Usefulness of cell block cytology for preoperative grading and typing of intraductal papillary mucinous neoplasms.

BACKGROUND: Precise histological diagnosis is important for the successful management of intraductal papillary mucinous neoplasms (IPMNs). OBJECT: The object of this study was to determine whether cell block cytology is useful for preoperative cytomorphological grading and typing of IPMNs. METHODS: The subjects were 23 patients with IPMN from whom pancreatic juice was collected via a pancreatic catheter and who subsequently underwent pancreatic resection. RESULTS: In 20 of the 23 cases, the quantity of cells collected for cell block cytology was sufficient to enable typing and grading of the IPMN. The rates of consistency between the results of typing and grading by cell block cytology and histological examination of the surgical specimen were 95% and 80%, respectively. Typing of the 10 main-duct/mixed-duct-type IPMNs by cell block cytology yielded 5 gastric types, 3 intestinal types, 1 oncocytic type, and 1 pancreatobiliary type, and the typing was consistent with the surgical diagnosis in all 10 cases. The results of typing of the branch-duct-type IPMNs by cell block cytology were identical to the results of histological typing in the surgical specimens in every case but one. However, the specificity of cell block cytology for grading IPMNs was 55.6%. CONCLUSIONS: The cell block cytological findings were fairly consistent with the histopathological features of the surgical specimens, thereby indicating that cell block cytology may be useful for preoperative and typing of IPMNs, but only play a supplementary role in grading IPMNs.

IL-8 in cerebrospinal fluid from children with acute encephalopathy is higher than in that from children with febrile seizure.

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.

A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer.

BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer. METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles. RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19). CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer.

PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

Malignant glomus tumor: a case report and review of the literature.

This report concerns a malignant glomus tumor, a rare soft tissue tumor that was examined immunohistochemically and ultrastructurally. It occurred in a 44-year-old male patient who had suffered from dull pain and stiffness in the right thigh for 10 months. Radiographic examination revealed a well-defined osteolytic lesion in the diaphysis of the right femur. Hypervascularity of the tumor was observed angiographically. Computed tomographic and magnetic resonance examinations showed an intramuscular mass invading the marrow space of the femur. Wide resection was performed after open biopsy. Histologically, round to polygonal tumor cells revealed a uniform appearance of round to ovoid nuclei with single large nucleoli and slightly eosinophilic cytoplasm, forming solid sheets of cells interrupted by vessels of varying size. A few mitotic figures and vascular invasion were observed. Immunohistochemically, vimentin and alpha-smooth muscle actin were stained intensely, and muscle actin was positive for tumor cells of the perivascular area. Tumor cells were negative for desmin, factor VIII-related antigen, S-100 protein, neurofilament, cytokeratin, and epithelial membrane antigen. Ultrastructurally, tumor cells were characterized by many cytoplasmic processes, pinocytotic vesicles, plasmalemmal dense plaques, and scattered microfilaments in the cytoplasm. Few cell junctions and focal basement membrane-like structures were observed. No recurrence or metastasis was noted 57 months after operation. This case was considered to be a malignant glomus tumor, that is, a glomangiosarcoma arising de novo.

Stress thallium-201 myocardial scintigraphy in patients with complete occlusion of the left main coronary artery.

Complete occlusion (CO) of the left main coronary artery (LMCA) is a rare but often fatal condition. The diagnosis is frequently missed because the signs and symptoms are often obscure and diverse. We describe three patients with CO-LMCA who showed unusual myocardial scintigraphic findings. The patients had extensive right-to-left collateral channels and decreased uptake and washout rates at the basal anterior and anterolateral portions of the heart wall during stress thallium-201 scintigraphy. The basal anterior to anterolateral portion of the heart wall is the most distant from the collateral artery and should be the most ischemic area shown during exercise, resulting in this scintigraphic pattern. This scintigraphic finding may be useful for the noninvasive diagnosis of CO-LMCA.

Malignant transformation of Nakamura type IV gastric polyp with CA 19-9 production.

In a 68-year-old Japanese man, a gastric polyp 24mm in diameter with a stalk 15 mm in diameter was diagnosed as well differentiated adenocarcinoma and treated by endoscopic polypectomy. Histologically, most of the resected tissue was adenoma, and atypical cells were papillarily proliferating to form adenocarcinoma in adenoma, a Nakamura type IV gastric polyp. Infiltration of carcinoma was limited to within the mucosal layer. Immunohistochemical study with anti-CA19-9 antibody revealed positive staining in carcinoma cells. Serum CA19-9 level, which showed slight elevation, returned to the normal range 1 month after the polypectomy. The proliferating cell nuclear antigen (PCNA) labeling index and DNA ploidy pattern were analyzed in the resected tissue. The PCNA labeling index was 30% in carcinoma, 17% in adenoma, and 0.1% in the normal tissue. The DNA ploidy pattern was diploid in adenoma and aneuploid in adenocarcinoma. These findings suggest that gastric adenoma, as well as colonic adenoma, may have the potential for malignant transformation.

[A case of asymptomatic urachal cyst in autopsy--histopathological study of urachal cyst and review of the literature of 99 cases during a 10 year period in Japan].

Disorders of urachal remnants are common. While urachal cysts are usually asymptomatic, infection may mimic a variety of acute abdomen. Here we report a very rare case of urachal cyst that protruded in the urinary bladder cavity and among 99 accumulated cases, only 4 cases have been reported similar to this case characterized by intravesical development from 1990 to 1999. An uninfected urachal cyst was found in a 79-year-old male who had died of bile duct carcinoma. The cyst showed ovoid protrusion into urinary bladder cavity from the dome (3.5 x 2.0 x 2.0 cm in size). Histopathologically, the cyst wall was thin and consisted of fibrous connective tissue with muscular tissue and peripheral nerve, and lined by cuboidal epithelium but no inflammatory cells could be seen. Urachal cysts occur in both sexes are affected with equal frequency, and frequently occur in a younger population. In clinical symptoms the umbilical manifestations are predominant in patients younger than 30 years old, while the bladder manifestations are predominant in those older than 30.

[Correlation between the prostatic vessels and vertebral venous system of the dog].

We examined the correlation between the intrapelvic vessels, especially prostatic vessels, and the vertebral venous system in the male dog by radiography. Aorta abdominalis branches the right and left external iliac arteries at the 6th lumbar vertebra, and is divided into the right and left internal iliac arteries and arteria sacralis mediana at the 7th lumbar vertebra. Arteria urogenitalis arises from the internal iliac artery at the middle of articulatio iliosacralis, and is divided into arteria vesicalis caudalis cranially and arteria prostatica caudally. Arteria prostatica is divided in the prostatic capsule and distributed to the prostatic parenchyma in which arteries form the network. Vena prostatica is distributed to the prostatic parenchyma, forming the network and entered vena urogenitalis after joining vena vesicalis caudalis. Vena urogenitalis joins the internal iliac vein, and then the common iliac vein and vena cava posterior after joining the external iliac vein. The anastomosis between the intrapelvic vein and the vertebral venous system is formed by the vena intervertebralis. The vertebral venous system is anastomosis with the vena cava posterior, the common iliac vein, the internal iliac vein and vena pudenda interna.

[Usefulness of 18F-FDG PET for diagnosis of cardiac sarcoidosis].

Cardiac sarcoidosis, the main cause of death among patients with sarcoidosis, frequently becomes clinically apparent when the disease is far advanced. To evaluate the usefulness of the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting cardiac sarcoidosis, 18F-FDG PET was performed in 16 patients with sarcoidosis (13 female, 63 +/- 12 yrs), compared with scintigraphic findings of 99mTc-MIBI and 67Ga. Ten of 16 patients were considered to have cardiac complications on clinical grounds with tissue confirmation such as positive endomyocardial biopsy, severe ventricular arrhythmia, more than second degree atrioventricular block, and echocardiographically proven ventricular dysfunction. Among these patients with cardiac complications, abnormal myocardial uptake of FDG were observed in all (100%), which confirms significantly higher frequency compared to 67Ga scintigraphy (50%) (abnormality of 99mTc-MIBI SPECT were observed in 80%). Although abnormal FDG accumulations were observed in region with decreased uptake of 99mTc-MIBI in many cases, localization of regional abnormality of each tracer was frequently independent. This discrepancy may reflect inflammatory and degenerative process of myocardium in cardiac sarcoidosis. 18F-FDG PET is thought to be a useful noninvasive method in detecting cardiac involvement of sarcoidosis and may provide a useful information on the activity of the disease.

[Clinical study of male patients with primary biliary cirrhosis (PBC)].

We studied 10 male and 23 female patients with PBC to determine whether the clinical and histological features of this disease differed in male and female patients. There were no significant difference between men and women in age distribution and biochemical examinations. In female patients, autoimmune associated conditions such as sicca syndrome, Raynaud syndrome and arthritis were observed 22%, 13% and 36%, respectively. By contrast, no male patients developed those conditions. 80% of the male patients and 70% of the female patients belonged to asymptomatic PBC, and early histological stage, such as Scheuer's I and II were observed 90% of the male patients and 78% of the female patients, respectively. No male patients showed clinical or histological progression during follow-up period (median was 64 months). Nevertheless, not a few female patients showed progression including 3 cases who died during the follow-up period (median was 47 months). We concluded that male patients with PBC tend to have favorable prognosis comparing to female patients.

[Is it able to simplify the classifications of staging and curability for pancreatic cancer?].

This study was undertaken to simplify the classifications of the staging and curability of pancreatic cancer by the Japan Pancreas Society (JPS). A total of 461 patients who underwent surgical resection from 1968 to 1997 were analyzed in this study in accordance with our new classification of staging and curability. This staging mainly consists of three factors based on tumor extent:invasion to the retroperitoneum (rp); invasion to the extrapancreatic nerve plexus (pl); and lymph node metastasis (n). Each factor is simply judged as + (positive) or - (negative). Curability is also judged simply based on whether the presence of tumor is detected or not, and the degree of lymph node dissection is not included in curability. Our staging and curability assessment is strongly associated with survival rates after surgery. The 5-year survival rate of stage I patients is 50% and curability of A is > or = 50%. It is concluded that it is possible to simplify the classification of the staging and curability of pancreatic cancer by the JPS.

[Diagnosis of tumor extension of ductal adenocarcinoma of the pancreas based on histological findings].

This study was undertaken to evaluate the diagnosis for tumor extension of ductal adenocarcinoma of the head of the pancreas based on histological investigation. From 1968 to 1995, 316 patients underwent radical resection and histological tumor extension was quite as follows; the rate of invasion to the anterior pancreatic capsule was 49%, invasion to the retroperitoneal tissue was 77%, invasion to the portal vein system was 38%, invasion to the extrapancreatic nerve plexus was 53% and lymph node metastases were 79%. 249 patients was performed extended radical operation consisted of regional lymphadenectomy, retroperitoneal dissection and resection of portal vein system, however non-curative resection was 52% with tumor invasion to dissected pancreatic surface in 88% of non-curative patients. And there was no 5-year survivor with non-curative resection. The extended radical operation should be indicated for patients who will have curative resection. Then, we set up clinical stage (CS; CSI approximately IV) by three factors related to resectability mostly; invasion to retroperitoneal tissue (RP), invasion to portal vein system (PV), invasion to major arterial system (A). It was also set up preoperative diagnostic criteria for RP, PV and A factor by computed tomography (CT) or abdominal angiography. From 1989 to 1995, 101 patients who had extended radical operation were investigated prospectively. The rate of accuracy of preoperative diagnosis of tumor extension were about 80% in each factor. Curability was 94% in CS I, 67% in CS II, 43% in CS III, respectively, and 3-year survival rate was 53% in CS I, 35% in CS II, 2-year survival rate was 8% in CS III. However, in CS IV the rate of non-curative resection was 77% and there was no 2-year survivor. It was concluded that extended radical operation of ductal adenocarcinoma of the head of the pancreas should be indicated for patients in less than CS III diagnosed by CT or angiography preoperatively.