Total Versus Near-total Thyroidectomy in Graves Disease: Results of the Randomized Controlled Multicenter TONIG-trial.

BACKGROUND: Previous data suggest that the incidence of hypoparathyroidism after surgery for Graves disease (GD) is lower after subtotal thyroidectomy compared to total thyroidectomy (TT). The present study evaluated the incidence of postoperative hypoparathyroidism after near-total (NTT) versus TT in GD. METHODS/DESIGN: In a multicenter prospective randomized controlled clinical trial, patients with GD were randomized intraoperatively to NTT or TT. Primary endpoint was the incidence of transient postoperative hypoparathyroidism. Secondary endpoints were permanent hypoparathyroidism, transient recurrent laryngeal nerve palsy (RLNP), reoperations for bleeding, inadvertently removed parathyroid glands, and recurrent hyperthyroidism after 12 months. RESULTS: Eighteen centers randomized 205 patients to either TT (n = 102) or NTT (n = 103) within 16 months. According to intention-to-treat postoperative transient hypoparathyroidism occurred in 19% (20/103) patients after NTT and in 21% (21 of 102) patients after TT (P = 0.84), which persisted >6 months in 2% and 5% of the NTT and TT groups (P = 0.34). The rates of parathyroid autotransplantation (NTT 24% vs TT 28%, P = 0.50) and transient RLNP (NTT 3% vs TT 4%, P = 0.35) was similar in both groups. The rate of reoperations for bleeding tended to be higher in the NTT group (3% vs 0%, P = 0.07) and the rate of inadvertently removed parathyroid glands was significantly higher after NTT (13% vs 3%, P = 0.01). An existing endocrine orbitopathy improved in 35% and 24% after NTT and TT (P = 0.61). Recurrent disease occurred in only 1 patient after TT (P = 0.34). CONCLUSION: NTT for GD is not superior to TT regarding transient postoperative hypoparathyroidism.

The plasminogen activator inhibitor system in colon cancer cell lines is influenced by the CO2 pneumoperitoneum.

PURPOSE: Laparoscopic surgery in the treatment of colon carcinoma causes pH value alterations as well as changes in fibrinolytic activity. This results in enhanced proliferation of colon carcinoma cells in vitro and also in enhanced growth of liver metastasis when compared to isobaric (gasless) laparoscopy in vivo. So far, the direct influence of CO(2) pneumoperitoneum on the invasiveness and metastatic capabilities of colon cancer cells remains unclear. We therefore evaluated transcripts of the uPA system. METHODS: The influence of CO(2) pneumoperitoneum on the gene expression of plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) was investigated in colon carcinoma cell lines (HT116, SW48, and WiDr) and mesothelial cells employing a pneumoperitoneum chamber in vitro. Quantitative gene expression data were collected using real-time RT-PCR and statistical analysis was performed by means of analysis of variance and Bonferroni correction. RESULTS: The expression of uPA and PAI-1 was increased in colon carcinoma cell lines when cultivated at pH 6.1, a value corresponding to intraabdominal pH values during CO(2) insufflation. Elevated PAI-1 mRNA levels were also observed when CO(2) was simultaneously applied with a pressure of 10 mmHg. In contrast, there were no significant changes in mesothelial cells in the investigated parameter. CONCLUSION: The conditions of CO(2) pneumoperitoneum cause changes in the expression of genes controlling the fibrinolytic activity. The increase of PAI-1 and uPA can contribute to the enhancement of metastasis and invasive potential of tumour cells. Therefore, changes in the conditions of laparoscopy may well optimise laparoscopic therapy in colon cancer.

Impact of vasoactive intestinal polypeptide and gastrin-releasing peptide on small bowel microcirculation and mucosal injury after hepatic ischemia/reperfusion in rats.

BACKGROUND AND AIMS: Alterations in microvascular perfusion of the intestine after hepatic ischemia/reperfusion have been suggested as an important cause of postoperative septic complications. We therefore investigated small bowel microcirculation and mucosal injury after liver ischemia/reperfusion in a rat model. Furthermore, we analyzed the effects of the regulatory peptides vasoactive intestinal polypeptide and gastrin-releasing peptide for their splanchnic vasoactivity. METHODS: Hepatic ischemia was induced by clamping of the left hepatic artery and vein for 40 min, followed by 60 min of reperfusion. The control group was treated similarly, but without clamping of the liver vessels. Ten minutes after clamping of the hepatic vessels, vasoactive intestinal polypeptide or gastrin-releasing peptide, respectively, were continuously infused intravenously in the experimental groups. Small bowel microcirculation and mucosal injury were assessed using intravital microscopy and the Chiu-score, respectively. RESULTS: The functional capillary density of the small intestine following ischemia and reperfusion of the left hepatic lobe significantly decreased compared to normal controls in both the mucosa and the smooth intestinal muscle. Red blood cell velocity decreased, whereas leukocyte-endothelium adherence, stasis index and the mucosal injury score increased. Administration of vasoactive intestinal polypeptide resulted in an increase of functional capillary density in the mucosa and of the red blood cell velocity and a decrease in the stasis index. The mucosal injury score was significantly higher in reperfused animals without treatment. The application of gastrin-releasing peptide resulted in an isolated increase of the red blood cell velocity. Leukocyte adherences could not be altered by the regulatory peptides. CONCLUSION: We conclude that hepatic ischemia/reperfusion injury leads to significant alterations of small bowel microcirculation and mucosal injury. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate the damage in a different manner.

Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate hepatic microvasculatory disturbances following intestinal ischemia and reperfusion.

BACKGROUND/AIMS: In addition to the primarily affected small bowel, intestinal ischemia and reperfusion (IIR) also leads to a marked decrease in hepatic microcirculation. The aim was to determine the potentially protective effect of the vasoactive hormones vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) on hepatic microcirculation following IIR. METHODS: Using a rat model, three animal groups were subjected to 40 min of intestinal ischemia, two of which were infused with either VIP or GRP (n = 12 each). Following reperfusion, hepatic intravital microscopy was performed. Portal venous perfusion, activities of serum glutamate pyruvate transaminase and alkaline phosphatase, mucosal injury in the small intestine and the expression of antioxidant enzymes glutathione peroxidase, copper-zinc-superoxide dismutase (Cu-Zn-SOD), glutathione reductase and catalase (CAT) in the liver were investigated. RESULTS: Infusion of either VIP or GRP improved hepatic microcirculation and bile flow when compared with the untreated IIR group. VIP and GRP increased portal venous blood flow during reperfusion. VIP reduced the extent of mucosal damage resulting from IIR. GRP caused a decrease in expression of CAT and Cu-Zn-SOD, whereas VIP simply reduced CAT expression. CONCLUSION: This study indicates that vasoactive hormones may attenuate intestinal and hepatic injuries and circulatory disturbances following IIR.

A new abdominal cavity chamber to study the impact of increased intra-abdominal pressure on microcirculation of gut mucosa by using video microscopy in rats.

OBJECTIVE: In experimental studies of capillary blood flow that use intravital video microscopy, organs are exposed in observation chambers implanted into the animal. In this article we describe an abdominal cavity chamber for intravital video microscopy of gut mucosa microcirculation during increased intra-abdominal pressure. DESIGN: Prospective, experimental animal study. SETTING: Research laboratory at a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: The abdominal cavity chamber was designed for implantation into the abdominal wall of rats after laparotomy, thus creating an expanded hermetic, abdominal cavity volume. Animals were assigned to three levels of intra-abdominal pressure: controls (group 1), 10 mm Hg (group 2), and 15 mm Hg (group 3). Intra-abdominal pressure was increased by intra-abdominal insufflation of gas. By using a fluorescent marker, we quantitatively assessed mucosa perfusion index, functional capillary density, red blood cell velocity, capillary diameters, and flow motion during increased intra-abdominal pressure by intravital video microscopy. Results were expressed as mean +/- SEM. Significance of differences was determined by analysis of variance and multiple comparison of means with post hoc test (*p <.05 groups vs. control;p <.05 group 3 vs. group 2). MEASUREMENTS AND MAIN RESULTS: When compared with controls, animals subjected to an intra-abdominal pressure of 10 and 15 mm Hg showed a significant stepwise decrease in mucosa perfusion index (88%, 71%*, 22%*), functional capillary density (665.4 +/- 71.7, 461.6 +/- 71.9*, 375.1 +/- 2.0*cm(-1)), and red blood cell velocity (0.50 +/- 0.04, 0.33 +/- 0.03*, 0.04 +/- 0.06*mm/sec), indicating a stepwise impairment of mucosal microcirculation. Capillary diameters and flow motion did not change with respect to intra-abdominal pressure. CONCLUSIONS: This novel animal model of intravital intestinal video microscopy that uses an abdominal cavity chamber is a feasible and sensitive experimental tool to study intestinal microcirculation during increased intra-abdominal pressure. Intra-abdominal pressure likely results in a severe impairment of mucosal microcirculation.