Inflammatory cytokines, appetite-regulating hormones, and energy metabolism in patients with gastrointestinal cancer.

This study investigated energy metabolism and its association with inflammatory cytokines and appetite- regulating hormones in patients with gastrointestinal cancer. Subjects were inpatients scheduled to undergo therapeutic intervention for diagnosed gastrointestinal cancer. Nutritional status on admission was assessed based on anthropometric measurements, nutrition screening results, food intake rate (energy intake/energy provided in hospital food), and biochemical test results. Fat-free mass (FFM) was measured using the bioelectrical impedance analysis. Resting energy expenditure (REE) and respiratory quotient were measured with indirect calorimetry, and basal energy expenditure (BEE) was calculated using the Harris-Benedict equation. A total 51 patients with gastrointestinal cancer were enrolled (17 with esophageal cancer, 15 with gastric cancer, and 19 with colorectal cancer); 16 had stage I disease, 11 had stage II, 13 had stage III, and 11 had stage IV. The levels of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α increased significantly with cancer stage progression (P<0.001; Jonckheere-Terpstra trend test). The REE/body weight and the REE/FFM tended to increase with cancer stage progression (P=0.064 and P=0.053, respectively; Jonckheere-Terpstra trend test). FFM showed a significant negative correlation with the level of TNF-α (P=0.008; Spearman's correlation coefficient). Also, food intake rate showed a significant negative correlation with levels of IL-6 and TNF-α (P<0.001). The level of active ghrelin was positively correlated with that of IL-6 and energy metabolism (P=0.004 and 0.016, respectively) and negatively correlated with food intake rate (P=0.035), which suggests a state of ghrelin resistance. In conclusion, this study confirmed increases in the levels of inflammatory cytokines with the progression of gastrointestinal cancer and suggested the possible association of such increases with decreased FFM and the increased energy metabolism. However, the increased levels of active ghrelin failed to compensate for cachexia in cancer patients.

Two independent families with strongly suspected hereditary diffuse gastric cancer based on the probands' endoscopic findings.

Hereditary diffuse gastric cancer (HDGC) is the most famous of hereditary gastric cancer syndromes with an autosomal dominant inheritance pattern, and its diagnosis can be made by identifying a pathogenic germline variant in CDH1. We report two independent families that were strongly suspected of having HDGC based on endoscopic findings (multiple tiny, pale areas) obtained in the probands; the probands were pathologically diagnosed as having signet ring cell carcinoma (SRCC) and were genetically confirmed to have a pathogenic CDH1 germline variant. Although the updated International Gastric Cancer Linkage Consortium (IGCLC)'s clinical guidelines for HDGC (2015) state that screening/surveillance endoscopy should be performed (Cambridge protocol), the endoscopic findings obtained in the two presently reported families suggest that pale areas should be suspected as indicating the presence of SRCCs, and biopsies should be performed in addition to obtaining a precise family history in cases suspected of having HDGC.

Severe Colitis with Portal Venous Gas Caused by Brachyspira pilosicoli Infection.

We herein report a case of Brachyspira pilosicoli-caused severe colitis presenting with portal venous gas. A 75-year-old man was admitted because of a fever, severe abdominal pain and bloody diarrhea. He was negative for anti-HIV antibodies. He had been in close contact with a dog earlier. Abdominal computed tomography detected severe wall-thickening and fat-stranding of the entire colon accompanied by portal venous gas. A smear examination of his stool showed many Gram-negative spiral rods, suggesting intestinal spirochetosis. A polymerase chain reaction assay using stool samples detected an amplified band specific for B. pilosicoli. He responded well to antimicrobial agents including metronidazole.

Efficacy and safety of cold forceps polypectomy utilizing the jumbo cup: a prospective study.

BACKGROUND/AIMS: There are few prospective studies on cold forceps polypectomy (CFP) using jumbo cup forceps. Therefore, we examined patients with diminutive polyps (5 mm or smaller) treated with CFP using jumbo cup forceps to achieve an adenoma-free colon and also assessed the safety of the procedure and the recurrence rate of missed or residual polyp after CFP by performing follow-up colonoscopy 1 year later. METHODS: We included patients with up to 5 adenomas removed at initial colonoscopy and analyzed data from a total of 361 patients with 573 adenomas. One-year follow-up colonoscopy was performed in 165 patients, at which 251 lesions were confirmed. RESULTS: The one-bite resection rate with CFP was highest for lesions 3 mm or smaller and decreased significantly with increasing lesion size. Post-procedural hemorrhage was observed in 1 of 573 lesions (0.17%). No perforation was noted. The definite recurrence rate was 0.8% (2/251 lesions). The probable recurrence rate, which was defined as recurrence in the same colorectal segment, was 17%. Adenoma-free colon was achieved in 55% of patients at initial resection. Multivariate analysis revealed that achievement of an adenoma-free colon was significantly associated with number of adenomas and years of endoscopic experience. CONCLUSIONS: CFP using jumbo biopsy forceps was safe and showed a high one-bite resection rate for diminutive lesions of 3 mm or smaller. The low definite recurrence rate confirms the reliability of CFP using jumbo biopsy forceps. Number of adenomas and years of endoscopic experience were key factors in achieving an adenoma-free colon.

Re-expression of Sall1 in podocytes protects against adriamycin-induced nephrosis.

The highly conserved spalt (sal) gene family members encode proteins characterized by multiple double zinc finger motifs of the C2H2 type. Humans and mice each have four known Sal-like genes (SALL1-4 in humans and Sall1-4 in mice). Sall1 is known to have a crucial role in kidney development. To explore the significance of Sall1 in differentiated podocytes, we investigated podocyte-specific Sall1-deficient mice (Sall1 KOp°d°/p°d°) using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes. Under physiological conditions, Sall1 KOp°d°/p°d° mice exhibited no proteinuria during their lifetime, but foot-process effacement was detected in some of the podocytes. To elucidate the role of Sall1 in injured podocytes, we used an adriamycin (ADR)-induced model of nephrosis and glomerulosclerosis. Surprisingly, the expression of Sall1 was elevated in control mice on day 14 after ADR injection. On day 28 after ADR injection, Sall1 KOp°d°/p°d° mice exhibited significantly higher levels of proteinuria and higher numbers of sclerotic glomeruli. Differentiated Sall1 KD podocytes showed a loss of synaptopodin, suppressed stress fiber formation, and, ultimately, impaired directed cell migration. In addition, the loss of Sall1 increased the number of apoptotic podocytes following ADR treatment. These results indicated that Sall1 has a protective role in podocytes; thus, we investigated the endoplasmic reticulum stress marker GRP78. GRP78 expression was higher in ADR-treated Sall1 KOp°d°/p°d° mice than in control mice. Sall1 appeared to influence the expression of GRP78 in injured podocytes. These results suggest that Sall1 is associated with actin reorganization, endoplasmic reticulum stress, and apoptosis in injured podocytes. These protective aspects of Sall1 re-expression in injured podocytes may have the potential to reduce apoptosis and possibly glomerulosclerosis.

[Cases of Three Patients with Gastric Cancer and Metastasis to the Skeletal Muscle].

Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.

B-type (brain) natriuretic peptide and pruritus in hemodialysis patients.

INTRODUCTION AND OBJECTIVE: While pruritus is a common complication in hemodialysis patients, the pathophysiological mechanisms remain obscure. Recently, B-type (brain) natriuretic peptide (BNP) has been defined as an itch-selective neuropeptide in pruriceptive neurons in mice, and higher serum levels of BNP are frequently observed in hemodialysis patients. The objective of the present study was to evaluate the role of serum BNP in pruritus in patients undergoing hemodialysis. PATIENTS AND METHODS: The current cross-sectional study was performed on 43 patients undergoing maintenance hemodialysis. A visual analog scale (VAS) measuring the general severity of pruritus (values from 0 to 10, with higher values indicating more severe pruritus) in daytime and at night was self-reported by patients. Each patient's background and laboratory tests, including serum BNP in the post-hemodialysis period, were collected. The correlation between VAS and clinical parameters was evaluated. RESULTS: Both daytime and nighttime VAS scores in diabetic patients were significantly less than those in nondiabetic patients. Multiple regression analysis revealed that pruritus in daytime was worsened by serum BNP (ß=2.0, t=2.4, P=0.03), calcium (ß=4.4, t=5.2, P<0.0001), and ß2-microglobulin (ß=2.0, t=3.0, P=0.007), while it was eased by age (ß=-2.2, t=-3.2, P=0.0004). Nocturnal pruritus was severe in nondiabetic patients (ß=1.7, t=3.8, P=0.0005) and weakened by the total iron binding capacity (ß=-2.9, t=-3.1, P=0.004). CONCLUSION: It is suggested that a higher level of serum BNP increases the pruritus of hemodialysis patients in daytime and that diabetic patients are less sensitive to itch, especially at nighttime.

Precursor-derived versus de-novo carcinogenesis depends on lineage-specific mucin phenotypes of intramucosal gland-forming gastric neoplasms.

AIMS: To clarify the lineage-specific carcinogenesis of gland-forming gastric neoplasms, by characterizing mucin phenotypes and proliferation patterns immunohistochemically using monoclonal antibodies against MUC2, MUC5AC, MUC6, CD10 and Ki67. METHODS AND RESULTS: We analysed 49 gland-forming intramucosal neoplasms, including 15 non-invasive low-grade neoplasms (group A), 10 non-invasive high-grade neoplasms (group B) and 24 intramucosal adenocarcinomas (group C). The mode of gland-forming gastric carcinoma development was different between the intestinal and gastric lineages. The pure intestinal-type accounted for 93% of group A, 50% of group B and 4.2% of group C tumours. A zonal pattern of cell proliferation was well retained in group A tumours and was lost size-dependently in group B tumours. These findings suggest that non-invasive low-grade neoplasms of the intestinal lineage progress to non-invasive high-grade neoplasms, but rarely to intramucosal adenocarcinomas. In tumours of the gastric lineage, which exhibited pure gastric or mixed phenotypes, the polarity of cell proliferation and differentiation was well retained in small (≦5 mm) tumours but was lost in larger tumours in groups B and C. CONCLUSIONS: Intramucosal adenocarcinomas of the gastric lineage may often arise de novo, develop in the proper gastric mucosa, and are partially derived from non-invasive high-grade neoplasms.

Genetic lineages of undifferentiated-type gastric carcinomas analysed by unsupervised clustering of genomic DNA microarray data.

BACKGROUND: It is suspected that early gastric carcinoma (GC) is a dormant variant that rarely progresses to advanced GC. We demonstrated that the dormant and aggressive variants of tubular adenocarcinomas (TUBs) of the stomach are characterized by loss of MYC and gain of TP53 and gain of MYC and/or loss of TP53, respectively. The aim of this study is to determine whether this is also the case in undifferentiated-type GCs (UGCs) of different genetic lineages: one with a layered structure (LS+), derived from early signet ring cell carcinomas (SIGs), and the other, mostly poorly differentiated adenocarcinomas, without LS but with a minor tubular component (TC), dedifferentiated from TUBs (LS-/TC+). METHODS: Using 29 surgically resected stomachs with 9 intramucosal and 20 invasive UGCs (11 LS+ and 9 LS-/TC+), 63 genomic DNA samples of mucosal and invasive parts and corresponding reference DNAs were prepared from formalin-fixed, paraffin-embedded tissues with laser microdissection, and were subjected to array-based comparative genomic hybridization (aCGH), using 60K microarrays, and subsequent unsupervised, hierarchical clustering. Of 979 cancer-related genes assessed, we selected genes with mean copy numbers significantly different between the two major clusters. RESULTS: Based on similarity in genomic copy-number profile, the 63 samples were classified into two major clusters. Clusters A and B, which were rich in LS+ UGC and LS-/TC+ UGC, respectively, were discriminated on the basis of 40 genes. The aggressive pattern was more frequently detected in LS-/TC+ UGCs, (20/26; 77%), than in LS+UGCs (17/37; 46%; P = 0.0195), whereas no dormant pattern was detected in any of the UGC samples. CONCLUSIONS: In contrast to TUBs, copy number alterations of MYC and TP53 exhibited an aggressive pattern in LS+ SIG at early and advanced stages, indicating that early LS+ UGCs inevitably progress to an advanced GC. Cluster B (enriched in LS-/TC+) exhibited more frequent gain of driver genes and a more frequent aggressive pattern than cluster A, suggesting potentially worse prognosis in UGCs of cluster B.

Feasibility of five days of consecutive leukocytapheresis for the treatment of ulcerative colitis: a preliminary study.

Leukocytapheresis (LCAP) has been applied for the treatment of steroid refractory ulcerative colitis (UC). A standard protocol employs one or two sessions of LCAP per week. Our aim was to determine whether five consecutive LCAP sessions can be performed safely and effectively for UC patients. Six patients with moderately active UC were enrolled. The patients received five days of consecutive LCAP in which the processing volume of blood was limited to 1500 mL per session. The hemoglobin levels in each patient gradually decreased, and the platelet count by the fifth session reached half of the value before the first session. The clinical activity index in two patients improved daily, and they went into remission with an improvement in the colonic endoscopic appearance after one week. This preliminary study showed that five consecutive LCAP sessions are safe and feasible for active UC patients. The therapeutic efficacy and suitable patients for this treatment protocol should be confirmed by further studies.

[Case report: periodical infliximab administration enabled closure of colostomy in fistulating perianal Crohn's disease].

A 29-year old woman with Crohn's disease was performed colostomy due to severe perianal abscess. Her disease had been easy to recur and she was admitted to hospital for intestinal bleeding caused by acute exacerbation in Crohn's disease on October 2006. The bleeding was stopped rapidly and clinical remission was maintained with bimonthly administration of infliximab. Finally, her colostomy was closed after 5 years 8 months. Periodical treatment of infliximab not only prevented recurrence but also enabled closure of colostomy in fistulating perianal Crohn's disease.

[Case of ulcerative colitis associated with drug-induced hypersensitivity syndrome (DIHS) by salazosulfapyridine].

We experienced a case of drug-induced hypersensitivity syndrome (DIHS) for salazosulfapyridine (SASP). After we started administration of SASP in a 26-year old man with ulcerative colitis (UC), he had symptoms resembling infectious mononucleosis, high fever, skin eruption, cervical lymphadenopathy, elevate white blood cell count with atypical lymphocyte, and liver dysfunction. We diagnosed the illness as drug-induced hypersensitivity syndrome (DIHS) due to SASP. We halted SASP and started administration of methylprednisolone and prednisolone but his condition deteriorated. We changed to administration of betamethasone and he recovered. In cases of DIHS accompanied by UC, we should administer drugs carefully and recognize serious complications.