Establishment of gemcitabine-resistant human pancreatic cancer cells and effect of brefeldin-a on the resistant cell line

To date, no therapy has been found to which pancreatic cancer responds with the exception of surgical resection in early stages. Recently, gemcitabine has become the standard of care for chemotherapy in those patients with advanced disease. Most pancreatic tumors however, develop resistance to gemcitabine. The aim of this study is to clarify the mechanism of resistance to gemcitabine in human pancreatic cells. Using a cell selection method, a human pancreatic cancer cell line resistant to gemcitabine was established. Cellular proliferation and viability were determined by MTT assay. The cell line with acquired resistance was also found to have cross resistance to fluorouracil. Brefeldin-A (BFA) has been used as a tool for studies of intracellular protein traffic, rather than as an anticancer drug. BFA displays the same effects on wild type cells and those with acquired resistance. Gemcitabine combined with BFA in low doses is significantly more effective than gemcitabine alone against MIA PaCa-2 cell line. Our data suggest that the gemcitabine-resistant and 5-FU-resistant pathways may partially overlap each other. In short, BFA may be used as a modulator of gemcitabine.     

Neurologic complications associated with influenza vaccination: two adult cases

We describe two adult cases of neurologic complications occurring after influenza vaccination. The first case was a 62-year-old man who experienced convulsions 5 days after vaccination, and the second case was a 70-year-old man who exhibited paraplegia 7 days after vaccination. Diagnoses of acute disseminated encephalomyelitis and transverse myelitis with acute motor axonal neuropathy were made, respectively, and steroid pulse therapy and intravenous gamma globulin therapy alleviated the patients' symptoms. Although the efficacy and cost benefit of influenza vaccination have been widely accepted, such neurologic complications might occur in the elderly or even in adults.     

Fatal acute pancreatitis with cystic formation in reactive systemic AA amyloidosis secondary to rheumatoid arthritis

We report a patient with reactive systemic AA amyloidosis secondary to rheumatoid arthritis who showed fatal acute pancreatitis with a cystic formation in the pancreas head. The pancreatitis rapidly worsened despite intensive treatment and resulted in death. In this patient severe deposition of amyloid in the gastrointestinal tract was considered to play an important role in the pathogenesis of the acute pancreatitis. This is an unusual complication in patients with AA amyloidosis, but we should consider it as a possible diagnosis when patients with AA amyloidosis show recurrent or intractable pain in the upper abdomen.     

Electrically communicating three-dimensional cardiac tissue mimic fabricated by layered cultured cardiomyocyte sheets

Calcium hydroxyapatite ceramics (CHA) are nontoxic materials, provoke little reaction from tissues, and by virtue of these properties represent a good starting point for creating bone substitutes. Although several porous CHAs have been used clinically, there have been few reports that CHA is fully replaced by newly formed bone, which may be due to its structure and the limited connectivity between pores. We recently developed a fully interconnected porous CHA (IP-CHA) by adopting a "foam-gel" technique. Structural analysis by scanning electron microscopy revealed that IP-CHA had spherical pores of uniform size that were interconnected by window-like holes. The surface of the wall structure was smooth, and hydroxyapatite particles were bound tightly to one another. Most of the interpore connections of IP-CHA ranged from 10 to 80 microm in diameter (average, 40 microm). When the cylindrical IP-CHA (diameter, 6 mm; height, 15 mm) was implanted into a rabbit femoral condyle, bone, and bone marrow with abundant vessels formed deep in the pores through the interpore connections. Within a period of 6 weeks, new bone had formed and penetrated to a distance of 3 mm from the surface of the IP-CHA implant. Furthermore, a compression test at 9 weeks revealed that the implanted IP-CHA steadily increased in strength to more than double the value of the initial test. These results indicate that the IP-CHA may have clinical utility as a superior bone substitute.     

Ventriculography Using ECG-Gated Multiple Diastolic Injection of Contrast Material in Pediatric Angiocardiography

In pediatric patients, the lower body weight limits the volume of contrast medium. Conventionally, angiocardiography is carried out with a single large bolus injection of contrast material. Angiocardiograms are used in pediatric patients with complex congenital heart diseases. In patients with complex congenital heart disease, especially with MAPCA, the volume of contrast medium used may be excessive. This would allow further injection to provide additional information. To reduce contrast medium used in the angiocardiogram in pediatric patients, we decided to use electrocardiogram (ECG)-gated multiple diastolic injection (EMDI). Three small boluses were injected during the diastolic phase of three consecutive cardiac cycles using a commercially-available power injector. Seventy-eight ventriculograms (47 left ventriculograms and 31 right ventriculograms) using EMDI were carried out on 53 patients with congenital heart disease. Total contrast medium volume with EMDI ventriculograms (mean [±SD] per body weight: 0.72 [±0.25] ml/kg) was significantly smaller than with conventional injection (1.01 [±0.36] ml/kg) (p <0.001). The grades of ventriculograms with EMDI tended to be slightly better than those with conventional injection (statistically not significant, p = 0.478). No short-run type premature ventricular contraction (PVC)s or intramural injection occurred in the ventriculograms with EMDI. PVCs tended to be less frequent in the ventriculograms with EMDI than in those with conventional injection (statistically not significant, p = 0.131). EMDI may be worthwhile in reducing ventricular ectopy when checking ventricular function by angiography, since hemodynamic conditions are less affected by small quantities of contrast medium and only during the filling phase of the ventricles. In conclusion, EMDI may be a useful method for reducing complications of ventriculography in pediatric angiocardiography.     

A case of amelanotic melanoma of the nasal cavity

A 68-year-old male visited Hospital A for treatment of epistaxis, his chief complaint. He was told that he had an easily-bleeding tumor in the nasal cavity. Based of biopsy, a diagnosis of amelanotic melanoma was made. Operation was performed for removal of the tumor. About 8 months after discharge, he visited Hospital B with complaints of lumbar pain and epistaxis. After biopsy at Hospital B, malignant lymphoma (diffuse large cell) was diagnosed, and the patient was referred to our hospital. On bone marrow puncture and biopsy, tumor cell infiltration was observed. Flow cytometric surface marker analysis revealed that these tumor cells were negative for CD45. Results of HE staining of the nasal cavity tumor were insufficient for diagnosis, and staining by immunohistochemistry was necessary to confirm the diagnosis. On immunohistochemical staining of the nasal cavity tumor tissue and bone marrow biopsy tissue, LCA, L26 and UCHL-1 were negative, and S-100 and HMB-45 positive. Recurrence of amelanotic melanoma accompanied by bone marrow infiltration was therefore diagnosed. The incidence of amelanotic melanoma with primary lesions in the nasal cavity is low. However, in making the diagnosis of a nasal cavity lesion, the possibility of such a melanoma should be kept in mind. In many cases, it is difficult to diagnose amelanotic melanoma with HE staining alone, and immunohistochemistry must be used.     

Retroperitoneoscopic nephron-sparing surgery of renal tumor using a microwave tissue coagulator without renal ischemia: comparison with open procedure

PURPOSE: It is ideal to use not a transperitoneal but a retroperitoneal approach for both open and endoscopic partial nephrectomy. We compared the results of retroperitoneoscopic nephron-sparing surgery for small renal tumors using a microwave tissue coagulator without renal pedicle clamping with those of a retroperitoneal open procedure. PATIENTS AND METHODS: Between 1996 and 2002, eight patients with small renal tumors underwent retroperitoneoscopic partial nephrectomy without renal ischemia, and nine patients with small renal tumors underwent open partial nephrectomy via a retroperitoneal approach. Both groups were operated on using a microwave tissue coagulator. RESULTS: Retroperitoneoscopic partial nephrectomy without renal ischemia was performed without any major or minor complications in any patient. The mean operation time for retroperitoneoscopic surgery was significantly longer than that for open partial nephrectomy (221.9 minutes v 145.9 minutes; P = 0.0004). However, the mean estimated blood loss for retroperitoneoscopic surgery was less than that for open partial nephrectomy (137.5 mL v 334.8 mL; P = 0.012). In addition, the retroperitoneoscopic group seemed to recover more rapidly than the open surgery group. CONCLUSIONS: Retroperitoneoscopic nephron-sparing surgery of small renal tumors using a microwave tissue coagulator without renal ischemia is feasible as minimally invasive procedure. It results in saving renal function, minimal blood loss, and rapid recovery.