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Localized Listeria infection predominantly occurs in the prosthetic and hip joints. We herein report a case of Listeria monocytogenes ankle osteomyelitis in a 73-year-old man receiving adalimumab who was transferred to our hospital because of suspected rheumatoid arthritis (RA) flare. He reported a four-month history of left ankle swelling. A surgical biopsy revealed L. monocytogenes osteomyelitis in the left tibia and talus bones. The patient was successfully treated with antibiotics and surgical debridement. Thus, infection due to L. monocytogenes can present as ankle osteomyelitis in immunocompromised patients and may mimic an RA flare.

Cold snare defect protrusions (CSDPs) include muscularis mucosa (MM) and submucosa tissue. CSDPs are thought to result from fragmentation of the specimen during shallow excision. Our aim in this study was to clarify whether CSDPs are associated with polyp fragmentation.We retrospectively analyzed 1026 neoplastic colorectal polyps resected by cold snare polypectomy for which the presence or absence of CSDPs was assessed from the endoscopic image. All prepared specimens were reviewed and assessed for the presence or absence of polyp fragmentation, and the proportion of MM on the stump was measured. In addition, the risk factors for CSDP occurrence were evaluated.CSDPs occurred in 116 of the 1026 polyps (11.3%). Polyp fragmentation was significantly associated with the occurrence of CSDP on univariate analysis (odds ratio [OR], 3.74; P .001) and multivariate analysis (OR, 3.13; P .001). The proportion of MM50% was significantly lower in the CSDP group than in the non-CSDP group (51.5% vs 70.9%, P .001). CSDPs were significantly associated with a large polyp size (OR, 1.32; P = .007) and a large specimen size (OR, 1.24; P .001) on multivariate analysis.The occurrence of CSDP was associated with less MM on the stump and fragmentation of the specimen. Clinically, the presence of CSDP is a good indicator of polyp fragmentation.

Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and β-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.

A 72-year-old Japanese man with diabetes mellitus and hypertension presented with an acutely elevated serum creatinine level, from 1.02 to 4.13 mg/dL over 2 months as measured by the enzymatic method by pure-auto S CRE-N(®). Renal biopsy could not identify the etiology of the elevating sCr. However, an elevated total protein level (8.2 g/dL) and lowering of the BUN and sCr ratio from 14.5 to 2.7 were found, and bone marrow biopsy showed less than 10% lymphoplasmacytic infiltration, compatible with monoclonal gammopathy of undetermined significance. The diagnosis of a false serum creatinine elevation due to monoclonal gammopathy of undetermined significance was confirmed with the serum cystatin C level at 1.05 mg/dL and the creatinine level of 0.97 mg/dL using Shikarikid-S CRE(®) method. Although cases of monoclonal gammopathy of undetermined significance with a false serum creatinine elevation as an initial presentation are rare, this condition should be considered in patients with paraproteinemia; measuring the renal function using cystatin C is important in such patients.

Background and aims Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. Methods Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. Results Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. Conclusions Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.

Pancreatic metastasis from colorectal cancer is rare, and there have been only a few reports of its preoperative diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunohistochemical staining. We herein describe the case of a 77-year-old woman in whom a solitary mass in the pancreatic tail was detected 11 years after rectal cancer resection. The patient also had a history of pulmonary tumor resection. We performed EUS-FNA and a histopathological examination showed adenocarcinoma with CD20+, CD7-, and CDX2+ (similar to her rectal cancer). EUS-FNA enabled a histopathological examination, including immunohistochemical staining, which helped to confirm the diagnosis of pancreatic and pulmonary metastasis from rectal cancer.

Background and Objective:Hepatocellular ballooning is an important histological parameter in the diagnosis of nonalcoholic steatohepatitis (NASH), and it is considered to be a morphological pattern that indicates the severity and the progression to cirrhosis and liver-related deaths. There remains uncertainty about the pathological criteria for evaluating the spectrum of non-alcoholic fatty liver disease (NAFLD) in liver biopsies. We introduce persistence images as novel mathematical descriptors for the classification of ballooning degeneration in the pathological diagnosis. Methods:We implemented and tested a topological data analysis methodology combined with linear machine learning techniques and applied this to the classification of tissue images into NAFLD subtypes using Matteoni classification in liver biopsies. Results:Digital images of hematoxylin- and eosin-stained specimens with a pathologist’s visual assessment were obtained from 79 patients who were clinically diagnosed with NAFLD. We obtained accuracy rates of more than 90% for the classification between NASH and non-NASH NAFLD groups. The highest area under the curve from the receiver operating characteristic analysis was 0.946 for the classification of NASH and NAFL2 (type 2 of Matteoni classification), when both 0- and 1-dimensional persistence images were used. Conclusions:Our methodology using persistent homology provides quantitative measurements of the topological features in liver biopsies of NAFLD groups with considerable accuracy.

We herein report a rare case of a patient who developed a spindle cell tumor at the inferior mesenteric artery clipping site. A 58-year-old man underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer. As follow-up, CT scans were performed every 6 months after the primary surgery. At the 1-year CT, an nodular soft tissue density mass measuring 54 mm in diameter was found in the mesentery. Although we initially suspected locoregional recurrence of the colon cancer resected 1 year earlier, PET-CT showed that the tumor was unrelated to the previous cancer. During the subsequent laparotomy, the mass appeared to originate from the inferior mesenteric artery clipping site, and it adhered to the jejunum and the left ureter. We completely resected the tumor and part of the jejunum, which we separated from the abdominal aorta and left ureter. The tumor was histologically diagnosed of a spindle cell tumor. The patient has been free from recurrence since the surgery more than 4.5 years ago. Preoperative PET-CT was helpful in ruling out local recurrence of colon cancer, which might have made palliative care a better option than surgical resection.

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically.

Study Objective To evaluate a new magnetic resonance imaging (MRI) grading system for preoperative differentiation between benign and variant-type uterine leiomyomas including smooth muscle tumors of uncertain malignant potential (STUMPs). Design Retrospective analysis (Canadian Task Force classification III). Setting Teaching hospital (Teine Keijinkai Hospital). Patients Three-hundred thirteen patient medical records were retrospectively reviewed if treated for uterine myomas and diagnosed with variant type leiomyomas or STUMPs (n = 27) or benign, typical leiomyomas (n = 286) and treated between January 2012 and December 2014. Intervention Uterine myoma classifications using MRI findings according to a 5-grade system (grades I–V) based on 3 elements. Measurements and Main Results Uterine myoma MRI classifications were based on 3 elements: T2-weighted imaging (high or low), diffusion-weighted imaging (high or low), and apparent diffusion coefficient values (high or low; apparent diffusion coefficient Conclusion This novel MRI grading system for uterine myomas may be beneficial in differentiating benign leiomyomas from STUMPs or variant type leiomyomas and could be a future effective presurgical assessment tool.

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis.Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]).The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Background Primary cardiac sarcomas are extremely rare. Furthermore, the myxofibrosarcomas are one of the rarest forms of cardiac sarcomas, and its prognosis is known to be quite poor. Case presentation This is a case of a 23-year-old man who presented with acute severe congestive heart failure caused by almost complete obstruction of the mitral valve due to a large left atrial tumor. The patient required endotracheal intubation before his arrival to the hospital, and underwent an emergent surgical excision of the tumor. The tumor had a complex shape and originated from the orifice of the right upper pulmonary vein. Because the tumor seemed to extend over most of the surface of the left atrium, it seemed impossible to reconstruct the left atrium had we done a complete transmural resection. Instead, we carefully peeled the tumor leaving the outer layer of the left atrial wall. We applied cryoablation to the attached site, in order to prevent a recurrence of the tumor. The pathology report revealed that the tumor was a myxofibrosarcoma, and it seemed to originate from the heart. The patient received radiation therapy after the surgery and continues to be alive and well after 1-year, without apparent recurrence. Conclusions Cardiac myxofibrosarcoma can cause acute, severe left-sided heart failure. Non-transmural atrial wall resection with cryoablation might be effective for patients with cardiac myxofibrosarcomas with extensive atrial attachment.

症例は70歳男性で，68歳時，後に肝過形成結節と診断された肝腫瘤精査目的で当院へ紹介された．HBV感染指標からB型肝炎ウイルス（HBV）遺伝子型Aeの持続感染による非活動性carrierと診断し，既往・生活歴と画像診断から非アルコール性脂肪性肝疾患の合併を疑った．経過観察から2年後，肝S6に直径20 mm大の新たな腫瘤性病変を認めたため血管造影CT等で精査を行い肝細胞癌（臨床病期II，肝障害度A）と診断，肝後区域切除術を施行した．手術標本に対する病理学的検討により，肝腫瘍は中分化型肝細胞癌病期II，非癌部肝はB型慢性肝炎（F1A1）及びBrunt分類grade 1， stage 0の非アルコール性脂肪性肝炎（NASH）と診断した． 肝発癌を呈した遺伝子型Ae HBV起因B型慢性肝炎及び非線維化NASH併発症例の報告は稀であり，HBV感染及び非アルコール性感疾患の肝病態と肝細胞癌危険因子の関連を考察する上で興味深いと考える．

症例は15年前左腎細胞癌に対して左腎摘手術を受けた既往のある80歳女性．CT上左肺S8，S10に腫瘤性病変を認めた．S8の腫瘤は内部不均一な造影効果を伴い，S10の腫瘤は内部均一な高濃度領域を示した．FDG-PETを施行したところ，S8病変においてSUVmax=9.5であり，S10病変のSUVmax=1.5に比べより高い集積を認めた．S8病変を転移巣，S10病変を良性疾患と判断し，胸腔鏡下左肺部分切除にて両方の病変を摘出した．術後切除標本病理結果は，いずれの病変も腎細胞癌原発のClear cell carcinomaの遠隔転移であった．S10病変は微小血管がより多く存在しており，造影CTにおいて強い造影効果示していると考えられた．一方S8病変の細胞異型度は，Grade2からGrade3相当，MIB-1/Ki-67値は18.9％と高値を示しており，FDGの高い集積性を示していると考えた．本症例における画像・病理組織学的相違を，若干の文献的考察を加えて報告する．

The topical administration of rebamipide (Mucosta®), an antiulcer agent, clinically increases the mucin level of tear film. The aim of this study was to report the histological changes of goblet cells following the topical administration of rebamipide to a patient with nevus of the lacrimal caruncle. A 62-year-old male exhibited a pigmented nodule located in the lacrimal caruncle in the left eye. An excisional biopsy and subsequent surgical resection were conducted at the caruncle, prior to and three months after topical rebamipide administration. Histologically, a biopsy specimen revealed a pigmented nevus beneath the caruncle epithelium containing a few goblet cells [4 cells/high power field (HPF)]. A few nevus cells were present at the surgical margin. By contrast, the secondary resected specimen obtained three months after the initiation of topical rebamipide treatment revealed the epithelium and nevus, where numerous goblet cells were present (28 cells/HPF), and mucin-like substances were markedly secreted from the goblet cells. Topical rebamipide markedly increased the number of goblet cells and stimulated the secretion of mucin-like substances in the caruncular tissue of a human patient. These results suggest that topical rebamipide is useful in patients following surgery and/or biopsy to support tissue repair of the ocular surface.

Background CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown. Methods Eighty pancreatic cancer specimens were stained immunohistochemically, and the results were correlated with the patients' clinicopathologic features. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. Result Immunohistochemical analysis of tumor cells showed that 29 patients (36.3%) were positive for CD40, and 17 patients (21.3%) had very high CD154 expression. The survival of patients who had very high CD154 expression was significantly better than that of others (P = 0.0198). Univariate and multivariate analysis revealed that very high CD154 expression in cancer cells was not an independent, favorable prognostic factor (risk ratio, 0.493; P = 0.0224). On in vitro proliferation assay, the growth of PK-45P and KP-4 cells was blocked by CD40 and CD154 blocking antibodies. Moreover, on in vitro cytokine assay, Th-2 cytokines from PK-45P and SUIT-2 were blocked by CD40 or CD154 blocking antibody. Conclusion These results suggest that the CD40–CD154 interaction would correlate with cell proliferation and secretion of cytokines in PDAC cells, and CD154 overexpression could be a favorable prognostic factor in PDAC patients. J. Surg. Oncol. 2011; 103:230–238. © 2010 Wiley-Liss, Inc.

CD4/8 status has been previously reported to be a critical factor in the prognosis of oesophageal squamous cell carcinoma (OSCC). In the current study, we investigated the effect of regulatory T cells (Treg; Foxp3; lymphocytes) on the status of CD4+ and CD8+ T cells in 122 patients with OSCC. Immunohistochemical analysis of Treg was performed using an antibody against Foxp3. The survival rate for low Foxp3 patients was significantly lower than for high Foxp3 patients (P=0.0028 by log-rank test), but Foxp3 status did not significantly correlate with prognosis in CD4/8(+/+) patients or CD4/8(+/-) or (-/+) patients (P=0.5185 and 0.8479, respectively, by log-rank test). We also found that Foxp3 status correlated with CD4/8 status (P=0.0002 by χ2 test) and that the variance of CD8/CD4 ratio in patients with low Foxp3 was larger than in patients with high Foxp3 (P

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) using the slow pull technique (SP-FNA) has recently attracted attention as an effective tissue acquisition technique. However, efficacy of SP-FNA with a 22-gauge conventional needle remains unclear. The aim of this study is to evaluate the diagnostic ability of SP-FNA with a 22-gauge needle.Patients with a pancreatic solid lesion were prospectively enrolled in this study. SP-FNA was performed at two needle passes with a 22-gauge needle. One dedicated pathologist evaluated the obtained samples in terms of quantity (Grade 0: scant; Grade 1: inadequate; Grade 2: adequate), quality (Grade 0: poor; Grade 1: moderate; Grade 2: good), and blood contamination (Grade 0: significant; Grade 1: moderate; Grade 2: low), and provided a pathological diagnosis. Additional EUS-FNA was performed by applying suction (SA-FNA). The evaluation points were as follows: diagnostic accuracy of SP-FNA compared with that of SA-FNA, and the quantity, quality, and blood contamination level of SP-FNA-obtained samples.We enrolled 40 cases. The diagnostic accuracy of SP-FNA was 90% (36/40). There was no significant difference in the accuracy between SP-FNA and SA-FNA (90% vs. 90%, p = 1.000). The samples obtained using SP-FNA were assessed as Grade 2 for quantity in 29 cases (73%), quality in 31 (78%), and blood contamination in 25 (63%).Adequate, high-quality, and unsubstantially blood-contaminated samples could be obtained using SP-FNA. The diagnostic ability of SP-FNA was 90%, which appeared to be similar to that of SA-FNA.

An archive autopsy case of a 50-year-old man who died of Hodgkin's lymphoma had a 4-year, 4-month history of dementia. After radiochemotherapy, the lymphoma subsided except for involvement of the spleen, but the dementia remained. Neuropathological examination revealed that the pathology was confined to the hippocampus, both hippocampi showing sclerosis without inflammation. Neurons of sector cornu ammonis (CA) 1 were completely lost whereas moderate neuron loss was also observed in sectors CA3 and 4, and the dentate gyrus. Neurons of sector CA2 were relatively well preserved and the subiculum was intact. There was no evidence of global hypoxia, or of neurodegenerative disorders with pathological changes affecting the hippocampus. Although there was a long preneoplastic history, and no inflammatory changes were found at autopsy, the present case of hippocampal sclerosis could be included in the category of paraneoplastic limbic encephalitis associated with Hodgkin's lymphoma or the Ophelia syndrome.

The purpose of this study is to investigate the clinical and histopathologic significance of hypoxia-inducible-factor 1alpha (HIF-1alpha) expression in oesophageal squamous cell carcinoma. One hundred and thirty surgically resected specimens of OSCC were immunohistochemically assessed for HIF-1alpha expression with monoclonal antibody. High HIF-1alpha immunostaining was detected in 40 specimens. The percentage of high HIF-1alpha expression cases increased with tumour stage according to pTNM system. High HIF-1alpha expression correlated with pTNM stage, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion and positive surgical margin. The overall survival rate was worse in patients with high HIF-1alpha pattern than in patients with low-expression pattern. Univariate analyses identified high HIF-1alpha positivity, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion, and a positive surgical margin as risk factors. Multivariate analyses indicated that depth of tumour invasion, lymph node metastasis and positive surgical margin, but not HIF-1alpha, were independent prognostic factors. Survival in patients with a high HIF-1alpha expression was significantly worse than in those with low expression in patient treated with adjuvant therapy.

Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg-Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67-year-old man, with a 2-year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p- and c-ANCA were negative. Electrophysiological studies revealed a severe sensory-motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS.

In recent years a novel problem has arisen in organ transplantation medicine, namely GVHD. The nervous system has been involved mainly at the level of the CNS and this can lead to a serious outcome for the patient. In rare cases, peripheral nerves may be affected and show acute or chronic polyneuropathy. Here a case is reported of polyneuropathy associated with chronic GVHD. A 32-year-old man, suffering from chronic GVHD following an allogeneic bone marrow transplantation (BMT) for malignant lymphoma at the age of 25, developed a motor dominant polyneuropathy 5 years later. Electrophysiologic studies demonstrated the demyelinating type of polyneuropathy. Biopsy specimens from skin and skeletal muscle disclosed perivascular lymphocytic infiltrates expressing T-cell markers. The sural nerve showed a loss of myelinated nerve fibers with epineurial fibrosis and rare occurrence of T cells, but without obvious vasculitic changes. The present case suggested that polyneuropathy could develop in association with chronic GVHD in some patients with a long-standing disease course.

BACKGROUND Caveolin-1 plays a regulatory role in several signaling pathways. Recently caveolin-1 was identified as a metastasis-related gene in prostate carcinoma. However, the clinical impact of caveolin-1 expression in esophageal carcinoma remains unknown. METHODS One hundred thirty surgical specimens of esophageal squamous cell carcinoma were immunohistochemically assessed for caveolin-1 expression by polyclonal antibody. Caveolin-1 immunoreactivity was correlated with patients' clinicopathologic parameters and outcome. RESULTS Positive caveolin-1 immunostaining was detected in 58 patients (44.6%). Positive caveolin-1 immunostaining correlated positively with pathologic stage (P = 0.029), pN (P = 0.023), and pM (P = 0.018). The overall survival rate was worse in patients with caveolin-1-positive tumors than in patients with caveolin-1-negative tumors (P = 0.0215). Univariate analyses identified caveolin-1 positivity (P = 0.0238), pT (P = 0.0002), pN (P < 0.0001), pM (P = 0.0002), lymphatic invasion (P = 0.0021), and positive surgical margin (P < 0.0001) as negative prognostic predictors. Multivariate analyses indicated that pT (P = 0.0296), pN (P = 0.0003), and a positive surgical margin (P = 0.0452) were independent prognostic factors. CONCLUSIONS Over-expression of caveolin-1 is associated with lymph node metastasis and a worse prognosis after surgery in esophageal squamous cell carcinoma. Cancer 2002;94:929–33. © 2002 American Cancer Society. DOI 10.1002/cncr.10329

We describe a case of mucin-secreting biliary adenoma associated with obstructive jaundice due to mucin production. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, large filling defects caused by mucin were observed in the dilated bile duct. Granular and/or papillary mucosa was noted from the hilar to the common bile duct by using percutaneous transhepatic cholangioscopy. Biopsy specimens taken from the papillary mucosa revealed slightly papillary projection without any evidence of malignancy. This lesion was diagnosed as mucin-secreting superficial adenoma and pancreatoduodenectomy was performed according to the malignant behavior. Using a histologic examination of the specimen, pure adenoma was documented. Since the surgical margin was positive, radiation was added for the residual adenoma in the intrahepatic bile ducts. The patient has been well without any evidence of recurrence for 21 months since her operation. It is only recently that the term ‘intraductal papillary mucinous tumor (IPMT)’, which is accepted as a distinct disease entity of pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to clinicopathologically resemble an IPMT of the pancreas.

IgG4-related disease is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. We herein report a case of lacrimal sac diverticulitis with marked IgG4-positive plasma cell infiltration. An 89-year-old woman presenting with right lower eyelid mass. Imaging modalities demonstrated a cystic orbital mass located beneath the globe and adjacent to enlarged lacrimal sac. Serological tests showed high IgG4 and normal IgG levels, measuring 242 and 1603 mg/dl, respectively. The orbital mass was surgically excised. Histologically, the excised tissue demonstrated marked inflammation with fibrosis surrounded by mononuclear epithelial cells. A variety of IgG and IgG4-positive plasma cells infiltrated the stroma. This patient was diagnosed as an IgG4-related lacrimal sac diverticulitis, based on current diagnostic criteria of IgG4-related disease. It is likely that IgG4-related inflammation occurs in a lacrimal sac diverticulum, which should be considered a differential diagnosis in inferior orbital tumors.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216–132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

To define mechanisms that may influence collateral circulation and angiogenesis, we investigated vascular endothelial growth factor (VEGF) mRNA expression in human hearts. In non-ischemic human hearts, VEGF mRNA was not detected in vessels, but was found in cardiomyocytes. In hearts with myocardial infarction, the intensity of the VEGF signal was much higher in smooth muscle cells of arterioles adjacent to necrosis and in infiltrating macrophages than in myocytes around the site of the necrosis. This study suggests that levels of VEGF expression are high in smooth muscle cells and macrophages around infarcted areas after myocardial infarction and that VEGF may play a role in promoting collateral circulation and angiogenesis in human ischemic hearts.

To retrospectively determine whether enhancement patterns in the pancreatic and equilibrium phases of computed tomography (CT) for pancreatic neuroendocrine neoplasms are related to prognostic factors of surgical and endoscopic ultrasound-guided fine-needle aspiration biopsy specimens. Twenty-five pancreatic neuroendocrine neoplasms in 22 patients underwent preoperative dynamic CT. Tumors were classified into two groups by enhancement patterns on preoperative CT. A washout pattern was defined as peak enhancement in the pancreatic phase with washout of at least 60 Hounsfield units in the equilibrium phase. Group 1 comprised tumors showing a washout pattern in more than half of tumor and Group 2 comprised tumors showing a washout pattern in less than half of the tumor. The Ki-67 index and the presence of vascular invasion were evaluated in surgical specimens. The Ki-67 index from biopsy specimens was compared with that from surgical specimens. There were 12 surgical specimens in Group 1 and 13 in Group 2. Group 2 showed significant correlations with larger Ki-67 indices (p

We have built a database on the Internet managing z-axis video for cytology (Zavic), and report on a new style of case discussion supported by the Zavic database. Z-axis video for cytology is a movie file derived from the video recording of a microscopic field with changes in the focus. We used it for the case presentation of EUS-FNA of pancreatic lesions on the Internet prior to a training workshop. The attendees were asked to observe the Zavic and to make diagnoses of 20 cases before the workshop. Fourteen attendees also observed lesions under a microscope on that day, and the results were compared with those of Zavic observation. The evaluation of the Zavic database (DB) was surveyed by a questionnaire. The average number of accurate diagnoses by 46 Zavic observers was 10.8. These accuracies for those who observed both the Zavic and glass slides were 11.57 and 11.43, respectively, for the videos and slides. Compared with Zavic observation alone, the diagnoses with glass slide observation were shifted to a correct diagnosis in two cases, but were shifted to an incorrect diagnosis in two cases. Approximately 60% of Zavic observers replied in the questionnaire that the movies on Zavic DB started to play within 3-4 seconds after clicking the play button. We successfully carried out the new style of case discussion supported by the Zavic DB. It was evaluated favorably by many attendees, who were psychologically still dependent on the glass slide observation.

Background Plasmacytoma is a localized mass of metastatic plasma cells. These lesions rarely involve the petroclival region and carry a high risk of progression to MM and poor prognosis. Case Description We report a 65-year-old woman who presented with a large clival plasmacytoma causing right trigeminal and abducens nerve palsies and was diagnosed with MM after transsphenoidal biopsy. She underwent neoadjuvant chemoradiotherapy followed by radical resection of the residual tumor. Conclusion We presented our treatment strategy including neoadjuvant chemoradiotherapy followed by radical resection of the lesion. The patient has experienced complete remission, and succeeding MRI revealed no evidence of local recurrence.

Human T-lymphotropic virus type I (HTLV-I) is known to be the causative agent of the chronic myelopathy, HTLV-I--associated myelopathy (HAM), and on rare occasions infection is also associated with the development of polyneuropathy. Here the authors present an HTLV-I--positive family of whom four members developed a chronic demyelinating polyneuropathy without HAM. Four female patients in a family from Hokkaido in Japan developed distal dominant paresthesia and muscle weakness in the second and third decades of their life. Neurological findings at ages ranging from 50 to 65 years included mild painful sensorimotor disturbances with atrophy of the distal parts of the extremities but without pyramidal signs or hyperactive tendon reflexes. Magnetic resonance imaging (MRI) findings of brain and spinal cord were unremarkable. Serum HTLV-I antibody levels were elevated at 1:8192 to 1:32,768, whereas those in cerebrospinal fluid were low at 1:4 to 1:8. Electrophysiological studies revealed polyphasic compound muscle action potentials with denervation potentials on nerve conduction studies and neurogenic patterns by electromyography, which were consistent with signs of chronic motor dominant demyelinating polyneuropathy. Sural nerve biopsy showed decreased myelinated fibers, occurrence of globule formation, myelin ovoid and remyelinated fibers, and an infiltration of CD68-positive macrophages with occasional CD4-positive T cells in the nerve fascicles. The polyneuropathy was responsive to steroid therapy. Analyses of serological human leukocyte antigen (HLA) types indicated that none of the patients possessed a high-risk HLA type known to be associated with adult T-cell leukemia (ATL), whereas they did have high responsive alleles to HTLV-I env similar to that observed in HAM. Nucleotide sequence analysis of the HTLV-I tax region demonstrated the B subgroup in all patients. This study suggests that HTLV-I infection can result in the development of a familial form of polyneuropathy that is associated with distinct HLA class I alleles, which might possibly involve a distinct virus subtype.

We report here a case of primary hepatic carcinoid tumor (PHCT) recurring in the remnant liver 13 yr and 10 mo after first resection. A 70-yr-old man developed four hypervascular tumors in the liver in December 2003. He had undergone curative left-lobe hepatectomy for PHCT in February 1990. Histopathological examination of the tumor biopsy specimen showed that the tumor was composed of uniform round-to-oval cells with solid arrangement and the tumor cells stained positive for chromogranin A, synaptophysin, and neuron-specific enolase. We diagnosed this case as an intrahepatic metastasis of PHCT with a long latency period, based on the fact that no primary site of carcinoid tumor could be found despite intensive examination and the immunohistochemical findings of the resected tumors were essentially same as those of PHCT in 1990. Although PHCT is reported to have a more favorable prognosis than other hepatic cancer or metastatic carcinoid tumor in the liver, long-term observation is recommended.

Background and Objectives Tumor-infiltrating lymphocytes form an important aspect of the host defense against an expanding neoplasm. CD8+ T cells have been identified as a prognostic factor in several cancers. Here, we investigate that the influence of CD8+ T cells on extrahepatic bile duct carcinoma (EBDC) patient survival. Methods CD8+ T cell immunoreactivity in 58 surgically resected EBDC specimens was investigated. The relationship between CD8+ T cell immunoreactivity and clinical and histopathologic features was analyzed. Results Thirty-two tumors (55%) possessed intratumoral CD8+ T cells. The degree of intratumoral CD8+ T cell immunoreactivity demonstrated a significant relationship to lower numbers of lymph node metastasis, reduced venous invasion, decreased perineural invasion, and better pTNM staging. Intratumoral CD8+ T cells were also associated with increased patient survival. Multivariate analysis indicated that the presence of intratumoral CD8+ T cells was an independent prognostic factors. Conclusions The infiltration of a cancer cell nest by CD8+ T cells is a reliable marker predicting increased survival of patients with EBDC. J. Surg. Oncol. 2003;84:224–228. © 2003 Wiley-Liss, Inc.

Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X-ray findings, class IIIb sputum cytology, and positive anti-Hu antibody established the diagnosis of PNS associated with small-cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti-Hu antibody. Relapse of SCLC 4 months later with re-appearance of anti-Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert-Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti-Hu antibody, and that initial signs of brainstem-cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a recently identified human tumor-associated antigen expressed on various cancer cells. It is thought that tumor cells evade immune surveillance by expression of RCAS1, which induces apoptotic cell death in receptor-positive immune cells. The purpose of our study was to investigate the relation between RCAS1 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemical analysis for RCAS1 was performed on paraffin-embedded specimens of 80 patients (mean age, 62 years) who underwent surgical resection for pancreatic adenocarcinoma. Of the 80 specimens, 77 (96%) were positive for RCAS1. No significant correlation was found between RCAS1 expression and age, gender, depth of invasion, tumor diameter, surgical margin, lymphatic invasion, venous invasion or histopathological grading. Borderline correlations between RCAS1 expression were noted for lymph node metastasis and stage (p = 0.0608 and 0.0934, respectively). RCAS1 expression was very frequently observed and the survival of patients with high RCAS1 expression was significantly shorter than that of those with low expression (p = 0.0012). Multivariate analysis using the Cox regression model indicated that high RCAS1 expression was an independent prognostic factor (risk ratio, 3.090; p = 0.0090). These results suggested that RCAS1 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection. © 2002 Wiley-Liss, Inc.