A comparison of transanal excision and endoscopic resection for early rectal cancer

AIM: To compare the outcomes of endoscopic resection with transanal excision in patients with early rectal cancer.METHODS: Thirty-two patients with early rectal cancer were treated by transanal excision or endoscopic resection between May 1999 and December 2007. The patients were regularly re-examined by means of colonoscopy and abdominal computed tomography after resection of the early rectal cancer. Complications, length of hospital-stay, disease recurrence and follow up outcomes were assessed.RESULTS: Sixteen patients were treated by endoscopic resection and 16 patients were treated by transanal excision. No significant differences were present in the baseline characteristics. The rate of complete resection in the endoscopic resection group was 93.8%, compared to 87.5% in the transanal excision group (P = 0.544). The mean length of hospital-stay in the endoscopic resection group was 2.7 ± 1.1 d, compared to 8.9 ± 2.7 d in the transanal excision group (P = 0.001). The median follow up was 15.0 mo (range 6-99). During the follow up period, there was no case of recurrent disease in either group.CONCLUSION: Endoscopic resection was a safe and effective method for the treatment of early rectal cancers and its outcomes were comparable to those of transanal excision procedures.     

Activation of submucosal 5-HT3 receptors elicits a somatostatin-dependent inhibition of ion secretion in rat colon

Background and purpose:

5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT₃ receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect.

Experimental approach:

Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current (I_sc) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay (elisa). Immunohistochemical techniques were used to study the expression of 5-HT₃ receptors, somatostatin and somatostatin receptors in colonic tissue.

Key results:

In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT₃ receptor antagonists enhanced 5-HT-induced increases in I_sc. However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT₃ receptor antagonists inhibited 5-HT-induced ΔI_sc. Pretreatment with a somatostatin-2 (sst₂) receptor antagonist in mucosa/submucosa preparations augmented 5-HT-induced ΔI_sc. Combination of sst₂ and 5-HT₃ receptor antagonists did not cause further enhancement of 5-HT-induced ΔI_sc. Moreover, both sst₂ and 5-HT₃ receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/submucosa preparations, an effect prevented by pretreatment with 5-HT₃ receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT₃ receptors on submucosal somatostatin neurons and of sst₂ receptors on colonic mucosa.

Conclusion and implications:

Activation of neuronal 5-HT₃ receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons.     

Effects of glyceollin I on vascular contraction in rat aorta

The present study was undertaken to investigate the molecular mechanisms by which glyceollin I inhibits vascular contraction in rat aorta. Rat aortic rings were treated with either glyceollin I or vehicle when vascular contraction reached plateaus. We measured the activity of GTP-RhoA and Rho GTPase-activating protein (RhoGAP) and the phosphorylation level of the myosin light chain (MLC₂₀), myosin phosphatase targeting subunit 1 (MYPT1), and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). Glyceollin I reduced vascular contraction whether endothelium is present or denuded. Glyceollin I reduced vascular contraction induced by NaF, U46619, phenylephrine, or PDBu. Blockers of K⁺ channels did not affect the vasorelaxation induced by glyceollin I. Glyceollin I reduced activation of RhoA as well as phosphorylation level of MLC₂₀. Glyceollin I also reduced phosphorylation of MYPT1 and CPI17 induced by NaF but not PDBu. However, glyceollin I had no direct effect on RhoGAP activation in vitro. Glyceollin I reduced vascular contraction, at least in part, through inhibition of the RhoA/Rho-kinase signaling pathway.     

Langerhans cell sarcoma arising from Langerhans cell histiocytosis: a case report

Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells that have overtly malignant cytologic features. It is a very rare disease and theoretically, it can present de novo or progress from an antecedent Langerhans cell histiocytosis (LCH). However, to our knowledge, LCS arising from an antecedent LCH has not been reported on. We present here a case of LCS arising from a pulmonary LCH. A 34 yr-old man who was a smoker, had a fever and a chronic cough. Computed tomographic (CT) scan revealed multiple tiny nodules in both lungs. The thoracoscopic lung biopsy revealed LCH. The patient quit smoking, but he received no other specific treatment. One year later, the follow up chest CT scan showed a 4 cm-sized mass in the left lower lobe of the lung. A lobectomy was then performed. Microscopic examination of the mass revealed an infiltrative proliferation of large cells that had malignant cytologic features. Immunohistochemical stains showed a strong reactivity for S-100 and CD68, and a focal reactivity for CD1a. We think this is the first case of LCS arising from LCH.     

Primary systemic anaplastic large cell lymphoma in a single Korean institution: clinical characteristics and treatment outcome

Despite advances in the characterization of anaplastic large cell lymphoma (ALCL), little data is available on Asian patients. We report here upon single Korean institution's experience regarding the clinical characteristics and outcomes of ALCL. We performed a retrospective study of 32 adults with ALCL. Most of the patients received anthracycline-based chemotherapy. Ann Arbor stage III-IV, B symptoms, high-intermediate/ high International Prognostic Index (IPI), and extranodal disease at diagnosis were present in 56%, 44%, 41%, and 63%, respectively. Compared with Western studies, the male/female ratio (4.3) was markedly higher and skin (9%) and bone involvement (9%) were less frequent. The staining results for anaplastic lymphoma kinase were positive in 6 (33%) of 18 cases available. The complete response (CR) rate was 62% (95% CI, 44-80%). With a median follow-up of 51.0 months, 5 yr overall survival was 40+/-11%. The 3 yr relapse-free survival for the 18 patients who achieved CR was 74+/-12%. Age, performance status, lactate dehydrogenase, extranodal disease sites number, and IPI were correlated with treatment response and survival. Our data suggest that Korean ALCL patients appear to have a higher male/female ratio, less frequent skin/bone involvement, and lower CR rate compared with those of Western studies.     

Role of nuclear Ca2+/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival

In response to biological and mechanical injury, or in vitro culturing, vascular smooth muscle cells (VSMCs) undergo phenotypic modulation from a differentiated "contractile" phenotype to a dedifferentiated "synthetic" one. This results in the capacity to proliferate, migrate, and produce extracellular matrix proteins, thus contributing to neointimal formation. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing cAMP or cGMP, are critical in the homeostasis of cyclic nucleotides that regulate VSMC growth. Here, we demonstrate that PDE1A, a Ca2+-calmodulin-stimulated PDE preferentially hydrolyzing cGMP, is predominantly cytoplasmic in medial "contractile" VSMCs but is nuclear in neointimal "synthetic" VSMCs. Using primary VSMCs, we show that cytoplasmic and nuclear PDE1A were associated with a contractile marker (SM-calponin) and a growth marker (Ki-67), respectively. This suggests that cytoplasmic PDE1A is associated with the "contractile" phenotype, whereas nuclear PDE1A is with the "synthetic" phenotype. To determine the role of nuclear PDE1A, we examined the effects loss-of-PDE1A function on subcultured VSMC growth and survival using PDE1A RNA interference and pharmacological inhibition. Reducing PDE1A function significantly attenuated VSMC growth by decreasing proliferation via G1 arrest and inducing apoptosis. Inhibiting PDE1A also led to intracellular cGMP elevation, p27Kip1 upregulation, cyclin D1 downregulation, and p53 activation. We further demonstrated that in subcultured VSMCs redifferentiated by growth on collagen gels, cytoplasmic PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas inhibiting nuclear PDE1A has the opposite effects. These suggest that nuclear PDE1A is important in VSMC growth and survival and may contribute to the neointima formation in atherosclerosis and restenosis.     

The effect of gynaecological laparoscopic surgery on cerebral oxygenation

During gynaecological laparoscopic surgery, alterations in cerebral blood flow and intracranial pressure are frequently reported. These changes affect cerebral perfusion pressure and thus may affect cerebral oxygenation. In this prospective study, the effect of gynaecological laparoscopic surgery on cerebral oxygenation was examined by following the changes in regional cerebral oxygen saturation (rSo2). Twenty-four female patients were enrolled. The mean rSo2 was 65.5 +/- 5.4% at baseline before surgery, 60.8 +/- 5.6% when the patient was placed in the Trendelenburg position, 57.1 +/- 9.3% after creation of pneumoperitoneum, and 64.0 +/- 7.3% after the completion of surgery. During the period of pneumoperitoneum, rSo2 fell below 50% in two hypercapnic patients. In comparison with baseline, rSo2 declined significantly in the Trendelenburg position. The creation of pneumoperitoneum itself did not decrease the average rSo2 value further unless the patients were hypercapnic.     

Testing the effects of treatment complications on a cognitive-behavioral intervention for reducing symptom severity

Patients (n = 231) diagnosed with solid tumors and undergoing chemotherapy were randomly assigned to the experimental arm (n = 114) or to conventional care (n = 117). A symptom severity index based on summed severity scores across 15 symptoms was the primary outcome. Building on previously published work, an analysis was undertaken to determine the effects of patient characteristics and treatment complications on reductions in symptom severity achieved by a trial of a cognitive-behavioral intervention (CBI). The impact of the intervention on symptom severity differed by the occurrence of neutropenic events, chemotherapy dose delays or dose reductions, and number of comorbid conditions. Patients with more comorbid conditions, as well as those who did not experience neutropenia or dose delay/reduction, who received the intervention reported lower severity at 20 weeks compared to those who received conventional care. This research begins to specify the clinical conditions under which CBIs are effective in lowering symptom severity.