Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Development of active jejunal glucose absorption in broiler chickens.

Growth in chickens, especially meat-type chickens (broilers), is extremely rapid, but studies on the regulatory mechanism of intestinal glucose absorption with growth are few, contradictory, and unclear. Here, we investigated the regulation of intestinal glucose absorption with growth in broiler chickens using oral glucose gavage, intestinal Evans blue transit, intestinal glucose absorption, scanning electron microscopy, and glucose absorption- and cell junction-related gene expression analyses. Peak blood glucose levels after oral glucose gavage occurred at 10 and 50 min in chickens at 1 wk (C1W) and 5 wk (C5W) of age, respectively. The area under the curve for glucose levels was greater for the C5W than the C1W (P = 0.035). The stain ratio in the small intestine in the C5W was lower than that in the C1W (P = 0.01), but there were no differences in the tissue regions stained with Evans blue and the migration distance of Evans blue from Meckel's diverticulum. In everted sac and Ussing chamber experiments, we observed reduced intestinal glucose uptake and electrogenic glucose absorption in the jejunum of the C5W. Phloridzin, an inhibitor of sodium/glucose cotransporter 1 (SGLT1), suppressed the glucose-induced short-circuit current in the C1W (P = 0.016) but not the C5W. Although the addition of NaCl solution stimulated the glucose-induced short-circuit current in the C1W, no differences between the treatments were observed (P = 0.056), which was also the case in the C5W. Additionally, tissue conductance was diminished in the C5W compared with that in the C1W. Moreover, in the C5W, the intestinal tract was more developed and the jejunal villi were enlarged. In conclusion, glucose absorption throughout the intestine could be greater in C5W than in C1W; however, reduced SGLT1 sensitivity, decreased ion permeability, and intestinal overdevelopment lead to decreased local glucose absorption in the jejunum with growth in broiler chickens. These data provide a detailed analysis of intestinal glucose absorption in growing broiler chickens, and can contribute to the development of novel feeds.

Circadian rhythm in hypothalamic leptin receptor (Ob-Rb) mRNA expressions and cerebrospinal fluid and circulating glucose and leptin levels in lactating rats.

In lactating animals, the food consumption increases several-fold for milk supply to the pups. The present study was conducted to clarify the relationship between the hyperphagia during lactation and hypothalamic leptin receptor (Ob-Rb) mRNA expression, cerebrospinal fluid (CSF) and circulating leptin and glucose levels. Food intakes significantly higher in lactation than in non-lactation at all time points (3 points: light phase, 4 points: dark phase) of the day. However, the expression of the hypothalamic Ob-Rb mRNA showed similar circadian rhythms in both the non-lactation and lactation, with only slight differences between the two groups. CSF leptin and glucose levels were constant throughout the day in both non-lactation and lactation, and there was almost no difference between the two groups at each time point. Circulating leptin and glucose levels showed circadian rhythms only in the non-lactating period, and were lower in lactation than in non-lactation, especially in the dark phase. In conclusion, the present study provides evidence that Ob-Rb mRNA expression fluctuates in the lactation period as well as in the non-lactation period, suggesting that the expression profile of whole hypothalamic Ob-Rb may not contribute to the difference in food consumption between lactation and non-lactation, and that chronic decrease in blood glucose levels may be associated with the increase in food consumption during lactation.

Age-related Regulation of Active Amino Acid Transport in the Ileum of Broiler Chickens.

Broiler chickens grow rapidly within a short period; in this regard, our group had previously reported a decrease in the active transport of glucose in the intestines of broiler chickens with their growth. Therefore, in this study, we compared the active transport process of amino acids in the intestines between 1- and 5-week-old broilers using everted sac, Ussing chamber techniques, and real-time quantitative polymerase chain reaction (RT-PCR). The everted sac experiment showed that amino acids were absorbed from all segments of the small intestine in both age groups. There were no significant differences in the serosal to mucosal ratio between 1- and 5-week-old broilers. The Ussing chamber experiment showed that amino acid-induced short-circuit current (ΔIsc) in the ileal epithelium was significantly greater in the 5-week-old chickens than in the 1-week-old chicks (P=0.035). Membrane conductance, an indicator of ion permeability, showed no significant difference between the two groups. Moreover, the mRNA expression levels of amino acid transporters (ASCT1, EAAT3, B0AT1, and y+LAT1) were significantly elevated in the distal ileum of the 5-week-old broilers compared to those in the 1-week-old broilers (P<0.05), while no significant differences were observed in the mRNA levels of ATB0'+, B0/+AT, rBAT, CAT1, and CAT2 in both groups. Our study provides clear evidence that age-dependent increase in the active transport of amino acid across the ileal epithelium is caused by the high expression of Na+-dependent amino acid transporters in broiler chickens.

[Case of Gastric Malignant Lymphoma Invading Other Organs with Bleeding Treated by Surgery].

A female in her late 50s experienced dyspnea and was transported by an ambulance. Her hemoglobin score was low, and CT imaging showed a giant tumor in her stomach. The tumor perforated her liver and invaded the abdominal wall and duodenum around the Treitz ligament. She required surgery because of the massive hemorrhage due to the tumor. Total gastrectomy with lateral segmentectomy of the liver and resection of the duodenum and the ileum around the Treitz ligament were performed. At 1.5 months after surgery, chemotherapy for malignant lymphoma was successfully initiated.

Advanced treatment technique for swine wastewater using two agents: Thermally polymerized amorphous silica and hydrated lime for color and phosphorus removal and sulfur for nitrogen removal.

The efficacy of advanced treatment of swine wastewater using thermally polymerized, modified amorphous silica and hydrated lime (M-CSH-lime) for color and phosphorus removal and sulfur for nitrogen removal was examined with a demonstration-scale treatment plant. The color removal rate was approximately 78% at M-CSH-lime addition rates of > 0.055 wt/v%. The PO43--P removal rate exceeded 99.9% with > 0.023 wt/v%. pH of the effluent from the M-CSH-lime reactor increased with the addition rate till a maximum value of 12.7, which was effective in disinfection. The recovered M-CSH-lime would be suitable as a phosphorus fertilizer because the total P2 O5 content was approximately 10%. The nitrogen oxide (NOx-N) removal rate by sulfur denitrification increased to approximately 80% when the NOx-N loading rate was around 0.1 kg-N/ton-S/day. It was suggested that the combination of the two processes would be effective in the advanced treatment of swine wastewater.

"Hook and roll technique" using an articulating hook cautery to provide a critical view during single-incision laparoscopic cholecystectomy.

We describe a new simple and easy technique called the "Hook and roll technique" (HRT) that uses an articulating hook cautery to provide a critical view during single incision laparoscopic cholecystectomy (SILC). A 2-cm incision is made at the umbilicus to insert three 5-mm trocars or a multichannel port. After dissection of the serosa of the dorsal and ventral sides of the gall bladder, including Calot's triangle, the angled tip of the hook cautery is inserted between the cystic artery and duct with its tip placed dorsally. The tip is then rotated in a clockwise manner to avoid bile duct injury, allowing the connective tissue between them to be hooked, coagulated and cut. This procedure is repeated several times, followed by dissection between the cystic artery and the liver bed to achieve a critical view. From December 2008 to May 2011, 121 patients underwent SILC using HRT in our hospital without any serious complications. This technique is suitable for SILC, as it is consists of simple procedures that can be performed safely and easily, even by left hand in a cross-over approach, and it allows complete dissection of Calot's triangle to achieve a critical view without using any dissector under dangerous in-line viewing.

Hormonal differences in peripheral blood and gene profiling in the liver and lymphocytes in Japanese black cattle with growth retardation.

Japanese Black cattle occasionally demonstrate growth retardation despite sufficient nutrient intake. To clarify hormonal and transcriptional characteristics, we investigated differences in blood components, including hormones, and differences in exhaustive gene expressions in the liver and peripheral lymphocytes of six cattle with growth retardation (GR cattle) and eight control cattle of the same age and pedigree with normal growth. Hematocrit values and concentrations of hemoglobin, serum albumin, total cholesterol, insulin-like growth factor 1 (IGF-1), thyroxine and insulin in GR cattle were significantly lower than those in controls. GR cattle also excreted higher levels of GH. We used three GR and three control cattle for a microarray analysis in the liver and found that 279 gene expressions were significantly different. However, gene expressions related to the GH-IGF-1 axis, such as the GH receptor and IGF-1, were not significantly different from those of controls. Immune-related gene expressions were significantly lower. To clarify these gene expression levels, peripheral lymphocytes were used for real-time RT-PCR. The expression rates of genes that were significantly lower in the liver, such as chemokine ligand 8, interferon gamma receptor 1 and immunoglobulin light chain VJ region were also significantly lower in three GR cattle than those in the three control cattle. These results suggest that the cause of growth retardation in the present study was due to other factors, not abnormal gene expressions of factors related to the GH-IGF-1 axis in the liver, and that GR cattle were susceptible to infectious disease.

The mechanism underlying the central glucagon-induced hyperglycemia and anorexia in chicks.

We investigated the mechanism underlying central glucagon-induced hyperglycemia and anorexia in chicks. Male 8-day-old chicks (Gallus gallus) were used in all experiments. Intracerebroventricular administration of glucagon in chicks induced hyperglycemia and anorexia from 30 min after administration. However, the plasma insulin level did not increase until 90 min after glucagon administration, suggesting that glucose-stimulated insulin secretion from pancreatic beta cells may be suppressed by central glucagon. The plasma corticosterone concentration significantly increased from 30 min to 120 min after administration, suggesting that central glucagon activates the hypothalamic pituitary adrenal (HPA) axis in chicks. However, central administration of corticotropin-releasing factor (CRF), which activates the HPA axis in chicken hypothalamus, significantly reduced not only food intake but also plasma glucose concentration, suggesting that CRF and the activation of the HPA axis are related to the glucagon-induced anorexia but not hyperglycemia in chicks. Phentolamine, an α-adrenergic receptor antagonist, significantly attenuated the glucagon-induced hyperglycemia, suggesting that glucagon induced hyperglycemia at least partly via α-adrenergic neural pathway. Co-administration of phentolamine and α-helical CRF, a CRF receptor antagonist, significantly attenuated glucagon-induced hyperglycemia and anorexia. It is therefore likely that central administration of glucagon suppresses food intake at least partly via CRF-induced anorexigenic pathway in chicks.

The differences in feeding-inhibitory responses to peripheral and central leptin between non-lactating and lactating rats.

This study was conducted to examine the contributions of central and peripheral leptin to hyperphagia in lactation. Lactating rats were mated at 7-8 weeks of age and housed singly with their litters. In experiment 1, food intakes were significantly (P<0.01) greater (350% on average) in lactation than in non-lactation throughout a day. Cerebrospinal fluid (CSF) leptin levels remained constant despite plasma leptin levels being significantly (P<0.05) greater in non-lactation than in lactation. In experiment 2, CSF leptin levels were not altered by i.v. injections of leptin (0.2 and 0.4 mg/kg body weight) despite that plasma leptin levels were dose dependently (P<0.01) increased. Moreover, i.v. administration of leptin significantly (P<0.05) decreased food intake in non-lactating rats but not in lactating rats. In experiment 3, nocturnal food intakes were temporarily (P<0.05) reduced in non-lactating and lactating rats. I.c.v. administration of a leptin antagonist (15 µg) blocked the reductions of food intakes. I.c.v. administration of leptin (10 µg) significantly (P<0.05) decreased cumulative food intakes during 24 h in both the physiological states. In conclusion, this study has presented new evidence that the hyperphagia of lactating rats could be partly due to depressed sensitivity of neurons contacting blood leptin. In contrast, the responsiveness of leptin receptors contacting CSF leptin may not differ between non-lactating and lactating rats. Furthermore, the levels of CSF leptin remained constant independent of those of blood leptin. Therefore, the expression of hypothalamic leptin receptors contacting CSF could be involved in the difference in food intake between non-lactating and lactating rats.

[A case of duodenal gastrointestinal stromal tumor treated by pancreas-sparing partial duodenectomy].

An 79-year-old man admitted our hospital for abdominal mass. Computed tomography showed a tumor measuring about 10 cm in diameter without any metastasis lesion and any sings of local infiltration. Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the third portion of the duodenum, and biopsy revealed tumor cells stained positive for c-kit. These findings were consistent with a GIST and we performed a partial resection of the duodenum sparing the pancreas. Gastrointestinal stromal tumors (GIST) were mainly located in the stomach and the small intestine. Duodenal localization is rare. Surgical approach for GISTs should basically be a partial resection. However, for GISTs located in the duodenum, the partial resection was sometimes difficult and pancreaticoduodenectomy (PD) may be needed, depending on the tumor size and the location of the tumor close to the papilla Vater. Since GIST grew expansively, rarely involving lymph nodes, PD may be an excessive procedure to treat the disease. For this reason pancreas-sparing partial duodenectomy has been introduced for the treatment of duodenal GIST.

[A long-term survival case of bilateral ovarian metastasis of progressive gastric cancer treated by chemotherapy].

We report a long-term survival case treated by chemotherapy with new anticancer drugs such as S-1, CPT-11 and docetaxel after bilateral overiectomy for bilateral ovarian metastases of progressive gastric cancer. A 68-year-old female, who had undergone total gastrectomy with D2 lymphadenectomy for scirrhous gastric cancer of Stage IIIA, was admitted because of ovarian metastasis. Laparoscopic bilateral ovariectomy was performed for ovarian metastases of the gastric cancer (Krukenberg tumor) 6 months after gastrectomy. Seven months after gastrectomy, 11-course of S-1 treatment (80 mg/m2) for bilateral ovarian metastases of the gastric cancer was administered. CT scan revealed mediastinal lymphadenopathy 2 years and 5 months after gastrectomy. Then, the drug was changed to docetaxel (60 mg/m2). After 9-course of docetaxel treatment, the mediastinal lymphadenopathy disappeared. For a treatment of grade 3 neuropathy, a 12-course CPT-11 was started after gastrectomy 3 years and 6 months ago. CT scan and PET-CT showed no new metastasis in 4 years and 10 months after gastrectomy.

Effects of central administration of glucagon on feed intake and endocrine responses in sheep.

This study was conducted to investigate effects of glucagon intracerebroventricularly administered on feed intake and endocrine changes in sheep. Four male sheep (48-55 kg BW) were used. The animals were acclimatized to be fed alfalfa hay cubes at 12.00 hour. Human glucagon (40 and 80 microg/0.5 mL) was injected into the lateral ventricle at 12.00 hour. Blood samples were taken every 10 min from 30 min before to 180 min after the glucagon injection. Soon after the injection, the animals were given alfalfa hay cubes, and the amounts of the feed eaten within 2 h were measured. Feed intakes were significantly (P < 0.05) suppressed by 80 microg of glucagon. Plasma glucose levels in control animals were gradually decreased after the feeding, whilst those in glucagon-treated animals were temporarily elevated just after the feeding and then kept higher than control levels. Plasma insulin was abruptly elevated after the feeding and was maintained at higher levels than before the feeding in all treatments. Plasma NEFA concentrations were decreased after the feeding in all treatments. A tendency of increase in plasma cortisol levels occurred in glucagon-injected animals. The present study provides the first evidence that glucagon directly acts on the brain, then inhibiting feeding behavior and inducing endocrine responses in ruminants.

Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep.

The present study was conducted to investigate roles of ghrelin in glucose-induced insulin secretion in fasting- and meal-fed state in sheep. Castrated Suffolk rams were fed a maintenance diet of alfalfa hay cubes once a day. Hyperglycemic clamp (HGC) was carried out to examine glucose-induced insulin response from 48 to 53 h (fasting state) and from 3 to 8 h (meal-fed state) after feeding in Experiment 1 and 2 respectively. Total dose of 70 nmol/kg body weight of D-Lys3-GHRP6, a GH secretagogue receptor 1a (GHS-R1a) antagonist, was intravenously administered at 0, 60, and 120 min after the commencement of HGC. In the fasting state, the ghrelin antagonist significantly (P < 0.01) enhanced glucose-induced insulin secretion. In the meal-fed state, i.v. administration of synthetic ovine ghrelin (0.04 microg/kg body weight per min during HGC) significantly (P < 0.05) enhanced glucose-induced insulin secretion. d-Lys3-GHRP6 treatment suppressed ghrelin-induced enhancement of the insulin secretion. In conclusion, ghrelin has an inhibitory and stimulatory role in glucose-induced insulin secretion via GHS-R1a in fasting- and meal-fed state respectively.

New laparoscopic double-stapling technique.

BACKGROUND: Laparoscopic surgery for colon cancer has been shown by several randomized, controlled trials to be an acceptable alternative to open surgery; however, laparoscopic rectal surgery has not been evaluated in a randomized trial. One of the most serious problems associated with laparoscopic rectal surgery are bowel clamping, irrigation, and transection of the rectum, and laparoscopic rectal surgery has not been as reliable as open rectal surgery. MATERIALS AND METHODS: We present our new technique, the laparoscopic double-stapling technique, which eliminates these problems. This technique uses curved Doyen forceps introduced through the wound just above pubis symphysis for clamping the rectal wall at the anal side of the tumor. An endolinear stapler (length 60 mm) is inserted through the same wound, applied at the rectal wall parallel and caudal to the Doyen forceps, and transects the rectum under pneumoperitoneum. We used this technique for eight cases of rectal surgery. RESULTS AND DISCUSSION: The laparoscopic double-stapling technique provided secure bowel clamping and rectal irrigation. The number of cartridges used in laparoscopic double-stapling technique cases was not more than 2, with an average of 1.6 per patient. None of the laparoscopic double-stapling technique cases experienced major complications. CONCLUSION: We consider that many cases of rectal cancer that are suitable for laparoscopic low anterior resection can undergo laparoscopic surgery by using this technique, which will improve the quality of rectal surgery.

Central administration of glucagon suppresses food intake in chicks.

Food intake in chickens is regulated in a manner similar to that in mammals. Corticotropin-releasing factor (CRF), which increases the plasma corticosterone concentration, plays an important role as a mediator of many appetite-suppressive peptides in the central nervous system in both species. Central administration of glucagon suppresses food intake in rats. However, the anorexigenic action of glucagon in chicks has not yet been identified. In the present study, we investigated the effects of central administration of glucagon on food intake in chicks. Intracerebroventricular administration of glucagon in chicks significantly suppressed food intake and significantly induced hyperglycemia. In contrast, peripheral administration of the same dose of glucagon did not influence food intake and plasma glucose concentration. These results suggest that glucagon functions in chicks as an appetite-suppressive peptide in the central nervous system. Intracerebroventricular administration of glucagon in chicks also significantly increased CRF mRNA expression and plasma corticosterone concentration, suggesting that CRF acts as a downstream molecule for a glucagon-induced appetite-suppressive pathway in chicks. It is likely that the induction of hyperglycemia by central administration of glucagon is involved in its anorexigenic action, because peripheral administration of glucose in chicks suppressed food intake. These results suggest that CRF- and/or hyperglycemia-mediated pathways are involved in the anorexigenic action of glucagon in chicks.

Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep.

Ghrelin is an endogenous ligand for the GH secretagogue/ghrelin receptor (GHS-R) and stimulates feeding behavior and GH levels in rodents and humans. A preprandial increase in plasma ghrelin levels is seen in sheep on programmed feeding, followed by a postprandial rise in plasma GH levels, but effects on food intake and endocrine function are not defined in this ruminant species. We administered ghrelin to female sheep in various modes and measured effects on voluntary food intake (VFI) and plasma levels of GH, LH, prolactin, and cortisol. Whether administered intracerebroventricularly or iv, ghrelin consistently failed to stimulate VFI. On the other hand, ghrelin invariably increased plasma GH levels and alpha,beta-diaminopropanoic acid-octanoyl3 human ghrelin was more potent than ovine ghrelin. Bolus injection of ghrelin into the third cerebral ventricle reduced plasma LH levels but did not affect levels of prolactin or cortisol. These findings suggested that the preprandial rise in plasma ghrelin that is seen in sheep on programmed feeding does not influence VFI but is likely to be important in the postprandial rise in GH levels. Thus, ghrelin does not appear to be a significant regulator of ingestive behavior in this species of ruminant but acts centrally to indirectly regulate GH and LH secretion.

Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep.

We previously demonstrated that a transient surge in plasma levels of ghrelin occurs just prior to a scheduled meal and that this surge is modified by the feeding regimen. This suggests that the ghrelin secretion is regulated by the autonomic nervous system, especially the cholinergic projections to the stomach. To test this hypothesis, we investigated changes in plasma ghrelin levels at feeding time in rams by administering cholinergic blockers (atropine and hexamethonium) and a cholinergic accelerator (metoclopramide). The average food intake in each group infused with atropine, hexamethonium, metoclopramide, and saline was 150+/-28, 137+/-46, 153+/-50, and 1075+/-25g, respectively. Plasma ghrelin concentrations increased (P<0.05) after i.v. infusion of hexamethonium and gradually decreased (P<0.05) after i.v. infusion of metoclopramide. Plasma ghrelin levels in hexamethonium-treated animals were greater (P<0.05) than those of atropine-treated animals. Plasma ghrelin levels were significantly (P<0.05) higher in sheep given i.v. infusions of atropine or hexamethonium than the levels in normal- or pair-fed sheep infused with saline. Plasma ghrelin levels were similar in metoclopramide-treated, pair-fed, and control animals. These results support the possibility that ghrelin secretion is regulated by cholinergic neurons of the vagus and that cholinergic activity suppresses ghrelin secretion in sheep.