Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL-like lymphoma cell line, OGU1.

Primary effusion lymphoma (PEL) is a rare B-cell lymphoma subtype that is characterized by lymphomatous effusion without the presence of masses, and it typically occurs in human immunodeficiency virus (HIV)-infected individuals. Lymphoma cells are universally positive for human herpesvirus 8 (HHV-8). Recently, a cavity-based effusion lymphoma that is similar to PEL without HHV-8 infection, called HHV-8-unrelated PEL-like lymphoma, has been reported in non-HIV-infected individuals. However, the pathophysiology of this lymphoma is largely undefined. We established a novel B-cell line OGU1 derived from a patient with HHV-8-unrelated PEL-like lymphoma. Notably, OGU1 cells produced vascular endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors retarded cell growth. Because VEGF acts as a vascular permeability and growth factor, it could play a role, at least in part, in the pathogenesis of this unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV-8-unrelated PEL-like lymphoma.

Epirubicin and cyclophosphamide followed by docetaxel as primary systemic chemotherapy in locally advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the activity and toxicity of epirubicin and cyclophosphamide (EC) followed by docetaxel as primary systemic chemotherapy (PST) in locally advanced breast cancer. PATIENTS AND METHODS: In this phase II trial, 46 patients with locally advanced breast cancer (T > 3 cm or N > 1) received epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles, followed by docetaxel (70 mg/m2) every 3 weeks for four cycles. Primary endpoints were pathological and objective response in the breast and axilla, and toxicities. RESULTS: The clinical response rate was 80.4% (95% confidence interval, 68.9-91.9%). Pathological response evaluation revealed 6 complete responses (CR: 13.0%). Patients with ER-negative tumors had a significantly higher rate of pathological CR than the others (33.3% vs. 3.2%; p = 0.0105). Febrile neutropenia occurred in 4 patients (8.7%). CONCLUSION: EC followed by docetaxel is an active and well-tolerated treatment as PST for locally advanced breast cancer.

Occult lung cancer incidentally found during surgery for esophageal and gastric cancer: a case report.

A 70-year-old male was admitted to our hospital because of advanced esophageal squamous cell carcinoma and early gastric adenocarcinoma. A esophagectomy and partial gastrectomy with three-field lymph node dissection (neck, mediastinum and abdomen) was performed. Both tumors had lymph node metastases. In addition, three mediastinal lymph nodes (two subcarinal lymph nodes and a middle thoracic paraesophageal lymph node) were involved with adenocarcinoma. To elucidate whether they were metastases from the gastric cancer, an immunohistochemical analysis was performed. The cancer cells in these lymph nodes were positive for cytokeratin (CK) 7 and negative for CK 20, thus suggesting metastasis from a nondigestive organ. Interestingly, they were positive for thyroid transcription factor 1 (TTF-1), indicating metastasis from a lung cancer. Since the preoperative computed tomographic scan showed no evidence of lung cancer, a diagnosis of metastases from an occult lung cancer was finally recorded. Ten months after surgery, the patient was alive without a recurrence or the appearance of a lung cancer.

Penile malignant melanoma in a hemodialysis patient.

A patient who was receiving hemodialysis treatment developed melanotic macules on the surface of the penis in 2002 and showed a tumor-like mass in the same region in July 2006. The patient presented with a pedunculated tumor of 3 cm in diameter on the right side of his penis. The tumor was resected for biopsy and was diagnosed as malignant melanoma. The melanoma was in stage IIIB with pT4 N1 M0. The patient received interferon-beta for a total of three courses. A computed tomography scan in the 10th postoperative month did not find any additional metastatic foci or recurrence of the tumor. In the present case, side effects caused by interferon were not observed. Therefore, particularly in dialysis patients, immune therapy might be favored over anticancer drug treatment.

Unruptured pseudoaneurysm of the cystic artery with acute calculous cholecystitis incidentally detected by computed tomography.

Pseudoaneurysm of the cystic artery is rare; to our knowledge, fewer than 30 cases have been reported worldwide. We report the first case of an unruptured pseudoaneurysm of the cystic artery with concurrent acute calculous cholecystitis. We incidentally detected the aneurysm by contrast-enhanced computed tomography (CT) in the edematous, thickened wall of the gallbladder neck in a 71-year-old man, whereas in most of the reported cases the disease presented as hemobilia. Because of the high risk of aneurysm rupture in this location, we avoided such interventions as percutaneous cholecystostomy and laparoscopic cholecystectomy. The aneurysm was localized pathologically in the undisrupted gallbladder wall, and elective open cholecystectomy with ligation of the cystic artery was performed successfully. Our case highlights the usefulness of CT for both diagnosis and patient management. Open cholecystectomy with ligation of the cystic artery is demonstrated as a reasonable first line of treatment for this unusual condition.

Collision carcinoma of the residual cervical esophagus 27 years after esophageal cancer surgery.

A case of collision carcinoma (squamous cell carcinoma and Barrett's adenocarcinoma) in the residual cervical esophagus of a 68-year-old woman at 27 years after subtotal esophagectomy for thoracic esophageal carcinoma is reported. The patient initially noticed cervical dysphagia in 2002, but did not seek treatment. In April 2004, the patient was referred to our department by a local physician with the diagnosis of carcinoma of the cervical esophagus. In September 2004, the patient underwent resection of the cervical esophagus and partial resection of the gastric tube combined with cervical lymph node dissection under a diagnosis of double cancer (i.e., metachronous cervical esophageal carcinoma and carcinoma of the gastric tube). Esophagogastric continuity was restored by transplantation of a free jejunal graft with vascular anastomosis. Pathological examination showed squamous cell carcinoma on the esophageal side of the esophagogastric anastomosis and columnar epithelium with a tongue-shaped extension across the anastomotic line that included Barrett's epithelium, as well as adenocarcinoma, on the gastric tube side. The squamous cell carcinoma and adenocarcinoma were contiguous, but there was a distinct border between them and no morphological transition. Immunohistochemical staining showed positivity for p53 in the squamous carcinoma cells, while it was negative in the adenocarcinoma cells. In contrast, HER2 (c-erb-2) was strongly positive in the adenocarcinoma cells, but negative in the squamous carcinoma. Based on these findings, it was concluded that two separate carcinomas had arisen at different sites and grown independently until they collided and merged to form a collision carcinoma.

Subdural hematoma associated with dural metastasis of gastric carcinoma: report of two cases.

We treated two cases of a subdural hematoma associated with dural metastasis of gastric cancer, from which both patients died. Case 1: A 60-year-old female patient was hospitalized with a diagnosis of type 4 gastric cancer of the antrum. The patient suddenly collapsed, and, subsequently, left hemiplegia and a depressed level of consciousness were noted. A head computed tomography (CT) scan revealed a subdural hematoma with midline shift. The patient was diagnosed with chronic subdural hematoma and underwent emergency burr hole irrigation. Case 2: A 73-year-old man was diagnosed with type 4 gastric cancer and a total gastrectomy plus splenectomy were performed together with dissection of the N1 and N2 lymph node groups (D2 dissection) in March 2006 (T3, N2, P0, H0, INFgamma, ly3, v0, por2). Postoperative adjuvant chemotherapy was performed using oral TS-1; following tests revealed no recurrence in the abdomen. In December 2006, gingival bleeding was noted with disseminated intravascular coagulation (DIC) and 10 days later, the patient was hospitalized with chief complaints of impaired consciousness and anorexia. CT scan revealed a right subdural hematoma with a midline shift. The patient was diagnosed with chronic subdural hematoma and underwent emergency burr hole irrigation and drainage. The dural biopsy of the two cases revealed adenocarcinoma noted in the dural blood vessel. Special staining revealed CEA-positive adenocarcinoma, and a diagnosis of the dural metastasis of gastric cancer was made. These patients' level of consciousness significantly improved postoperatively. However, DIC developed concurrently, and the patients died on the 13th and 14th postoperative day, respectively.

[2-year complete remission after withdrawal of methotrexate in a rectal methotrexate-associated diffuse large B-cell lymphoma].

A 71-year-old man, who had been receiving methotrexate (MTX) and prednisolone for the treatment of rheumatoid arthritis, was admitted to our hospital in August of 2004 with rectal hemorrhage. Histological examination of an ulcerative lesion of the rectum revealed diffuse large B-cell lymphoma (DLBCL). Chemotherapy with the CHOP regimen with dose reduction following cessation of MTX was initiated. However, the patient experienced septic shock secondary to febrile neutropenia and was then followed up without chemotherapy. The DLBCL rectal lesion regressed spontaneously thereafter and had resolved completely without treatment 2 years after the initial presentation, suggesting that the withdrawal of MTX led to regression of the DLBCL. The DLBCL in our patient is compatible with MTX-associated lymphoproliferative disorders. Immunoglobulin gene rearrangement and Epstein-Barr virus (EBV) infection found in tumor cells indicated that the EBV was involved in the monoclonal proliferation of B-cells in this patient whose immune function was suppressed by MTX therapy.

The combination of epirubicin plus docetaxel as neoadjuvant chemotherapy in locally-advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the activity and toxicity of epirubicin plus docetaxel as neoadjuvant chemotherapy for locally advanced breast cancer. PATIENTS AND METHODS: In this single-center, phase II trial, twenty-one patients with locally advanced breast cancer (T>3 cm or N>1) received epirubicin (70 mg/m2) and docetaxel (60 mg/m2) on Day 1 of each cycle for up to 6 cycles. RESULTS: Clinically complete responses (CR) were observed in 5 patients and partial responses were observed in 14 patients. The clinical response rate was 90.5% (95% confidence interval, 78.0-99.9). Eleven patients (52.4%) underwent breast conserving surgery. Pathological response evaluation revealed 2 CR (9.5%). Grade 4 neutropenia was recorded in 81.0% of the patients and febrile neutropenia occurred in 1 patient. CONCLUSION: The combination of epirubicin plus docetaxel was an active and well-tolerated treatment for locally-advanced breast cancer.

The efficacy of endoscopic mucosal resection in the diagnosis and treatment of group III gastric lesions.

BACKGROUND: The efficacy of endoscopic mucosal resection (EMR) in diagnosing and treating group III lesions was analyzed. PATIENTS AND METHODS: Forty-three patients, with group III lesions confirmed by histopathological examination of the biopsy specimens, were included. All of these patients underwent EMR. The final diagnosis after EMR broadly classified the lesions as adenocarcinoma or adenoma. The clinicopathological features and therapeutic results were analyzed. RESULTS: Adenocarcinoma was identified in 16 patients (37.2%) and adenoma in 27 patients (62.8%). There were no differences in gender, age, lesion site, macroscopic type, or maximum diameter between the two groups. A significant difference in the maximum diameter of elevated lesions (p<0.05) was found between adenocarcinomas and adenomas, with the elevated lesions of adenocarcinomas measuring more than 10 mm. No residual focus recurrence was found among the adenomas. CONCLUSION: We conclude that EMR is effective and useful in diagnosing and treating group III lesions.

Histopathological diagnosis and prognostic factors in adrenocortical carcinoma.

A great majority of adrenocortical tumors are benign, and many adrenocortical carcinomas (ACC) are obviously malignant at presentation. The histopathological diagnosis of ACC is occasionally difficult, particularly with stage I and stage II disease. The prognosis of ACC is generally poor. Surgery is the major treatment, with chemotherapy and radiotherapy being applicable to only restricted patients. The Weiss criteria are useful in diagnosing the common adult type of ACC. Histopathological prognostic factors of ACC have not been fully established because of the rarity of the disease. In this article, we first describe the current histopathological diagnostic and prognostic factors of ACC, highlighting the special types of ACC to which Weiss's criteria are not fully applicable. These special type tumors include pediatric adrenocortical tumors, oncocytomas, and aldosterone-producing tumors of pure zona glomerulosa type. Then we present three cases with unusual small adrenocortical tumors. One patient had an unequivocal ACC showing metastatic disease. One had a histologically defined ACC with no metastasis or macroscopic invasion. The third was a pediatric patient with a tumor showing a nodule-in-nodule pattern with insulin-like growth factor II expression.

[Adult choroid plexus papilloma of the posterior fossa: extraventricular location].

Choroid plexus papillomas (CPPs) are rare neuroectodermal neoplasms accounting for 0.4% of all intracranial neoplasms in adults. Most of them are located in the posterior fossa in adults. Although CPPs commonly arise from the 4th ventricle, they occasionally extend to extraventricular space. Furthermore some occur primarily in the extraventricular region. It is difficult to diagnose CPP preoperatively when the main portion of the tumor is not located in the 4th ventricle. We present a case of a 54-year-old male manifesting slurred speech, nystagmus and cerebellar ataxia. Magnetic resonance imaging demonstrated an intracerebellar solid tumor with multilocular cysts, extending towards both the right lateral medullary region and the foramen of Luschka. Computed tomography scans showed patchy calcification at the periphery of the solid component. Angiographically, via the right posterior inferior cerebellar artery revealed the tumor was faintly opacified. Preoperative diagnosis included meningiomas, low-grade astrocytomas, ependymomas or CPPs, but none of them had neuroradiologically decisive findings. Tumor was subtotally resected through a right suboccipital craniectomy. A calcified solid portion adhering to the lower cranial nerves was left unresected. The pathological finding was CPP. CPP should be considered among calcified and enhanced masses in the lateral medullary to cerebellopontine angle space in adults, even if the main portion of the tumor is not located in the 4th ventricle.

Unusual chromaffin cell differentiation of a neuroblastoma after chemotherapy and radiotherapy: report of an autopsy case with immunohistochemical evaluations.

Neuroblastomas are derived from neural crest cells that are capable of multilineage differentiation. Ganglionic neuronal differentiation of childhood neuroblastoma is seen with increasing age, leading to more differentiated tumors called ganglioneuroblastomas or ganglioneuromas. Despite the fact that neuroblastomas most often arise from the adrenal medulla, chromaffin-cell differentiation in neuroblastomas is not widely recognized. Tumor cells with a chromaffin-cell nature have only been detected using histochemical techniques in neuroblastoma cell lines or focal areas of certain in vivo tumors. We describe a neuroblastoma that exhibited an unusual differentiation toward chromaffin cells in a patient that had been treated with surgery, intensive chemotherapy, and radiotherapy. Although a biopsy specimen of the retroperitoneal primary tumor was extensively necrotic, possibly because of a previous chemotherapy regimen, surgically resected metastatic tumors of bilateral ovaries were viable and diagnosed as poorly differentiated neuroblastomas according to the International Neuroblastoma Pathology Classification system. However, metastatic tumors of bilateral lungs examined at the time of autopsy exhibited histologic features similar to those of a pheochromocytoma/paraganglioma, and immunohistochemical examinations demonstrated that these tumors were composed of extra-adrenal chromaffin cells. This case confirms that neuroblastomas in childhood can transform into pheochromocytoma/paraganglioma-like tumors under special conditions.

Uterine cervical diverticulum resembling a degenerated leiomyoma.

BACKGROUND: Uterine diverticulum is a very rare anomaly. Most previously reported cases were called "pregnancy-associated sacculations," and only 2 cases were considered true uterine diverticula. CASE: A 41-year-old woman presented with fever and lower abdominal pain. An extrauterine mass was detected, and a hysterectomy was performed. Pathological examination revealed a cystic uterine diverticulum lined with cervical glands and myometrium arising from the cervix. The final diagnosis was an infected uterine cervical diverticulum. CONCLUSION: Cervical diverticulum is a rare lesion that should be added to the differential diagnosis of a woman presenting with a pelvic mass.

Different expression of cyclooxygenase-2 in biliary epithelia of bile duct cancer with or without pancreaticobiliary maljunction.

BACKGROUND: Cyclooxygenase-2 (COX-2) has been reported to play an important role in the pathogenesis of a variety of cancers. Little is known about the relationship between bile duct cancer associated with pancreaticobiliary maljunction (PBM) and COX-2. MATERIALS AND METHODS: We compared the expression of COX-2 in bile duct epithelium in bile duct cancer with or without PBM. RESULTS: Immunohistochemical analysis showed that the rate of positive COX-2 expression was 42.9% for cancerous lesions and 7.1% for noncancerous lesions in cases of bile duct cancer without PBM. On the other hand, no positive expression of COX-2 was observed in cancerous lesion of bile duct cancer with PBM. Twenty % of the noncancerous bile duct mucosa with PBM was positive for COX-2. CONCLUSION: COX-2 is expressed in bile duct cancer while it is not expressed in bile duct cancer accompanied by PBM.

Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM).

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.

Expression of cyclooxygenase-2 in malignant and benign breast tumors.

Cyclooxygenase-2 (COX-2) is reported to play an important role in carcinogenesis. We examined COX-2 expression in patients with breast cancer and benign breast tumors. Immunohistochemical staining revealed a high level of COX-2 expression in malignant lesions of invasive ductal carcinoma (IDC) at a rate of 40% and a low level of expression in 15% of adjacent normal-appearing breast epithelia. Similarly, in ductal carcinoma in situ (DCIS), a high level of COX-2 expression was found in 80% of malignant lesions and a low level of expression in 50% of normal epithelia. Reverse transcriptional polymerase chain reaction (RT-PCR) performed in 7 of these cases disclosed that COX-2 expression was restricted to the malignant lesion. Further, all 10 cases of fibroadenoma and 10 cases of intraductal papilloma, both of which are benign tumors, had a high level of COX-2 expression. When overexpression of COX-2 was analyzed in relation to the clinicopathological features of the patients, no characteristic correlation was noted. Our results demonstrated that COX-2 is expressed in mammary tissue during tumorigenesis of the breast gland, suggesting that the cyclooxygenase isoenzyme may be a target for the prevention and treatment of breast cancer.

Expression of twist and wnt in human breast cancer.

Twist, a transcription factor of the basic helix-loop-helix class, has been suggested to have oncogenic properties. We reported Twist expression was regulated by Wnt/beta-catenin signaling and that both Wnt-1 and Twist could contribute to mammary tumorigenesis. The aim of this study was to demonstrate the expression of Twist, Wnt-1 and Wnt-2 in human breast cancer tissue. We examined the expression in patients with breast cancer by RT-PCR and immunohistochemistry. RT-PCR of twenty-three pairs of cancer and normal breast tissue revealed that Twist was up-regulated in 69.6% (16/23) of the cancer lesions and 21.7% (5/23) of the normal breast tissues. Wnt-2 was up-regulated in all of the cancer lesions and 13.0% (3/23) of the normal breast tissues, whereas Wnt-1 was expressed in both the cancer and normal breast tissues of the five cases examined. Immunohistochemical analyses revealed that Twist was positively expressed in 52.2% (12/23) of the cancer lesions and 34.8% (8/23) of the normal breast tissues. Twist and Wnt-2 are highly expressed in breast cancer tissue, suggesting that both molecules could play important roles in mammary carcinogenesis.

Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis.

BACKGROUND: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECCF) and has a function of angiogenesis in vitro and in several types of human carcinoma tissues. We have reported that expression of dThdPase was an independent prognostic factor in 116 gastric carcinomas by immunohistochemical analysis. MATERIALS AND METHODS: In the present study, we updated the analysis of recurrence in 116 patients with gastric carcinomas to find how dThdPase plays an important role in progression of gastric carcinoma. RESULTS: Expression of dThdPase was significantly involved in the progression and metastasis of gastric carcinoma. Further, the proportion of recurrence of the patients with dThdPase-positive gastric carcinoma (23 out of 50, 46.0%) was significantly higher than that with -negative gastric carcinoma (5 out of 66, 7.6%) (p < 0.05). Interestingly, the proportion of hematogenous metastasis (liver, lung) of the patients with dThdPase-positive gastric carcinoma (8 out of 8, 100%) was significantly higher than that with -negative gastric carcinoma (0 out of 8, 0%)) (p < 0.05). The proportion of peritoneal metastasis of the patients with dThdPase-positive gastric carcinoma (10/13, 76.9%) was also significantly higher than that with -negative gastric carcinoma (3 out of 13, 23.1%)) (p < 0.05). CONCLUSION: These findings suggested that dThdPase promotes hematogenous and peritoneal metastases in gastric carcinoma. Inhibition of dThdPase may suppress hematogenous and peritoneal metastases in gastric carcinoma and improve prognosis of patients with gastric carcinoma.