Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice

Transforming growth factor beta (TGF-beta) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth. To directly address the role of TGF-beta signaling in liver regeneration in vivo, the TGF-beta type II receptor gene (Tgfbr2) was selectively deleted in hepatocytes by crossing "floxed" Tgfbr2 conditional knockout mice with transgenic mice expressing Cre under control of the albumin promoter. Hepatocytes isolated from liver-specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF-beta1. The peak of DNA synthesis after 70% partial hepatectomy occurred earlier (36 vs. 48 hours) and was 1.7-fold higher in R2LivKO mice compared with controls. Accelerated S-phase entry by proliferating R2LivKO hepatocytes coincided with the hyperphosphorylation of Rb protein and the early upregulation of cyclin D1 and cyclin E. However, by 120 hours after partial hepatectomy, hepatocyte proliferation was back to baseline in both control and R2LivKO liver. Regenerating R2LivKO liver showed evidence of increased signaling by activin A and persistent activity of the Smad pathway. Blockage of activin A signaling by the specific inhibitor follistatin resulted in increased hepatocyte proliferation at 120 hours, particularly in R2LivKO livers. In conclusion, TGF-beta regulates G(1) to S phase transition of hepatocytes, but intact signaling by TGF-beta is not required for termination of liver regeneration. Increased signaling by activin A may compensate to regulate liver regeneration when signaling through the TGF-beta pathway is abolished, and may be a principal factor in the termination of liver regeneration.     

Flow cytometric detection of cytomegalovirus antigen in peripheral blood cells after bone marrow transplantation

We report 13 normal peripheral blood stem cell (PBSC) donors who had a second PBSC collection for allogeneic transplantation performed after the first. The median interval between the first and second collection was 5 months. Mobilization was achieved with filgrastim (12 μg/kg/d). No significant difference was found in the median pre-apheresis leucocyte count (×10⁹/l) between the two donations (40.2 v 38.5; P  = 0.91). The median apheresis yield (×10⁶ CD34⁺ cells/litre blood processed, first apheresis) was also similar (28 v 27.3; P  = 0.91). Filgrastim-related adverse events were comparable. These data suggest that second PBSC collections are feasible, similarly tolerated and provide comparable apheresis yields.     

Aortoesophageal fistula following nasogastric tube placement

A 78-year-old woman was admitted to our hospital because of fresh cerebral infarction. She had been diagnosed as having rheumatoid arthritis, but had not been treated for 50 years. She could not take in sufficient food. Upper gastrointestinal endoscopy revealed no esophageal or gastric lesions, but the procedure was difficult because of her stiff neck from severe rheumatoid degenerative changes of the cervical spine. A nasogastric (NG) tube was placed, and enteral nutrition was initiated. On the 15th day from initiation of enteral nutrition, she presented hematemesis, and suddenly went into a state of shock and died. An autopsy revealed two esophageal ulcers, one of which penetrated into the descending thoracic aorta. The patient was diagnosed with hemorrhagic shock due to aortoesophageal fistula. We suspect that the NG tube compressed the esophageal wall, and ischemia caused the ulcers.     

Peptic ulcer is prevalent among shift workers

To elucidate sleep disturbances in the etiology of peptic ulcers, the prevalence of peptic ulcer disease was compared among shift workers and daytime workers. The subjects (N=11,657) were employees of various institutions, such as factories, banks, or schools, and had undergone a mass x-ray examination of the upper gastrointestinal tract. With present shift workers (N=2269), the prevalence of gastric ulcers was 2.38% (N=54) and that of duodenal ulcers, 1.37% (N=31). With the past shift workers (N=2111), the prevalence of gastric ulcers was 1.52% (N=32) and that of duodenal ulcers, 0.62% (N=13). On the contrary, with the daytime workers (N=6525) the prevalence of gastric ulcer was 1.03% (N=67) and that of duodenal ulcer, 0.69% (N=45). The working schedule for 752 examinees was unknown. The prevalence of gastric and duodenal ulcers was higher with shift workers than daytime workers. Thus, shift work involving sleep disturbances may play an important role in the development of peptic ulcers.     

Splenic accumulation of Tc-99m HMDP in a patient with severe alcoholic cirrhosis of the liver

The authors report unusual splenic accumulation of Tc-99m hydroxymethylene diphosphonate (HMDP) on bone scintigraphy of a patient with alcoholic cirrhosis of the liver. Laboratory studies showed hemolytic anemia and hemochromatosis resulting from alcohol abuse, both of which are thought to be related to the diffuse splenic uptake observed. When diffuse splenic accumulation by Tc-99m HMDP is seen, the existence of alcoholic hepatopathy might be considered.     

Mediastinal lymph node metastases from nonsmall cell bronchogenic carcinoma: reevaluation with CT

We evaluated the sensitivity of CT for detecting mediastinal lymph node metastases in patients with nonsmall cell bronchogenic carcinoma. Computed tomography of 208 cases of surgically proven bronchogenic carcinoma from three institutes was evaluated retrospectively using specific diagnostic criteria. These consisted of two size thresholds for specific mediastinal node regions: 13 mm short transverse diameter for nodes in the subcarinal, precarinal, and tracheobronchial regions and 10 mm for other regions. Based on these criteria, the overall sensitivity of CT was 69%, specificity 94%, and accuracy 86% for detection of metastasis. In cases of adenocarcinoma, sensitivity was 61%, specificity 93%, and accuracy 81%, and in those of squamous cell carcinoma the respective values were 86, 94, and 92%. Comparison between the results using the present criteria with the former criterion of 10 mm short transverse diameter for all mediastinal nodes revealed that the number of false-positive cases decreased markedly. We conclude that more accurate CT evaluation of mediastinal lymph node metastasis in nonsmall cell bronchogenic carcinoma can be achieved with specific size criteria for specific mediastinal regions.     

A case of cavernous hemangioma in which malignancy was preoperatively excluded by FDG-PET

A contrast-enhanced mass was revealed by computed tomography and magnetic resonance imaging in the left pelvic cavity of a 71-year-old man. Although the mass appeared to be a cavernous hemangioma, malignancy could not be ruled out. Abdominal angiography was performed but failed to rule out malignancy because it revealed vascular dislocation and encasement. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) was then performed, and suggested a benign tumor, with a standardized uptake value (SUV) of 1.7. Following this finding, because the tumor was large and rupture could not be ruled out, we decided to perform surgery. The resected tumor was a benign cavernous hemangioma, consistent with the result obtained by FDG-PET.     

Serial MRI of cerebral infarcts before and after removal of an atrial myxoma

We describe a cerebral infarct caused by atrial myxoma. A 30-year-old woman with an atrial myxoma presented with a right hemisensory deficit. MRI carried out before and after removal of the myxoma, showed multiple small bilateral white-matter infarcts which increased in number up to the surgery. A lesion in the left thalamus, which enlarged and showed contrast enhancement 4 months before surgery, resembled an old cerebral infarct by the time the myxoma was removed. The number of lesions stopped increasing after surgery. We suggest that atrial myxomas should be removed even in asymptomatic patients, to prevent cerebral infarcts due to embolism of tumour or thrombus.     

Transrectal robotic natural orifice translumenal endoscopic surgery (NOTES) applied to intestinal anastomosis in a porcine intestine model

Background

Natural orifice translumenal endoscopic surgery (NOTES) is a minimally invasive operation using devices such as flexible endoscopes and linear or circular staplers. Nevertheless, hand-sewn anastomosis in NOTES remains challenging. This study aimed to investigate the feasibility of transrectal robotic NOTES requiring intracorporeal small intestinal anastomosis and closure of the rectal anterior wall incision in a relevant human model.

Methods

The authors developed a flexible rectal proctoscope with a diameter of 43 mm for transrectal robotic NOTES. Small intestinal anastomosis was performed in a porcine intestinal transrectal NOTES model using two robotic arms and a camera inserted through the proctoscope and a rectal anterior wall incision. The quality of transrectal small intestinal anastomosis using the da Vinci surgical system (transrectal robotic NOTES group) was compared with that of transabdominal anastomosis using the da Vinci surgical system (transabdominal robot-assisted surgery group) and transrectal anastomosis using traditional transanal endoscopic microsurgery (TEM) instruments (TEM NOTES group). The quality of transrectal rectal anterior wall suturing in the transrectal robotic NOTES group was compared with that of the TEM NOTES group and the open surgical instruments group (open group).

Results

Robotic intracorporeal suturing was performed successfully in the porcine intestine model. During small intestinal anastomosis, burst pressure in the transrectal robotic NOTES group (67.7 ± 29.3 mmHg) was similar to that in the transabdominal robot-assisted surgery group (73.3 ± 18.2 mmHg) but significantly higher than in the TEM NOTES group (20.3 ± 24.0 mmHg; p < 0.01). During rectal anterior wall suturing, the burst pressure did not differ significantly between the transrectal robotic NOTES group (149.9 ± 81.1 mmHg) and the open group (195.0 ± 60.5 mmHg).

Conclusions

The preliminary safety and efficacy of transrectal robotic NOTES was established. Further studies are required to determine the practical feasibility of this procedure.