Cardiac metastasis from lung adenocarcinoma causing atrioventricular block and left ventricular outflow tract obstruction

Cardiac metastasis from lung cancer is rarely diagnosed antemortem, as it usually causes no symptoms or signs. We report the case of a 56-year-old man with recurrent lung adenocarcinoma in whom developed a large mass in the ventricular septum, complete atrioventricular block, and obstruction of the left ventricular outflow tract.     

Pancreatic arteriovenous malformation combined with portal thrombosis

We encountered a case of portal vein thrombosis (PVT) after treatment for portal hypertension due to pancreatic arteriovenous malformation (PAVM). A 75-year-old man was admitted for the treatment of esophageal varices. Diffuse PAVM and aneurysm in the celiac and superior mesenteric arteries were detected via abdominal computed tomography and angiography. Although endoscopical sclerotherapy was performed, PVT was identified after the treatment and variceal bleeding continued. Autopsy was performed and the thrombus and malformation were pathologically confirmed. This case indicates that PVT can be associated with PAVM.     

Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model

BACKGROUND AND AIM: In patients with a high risk of peritoneal dissemination of colon cancer, a treatment adjuvant to surgical resection would improve their prognosis. We aimed to determine whether radioimmunotherapy employing radiolabelled monoclonal antibody would work in this situation. METHODS: A murine model of peritoneal dissemination was established in female Balb/c nu/nu mice by intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody, radiolabelled with (131)I by the chloramine-T method was conducted intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively. RESULTS: Radioimmunotherapy at any timing improved survival of mice as compared with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(-1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained when radioimmunotherapy was conducted on day 0. CONCLUSION: These results indicate that intraperitoneal radioimmunotherapy may effectively kill colon cancer cells disseminated in the peritoneal cavity before formation of tumours and, therefore, may work as an adjuvant treatment to prevent peritoneal metastasis of colon cancer.     

Molecular embryology for an understanding of congenital heart diseases

Congenital heart diseases (CHD) result from abnormal morphogenesis of the embryonic cardiovascular system and usually involve defects in specific structural components of the developing heart and vessels. Therefore, an understanding of “Molecular Embryology”, with specific focus on the individual modular steps involved in cardiovascular morphogenesis, is particularly relevant to those wishing to have a better insight into the origin of CHD. Recent advances in molecular embryology suggest that the cardiovascular system arises from multiple distinct embryonic origins, and a population of myocardial precursor cells in the pharyngeal mesoderm anterior to the early heart tube, denoted the “second heart field”, has been identified. Discovery of the second heart field has important implications for the interpretation of cardiac outflow tract development and provides new insights into the morphogenesis of CHD.     

Cbln1 binds to specific postsynaptic sites at parallel fiber–Purkinje cell synapses in the cerebellum

Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is a unique molecule that is not only required for maintaining normal parallel fiber (PF)–Purkinje cell synapses, but is also capable of inducing new PF synapses in adult cerebellum. Although Cbln1 is reportedly released from granule cells, where and how Cbln1 binds in the cerebellum has remained largely unclear, partly because Cbln1 undergoes proteolysis to yield various fragments that are differentially detected by different antibodies. To circumvent this problem, we characterized the Cbln1-binding site using recombinant Cbln1. An immunohistochemical analysis revealed that recombinant Cbln1 preferentially bound to PF–Purkinje cell synapses in primary cultures and acute slice preparations in a saturable and replaceable manner. Specific binding was observed for intact Cbln1 that had formed a hexamer, but not for the N-terminal or C-terminal fragments of Cbln1 fused to other proteins. Similarly, mutant Cbln1 that had formed a trimer did not bind to the Purkinje cells. Immunoreactivity for the recombinant Cbln1 was observed in weaver cerebellum (which lacks granule cells) but was absent in pcd cerebellum (which lacks Purkinje cells), suggesting that the binding site was located on the postsynaptic sites of PF–Purkinje cell synapses. Finally, a subcellular fractionation analysis revealed that recombinant Cbln1 bound to the synaptosomal and postsynaptic density fractions. These results indicate that Cbln1, released from granule cells as hexamers, specifically binds to a putative receptor located at the postsynaptic sites of PF–Purkinje cell synapses, where it induces synaptogenesis.     

A surgical case of descending colon cancer with abdominal wall abscess after drainage of abscess

We report a surgical case of descending colon cancer with abdominal wall abscess. A 72-year-old man was admitted to a hospital because of left lower abdominal mass with slight pain. An abdominal CT showed a left lower abdominal wall abscess adjacent to the descending colonic wall thickening. We diagnosed an abdominal wall abscess due to descending colon cancer or colon diverticulitis. The abscess was drained under local anesthesia releasing foul-smelling pus and air. After abscess drainage and general improvement in his condition, we conducted subtotal colectomy with lymph node dissection and excision of abdominal wall abscess cavity. Pathological findings indicated moderately differentiated adenocarcinoma of the descending colon (pT4, pN0, sH0, sP0, sM0, fStage II). The carcinoma had invaded the abdominal wall and transverse colon, but the cancer cells were not shown in the abdominal wall abscess cavity. In abdominal wall abscess treatment, colon cancer should be considered as a potential underlying cause. CT proved useful for assessing the status of the tumor and the abscess. We conducted a radical operation for descending colon cancer after the drainage for abdominal wall abscess.     

Successful allogeneic stem cell transplantation in two patients with acute myelogenous leukaemia and invasive aspergillosis by antifungal combination therapy

Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in patients who undergo haematopoietic stem cell transplantation (HSCT). History of IA before allogeneic HSCT is still challenging because of the high risk of recurrence after HSCT. Recent advances in early‐stage diagnosis and new, more effective classes of antifungal agents have improved the management of IA in the HSCT recipients. We report two cases with acute myelogenous leukaemia after primary failure of induction chemotherapy with the patients developing pulmonary IA. They responded well to a combination of voriconazole (VCZ) and micafungin, resulting in a remarkable reduction of pulmonary IA lesions at short intervals. Thereafter, antifungal therapy was switched to liposomal amphotericin B (L‐AmB), followed by conditioning regimen for allogeneic HSCT, because of the possibility of VCZ altering the metabolism of chemotherapeutic agents and calcineurin inhibitors. Successful engraftment was achieved without severe adverse side‐effects or aggravation of IA after HSCT. Combining VCZ with micafungin followed by L‐AmB throughout HSCT could be advantageous in stabilising IA in HSCT patients.     

Exploration of endocrine-disrupting chemicals on estrogen receptor α by the agonist/antagonist differential-docking screening (AADS) method: 4-(1-Adamantyl)phenol as a potent endocrine disruptor candidate

We established a novel screening method to survey endocrine-disrupting chemicals by means of in silico docking calculations. Endocrine disruptors target the human nuclear receptor, which bind a chemical in a pocket presenting in the ligand-binding domain (LBD). The LBD alters its conformation, depending upon the binding of either agonist or antagonist. We discovered that the chemicals can be differentiated into either agonist or antagonist by the docking calculations of the chemical for the LBD. We used the crystal structures of both agonist-bound LBDs and antagonist-bond LBDs as templates in the docking calculations, and estimated binding energies to discriminate between agonist and antagonist bindings. This agonist/antagonist differential-docking screening (AADS) method predicted, for example, 4-(1-adamantyl)phenol as an agonist of the human estrogen receptor α (hERα). Indeed, this compound, one of the essential raw materials for nanoporous organosilicate thin films, was confirmed to exhibit strong agonist activity in the reporter-gene assay for hERα with a high binding affinity. The AADS method is an approach that appears to foresee both the binding ability and the agonist/antagonist function of chemicals for the target nuclear receptors.     

Radiofrequency ablation with hand-assisted laparoscopic surgery for the treatment of hepatocellular carcinoma in the caudate lobe

OBJECTIVE: To assess the feasibility and safety of radiofrequency ablation (RFA) with hand-assisted laparoscopic surgery (HALS) for hepatocellular carcinoma (HCC) in the caudate lobe with severe liver dysfunction. SUMMARY BACKGROUND DATA: HCC in the caudate lobe remains one of the most difficult locations where various treatments tend to pose problems regarding the optimal surgical approach. The technique of HALS has thus been proposed as a useful method for performing a safe RFA therapy. For this study, we assessed the feasibility and safety of RFA with HALS for the treatment of HCC in the caudate lobe with liver dysfunction. PATIENTS AND METHODS: Between July 1999 and February 2005, 5 patients who suffered from HCC in the caudate lobe were indicated for RFA. The percutaneous puncture was difficult and all patients have severe liver dysfunction with viral chronic hepatitis. Therefore, RFA was assisted by an inserted hand through a minimal skin incision under laparoscopic inspection. An intraoperative endoscopic ultrasound examination was performed before RFA to determine the tumor region. The hand-assisted minimal dissection around the caudate lobe was required to detect tumor and avoid injuries of other tissues. RFA for HCC was performed using a cooled-tip (Radionics Inc, Burligton, MA) connected to a RF generator under the programmed cyclic impedance. RESULTS: The surgical procedures consisted of 5 RFA to tumors in the caudate lobe with HALS, which was performed safely, and a postoperative computed tomography scan revealed a sufficient ablation in all patients. There was no operative mortality but 1 patient had minor bile leakage, which was treated conservatively, and all patients recovered and thus were eventually discharged. One patient had local recurrence after 3 months, 3 patients had tumor recurrences in another segment after 6 months. At a mean follow-up 32.2 months, all patients were still alive. CONCLUSIONS: RFA with HALS is considered to be a safe and feasible technique for HCC in the caudate lobe with liver dysfunction.