Treatment Outcome of Nab-paclitaxel Plus Gemcitabine for Leptomeningeal Carcinomatosis from Pancreatic Ductal Adenocarcinoma: An Autopsy Case Report.

A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

Spontaneous Development of Acute Obstructive Suppurative Pancreatic Ductitis Associated with Pancreatic Carcinoma: A First Case Report.

A 68-year-old man with a history of diabetes mellitus was admitted to our hospital with a diagnosis of acute pancreatitis. Abdominal computed tomography revealed a suspicious tumor in the body of the pancreas, along with a dilated main pancreatic duct and edema of the pancreatic tail. Endoscopic retrograde pancreatography was performed after treating the patient's pancreatitis. When a cannula tip was advanced beyond the stenosis, deep into the distal pancreatic duct, thick white pus was evacuated. A bacteriological examination of the aspirated pancreatic juice revealed Enterobacter cloacae, and a cytological examination revealed adenocarcinoma. The diagnosis was acute obstructive suppurative pancreatic ductitis associated with pancreatic carcinoma.

Induction of cell death in pancreatic ductal adenocarcinoma by indirubin 3'-oxime and 5-methoxyindirubin 3'-oxime in vitro and in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. To identify potential effective therapeutic drugs for PDAC, we established a screening system based on spheroid formation using 170#3 mouse PDAC cells with or without fibroblasts. We found that indirubin 3'-oxime (Indox) and 5-methoxyindirubin 3'-oxime (5MeOIndox) inhibited PDAC cell proliferation. Furthermore, PDAC xenograft growth was also inhibited in BALB/c nu/nu mice after administration of Indox and 5MeOIndox. Both phosphorylated CDK1 and cyclin B1 levels in 170#3 cells were significantly reduced by treatment with Indox and 5MeOIndox in vitro and in vivo. Cell cycle analysis revealed that 5MeOIndox, but not Indox, induced G2/M arrest. Annexin V-propidium iodide double-staining analysis demonstrated that Indox induced abundant non-apoptotic cell death of 170#3 cells, while 5MeOIndox predominantly induced early apoptosis, indicating that the cytotoxicity of 5MeOIndox is lower than that of Indox. These results suggest that one mechanism of 5MeOIndox is to induce G2/M arrest of PDAC cells via inhibition of CDK1/cyclin B1 levels, thereby leading to apoptosis. Our findings suggest 5MeOIndox as a potential useful anticancer agent in PDAC.

Solitary Variceal Rupture in the Small Intestine.

A 70-year-old man was referred to our hospital to undergo treatment for hepatocellular carcinoma. In hospital, he complained of hematochezia and a laboratory analysis revealed a decreased level of hemoglobin. Abdominal computed tomography revealed a tumor in the small intestine, with slow enhancement of the dorsal region. Double-balloon enteroscopy revealed a submucosal tumor with a depression in the jejunum. Partial enterectomy was performed and a pathological examination demonstrated the presence of a solitary varix. Solitary varix in the small intestine has not been reported previously. We herein report an extremely rare case of solitary varix in the jejunum.

A rare case of a pineoblastoma with a rhabdomyoblastic component.

Pineal anlage tumor (PAT) is a rare subtype of pineoblastoma (PB), which shows a poor prognosis. We report a case of a 5-year-old boy with PB with a rhabdomyoblastic component. He presented at a local clinic with vomiting and was transferred to our hospital following discovery of a pineal mass. An endoscopic biopsy was performed and was diagnosed as a PB with a rhabdomyoblastic component. Histopathology of PAT is characterized by both neuroectodermal and ectomesenchymal differentiation, and only a few confirmed cases have been reported. Although the histopathological features of the reported case resembled that of PAT, the ectomesenchymal component in the presented case was only a rhabdomyoblastic one. Therefore, we have diagnosed this case as PB with a rhabdomyoblastic component. As PAT is a rare pineal tumor, clinical, histopathological and genetic evaluation of additional cases is needed to define the characteristics of PAT as one of the pineal gland tumors.

Idiopathic Hypertrophic Spinal Pachymeningitis.

A 63-year-old man revealed a four-month history of muscle weakness of the lower limbs, hypoesthesia of the L5 and S1 area and ischuria. On MRI, the spinal cord was compressed by an encircled mass, which showed hypointensity on T1- and T2-weighted images with gadolinium enhancement at the Th11 to Th12 vertebra. Because of the rapid progression of myelopathy, posterior decompression was performed and idiopathic hypertrophic spinal pachymeningitis (HSP) was finally diagnosed. The patient's neurological signs markedly improved with postoperative corticosteroid treatment. Idiopathic HSP is a clinical emergency and early surgical intervention is essential to prevent irreversible damage to the nervous system.

Proximal tubule morphology in rats with renal congestion: a study involving the in vivo cryotechnique.

The present study aimed to examine the changes induced in proximal tubules by renal congestion using the in vivo cryotechnique (IVCT). Twelve male Wistar rats were divided into four equal groups: group 1 (the control); groups 2 and 3, which were subjected to 2 and 5 min of congestion, respectively; and group 4, which was subjected to 5 min of congestion followed by 10 min of recirculation. Under anesthesia, renal congestion was induced in the bilateral kidneys by ligating the inferior vena cava just above the branching renal veins. The left kidneys, which were subjected to the IVCT, were then compared with the right kidneys, which underwent a conventional fixation method. Among the left kidneys, the proximal tubules in group 1 consisted of cuboidal cells and had open lumina. In the congestive groups, the diameters of the proximal tubules were increased, and their lumina were obstructed by swollen cells and ischemia-associated cell debris. In group 4, the proximal tubules were still dilated, as seen in the congestive groups; however, the swollen cells had recovered their cuboidal form, and the cell debris had disappeared from the tubules' lumina. The present study demonstrated the in vivo morphology of proximal tubules in living rats subjected to congestion, which was unclear using conventional fixation methods.

A surgical case of mitral regurgitation due to active infective endocarditis with idiopathic thrombocytopenic purpura.

A 71-year-old woman with idiopathic thrombocytopenic purpura (ITP), who had been treated with steroid and cyclosporine, was admitted in an emergency with fever and dyspnea. The diagnosis was mitral regurgitation due ton infective endocarditis. Although she received treatments for infection and cardiac failure, the cardiac failure could not be controlled. After high-dose γ-globulin therapy, an emergency operation was performed during the active phase of infective endocarditis. Rapid platelet transfusion was administered after weaning from extracorporeal circulation. She recovered and was discharged without postoperative bleeding and re-infection.The treatment course of elective cardiac surgery complicated with ITP has been established, but the course of emergency surgery has not been established because of the small number of cases reported. Since few patients have undergone emergency surgery for active infective endocarditis, we had difficulty in deciding the time of surgery and treatment for increasing the number of platelets before surgery, it was considered that the case provided us with useful suggestion for the future treatment for urgent surgery complicated with ITP.

Increases in Nonspecific Immunoglobulin E and Eosinophils after H. pylori Eradication.

Helicobacter pylori infection has been reported to be inversely associated with allergic disorders. We by chance experienced a patient with atrophic gastritis who presented marked elevations of both nonspecific serum immunoglobulin E and eosinophil counts after H. pylori eradication. A 49-year-old Japanese man received eradication of H. pylori using lansoprazole 60 mg/day, amoxicillin 1,500 mg/day, and clarithromycin 400 mg/day for 7 days. Serum immunoglobulin E increased to more than four times its pretreatment level, 306 → 485 → 1,325 U/ml, and peripheral eosinophil counts increased to more than three times, 99 → 139 → 298 per µl. Deducing from the current case, H. pylori eradication might develop allergic disorders in some patients.

Long term changes in platelet counts after H. pylori eradication in non-ITP patients.

Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 109/l by 5-6 months, 1 year, 2 years and 3 years or more (from 24.2+/-5.6 to 23.1+/-5.0, 23.0+/-5.0, 22.1+/-4.5, 22.4+/-5.6, and 21.6+/-5.3 × 109/l: p = <0.0001, <0.0001, 0.0001, 0.0052, and <0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 109/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.

[Autopsy case of corticosteroid-induced invasive pulmonary aspergillosis with cavity-formation].

Invasive pulmonary aspergillosis (IPA) is an important and fatal complication in the patients with neutropenic or immunosuppressed condition. In spite of intensive treatment with anti-fungal drugs, the prognosis of the patients who have been suffered from IPA is extremely poor. This case was an 85-year-old Japanese man who was diagnosed as idiopathic thrombocytopenic purpura (ITP). He underwent high-dose corticosteroids and gamma-globulin therapy. During the hospitalization, he complained respiratory symptoms, and the abnormal shadow suggesting pulmonary infiltration and cavitation was pointed out on chest imaging. He was diagnosed as IPA because of high level of serum beta-D-glucan and positive for aspergillus antigen. Although he underwent intensive care with anti-fungal drug administration and artificial respiration, he died of respiratory distress on the 68th hospitalization. Postmortem examination disclosed severe bronchopneumonia, cavitation and pulmonary arterial thrombi in both lungs. Histological examination showed widely distributed epitheloid cell granulomata with central necrosis containing aspergillus hyphae, and vasodestructive growth of fungus with occasional organized thrombi.

Immunohistochemical analyses of parathyroid hormone-dependent downregulation of renal type II Na-Pi cotransporters by cryobiopsy.

The "in vivo cryotechnique" (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and "cryobiopsy" (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi-IIc at the BBM, being controlled by a different mechanism. In this method, the PTH-induced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level.

Extraskeletal myxoid chondrosarcoma: a study using a quick-freezing and deep-etching method.

A case of extraskeletal myxoid chondrosarcoma (ESMC), which developed in the right thigh of a middle-aged Japanese woman, was studied using immunohistochemistry, conventional electron microscopy, and the quick-freezing and deep-etching (QF-DE) method. In addition to typical light microscopic findings of ESMC, conventional electron microscopy indicated that the tumor cells had features of chondrocytes. Immunohistochemically, the tumor cells showed a positive immunoreaction for S100 protein. A diagnosis of ESMC was made. An interesting observation was the ultrastructural features of collagen fibrils in the myxoid matrix highlighted by the QF-DE method. These collagen fibrils consisted of relatively thin collagen (20-35 nm) with pleated surface structures. The surface striation at 65 nm was obscure. We consider that such a finding of collagen fibrils identified by the QF-DE method is one of the characteristics of the myxoid matrix of ESMC, and this is useful for the differential diagnosis of myxoid soft tissue tumors.

Duodenal stenosis caused by cystic dystrophy in heterotopic pancreas: report of a case.

We herein describe the first reported case of duodenal stenosis caused by cystic dystrophy in heterotopic pancreas (CDHP) in Asia. A 63-year-old man was admitted to the hospital presenting with nausea and vomiting of 2 days' duration. Laboratory examinations showed an elevation in both the serum amylase level (275 IU/l) and white blood cell count (13 600/microl). A 3-cm-diameter tumor close against the duodenum was pointed out from the results of computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP); the tumor contained a cystic and solid component. Endoscopic examinations and an upper gastrointestinal series showed stenosis of the second portion of the duodenum without any mucosal change. The tumor was considered to be located at the submucosal layer of the second duodenum. The biopsy specimen of the duodenum revealed no malignancy. We strongly doubted the presence of a malignant submucosal tumor in the duodenum based on the findings of diagnostic imaging, and a pancreaticoduodenectomy was thus performed. Histopathologically, the lesion was diagnosed to be CDHP. The postoperative course was uneventful. The patient was symptomatic but was free of any symptoms after surgery. He continues to be regularly followed up on an outpatient basis and has had no recurrence of symptoms. This case demonstrates the need to consider CDHP in the differential diagnosis as a rare cause of duodenal stenosis.

Chondrosarcoma with myxoid change: a study using a quick-freezing and deep-etching method.

A middle-aged Japanese woman visited the Orthopedics Department of Nihon University Nerima Hikarigaoka Hospital complaining of pain in the left hip joint that had started approximately 8 months earlier. Following several examinations, including imaging diagnoses, an incisional biopsy demonstrated a malignant acetabular bone tumor, which was removed and examined by a quick-freezing and deep-etching (QF-DE) method, conventional electron microscopy, and light microscopy. Histologically, the tumor was a chondrosarcoma with marked myxoid changes. An interesting extracellular matrix was observed by the QF-DE method. The myxoid area consisted of a fine meshwork of proteoglycans (PG) without obvious aggrecans, which resembled that of PG usually present in the pericellular matrix of normal cartilage. Thin collagen fibrils with pleated surface structures of regular periodicity were also seen, which were sparsely distributed in wide areas except for the pericellular matrix. These collagen fibrils were of the type that are mainly located in the pericellular side of the territorial matrix in normal cartilage. A myxoid matrix consisting of thin collagen fibrils on the background of pericellular type PG suggested that the myxoid matrix in the chondrosarcoma resembled those of the pericellular and pericellular sides of the territorial matrices in normal cartilage.

[Review of relationship between alcohol drinking and esophageal varices].

The adequate treatment for patients with thrombocytopenia, encephalopathy, ascites and esophagogastric varices due to portal hypertension are very important. This review explains the relations between heavy drinkers and symptoms of portal hypertension, especially with regard to the form of esophageal varices. Between heavy drinker and non-heavy drinker, there was no significant differences for form, color and red color sign of varices. In heavy drinker, the ratio of strong red color sign might be higher than non-heavy drinker. Value of portal pressure in heavy drinker might be higher. These results can bring sudden variceal bleeding in heavy drinkers.

[Hepatectomy and perisurgical management for heavy drinker with hepatocellular carcinoma].

Hepatic resection is the first choice of treatment for hepatocellular carcinoma (HCC), and has the best results among the therapeutic options. Preoperative evaluation of liver function in patients and perioperative management for patients, to prevent postoperative complications, are very important. Postoperative pulmonary complications, including pneumonia and atelectasis, were frequently shown in patients who had past history of heavy alcohol-intake. Postoperative pulmonary complications in heavy drinkers were associated with their habit of smoking. Temperance and non-smoking should be required, when hepatectomy will be performed for heavy drinker.

Application of a quick-freezing and deep-etching method to pathological diagnosis: a case of elastofibroma.

A case of elastofibroma in a middle-aged Japanese woman was examined by the quick-freezing and deep-etching (QF-DE) method, as well as by immunohistochemistry and conventional electron microscopy. The slowly growing tumor developed at the right scapular region and was composed of fibrous connective tissue with unique elastic materials called elastofibroma fibers. A normal elastic fiber consists of a central core and peripheral zone, in which the latter has small aggregates of 10 nm microfibrils. By the QF-DE method, globular structures consisting of numerous fibrils (5-20 nm in width) were observed between the collagen bundles. We could confirm that they were microfibril-rich peripheral zones of elastofibroma fibers by comparing the replica membrane and conventional electron microscopy. One of the characteristics of elastofibroma fibers is that they are assumed to contain numerous microfibrils. Immunohistochemically, spindle tumor cells showed positive immunoreaction for vimentin, whereas alpha-smooth muscle actin, desmin, S-100 protein and CD34 showed negative immunoreaction. By conventional electron microscopy, the tumor cell had thin cytoplasmic processes, pinocytotic vesicles and prominent rough endoplasmic reticulum. Abundant intracytoplasmic filaments were observed in some tumor cells. Thick lamina-like structures along with their inner nuclear membrane were often observed in the tumor cell nuclei. The whole image of the tumor cell was considered to be a periosteal-derived cell, which would produce numerous microfibrils in the peripheral zone of elastofibroma fibers. This study indicated that the QF-DE method could be applied to the pathological diagnosis and analysis of pathomechanism, even for surgical specimens obtained from a patient.

Survivin as a prognostic factor for osteosarcoma patients.

PURPOSE: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult -tissues. However, survivin expression has been detected in various human cancers and -correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expression in osteosarcoma tissues and clinicopathological parameters. METHODS: There were 22 osteosarcoma patients in our hospital with paraffin-embedded -tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. RESULTS: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p<0.01). Moreover, there was a statistically significant difference in survivin mRNA expression between -patients with and without metastasis (p<0.01). CONCLUSION: We concluded that high levels of survivin mRNA expression suggest poor prognosis for osteosarcoma patients.

Osteopontin expression in ulcerative colitis is distinctly different from that in Crohn's disease and diverticulitis.

BACKGROUND: The aim of the present work was to assess osteopontin (OPN) expression in the colon tissues of ulcerative colitis (UC), Crohn's disease (CD), and diverticulitis (Div) patients. METHODS: This study included three groups: the UC group, CD group, and Div group. Immunohistochemical staining was performed, using an immunoperoxidase method. RESULTS: Regarding OPN expression in intestinal epithelial cells, no difference was noted among the three groups. However, in the submucosa of the UC group, the ratio of two types of large cells (oval and spindle-shaped) expressing OPN was 61.2 +/- 14.4% (mean +/- SD), which was significantly higher than that in the CD group (14.9 +/- 7.0%; P < 0.05) and that in the Div group (11.2 +/- 6.1%; P < 0.05). In addition, in the UC group, the ratio of these cells in the subserosa (50.1 +/- 15.0%; mean +/- SD) was significantly higher than that in the CD group (16.9 +/- 6.2%; P < 0.05) and that in the Div group (12.6 +/- 5.7%; P < 0.05). In a serial section study, the oval-shaped cells were stained for anti-CD 68, while the spindle-shaped cells were stained for anti-vimentin. CONCLUSIONS: OPN in two types of large colon-infiltrating cells is possibly related to one of the pathogenic factors of UC.