneal carcinomatosis were treated with hyperthermia and gene therapy using the HVJ-liposome-carrying HSP-tk. Assessment by luciferase assay demonstrated highly inducible and tumor-specific promoter activity in vitro and in vivo. Cytotoxic assays showed that cells transfected with HSP-tk became more sensitive to GCV with heating. A synergistic effect was also observed when treated with a non-heat-inducible cytomegalovirus (CMV) promoter-mediated HSV-tk/GCV and heating, indicating bystander killing. The HVJ-liposome-carrying HSP-tk/GCV combined with hyperthermia significantly inhibited the growth of subcutaneous tumors and prolonged survival of mice with peritoneal carcinomatosis. We conclude that the combination of suicide gene therapy with hyperthermia can provide a promising treatment modality for advanced gastric cancer.

Pseudomyxoma peritonei accompanied by intraductal papillary mucinous neoplasm of the pancreas.

We describe a case of pseudomyxoma peritonei (PMP) successfully managed with intraperitoneal hyperthermic chemoperfusion. This case is unique due to the concurrent presence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The patient presented with abdominal fullness. Abdominal computed tomography revealed massive ascites, thickened peritoneum, and a cystic lesion of the pancreas. Cytological examination of ascitic fluid sample showed mucin-rich atypical cells. Endoscopic retrograde pancreatography revealed a cystic lesion with the defect probably due to mural nodule and mucin, communicating with the pancreatic duct. At exploratory laparotomy, massive ascites and multiple nodules were identified within the peritoneal cavity. No primary tumour, including mucinous neoplasm of the appendix, was found. Histopathological examination of the omentum showed mucinous adenocarcinoma in pools of mucoid material, consistent with PMP. The relation between PMP and IPMN of the pancreas was possible, but not conclusive. The patient received intraperitoneal perfusion of saline heated to 42 degrees C containing cisplatin, etoposide, and mitomycin C, followed by 24 courses of postoperative chemotherapy with gemcitabine. The patient remains in good general condition with no signs of progression of PMP for 2 years, but with a gradual and progressive enlargement of the pancreatic cystic lesion.