These findings suggest that an increase of nitric oxide mediates nonadrenergic, noncholinergic inhibitory nerves and plays an important role in the dysmotility observed in the colons of patients with slow-transit constipation.

Pylorus-preserving distal gastrectomy (PPG) has frequently been performed on patients with early gastric cancer in Japan to prevent the postgastrectomy syndrome seen after conventional distal gastrectomy (CDG). The long-term postoperative quality of life (QOL) and gastric emptying function in patients after PPG has not been assessed in detail. To clarify the usefulness of PPG for treating early gastric cancer we investigated the relation between postgastrectomy syndrome and gastric emptying function 5 years after PPG and then compared the results with those 5 years after CDG. Altogether, 32 patients who underwent curative gastrectomy at our clinic for early gastric cancer (submucosal cancer without lymph node metastasis) were studied. Ten subjects who underwent PPG with D2 lymphadenectomy without preserving the hepatic and pyloric branches of the vagal nerve [group A: eight men, two women; age 33-70 years (mean 60.7 years)] were interviewed and asked about appetite, weight loss, epigastric fullness, reflux esophagitis, and early dumping syndrome. They were compared with patients after CDG [group B: 36-72 years (mean 63.6 years)]. Esophagogastric endoscopy, abdominal ultrasonography, and gastric emptying function were also studied. The gastric emptying time of a semisolid diet was measured with a radioisotope method using (99m)Tc-labeled rice gruel; the gastric emptying time of a liquid diet was measured with the acetaminophen method using orange juice. The control subjects (group C) consisted of 18 healthy volunteers (10 men, 8 women) without gastrointestinal symptoms aged 38 to 68 years (mean 60.8 years). The following results were obtained: PPG (group A) alleviated postoperative gastrointestinal symptoms such as appetite loss, reflux esophagitis, early dumping syndrome, lost body weight, endoscopic reflux esophagitis, endoscopic gastritis in the remnant stomach, and postogastrectomy cholecystolithiasis better than did CDG (group B). The only weak point with the PPG procedure was that it produced a feeling of epigastric fullness. The pattern of the gastric emptying curve for the semisolid diet was almost the same among groups A, B, and C, although delayed gastric emptying was clearly more frequent in group A than in group B or C ( p < 0.05). Gastric emptying with the liquid diet in group B was significantly faster than that in groups A and C ( p < 0.01). Gastric emptying in groups A and C was similar. These results showed that PPG improved the postoperative QOL, but the delayed emptying of semisolid diet after PPG led to a feeling of epigastric fullness after meals due to retention of contents in the residual stomach. Epigastric fullness after meals continued in many patients after PPG. Thus the only disadvantage of the PPG procedure is the sensation of epigastric fullness and gastric stasis due to delayed gastric emptying of a semisolid diet.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms in humans and myeloid-derived suppressor cells (MDSCs) contribute to the negative regulation of immune responses in the context of cancer and inflammation. In order to investigate the pathophysiology of thyroid cancer, peripheral blood mononuclear cells (PBMCs) were obtained from 49 patients with thyroid cancer, 18 patients with non-cancerous thyroid diseases and 22 healthy volunteers. The MDSC levels were found to be higher in patients with any type of thyroid cancer (P<0.05), patients with ATC (P<0.001) and patients with medullary thyroid carcinoma (P<0.05), when compared to patients with non-cancerous thyroid diseases. The MDSC levels were also higher in patients with stage III-IV thyroid cancer compared to those in patients with non-cancerous thyroid diseases (P<0.05). The stimulation index (SI) of phytohemagglutinin (PHA)-induced lymphocyte blastogenesis was significantly lower, the C-reactive protein (CRP) levels were significantly higher and the serum albumin levels were significantly lower in patients with ATC compared to those in patients with non-cancerous thyroid diseases. The SI was significantly lower in stage III and IV thyroid cancer compared to that in non-cancerous thyroid disease (P<0.05). Furthermore, the CRP levels were higher and the concentration of albumin was lower in stage IV thyroid cancer compared to those in non-cancerous thyroid disease (P<0.05). Patients with thyroid carcinoma were then classified into one of two groups according to a %PBMC of MDSC cut-off level of 1.578, which was the average %PBMC of MDSC of patients with any type of thyroid carcinoma. In patients with higher MDSC levels, the production of CRP and interleukin (IL)-10 was significantly higher (P<0.05) and the albumin levels were significantly lower (P<0.05) compared to those in patients with lower MDSC levels. These data indicate that MDSCs are increased in patients with ATC. Furthermore, these patients exhibited suppression of cell-mediated immune responses, chronic inflammation and nutritional impairment.

Vascular endothelial growth factor (VEGF) reportedly has an important role in the progression of malignant neoplasms and has been reported to induce myeloid-derived suppressor cells (MDSCs) that appear in cancer and inflammation. In the present study, serum concentrations of VEGF were measured in patients with digestive system cancer and the correlations with nutritional damage, immune suppression and systemic inflammation were analyzed. A significant increase in VEGF serum levels was observed in patients with esophageal, gastric and colorectal cancers compared with healthy volunteers. Levels of VEGF were inversely correlated with the serum concentrations of albumin, prealbumin and retinol-binding protein. The serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC counts. VEGF levels were also correlated with neutrophil and neutrophil/lymphocyte counts and inversely correlated with lymphocyte count. Serum VEGF levels were divided at a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. The stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels and MDSC counts tended to be higher in this group. These results demonstrated that increased production of VEGF was correlated with systemic inflammation, nutritional impairment and the inhibition of cell-mediated immunity involving MDSCs.