Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn's disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.
Anticholesteremic Agents/therapeutic use ; Bile Acids and Salts/*physiology ; Crohn Disease/complications ; Diarrhea/*etiology/pathology/therapy ; Feces/chemistry ; Fibroblast Growth Factors/deficiency ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/complications

We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schonlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients.
Adult ; Aged ; Aged, 80 and over ; Arthralgia/epidemiology/etiology ; C-Reactive Protein/analysis ; Child ; Child, Preschool ; Diarrhea/epidemiology/etiology ; Extremities/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin A/blood ; Immunosuppressive Agents/therapeutic use ; Infant ; Middle Aged ; Odds Ratio ; Prognosis ; Purpura, Schoenlein-Henoch/complications/*diagnosis/drug therapy/*pathology ; Renal Insufficiency/epidemiology/etiology ; Retrospective Studies ; Young Adult

Chronic diarrhea with a 35 kg weight loss (75 kg to 40 kg) occurred during 2 years in an alcoholic patient was diagnosed with Isospora belli infection in the Republic of Korea. The patient, a 70-year old Korean male, had been a heavy drinker for more than 30 years. He was admitted to the Seoul National University Hospital because of long-standing diarrhea and severe weight loss. He had an increased white blood cell (WBC) count with high peripheral blood eosinophilia (36.8-39.9%) and lowered protein and albumin levels but without any evidence of immunosuppression. A parasitic infection was suspected and fecal examination was repeated 3 times with negative results. Peroral endoscopy with mural biopsy was performed in the upper jejunum. The biopsy specimens revealed villous atrophy with loss of villi together with various life cycle stages of I. belli, including trophozoites, schizonts, merozoites, macrogamonts, and microgamonts. The patient was treated successfully with oral doses of trimethoprim 160-320 mg and sulfamethoxazole 800-1,600 mg daily for 4 weeks. A follow-up evaluation at 2.5 years later revealed marked improvement of body weight (68 kg), increased protein and albumin levels, and normal WBC count with low eosinophils (3.1%). This is the first clinical case of isoporiasis with demonstration of various parasitic stages in the Republic of Korea.
Aged ; Alcoholism/*complications ; Antiparasitic Agents/administration & dosage ; Diarrhea/drug therapy/*etiology/parasitology/*pathology ; Humans ; Isospora/*isolation & purification ; Isosporiasis/*diagnosis/drug therapy/parasitology/*pathology ; Male ; Republic of Korea ; Sulfamethoxazole/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage

OBJECTIVEThe purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).

METHODSFour hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model.

RESULTSA total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea.

CONCLUSIONSThe genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Chemoradiotherapy, Adjuvant ; adverse effects ; Cyclin D1 ; genetics ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Diarrhea ; chemically induced ; etiology ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Polymorphism, Single Nucleotide ; Postoperative Period ; Prospective Studies ; Rectal Neoplasms ; genetics ; pathology ; surgery ; therapy ; Risk Factors

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Adult ; Aged ; Aged, 80 and over ; Anorexia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Diarrhea/chemically induced ; Disease-Free Survival ; Fatigue/chemically induced ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Invasiveness ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Portal Vein/*pathology ; Proportional Hazards Models ; Tomography, Spiral Computed ; Venous Thrombosis/*drug therapy/pathology

Celiac disease is a chronic absorptive disorder of the small intestine caused by gluten. The prevalence rate of celiac disease is 1% in Western countries. But, it is rare in Asian countries, and there is no celiac disease reported in Korea. Here, we report a case of celiac disease. An 36-years-old woman complained non-specific abdominal pain and diarrhea. She had anemia and was taking medication for osteoporosis. Colonoscopy showed no abnormality except shallow ulcer at the terminal ileum. Gastroduodenoscopy showed micronodularity at the duodenum 2nd and 3rd portion. Capsule endoscopy and enteroscopy showed villous atrophy and blunting of villi from the duodenum. Small intestinal pathology showed villous atrophy with lymphocyte infiltration. After gluten free diet, diarrhea, abdominal pain, anemia and osteoporosis were improved. And, she felt well-being sensation. This is a first case of celiac disease in Korea.
Abdominal Pain/etiology ; Adult ; Anemia/etiology ; Capsule Endoscopy ; Celiac Disease/complications/*diagnosis/diet therapy/pathology ; Diarrhea/etiology ; Diet, Gluten-Free ; Duodenum/pathology ; Endoscopy, Gastrointestinal ; Female ; Humans ; Ileum/pathology ; Intestinal Mucosa/pathology ; Osteoporosis/etiology ; Tomography, X-Ray Computed ; Treatment Outcome

We report herein a case of intestinal amyloidosis with grave prognosis that caused intractable diarrhea and intestinal pseudo-obstruction, alternately in spite of intensive conservative treatment. A 44-year-old woman was admitted for fever, diarrhea, and crampy abdominal pain which had been continuned during 6 months. Abdomen CT scan showed edematous wall thickening of the small bowel and right colon, and colonoscopic biopsy revealed amyloid deposition in the mucosa. Monoclonal light chains in serum and/or urine were not detected and highly elevated serum amyloid A was shown. In spite of intensive treatment including oral prednisolone and colchicine, diarrhea and intestinal pseudo-obstruction developed alternately, general status rapidly got worsened and died after two months.
Administration, Oral ; Adult ; Amyloidosis/complications/*diagnosis/drug therapy ; Anti-Inflammatory Agents/therapeutic use ; Colchicine/therapeutic use ; Colonoscopy ; Diarrhea/*etiology ; Female ; Humans ; Intestinal Mucosa/pathology ; Intestinal Pseudo-Obstruction/*diagnosis/etiology ; Prednisolone/therapeutic use ; Serum Amyloid A Protein/metabolism ; Tomography, X-Ray Computed ; Tubulin Modulators/therapeutic use

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Capecitabine ; Class I Phosphatidylinositol 3-Kinases ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease Progression ; Disease-Free Survival ; Exanthema ; chemically induced ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Hand-Foot Syndrome ; etiology ; Humans ; Middle Aged ; Mutation ; Neoplasm Staging ; Phosphatidylinositol 3-Kinases ; genetics ; Quinazolines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction

OBJECTIVETo evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.

METHODSThree hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.

RESULTSAmong the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).

CONCLUSIONSThe capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Adult ; Agranulocytosis ; chemically induced ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Diarrhea ; chemically induced ; Disease Progression ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hand-Foot Syndrome ; etiology ; Humans ; Leukopenia ; chemically induced ; Maintenance Chemotherapy ; Middle Aged ; Neoplasm Staging ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives

Pseudomembranous colitis is mainly caused by antibiotics and Clostridium difficile infection. But conditions such as gastrointestinal surgery, antacid medication, anti-neoplastic agent or immunosuppressive agent which influences the normal flora of colon can induce colitis without the administration of any antibiotics. We experienced a 13 year-old male who was taking low-dose methotrexate for juvenile rheumatoid arthritis complained diarrhea and abdominal pain for 3 weeks. Sigmoidoscopic findings revealed diffuse patch yellowish pseudomembranes on the rectum. Histologic finding was compatible to pseudomembranous colitis. His symptom was improved after stop taking methotrexate and the administration of metronidazole. If a patient treated with immunosuppressive agents or antineoplastic agents complains diarrhea, fever or abdominal pain and has not improved with conservative care, pseudomembranous colitis should be taken into account as a differential diagnosis and prompt treatment is required for better prognosis.
Abdominal Pain/etiology ; Adolescent ; Anti-Infective Agents/therapeutic use ; Antirheumatic Agents/*adverse effects/therapeutic use ; Arthritis, Juvenile Rheumatoid/*drug therapy ; Diagnosis, Differential ; Diarrhea/etiology ; Enterocolitis, Pseudomembranous/*diagnosis/drug therapy/pathology ; Humans ; Male ; Methotrexate/*adverse effects/therapeutic use ; Metronidazole/therapeutic use ; Sigmoidoscopy ; Tomography, X-Ray Computed