Fetal cardiac capillary hemangioma resulting in tachyarrhythmia.

We present the case of a fetus with cardiac capillary hemangioma in the right atrial cavity. The tumor showed dramatic growth between the 28th and 32nd week of gestation and resulted in tachyarrhythmia. The patient was born at the 33 weeks of gestation weighing 2430 g via urgent cesarean section because the rapidly growing cardiac tumor caused incessant tachyarrhythmia, pericardial effusion, and fetal circulatory incompetence. Coronary angiography revealed that the right coronary artery drained into the tumor. Due to hemodynamic deterioration, the patient underwent subtotal resection of the tumor on the 2nd day after birth. Histopathological examination revealed an undifferentiated capillary hemangioma. The patient was discharged at the age of 86 days, as the tachyarrhythmia and hemodynamic incompetence had subsided; however, bradycardia and intermittent atrioventricular conduction disturbance gradually developed. Capillary hemangioma, a rare primary cardiac space-occupying tumor in children, can invade the conduction system.

Brain-derived neurotrophic factor/tropomyosin-related kinase B signaling pathway contributes to the aggressive behavior of lung squamous cell carcinoma.

The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC. Immunohistochemical high expression of TrkB was significantly correlated with vascular invasion (P=0.004), lymph node metastasis (P<0.001), and advanced stage (P=0.0015). The overall survival of the patients with TrkB-high expression was significantly shorter than those with TrkB-low expression (P=0.0110). TrkA/TrkC expressions were not predictors of poor prognosis. An in vitro assay demonstrated that the inhibition of brain-derived neurotrophic factor (BDNF) (a TrkB ligand) and TrkB by K252a (a Trk inhibitor) or siRNA (BDNF-siRNA, TrkB-siRNA) suppressed the invasion, migration, and proliferative activities of lung SCC cells. The administration of recombinant human BDNF (rhBDNF) enhanced the invasion, migration, and proliferation activities, which were abrogated by K252a. TrkB-siRNA transfection increased the protein expression of E-cadherin and decreased vimentin expressions in lung SCC cells. Matrix metalloproteinase-2 (MMP-2)-mediated gelatin degradations were decreased in lung SCC cells transfected with TrkB-siRNA. Thus, TrkB-high expression is an indicator of poor prognosis in lung SCC, probably due to invasion/proliferation activities promoted by the BDNF/TrkB signaling pathway, which could become a therapeutic target for lung SCC.

Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases.

Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.

A Rare Case of Pulmonary Tumor Thrombotic Microangiopathy Associated with Micropapillary Urothelial Carcinoma of the Urinary Bladder: An Autopsy Case.

A 70-year-old woman was hospitalized with dyspnea. A transthoracic echocardiogram indicated an elevated systolic pulmonary artery pressure, and the cytology specimens obtained using a pulmonary artery catheter confirmed adenocarcinoma metastasis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected high-signal-intensity lesions in the urinary bladder. The patient died of respiratory failure and a postmortem examination was performed. Tumor cells in the bladder were immunohistochemically positive for GATA3, indicating micropapillary urothelial carcinoma, which is a rare variant of urothelial carcinoma and considered an adenocarcinoma subtype. This case is the first autopsy case of pulmonary tumor thrombotic microangiopathy (PTTM) associated with micropapillary urothelial carcinoma of the urinary bladder.

Morphological, immunohistochemical, and genomic analyses of papillary renal neoplasm with reverse polarity.

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3 but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities, including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from PRCC.

Characteristic gene expression in stromal cells of gastric cancers among atomic-bomb survivors.

To elucidate the mechanism of radiation-induced cancers, molecular analysis of cancers in atomic-bomb survivors is important. In our study, we developed a custom oligonucleotide array of 208 genes. We analyzed gene expression profiles of gastric cancers (GCs) from atomic-bomb survivors and identified 9 genes with significantly lower expression in GCs from exposed patients than in GCs from nonexposed patients. Among these 9 genes, expression of versican and osteonectin was investigated in greater detail using immunohistochemistry in 116 GCs from 64 exposed and 52 nonexposed patients who developed GC after the bombing. In the Stage I/II GCs, the clinicopathologic, phenotypic and proliferative characteristics of GCs from exposed and nonexposed patients did not differ significantly; however, versican and osteonectin were expressed at much lower levels in the area of tumor-associated stroma of exposed patients than in nonexposed patients (p = 0.026 and p = 0.024, respectively). These results suggest that the characteristics of tumor-associated stromal cells differ between GCs from exposed and nonexposed patients.

Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients.

Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long-term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC-specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC-1) is a candidate gene for cancer-specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme-linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean +/- SE, 36.3 +/- 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 +/- 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19-9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC.

Transcriptome dissection of gastric cancer: identification of novel diagnostic and therapeutic targets from pathology specimens.

Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. 'Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-alpha upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer.

Laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons: A case report.

Persistent mesocolon is an embryological anomaly of the colon resulting from failure of the primitive dorsal mesocolon to fuse with the parietal peritoneum. We herein present a case of laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons and a right-bound inferior mesenteric artery. Preoperative 3-D CT demonstrated that the sigmoid colon had shifted to the right abdomen and was located under the ascending colon. Moreover, the inferior mesenteric artery and vein traveled toward the right abdomen accompanied by the mesentery of the descending colon. Adhesiolysis between the ascending and sigmoid colon was initially performed, and the sigmoid colon was placed in its normal position. The inferior mesenteric artery was then divided with lymph node dissection using a medial approach, and high anterior resection was completed. An understanding of the anatomical characteristics of persistent mesocolon is important to ensure safe laparoscopic surgery.

A case of non-alcoholic steatohepatitis complicated with severe acute pancreatitis induced by decreased lipoprotein lipase and hepatic triglyceride lipase activity levels in a young Japanese woman.

We report a case of non-alcoholic steatohepatitis complicated with acute pancreatitis induced by hypertriglyceridemia in a young Japanese woman. A precise examination of the lipid profile showed decreased lipoprotein lipase (LPL) and hepatic triglyceride lipase activity levels, while the LPL mass was at the minimum level of the normal range.

Stage IV gastric cancer successfully treated by multidisciplinary therapy including chemotherapy, immunotherapy, and surgery: a case report.

BACKGROUND: The prognosis of stage IV gastric cancer (GC) still remains unfavorable. Multidisciplinary approaches should therefore be considered to improve the survival of patients with stage IV GC. We report here a case of primary GC with potentially unresectable metastasis, successfully treated by a multidisciplinary approach including chemotherapy, immunotherapy, and surgery. CASE PRESENTATION: A 74-year-old man presented with multiple left neck masses. Abdominal computed tomography showed a thickened gastric wall and multiple lymphadenopathies including left supraclavicular lymph node. Gastroenterological endoscopy revealed tumor lesions in the gastric cardia. Tumor biopsy indicated a pathological diagnosis of poorly differentiated adenocarcinoma. Open left cervical lymph node biopsy showed histological features identical with the gastric tumor, indicating left clavicle lymph node metastasis of GC. After 2 years of chemo-immunotherapy with S-1/CDDP, paclitaxel, and cytokine-activated killer cells, lesions other than the stomach lesion had regressed to undetectable on imaging studies. The patient then underwent laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction followed by adjuvant chemo-immunotherapy with paclitaxel and S-1 for 1 year, and immunotherapy with tumor lysate-pulsed dendritic cell-activated killer cells for 5 years. The patient remained well after 5 years and 6 months of follow-up, with no signs of recurrence. CONCLUSION: Therapeutic combinations including immunotherapy may thus allow surgery to be performed in patients previously considered unsuitable for surgical intervention, potentially leading to a clinical cure, as in the current case.

Primary combined small cell carcinoma and squamous cell carcinoma of the oropharynx with special reference to EGFR status of small cell carcinoma component: Case report and review of the literature.

Combined small cell carcinoma (SCC) and squamous cell carcinoma (SqCC) of the oropharynx is extremely rare and shows an aggressive clinical course. There are only 5 reported cases of combined SCC and SqCC in the English language literature. Here, we report a 59-year-old male presenting with a right tonsillar mass. The mass was biopsied, and the histological findings showed a proliferation of small-sized tumor cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for neuroendocrine markers (synaptophysin, chromogranin A, and CD56). Our first diagnosis was tonsillar small cell carcinoma. We treated the patient with concurrent chemoradiotherapy together with cisplatin followed by surgery. The resected tonsillar specimen showed a residual tumor composed of SCC and SqCC, and lymph nodes showed metastatic tumor cells of the SCC component. Immunohistochemically, the SCC component was positive for all neuroendocrine markers and p16; on the other hand, the SqCC component was positive for p40, p63, p16, and EGFR. Fluorescence in situ hybridization revealed that neither component showed any EGFR gene copy number gain. The patient was treated with adjuvant chemotherapy consisting of irinotecan and cisplatin. Liver and bone metastases developed, resulting in the death of the patient. We discuss the present case and review similar cases. Most cases of combined SCC and SqCC occur regardless of p16 status, and a therapeutic strategy has yet to be determined. Further examination of this kind of combined tumor is necessary.

Syndrome of inappropriate antidiuretic hormone secretion in a case of olfactory neuroblastoma without anti-diuretic hormone immunoreactivity: A case report and review of the literature.

Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.

Drug-induced Liver Injury Associated with Mosapride Citrate: A Report of Two Cases.

We herein report two cases of drug-induced liver injury (DILI) due to mosapride. Case 1: A 78-year-old man was admitted with elevated transaminase levels. The cessation of mosapride led to the improvement of elevated liver enzyme levels. Case 2: A 54-year-old man was admitted with jaundice. Mosapride was discontinued immediately, and methylprednisolone was administered for acute liver failure. The patient's data showed improvement, and he was discharged on Day 32. In both cases, mosapride gave a positive response to a drug-induced lymphocyte stimulation test (DLST), and the patient's score based on the criteria for DILI was "highly probable".

A case of primary biliary cirrhosis in a patient with rheumatoid arthritis.

The true prevalence of PBC in RA is not well known. Herein, we report an unusual case of a patient with PBC and RA, and discuss the association between these two diseases. PBC should be ruled out in the differential diagnosis of patients with RA having abnormal liver function tests.

Dual gain of HER2 and EGFR gene copy numbers impacts the prognosis of carcinoma ex pleomorphic adenoma.

We investigated the potential roles of HER2 and EGFR and evaluated their prognostic significance in carcinoma ex pleomorphic adenoma (CXPA). We analyzed HER2 and EGFR overexpression status using immunohistochemistry (IHC) and gene copy number gain by chromogenic in situ hybridization (CISH) in 50 cases of CXPA (40 ductal-type and 10 myoepithelial-type CXPAs). Salivary duct carcinoma was the most common histologic subtype of malignant component (n = 21). Immunohistochemistry positivity and chromogenic in situ hybridization positivity were closely correlated in both HER2 and EGFR. HER2 CISH positivity (mostly gene amplification) and EGFR CISH positivity (mostly gene high polysomy) were present in 19 (40%) and 21 (44%) cases, respectively, and were each significantly correlated with poor outcome (P = .0009 and P = .0032, respectively). Dual gain of HER2 and EGFR gene copy numbers was present in 11 cases (23%) and was the most aggressive genotype. HER2 CISH positivity was more frequently present in ductal-type CXPAs (47%) than in myoepithelial-type CXPAs (10%), whereas the prevalence of EGFR CISH positivity was similar in both histologic subtypes (42% and 50%, respectively). Our results suggest that HER2 and EGFR gene copy number gains may play an important role in the progression of CXPA, in particular ductal-type CXPAs. HER2 CISH-positive/EGFR CISH-positive tumors may be the most aggressive subgroup in CXPA. The molecular subclassification of CXPA based on the HER2 and EGFR status may be helpful for prognostic prediction and decisions regarding the choice of therapeutic strategy.

Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma.

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.

Prognostic significance of urine N1, N12-diacetylspermine in patients with non-small cell lung cancer.

BACKGROUND: Recently N(1),N(12)-diacetylspermine, a diacetylated polyamine derivative, was recognized as a tumor marker in patients with several kinds of cancers. However, the significance of its levels in urine as a prognostic factor has not been elucidated. In the present study, we examined whether the urine N(1),N(12)-diacetylspermine levels can be used as a prognostic factor in patients with NSCLC. PATIENTS AND METHODS: Urine samples from 251 patients with NSCLC were collected prior to surgery and the urinary N(1),N(12)-diacetylspermine concentration was measured. Thereafter, all 251 patients underwent curative surgery and the analysis of prognosis was performed for over 10 years. Out of the 251 patients, 91 had recurrent disease. The significance of the urinary N(1),N(12)-diacetylspermine level as a prognostic factor among all 251 patients and among the 91 patients with recurrence was evaluated. RESULTS: Univariate analysis of all 251 patients showed that the level of urinary N(1),N(12)-diacetylspermine was a significant prognostic factor for disease-free survival and overall survival; however, multivariate analysis showed it had no significance. Conversely, the univariate and multivariate analyses of post-recurrent survival of the 91 patients with recurrence showed that urinary N(1),N(12)-diacetylspermine was an independent prognostic factor for post-recurrent survival. CONCLUSION: Patients with recurrence with positive urinary N(1),N(12)-diacetylspermine should undergo more intensive care and determination of urinary N(1),N(12)-diacetylspermine may contribute to improvement of prognosis of NSCLC.

Insulin-like growth factor II messenger RNA-binding protein 3 expression in gastrointestinal mesenchymal tumors.

Insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) is a recently identified biomarker demonstrated to be useful in diagnosis and prognostic prediction for several kinds of malignant tumors. However, the clinicopathologic and diagnostic value of IMP3 in mesenchymal tumors of the gastrointestinal tract is not clear. In this study, we examined the immunohistochemical expression of IMP3 in gastrointestinal stromal tumor (GIST) (n = 150), malignant melanoma (n = 17), malignant mesothelioma (n = 6), leiomyosarcoma (n = 6), inflammatory myofibroblastic tumor (IMT) (n = 12), desmoid fibromatosis (n = 8), leiomyoma (n = 20), and schwannoma (n = 20). Focal (≥10%) or diffuse (≥50%) expression with strong staining for IMP3 was judged as positive. We found that malignant melanomas (16/17 cases, 94.1%), malignant mesotheliomas (5/6 cases, 83.3%), IMTs (7/12 cases, 58.3%), and leiomyosarcomas (2/6 cases, 33.3%) were positive for IMP3. Among IMTs and leiomyosarcomas, IMP3-positive cases were histologically and/or clinically aggressive subtypes. Other kinds of tumors, including GIST, desmoid fibromatosis, leiomyoma and schwannoma, were essentially negative for IMP3. Our results suggest that IMP3 may be an ancillary tool in identifying aggressive abdominal mesenchymal tumors other than GIST.