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1.  Photoacoustic Tomography of Human Hepatic Malignancies Using Intraoperative Indocyanine Green Fluorescence Imaging 
PLoS ONE  2014;9(11):e112667.
Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions.
PMCID: PMC4224503  PMID: 25379674
2.  Comparison of Attenuation of Striated Muscle between Postmortem and Antemortem Computed Tomography: Results of a Longitudinal Study 
PLoS ONE  2014;9(11):e111457.
We evaluated the postmortem changes of striated muscle by comparing computed tomography (CT) images obtained postmortem and antemortem in the same patients.
Materials and Methods
We studied 33 consecutive patients who underwent antemortem CT, postmortem CT, and pathological autopsy in our tertiary care hospital between April 2009 and December 2010. Postmortem CT was performed within 20 h after death and was followed by pathological autopsy. Pathological autopsy confirmed the absence of muscular diseases such as amyotrophic lateral sclerosis, muscular dystrophy, myositis, and myasthenia, in all of the patients. The CT attenuation values of four cardiac muscle sites (anterior wall of the left ventricle, left ventricular free wall, posterior wall of the left ventricle, and the ventricular septum) and two skeletal muscle sites (the pectoralis major muscle and the erector spinae muscle) were compared between antemortem and postmortem CT using paired t test.
Striated muscle had significantly greater attenuation on postmortem CT than on antemortem CT (P<0.001) in all six tissue sites. No significant association was found between postmortem change in the CT attenuation of striated muscle and gender, age, or elapsed time since death.
This is the first longitudinal study to show hyperattenuation of striated muscle on postmortem CT images compared with antemortem CT images in the same patients.
PMCID: PMC4218726  PMID: 25365255
3.  Squamous cell carcinoma in a duplicated renal pelvis 
We report an extremely rare case of squamous cell carcinoma (SCC) of the renal pelvis associated with an incompletely duplicated renal pelvis and ureter. A 71-year-old woman presented with left lower back pain and gross hematuria. Urinary cytology showed atypical squamous cells. Computed tomography, magnetic resonance imaging and retrograde pyelography revealed left incompletely duplicated renal pelvis and ureter and a mass in the left upper renal pelvis. A clinical diagnosis of left renal pelvic cancer was made and the patient underwent total nephroureterectomy. Histological examination of the resected specimen revealed SCC with marked keratinization in the upper renal pelvis. The tumor had invaded the renal parenchyma and perinephric fat. There was no urothelial carcinoma component. The pathological stage was pT4 N0. There was no evidence of recurrence 6 months postoperatively. Because the prognosis of SCC of the upper urinary tract is poor, urologists and pathologists should be aware that SCC may develop in duplicated urinary systems.
PMCID: PMC4270515  PMID: 25550838
Cancer; congenital anomaly; duplex kidney; immunohistochemistry; pathological diagnosis; prognosis
4.  Congenital neuroblastoma with placental involvement 
We describe an extremely rare case of congenital neuroblastoma with placental involvement. A fetus with a left abdominal mass detected during ultrasonography at 23 weeks’ gestation developed hydrops fetalis by 26 weeks’ gestation. The mother developed hypertension at 26 5/7 weeks’ gestation. Based on a clinical diagnosis of pregnancy-induced hypertension, labor was induced at 26 6/7 weeks. However, intrauterine fetal death was diagnosed during delivery. Postmortern examination revealed a solid tumor at the site of the left adrenal gland. Histological examination of the tumor revealed dense proliferation of small round tumor cells with sparse cytoplasm and hyperchromatic nuclei. Some tumor-cell complexes contained abundant neurofibrils and Hormer-Wright rosettes were observed. A diagnosis of neuroblastoma of the left adrenal gland was made. The liver was markedly enlarged and was extensively replaced by neuroblastoma cells. In addition, small nests of tumor cells were detected in the blood vessels of various organs including the heart, lung, spleen, kidneys, stomach, small and large intestine, thyroid gland, testis, spinal cord, and bone marrow. Histological examination of the enlarged placenta revealed numerous neuroblastoma cells in the villous fetal capillary spaces. The present case was unusual in that the tumor cells were found not only in the chorionic villi, but also in the intervillous space of the maternal vascular system. However, there was no clinical evidence of maternal metastasis.
PMCID: PMC4270547  PMID: 25550872
Autopsy; fetal malignancy; immunohistochemistry; tumor thrombus; metastasis
5.  In-Stent Restenosis Exacerbated by Drug-Induced Severe Eosinophilia after Second-Generation Drug-Eluting Stent Implantation 
Patient: Male, 83
Final Diagnosis: In-stent restenosis
Symptoms: Chest discomfort
Medication: —
Clinical Procedure: Cardiac catheterization
Specialty: Cardiology
Unusual clinical course
In-stent restenosis (ISR) is still a recognized clinical problem in the era of drug-eluting stent (DES). Some previous studies have suggested that circulating eosinophils play an important role in both restenosis and thrombosis after DES implantation. However, the contribution of eosinophils to the pathogenesis of ISR has not yet been concisely clarified.
Case Report:
We present the case of an 83-year-old male Japanese patient with ISR exacerbated by drug-induced severe eosinophilia. He had previous histories of coronary stent implantations by DES and was referred to our hospital because of erythema with severe eosinophilia (maximum was 6500/μl [48% of total white blood cell count]). Around the same time, the patient developed ISR, for which a stent was deployed 2 years earlier. Arterial wall injury due to the increase in circulating eosinophils was verified in several findings, such as the increase of D-dimer and brain natriuretic peptide. In addition, the histology of the resected tissue from erythema demonstrated that the nuclei of endothelial cells were swollen where eosinophils and lymphocytes heavily infiltrated into the extravascular space, suggesting the presence of vascular injury. This injury due to the increase in circulating eosinophils may have a marked impact on the pathologic process of ISR in DES implantation.
Just a few anecdotal reports are available of ISR occurring in the setting of hypereosinophilia. The clarification of the mechanism in this patient provides a new effective therapeutic strategy against ISR in the setting of DES implantation.
PMCID: PMC4168766  PMID: 25227966
Coronary Restenosis; Drug-Eluting Stents; Eosinophilia
6.  Huge pyogenic cervical cyst with endometriosis, developing 13 years after myomectomy at the lower uterine segment: a case report 
BMC Women's Health  2014;14:104.
Surgical site infections are potential complications following open myomectomy. These infections usually develop immediately after the surgery, and are most often located in the myometrium. Pyogenic cervical cysts are rare and have not been previously reported to occur at the site of myomectomy.
Case presentation
A 41-year-old nulligravida Japanese woman was referred to our hospital with a large cervical cyst (>15 cm in diameter). She had undergone a myomectomy 13 years previously, and the surgical site had extended to the endocervical gland. Standard blood tests did not show any evidence of inflammation. The patient underwent a total abdominal hysterectomy, which revealed that the cyst contained multiple components, including Escherichia coli, old blood, and evidence of endometriosis. A pathological review did not show malignant cells within the cyst. The pyogenic cyst originated from the upper anterior cervix, which was one of the sites involved in the previous myomectomy.
We reported a huge pyogenic cervical cyst exhibiting signs of endometriosis, in the vicinity of the uterine scar from the open myomectomy. The previous surgery and endometriosis might have contributed to the formation of this rare pyogenic cyst.
PMCID: PMC4155767  PMID: 25186472
Cervical pyogenic cyst; Uterine fibroid; Myomectomy scar; Endometriosis
7.  Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination 
Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma.
PMCID: PMC4203267  PMID: 25337296
MALT lymphoma; autoimmune neutropenia; immune thrombocytopenia; corticosteroid; combination chemotherapy
8.  Xanthogranulomatous inflammation of the perimetrium with infiltration into the uterine myometrium in a postmenopausal woman: a case report 
BMC Women's Health  2014;14:82.
Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis.
Case presentation
A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation.
The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract.
PMCID: PMC4105790  PMID: 25027857
Xanthogranulomatous inflammation; Myometrial infiltration; Perimetritis
9.  A 90Y-labelled anti-ROBO1 monoclonal antibody exhibits antitumour activity against hepatocellular carcinoma xenografts during ROBO1-targeted radioimmunotherapy 
EJNMMI Research  2014;4:29.
ROBO1 is a membrane protein that functions in axon guidance. ROBO1 contributes to tumour metastasis and angiogenesis and may have potential as a target protein of immunotherapy because ROBO1 is specifically expressed at high levels in hepatocellular carcinoma. In this study, we examined biodistribution and radioimmunotherapy (RIT) using a radioisotope-labelled anti-ROBO1 monoclonal antibody (MAb) against hepatocellular carcinoma models.
ROBO1-positive HepG2 human hepatocellular carcinoma xenograft nude mice were used in this study. We conjugated anti-ROBO1 MAb with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and the conjugates were labelled with 111In and 90Y. To study biodistribution, the 111In-DOTA-anti-ROBO1 MAb was injected into HepG2 xenograft mice via the tail vein. To evaluate any antitumour effect, a RIT study was performed, and the 90Y-DOTA-anti-ROBO1 MAb was injected via the tail vein. Tumour volume, mouse weight, and blood cell count were periodically measured throughout the experiments. The tumours and organs of mice were collected, and a histopathological analysis was carried out.
The tumour uptake of 111In-anti-ROBO1 MAb in HepG2 xenograft mice was 15.0% ± 0.69% injected dose per gram at 48 h after injection.
Immunotherapy with cold-anti-ROBO1 MAb (70 μg) did not cause a significant antitumour effect. RIT with 6.7 MBq of 90Y-anti-ROBO1 MAb caused significant tumour growth suppression. Transient body weight loss and bone-marrow suppression were observed. Histopathological analyses of tumours revealed the fatal degeneration of tumour cells, significant reduction of the Ki-67 index, and an increase of the apoptosis index. Normal organs showed no significant injury, but a transient reduction of hematopoietic cells was observed in the spleen and in the sternal bone marrow.
These results suggest that RIT with 90Y-anti-ROBO1 MAb is a promising treatment for ROBO1-positive hepatocellular carcinoma.
PMCID: PMC4077627  PMID: 25006547
Hepatocellular carcinoma; Radioimmunotherapy; ROBO1; 90Y; Biodistribution
10.  A Case of Urinary Bladder Urothelial Carcinoma with Squamous, Glandular, and Plasmacytoid Differentiation 
Case Reports in Oncology  2014;7(2):362-368.
We report an extremely rare case of urothelial carcinoma (UC) of the urinary bladder with diverse histological differentiation into squamous, glandular, and plasmacytoid components. A 65-year-old man presented with gross hematuria. Cystoscopy showed a papillary-growing tumor with a wide-based stalk on the left wall of the urinary bladder. Based on the clinical diagnosis of locally invasive bladder cancer, the patient underwent radical cystectomy. Histological examination of the cystectomy specimen revealed UC with histological differentiation into multiple tumor subtypes. The tumor was composed of squamous cell carcinoma with marked keratinization, adenocarcinoma characterized by tall columnar cells with scattered goblet cells, conventional high-grade invasive UC and UC in situ, and plasmacytoid UC composed of discohesive cancer cells with eccentric nuclei and eosinophilic cytoplasm that diffusely infiltrated the bladder wall through the serosal surface. Immunohistochemically, the loss of membranous E-cadherin expression was noted only in the plasmacytoid UC component. The patient developed local recurrences 2 months postoperatively and died of the disease 6 months postoperatively. It is critical to correctly diagnose the histological variants of UC to predict a patient's prognosis and to determine the optimal treatment.
PMCID: PMC4067719  PMID: 24987357
Bladder cancer; E-cadherin; Histological variant; Immunohistochemistry; p63; Pathological diagnosis; Prognosis
11.  Pulmonary mucormycosis with embolism: two autopsied cases of acute myeloid leukemia 
Mucormycosis is an increasingly important cause of morbidity and mortality for patients with hematological malignancies. The diagnosis of mucormycosis usually requires mycological evidence through tissue biopsy or autopsy because the signs and symptoms are nonspecific and there are currently no biomarkers to identify the disease. We herein present two autopsied cases of acute myeloid leukemia with prolonged neutropenia who developed invasive mucormycosis accompanied by pulmonary artery embolism. Our cases were featured by unexplained fever and rapidly progressive dyspnea. Computed tomography scan detected nodular lesions or nonspecific consolidations in the lungs. Cultures, cytological study, and serum fungal markers consistently gave negative results. Autopsy revealed embolism of the pulmonary artery which consisted of fibrin clots by filamentous fungi. Genomic DNA was extracted from the paraffin-embedded clots and was applied to polymerase chain reaction amplification, leading to the diagnosis of infection by Rhizopus microsporus. We should carefully search for life-threatening pulmonary embolism when patients with hematological malignancies develop pulmonary mucormycosis.
PMCID: PMC4097268  PMID: 25031775
Rhizopus microsporus; mucormycosis; pulmonary embolism; acute myeloid leukemia; neutropenia
12.  Esophageal intramucosal hematoma after peripheral blood stem cell transplantation: case report and review of literature 
Esophageal complications occur after hematopoietic stem cell transplantation (HSCT). There are, however, only limited reports on the etiology or management of esophageal complications. Here, we report the occurrence of intramucosal hematoma presenting continuous esophageal hemorrhage in a 34 year-old man following the second peripheral blood stem cell transplantation for acute myeloid leukemia. His hematemesis started 2 months after HSCT and was repeated in supportive care. On day 156, he underwent total esophagectomy as a result of uncontrollable massive hematemesis. Histopathological testings of the resected esophagus confirmed intramucosal hematoma as a cause of hematemesis. This case highlights intramucosal hematoma as one of the important etiologies of esophageal complications following HSCT.
PMCID: PMC4069927  PMID: 24966988
Esophageal hemorrhage; intramucosal hematoma; esophagectomy; hematopoietic stem cell transplantation
13.  DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus 
Gastric cancer is a leading cause of cancer death worldwide, and significant effort has been focused on clarifying the pathology of gastric cancer. In particular, the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer; for example, aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis. The etiological viewpoint is also essential for the study of gastric cancers, and two distinct pathogens, Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), are known to participate in gastric carcinogenesis. Chronic inflammation of the gastric epithelium due to H. pylori infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric cancer. In addition, EBV infection is known to cause extensive methylation, and EBV-positive gastric cancers display a high methylation epigenotype, in which aberrant methylation extends to not only Polycomb repressive complex (PRC)-target genes in embryonic stem cells but also non-PRC-target genes. Here, we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with H. pylori and EBV.
PMCID: PMC3983447  PMID: 24744581
Gastric cancer; Epigenetics; DNA methylation; Epstein-Barr virus; Helicobacter pylori
14.  Alpha-synuclein immunohistochemistry of gastrointestinal and biliary surgical specimens for diagnosis of Lewy body disease 
In Lewy body disease, Lewy pathology (LP: the accumulation of α-synuclein in neuronal perikarya and processes as Lewy bodies and Lewy neurites and dots, respectively) is observed in the central and peripheral nervous systems. Previous autopsy or biopsy studies of individuals with Lewy body diseases (LBDs) indicated that LP could be observed in the peripheral nerves of the gastrointestinal (GI) systems. The aim of this study is to clarify whether examination of GI and biliary surgical specimens would be useful for diagnosing LBD. We analyzed eight patients diagnosed clinically with LBD and with medical histories of GI or biliary surgery at our hospital. LP was identified by using α-synuclein immunohistochemistry in GI and biliary surgical specimens obtained before, at or after the clinical onset of LBD. LP was frequently observed in Auerbach’s plexus, Meissner’s plexus and the subserosal nerve fascicles within the GI and biliary surgical specimens. LP was observed in the specimens obtained 7 years before the onset of LBD. Our approach does not require any invasive procedures for patients. The immunohistochemical analysis of anti- α-synuclein antibody to archival GI or biliary surgical specimens from patients with clinically suspected LBD may contribute to clinical diagnosis of LBD.
PMCID: PMC4014253  PMID: 24817969
α-synuclein; gastrointestinal and biliary tract; Lewy body disease; Lewy pathology; surgical specimen
15.  Concurrent Activation of Acetylation and Tri-Methylation of H3K27 in a Subset of Hepatocellular Carcinoma with Aggressive Behavior 
PLoS ONE  2014;9(3):e91330.
Analysis of acetylation and tri-methylation of the same residue of histone molecules might identify a subset of hepatocellular carcinoma (HCC) with aggressive behavior. In the present study, we examined acetylation and tri-methylation of lysine 27 on histone H3 (H3K27ac and H3K27me3, respectively) because these two modifications are known to exhibit opposite effects (enhancing and silencing) on gene expression. Neoplastic and non-neoplastic tissues from 198 HCC cases were immunostained with specific monoclonal antibodies against H3K27ac and H3K27me3. The stained tissues were evaluated by an image analyzing program to generate histological scores (H-scores, range 0–300), which were determined by multiplying the percentage of positive-stained cells with the classified immunohistochemical marker intensity (0–3). HCC tissues showed significantly higher H3K27ac (156.7±86.8) and H3K27me3 H-scores (151.8±78.1) compared with the background liver (40.3±33.0 and 64.7±45.6, respectively) (both P<0.001). The cases with H-scores of high-H3K27ac/high-H3K27me3 (n = 54) showed significant correlation with poor differentiation of morphology (P<0.01) and p53-positive staining (P<0.05), and poor prognosis (P<0.01). Confocal microscopy revealed segregated intranuclear localization of both modifications in the individual cancer cells: H3K27ac localization in central euchromatin regions and H3K27me3 in peripheral heterochromatin regions. Concurrent acetylation and methylation at H3K27 occurs in HCC cells in association with p53 abnormalities. These findings demonstrate that image analyzer-assisted H-scores of H3K27ac and H3K27me3 identified an aggressive subgroup of HCC, and could serve as a prognostic marker for HCC.
PMCID: PMC3948868  PMID: 24614346
16.  Long-term results of radical prostatectomy with immediate adjuvant androgen deprivation therapy for pT3N0 prostate cancer 
BMC Urology  2014;14:13.
Radical prostatectomy is used to treat patients with clinically localized prostate cancer, but there have been few reports of its use in locally advanced disease. We evaluated the long-term results of radical prostatectomy and immediate adjuvant androgen deprivation therapy in Japanese patients with pT3N0M0 prostate cancer.
We retrospectively reviewed 128 patients with pT3N0M0 prostate cancer who underwent radical prostatectomy at our institute from 2000 to 2006. All pT3N0 patients were treated with adjuvant androgen deprivation therapy shortly after radical prostatectomy. Immediate adjuvant androgen deprivation therapy was continued for at least 5 years. Twenty-three were excluded because of preoperative hormonal therapy, missing data, or others. Death from any cause, death from prostate cancer, clinical recurrence and hormone-refractory biochemical progression were analyzed by Kaplan-Meier graphs. Relative risks of progression were estimated using Cox proportional hazards models with 95% confidence intervals.
The 10-year hormone-refractory biochemical progression-free survival rate was 88.3% and the cancer-specific survival rate was 96.3% after a median follow-up period of 8.2 years (range 25.6-155.6 months). Higher clinical stage (p = 0.013), higher Gleason score at biopsy (p = 0.001), seminal vesicle invasion (p = 0.003) and microlymphatic invasion (p = 0.006) were predictive factors for hormone-refractory biochemical progression by univariate analyses. Multivariate analyses identified Gleason score at biopsy (p = 0.027) and seminal vesicle invasion (p = 0.030) as independent prognostic factors for hormone-refractory biochemical progression. None of the patients with clinical T1 cancers (n = 20), negative surgical margin (n = 12), or negative perineural invasion (n = 11) experienced hormone-refractory biochemical progression.
Radical prostatectomy with immediate adjuvant androgen deprivation therapy may be a valid treatment option for patients with pT3N0M0 prostate cancer.
PMCID: PMC3912934  PMID: 24476554
Adjuvant androgen deprivation therapy; Pathological T3; Prognosis; Prognostic factor; Prostate cancer; Radical prostatectomy
17.  Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach. A case report focusing on its characteristic growth pattern 
Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor of the stomach. We report herein a case with CT findings, which illustrate the characteristic growth pattern of PAMT. A 27-year-old female patient visited our hospital because of epigastric pain and anemia. The CT scan showed a heterogeneous tumor in the gastric antrum, which was drastically enhanced with contrast medium, and consisted of a number of highly stained small nodules around the tumor rim. The resected tumor, 4.6 cm in size, was c-kit negative and SMA-positive by immunohistochemistry, and composed of bland spindle cells which were separated by abundant myxomatous stroma. The tumor showed plexiform growth in the entire stomach wall, with multiple nodules protruding outward within the serosa. The CT findings in this case reflect the characteristic PAMT growth pattern, and are distinct enough to differentiate it from gastrointestinal stromal tumor (GIST).
PMCID: PMC3925914  PMID: 24551290
PAMT; GIST; diagnosis; CT
18.  HER2 protein overexpression and gene amplification in upper urinary tract urothelial carcinoma-an analysis of 171 patients 
Upper urinary tract urothelial carcinomas (UUTUC) are infrequent and show an occurrence of about 5-10% of all urothelial carcinomas. In this study, we investigated the HER2 status of 171 UUTUC patients with nephroureterectomy. The number of patients is the largest of any HER2 study. All 171 cases were analyzed for both HER2 overexpression using immunohistochemistry and HER2 gene amplification using dual-color in situ hybridization. The scoring system proposed by the ASCO/CAP and ToGA trials was used. Out of 171 patients, 140 patients had a HER2 score-0 or score-1 (81.9%), 17 a score-2 (9.9%), and 14 a score-3 (8.2%) with immunohistochemistry. HER2 gene amplification was observed in 31 out of 171 cases (18.1%). A good correlation was observed between protein overexpression and gene amplification (p<0.0001). Twenty-three UUTUC (13.5%) were determined as HER2-positive cancer according to ASCO/CAP and ToGA criteria. HER2 positivity in patients over 70 years old was higher than that of patients under 70 years old (p=0.0132). HER2 expression correlated to a high histological grade (p=0.0003) and the coexistence of a high grade carcinoma in situ (p=0.0089). No HER2-positive cancer was observed in patients with renal pelvic UUTUC (0 out of 76, p<0.0001). HER2-positive UUTUC showed a shorter recurrence time in the residual urinary bladder after nephroureterectomy with Kaplan-Meier analysis (p=0.0284) and multivariate analysis (p=0.0034). The results suggest that HER2 positivity in UUTUC is an independent predictive marker for early recurrence of urothelial carcinoma in the residual urinary bladder after surgery.
PMCID: PMC3925916  PMID: 24551292
HER2; immunohistochemistry; DISH; urothelial carcinoma; upper urinary tract; tissue microarray
19.  Poorly differentiated mesenteric carcinoma of unknown primary site detected by abscess formation: case report 
Carcinoma of unknown primary site (CUP) is said to account for approximately 3 to 5% of all carcinomas. However, an isolated lesion in the abdominal cavity is rare, and there are no reports describing associated abscess formation.
Case presentation
A 76-year-old woman had consulted a previous physician complaining of fever and right lower quadrant abdominal pain. Enhanced computed tomography (CT) showed an abscess formation around the cecum. She was treated conservatively with antibiotics, but the symptoms relapsed and she consulted our hospital. Enhanced CT showed a persistent abscess, a tumorous lesion in the mesentery and right hydronephrosis. Because malignancy could not be ruled out, surgical treatment was selected. At laparotomy, encapsulated abscesses were found on the mesenteric side and outside of the ileocecal region. When we raised the ileocecal region, a tumor was found to be fixed to the right ureter, and there was leakage of white, solid tumor content. This tumor content was submitted to intraoperative frozen section diagnosis which revealed a carcinoma. Ileocecal resection with D3 lymph node dissection and retroperitoneal tumor resection was thus performed. There were no abnormal findings in the uterus and adnexa, nor any evidence of peritoneal dissemination. We regarded this case as an incomplete resection and chemotherapy with paclitaxel and carboplatin was administered. The patient has remained alive and disease-free for almost one year since the primary operation.
We described a case with mesenteric CUP discovered during surgery for an intra-abdominal abscess. It is necessary to pay attention to treatment-resistant intraperitoneal abscesses as they may accompany a tumor.
PMCID: PMC3896797  PMID: 24397776
Carcinoma of unknown primary site; Abscess; Mesentery
20.  Transformation of follicular lymphoma in the retroperitoneal muscles demonstrated by CT-guided needle biopsy of FDG-avid lesions; case series 
We herein report two cases of relapsed follicular lymphoma (FL) with transformation in the retroperitoneal muscles. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) showed high uptakes in the retroperitoneal muscles. We considered excisional biopsy at first, since it is definitely the most reliable means to obtain histological diagnosis. However, excisional biopsy of the retroperitoneal muscles is challenging for anatomical reasons. Moreover, our patients were kept under poor performance status. Thus, CT-guided percutaneous needle biopsy of FDG-avid retroperitoneal muscles was performed. Histopathological examination of the biopsied specimens demonstrated proliferation of transformed large B cells in both cases. Sheets of large B cells were also recorded in one case. CT-guided needle biopsy is less prioritized than excisional biopsy because of limited information on tissue architecture and increasingly complicated WHO classification. Our series indicate that image-guided needle biopsy of FDG-avid lesions is sufficient for the diagnosis of transformation. Higher priority should be given to this method in the setting of transformed aggressive lymphoma.
PMCID: PMC3885497  PMID: 24427363
Follicular lymphoma; transformation; retroperitoneum; FDG-avid; CT-guided needle biopsy
21.  High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy 
Heat shock protein 105 (Hsp105) is one of the cancer/testis antigens, which is overexpressed in a variety of cancer cells, including urinary bladder cancer, and has been investigated as a target molecule for immunotherapy due to its immunogenicity. In this study, we assessed the expression of Hsp105 in primary bladder cancer samples from 84 patients treated with radical cystectomy, using immunohistochemical analysis, and investigated its correlation with clinicopathological characteristics and cancer-specific survival. The immunoreactivity of Hsp105 expression was evaluated as a score of 0–3, according to the intensity of the signal. The Hsp105 expression was high (score 2 or 3) in 31 cases and low (score 0 or 1) in 53 cases; however, it was not significantly correlated with age, nuclear grade, pathological tumor stage and previous intravesical Bacillus Calmette-Guérin immunotherapy. Female gender, lymphovascular invasion and lymph node metastasis were associated with low Hsp105 scores, although the differences were not statistically significant (P=0.071, 0.061 and 0.175, respectively). However, a high Hsp105 score was significantly associated with a favorable prognosis (P=0.017) and was identified as an independent prognostic factor by multivariate analysis (P=0.032; hazard ratio, 2.34). These findings suggested that the expression of Hsp105 may be a novel indicator of a favorable prognosis in bladder cancer.
PMCID: PMC3915630  PMID: 24649305
heat shock protein 105; immunohistochemistry; bladder cancer; prognostic marker
22.  Correction: Heart Wall Is Thicker on Postmortem Computed Tomography Than on Ante Mortem Computed Tomography: The First Longitudinal Study 
PLoS ONE  2013;8(10):10.1371/annotation/7bae7ece-15f5-43ca-9f98-592df8543978.
PMCID: PMC3805600
23.  Simple preoperative computed tomography image analysis shows good predictive performance for pathological vessel invasion in clinical stage IA non-small cell lung cancer† 
Pathological vessel invasion is a well-known prognostic factor in early-stage, non-small cell lung cancer and preoperative predicting vessel invasion may enable us to improve prognosis by additional interventions. We evaluated the importance of vessel invasion as a prognostic factor in clinical stage IA non-small cell lung cancer and predictive performance of simple diameter-based computed tomography image analysis for vessel invasion.
The study design was retrospective, and we reviewed 398 patients who underwent surgical resection of clinical stage IA non-small cell lung cancer from 1999 to 2009. The prognostic factors for recurrence-free survival were examined by univariate and multivariate analyses. Additionally, we analyzed preoperative high-resolution computed tomography images of patients with adenocarcinoma. The greatest diameter of the tumor in the lung window and the length of the consolidation part of L in the mediastinal window were measured. Then the ratio (mediastinal window/lung window) was calculated, and the correlation between the ratio (mediastinal window/lung window) and vessel invasion was analyzed by receiver operating characteristic analysis.
Sixty-eight recurrences occurred. Multivariate analysis revealed that vessel invasion, high preoperative serum carcinoembryonic antigen, and history of other malignancy were independent prognostic factors; their hazard ratios were 2.98, 2.45, and 1.98, respectively. The receiver operating characteristic analysis showed that the area under the curve was 0.75. When we set the cut-off value of the ratio (mediastinal window/lung window) at 0.67, the sensitivity and specificity were 75% and 72%, respectively.
Vessel invasion had the greatest impact on recurrence in clinical stage IA non-small cell lung cancer. Our simple computed tomography image analysis showed good predictive performance for vessel invasion.
PMCID: PMC3445341  PMID: 22740516
Lung cancer; Diagnosis; Pathology; Computed tomography
24.  Successful Treatment of Mediastinal Unicentric Castleman's Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization 
Case Reports in Medicine  2013;2013:354507.
Unicentric Castleman's disease is a rare, benign lymphoproliferative disorder that is curable with surgical resection. However, significant bleeding often occurs during surgery because of tumor hypervascularity. We herein present a case of hyaline-vascular-type mediastinal unicentric Castleman's disease, successfully resected using video-assisted thoracoscopic surgery with preoperative embolization. In the present case, tumor hypervascularity and feeding vessels were revealed by computed tomography (CT), which led us to perform preoperative angiography and embolization to the tumor feeding arteries to reduce intraoperative bleeding. Castleman's disease should be considered in the differential diagnosis of hypervascular mediastinal tumors. Tumor vascularity should be assessed prior to surgery, and preoperative embolization should be considered.
PMCID: PMC3806124  PMID: 24198836
25.  Heart Wall Is Thicker on Postmortem Computed Tomography Than on Ante Mortem Computed Tomography: The First Longitudinal Study 
PLoS ONE  2013;8(9):e76026.
To evaluate the postmortem changes of the heart wall on postmortem (PM) computed tomography (CT) in comparison with those on ante mortem CT (AMCT), and in comparison with the pathological findings, obtained in the same patients.
Materials and Methods
We studied 57 consecutive patients who had undergone AMCT, PMCT, and pathological autopsy in our tertiary care hospital between April 2009 and December 2010. PMCT was performed within 20 hours after death, followed by pathological autopsy. The cardiac chambers were measured at five sites on both AMCT and PMCT by two board-certified radiologists who were not provided with clinical information. The differences in heart wall thickness between AMCT with and without contrast medium, between AMCT and PMCT, and between PMCT and pathological anatomy were evaluated statistically. Confounding factors of postmortem change such as gender, presence of arteriosclerosis, the organ related to cause of death, age, and elapsed time since death were examined statistically.
No significant differences were observed on AMCT in comparison of contrasted and non-contrasted images. The heart wall was significantly thicker on PMCT than on AMCT (p < 0.0001) at all five measurement sites. The heart wall was significantly thicker on PMCT than on pathology specimens when measured in accordance with pathological standard mensuration. However, no significant difference was observed between PMCT measurements and those of pathology specimens at any site when the papillary muscles and epicardial fat were included. No significant association was found between postmortem change in heart wall thickness and gender, presence of arteriosclerosis, the organ related to cause of death, age, or elapsed time since death.
This is the first longitudinal study to confirm greater thickness of heart wall on postmortem images compared with ante mortem images, in the same patients. Furthermore, the postmortem changes on CT were supported by the pathological findings.
PMCID: PMC3785517  PMID: 24086680

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