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Undifferentiated neoplasms of unknown primary sites are rare. It is difficult to identify their characteristics and determine the appropriate chemotherapy regimen to be used. Undifferentiated/rhabdoid carcinoma is reportedly associated with loss of SWI/SNF chromatin remodeling complexes, such as observed in SMARCA4-deficient tumors. However, little is known about SMARCA2/BRM-deficient tumors. A 48-year-old man presented with low back pain. Computed tomography (CT) revealed intraperitoneal lymph nodes and multiple bone metastases that invaded the thoracic and lumbar spinal canals. The primary tumor was not identified despite the standard diagnostic methods being used. CT-guided needle biopsy of right iliac bone metastasis showed that the tumor had an undifferentiated/rhabdoid morphology. Immunostaining revealed that the tumor was SMARCA2/BRM-deficient despite both SMARCB1/INI1 and SMARCA4/BRG being retained. We found no genomic alterations during domestic next-generation sequencing panel profiling, which can identify 114 genes. Thus, he was diagnosed with SMARCA2/BRM-deficient undifferentiated/rhabdoid carcinoma of an unknown primary site with multiple bone metastases and intraperitoneal lymph node metastasis. We administered radiotherapy to the thoracic and lumbar spine to improve cord compression, and carboplatin (CBDCA) and paclitaxel regimen was chosen as first-line chemotherapy, but this was discontinued due to an anaphylactic shock. We then selected the CBDCA and gemcitabine regimens; however, the patient did not continuously receive the regimen due to myelosuppression. Radiation therapy effectively relieves pain and cord compression. To our knowledge, this is the first reported case of SMARCA2/BRM-deficient undifferentiated/rhabdoid carcinoma of an unknown primary site. Further studies are needed to improve SWI/SNF-deficient tumor identification methods.

The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined.To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC.The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis.Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR.pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.

Background Microcystic pancreatic serous cystadenoma (SCA) can be managed without surgery in selected patients. However, the preoperative diagnosis of microcystic SCA remains challenging, and it is potentially misdiagnosed as other pancreatic cystic neoplasms or solid tumors, especially small microcystic SCA. Case presentation This was a case of a 27-year-old male patient with microcystic SCA causing difficulty in the differential diagnosis from pancreatic neuroendocrine neoplasm (pNEN). A pancreatic tail mass was incidentally discovered on abdominal ultrasound (US). A contrast-enhanced computed tomography (CT) scan revealed a solid tumor measuring 13 mm with early enhancement in the arterial phase at the pancreatic tail. The tumor showed low intensity on T1-weighted magnetic resonance image, high intensity on T2-weighted image, and a slightly hyperechoic mass on endoscopic US (EUS). EUS-fine needle aspiration (EUS-FNA) did not lead to a definitive diagnosis. The tumor was clinically diagnosed as a pNEN, and a laparoscopic spleen-preserving distal pancreatectomy using the Warshaw technique was performed. The final histopathological diagnosis was microcystic SCA. Conclusion Small microcystic SCA is difficult to distinguish from a hypervascular pancreatic tumor such as pNEN on imaging studies, and it is necessary to focus on the tumor echogenicity of EUS to differentiate microcystic SCA from pNEN preoperatively.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal cancer. A 75-year-old Japanese female presented with gross hematuria. Computed tomography revealed two tumors in the left kidney, which were resected. Immunohistochemistry indicated negative staining for the B subunit of SDH (SDHB) in the resected specimen, leading to a final diagnosis of SDHB-deficient RCC. Genetic testing for SDHB showed a RCC germline variant in exon 6 (NM_003000.3:c.642 G > C) that was previously reported but associated with a novel phenotype (i.e., RCC). Twenty-six years prior, her daughter, who was 25 years old at the time, had undergone radical nephrectomy for a pathologic diagnosis of renal oncocytoma of the right kidney; SDHB immunostaining of her daughter’s tumor was also negative retrospectively. We confirmed that her daughter carried the germline variant in SDHB exon 6, similar to the patient. The patient had no evidence of disease progression at 15 months after surgery.

Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer., This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin.

Respiratory epithelial adenomatoid hamartoma (REAH) is classified as a histopathologic diagnosis and often identified in sinus surgery for chronic rhinosinusitis (CRS). The purpose of this study was to clarify the frequency and predictors of REAH and prognosis of CRS with REAH in CRS cases.In the first study, we histologically reviewed sinonasal polyps and mucosal tissue specimens obtained from patients who underwent endoscopic sinus surgery (ESS) for CRS to reveal how many REAH were involved in ESS cases. We compared REAH and non-REAH groups in terms of preoperative symptoms and endoscopic, imaging and blood examination findings to elucidate predictors of REAH genesis. In the second study, we compared the data 3 months after surgery such as endoscopic and imaging findings and olfactory test to evaluate prognosis of CRS with REAH.The prevalence of REAH was 15.5% of all 304 cases in the first and second studies combined. Higher polyp score in the middle meatus was an independent predictor of the presence of REAH (Higher polyp score in the middle meatus is an independent predictor of REAH. Olfactory function is difficult to recover after surgery in REAH patients because it is associated with recurrent polyps in the olfactory cleft.

Background Hepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis. Case presentation A 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half. Conclusion Hepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.

A woman in her seventies complained of chest pain during exertion and visited a local hospital. Computed tomographic scan showed right renal cell carcinoma with inferior vena cava (IVC) tumor thrombus extending above the diaphragm, and the patient was referred to our hospital. She was diagnosed with right renal cell carcinoma cT3cN0M0, with level IV IVC thrombus by Mayo classification. Axitinib and pembrolizumab were administered against intractable advanced renal cell carcinoma. The dose of axitinib was reduced due to grade 3 liver dysfunction. Right nephrectomy together with IVC thrombectomy was performed because the primary lesion had shrunk, and the level of IVC thrombus had become level III. The pathological results were clear cell carcinoma, pT3c, G3, Fuhrman grade3, INFA, v1, and ly0. Axitinib and pembrolizumab might be a presurgical option against an intractable renal cell carcinoma with an IVC thrombus.

Primary cilia, antenna-like structures of the plasma membrane, detect various extracellular cues and transduce signals into the cell to regulate a wide range of functions. Lipid rafts, plasma membrane microdomains enriched in cholesterol, sphingolipids and specific proteins, are also signalling hubs involved in a myriad of physiological functions. Although impairment of primary cilia and lipid rafts is associated with various diseases, the relationship between primary cilia and lipid rafts is poorly understood. Here, we review a newly discovered interaction between primary cilia and lipid raft dynamics that occurs during Akt signalling in adipogenesis. We also discuss the relationship between primary cilia and lipid raft-mediated Akt signalling in cancer biology. This review provides a novel perspective on primary cilia in the regulation of lipid raft dynamics.

Benign fibrous histiocytoma (BFH) is a rare benign primary bone lesion that occurs most frequently in the nonmetaphysis region of the long bones and the pelvic bones. The talus is a rare location for a BFH, which has not been reported previously in the literature. We report the case of a 19-year-old male patient with BFH of the talus, who was treated with curettage, followed by filling of the bone defect with calcium phosphate cement. The patient was free of pain and without local recurrence 5 years after the surgery. We describe the detailed radiographic findings of this rare lesion and discuss the differential diagnosis of such talar lesions.

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

To compare the efficacy and safety of continuous saline bladder irrigation (CSBI) to a single immediate instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) in patients with high grade primary non-muscle invasive bladder cancer (HG-NMIBC).This study retrospectively reviewed 250 patients with primary NMIBC who were enrolled in a prospective randomized trial of CSBI vs single instillation of mitomycin C (SI-MMC) immediately after TURBT. Results of histopathology were re-reviewed using the World Health Organization (WHO) 2004/2016 classification. Of the 250 patients, 151 HG-NMIBC patients (78 in the CSBI group and 73 in the SI-MMC group) were evaluated according to the recurrence and progression rates and adverse events.The median follow-up period was 58 months. No significant differences for patients' characteristics were observed between the CSBI group and SI-MMC group. There was no statistically significant difference between the CSBI group and SI-MMC. group regarding recurrence rates of 12, 18 and 24 months (25.6% vs 23.3%、28.5% vs 23.3% and 32.1% vs 28.8%, respectively), time to first recurrence (12.6 ± 11 vs 12.4 ± 10.1 months) and progression rate (8.9% vs 8.2%). The incidence of adverse events was significantly lower in the C.S.B.I. group.The difference of recurrence and progression rate between CSBI and SI-MMC after TURBT was not statistically significant in HG-NMIBC, although a larger study is necessary to prove its equivalence or non-inferiority. CSBI after TURBT is easy to administer with a reduced risk of adverse events, and may be a treatment choice for patients with HG-NMIBC.

SOX11 is a transcription factor in the SOX family of genes that regulate multiple cellular events by influencing the expression of key genes in developmental, physiological, and tumorigenic cells. To elucidate the role of SOX11 in prostate cancer cells, PC-3 prostate cancer cells were cloned (S6 and S9 cells) to highly express SOX11. We demonstrated that both S6 and S9 lose vimentin expression, acquiring epithelial marker proteins, which indicates the Epithelial state phenotype. S6 and S9 cells have cancer-promoting characteristics that include higher migratory properties compared with control cells. The mechanisms that are responsible for the enhanced migration are cofilin activity and keratin 18 expression. TCGA (The Cancer Genome Atlas) dataset analysis revealed that metastatic prostate cancer tumors tend to have more SOX11 gene amplification compared with primary tumors. These results suggest the tumor promotive role and epithelial protein induction of SOX11 in prostate cancer cell.

The phosphidation of a ZnO/GaN solid solution photocatalyst enhanced significantly its activity for water splitting. The photocatalysts were heated with phosphorus in a vacuum-sealed quartz tube. Activation due to phosphidation was restricted within the narrow temperature range of 823–873 K, and varying amounts of P were added to the solid solution. In addition to X-ray diffraction peaks due to ZnO/GaN, active phosphide ZnO/GaN provided a single GaP peak with diffraction angles higher than normal GaP by 2θ = 0.20–0.44°, indicative of the formation of a GaP1−xNx alloy system. The diffraction peaks were simulated using first principles Ab inito calculations on molecular models of Ga32P32−yNy. The comparison with experimental shifts showed that the highest activity was induced in an x range of 0.034–0.074 of GaP1−xNx.

We report a case of calcified amorphous tumor (CAT) of the heart in a 60-year-old Japanese man on hemodialysis. Because the masses in the mitral annulus developed during two-year echocardiographic follow-up, he underwent surgical resection with mitral valve replacement. Histological examination showed that the tumor contained multiple calcified nodules, which confirmed the diagnosis of CAT. This case report reinforces the need to deeply and periodically investigate for cardiac involvement of CAT in all patients on hemodialysis.

Background We report a rare case of 10-month-old female who underwent living donor liver transplantation (LDLT) for syndromic biliary atresia with preduodenal portal vein (PV) and its severe stricture owing to the previous Kasai portoenterostomy. Because we successfully performed “left at right liver transplantation (LAR-LT) and graft rerotation” in this case, we are present tips and pitfalls for this operation. Methods Preoperative computed tomography scan showed that her preduodenal PV was stenotic from the confluence of the superior mesenteric vein and splenic vein to hepatic hilum, which made us consider the necessity of ≥3 cm interposition vein graft to complete a safe PV anastomosis. To reduce a gap between donor and recipient's PV, we decided to put a left lateral section graft at the right subphrenic space called left-at-right liver transplantation. Thus, LDLT was performed with an identical lateral sectional graft from her father. After total hepatectomy, we implanted a graft in her right subphrenic space, and anastomosed the donor left hepatic vein to her inferior vena cava. Then, we anastomosed an interposition graft harvested from her left internal carotid vein to her PV. Results Even after reflowing PV flow, because the duodenum compressed the interposition vein graft, PV flows were totally insufficient. Therefore, we flipped a liver graft 180° from right to left upper abdominal cavity, which could reduce the gap between PVs and acceptable PV flow was obtained. Conclusions In the present case, LAR-LT could reduce the distance of PVs. In addition, our rerotation method could be useful to alleviate tension on the PV anastomosis caused by preduodenal PV.

For multiple low-grade malignant tumors located in the pancreatic head and tail, middle-segment-preserving pancreatectomy (MSPP) is sometimes indicated. However, MSPP has rarely been performed laparoscopically. Here we report the first case of laparoscopic MSPP for multiple pancreatic neuroendocrine tumors diagnosed preoperatively under an endoscopic ultrasound-guided fine-needle aspiration biopsy. A 70-year-old man had multiple small tumors located in the pancreatic head, body and tail. Endoscopic ultrasound-guided fine-needle aspiration biopsy with immunohistochemical staining made a definitive diagnosis of a pancreatic neuroendocrine tumor (G1). To preserve the 5-cm pancreas body, we successfully performed laparoscopic MSPP: subtotal stomach-preserving pancreaticoduodenectomy followed by distal pancreatosplenectomy. Pathological examination revealed negative surgical margin after resection. Postoperative course was uneventful, and at 14 months after the operation, the patient remains tumor-free. The patient has discontinued insulin supplement therapy but does use an oral hypoglycemic agent. Laparoscopy-assisted MSPP, with reconstruction through a 6-cm transverse incision, can be safely performed for selected cases of borderline and malignant lesions.

Objectives This study aimed to clarify whether pretreatment human equilibrative nucleoside transporter (hENT1) expressions in endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) specimens obtained from resectable, borderline resectable, and locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC) are concordant with those in the resected specimen after gemcitabine-based chemoradiotherapy (Gem-CRT) and to validate the utility of hENT1 expression using EUS-FNAB samples as a prognostic marker. Methods We evaluated the relationship between hENT1 expressions assessed by immunohistochemical staining and clinical outcomes in 51 of 76 patients with PDAC who were diagnosed by EUS-FNAB and received preoperative Gem-CRT. Results The concordance rate of hENT1 expressions was 89.2% (K = 0.681). Median survival time (month) in the 51 whole patients and 37 patients with resection was significantly longer in hENT1 positive than in hENT1 negative: 25.0 and 30.0 versus 9.0 and 9.0, respectively. A multivariate analysis confirmed that hENT1 expression was an independent prognostic factor in both whole patients and those with resection. Regardless of T3 and T4, hENT1-positive patients with resection had significantly better prognosis than hENT1-negative patients, whose prognosis was similar to those without resection. Conclusions The assessment of hENT1 expression using EUS-FNAB samples before Gem-CRT provides important information on patients with PDAC who can benefit from curative-intent resection.

Objective To elucidate the patterns of and risk factors for deterioration of renal function after chemotherapy in metastatic testicular cancer survivors using the estimated glomerular filtration rate. Methods A total of 96 patients who were treated with cisplatin-based chemotherapy for metastatic testicular cancer between January 1981 and December 2010 were enrolled in this study. The estimated glomerular filtration rate was based on the serum creatinine concentration using the formula of the Japanese Society of Nephrology. Risk factors for chronic kidney disease were examined by multivariate logistic-regression analysis. Results The median follow-up period was 70 months (range 15–342). The median pretreatment estimated glomerular filtration rate was 98 mL/min/1.73 m2 (range 44–216), and it gradually decreased for 1 year after the end of chemotherapy, although there was no significant change in estimated glomerular filtration rate beyond 1 year. One year after chemotherapy, 22 of 96 patients (23%) showed chronic kidney disease (less than 60 mL/min/1.73 m2 estimated glomerular filtration rate). The multivariate analysis showed that the patients with mild renal damage (estimated glomerular filtration rate 60–89 mL/min/1.73 m2) and elevated blood pressure (higher than 130/80 mmHg) before treatment had a significant risk with odds ratios of 2.63 (95% confidence interval 1.09–6.73) and 4.22 (95% confidence interval 1.45–12.6), respectively. Conclusions Close monitoring of renal function is important for at least 1 year after chemotherapy for testicular cancer, especially in patients having elevated blood pressure and/or mild renal damage before chemotherapy.

Purpose The objective of this study was to evaluate the major factors influencing on FDG uptake in non-small cell lung cancer (NSCLC) by investigating histological difference in the expression of glucose transporters 1 and 3 (Glut-1 and Glut-3) and tumour size. Methods This study enrolled 32 patients including 9 with squamous cell carcinoma (SCC) and 23 with adenocarcinoma (AC). The AC cases comprised 16 AC with mixed subtypes (AC-mixed) and 7 localized AC in situ (localized bronchioloalveolar carcinoma). Partial volume effect corrected maximum standardized uptake values (cSUVmax) and tumour size were obtained using FDG PET/CT. Glut-1 and Glut-3 expression were evaluated using five-point grading scales. Results Overexpression of Gluts was observed at high rates (88% for Glut-1 and 97% for Glut-3). They were mutually correlated. cSUVmax showed better correlation with size than with Gluts overexpression. AC and SCC showed a high positive expression rate for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher in SCC than AC. In addition, localized AC in situ revealed a considerably higher positive expression rate and similar degrees of overexpression for both Glut-1 and Glut-3 compared with AC-mixed. By contrast, localized AC in situ alone was significantly smaller in both cSUVmax and size than either SCC or AC-mixed. No significant difference was found in cSUVmax or size between SCC and AC-mixed. Conclusions The FDG uptake of NSCLC might be dependent on size rather than on overexpression of Glut-1 or Glut-3. Low FDG uptake in localized AC in situ might result from its small size rather than Glut overexpression.

We herein report our findings for an asymptomatic 65-year-old man presenting with multiple solitary leiomyomas in the esophagus, who was undergoing follow-up for primary aldosteronism with high levels of serum progesterone. Esophageal endoscopy and computed tomography showed multiple submucosal tumors with calcification in the thoracic esophagus. A subtotal esophagectomy was performed because the possibility of malignancy could not be ruled out based on a needle biopsy taken of the specimen. The final resected specimen showed eight solitary, encapsulated nodules between the middle and lower thoracic esophagus. Histopathological examinations showed these nodules to have the typical histological findings of leiomyomas. In addition, staining with antibodies against the progesterone receptor revealed diffuse expression in the nuclei of the leiomyoma cells. Only four cases with more than eight solitary leiomyomas have been reported, including the current case. However, this is the first reported case where primary aldosteronism with elevated serum progesterone levels has been implicated in the pathogenesis of multiple solitary leiomyomas in the esophagus.

To evaluate changes in blood pressure during adrenal radiofrequency ablation (RFA) and analyze histopathologic outcomes in swine adrenal glands. Animal Care Committee approval was obtained for this study. After laparotomy, a single adrenal gland was ablated from each of six animals (six RF sessions total). An internally cooled-tip RF electrode was placed along the long axis of the adrenal gland, and RF energy was applied for 10 min in each adrenal gland. Blood pressure and heart rate were monitored, and serum epinephrine, norepinephrine, and cortisol levels were measured before, during, and after RFA. Histological study was performed using hematoxylin-eosin staining. RFA was completed according to a planned protocol in all adrenal glands. Blood pressure increased to >200 mm Hg after an increase in heart rate during all six RF sessions. Mean serum epinephrine and norepinephrine levels increased significantly during RFA. However, mean cortisol levels showed no significant increase during or after RFA. Histological studies showed adrenal cell necrosis throughout the adrenal glands in all but one pig, with the mean necrosis rate being 99.1 ± 2.3% (range 94.3–100%). Adrenal RFA causes extensive adrenal cell damage and causes catecholamine-induced hypertension.

e15176Background: Complexes of Cholesteryl pullulan and NY-ESO-1 antigen (CHP-NY-ESO-1) present multiple epitope peptides to both the MHC class I and class II pathways. MIS416 is a non-toxic microp...

Rho family protein regulates variety of cellular functions as cytoskeletal organization, cell proliferation and apoptosis. In the present study, we demonstrate that RhoB-overexpressed prostate cancer cells showed an enhanced cell motility and the administration of the GSK-3 inhibitors inhibited this increase in migration. Among the extracellular matrix and adhesion-related molecules, MMP1 RNA expression was increased in RhoB-overexpressed cells, administration of MMP inhibitor suppressed the collagen gel invasion in these cells. This is the first report evaluating RhoB function and the downstream signaling events in prostate cancer cell. Our results indicate that RhoB promotes cell motility and invasion in a metastatic prostate cancer cell.

症例は80歳男性．近医で軽度の肝機能異常を指摘され，腹部超音波検査を受けたところ膵体部に20mm大の内部エコー均一な低エコー腫瘤を指摘され当院に精査入院．造影CTでは，膵体部に動脈相で造影効果に乏しく，門脈相で腫瘍辺縁部に軽度の造影効果を示す20mm大の腫瘍を認め，FDG-PETでは，SUV 3.3と軽度の集積を認めた．内分泌腫瘍を疑い血中膵ホルモンを測定するとグルカゴンが610pg/ml と上昇していた．確定診断のためにEUS-FNABを施行した．組織所見では内分泌腫瘍と考えられ，免疫染色でグルカゴン陽性であった．無症候性グルカゴノーマの診断で，腹腔鏡補助下に脾合併膵体尾部切除を行った．切除標本では，25mm大の白色調腫瘍を認め，免疫染色でグルカゴン陽性であり，また脾動脈周囲リンパ節転移を認め，well differentiated endocrine carcinoma（glucagonoma）と診断された．術後3年の現在再発無く元気である．

非機能性膵内分泌腫瘍，特に2cm以下では主膵管に浸潤することは極めて稀である．我々は1.2cmの小非機能性膵内分泌腫瘍が主膵管に浸潤·狭窄を来した1例を経験した．症例は58歳男性．健康診断を契機にCTで膵腫瘍を発見された．造影CTでは膵体部に早期層で濃染される1cm大の腫瘍および尾側膵管の拡張を認め，ERPでは尾部膵管に拡張を認めた．EUSでは膵体部に10mm大の類円形腫瘤を認めた．腫瘍マーカーや内分泌検査に異常はなかった．主膵管浸潤を伴う非機能性膵内分泌腫瘍と診断し，腹腔鏡補助下脾合併膵体尾部切除術を施行した．病理所見ではwell-differentiated endocrine carcinomaで，主膵管内への浸潤と膵近傍の脂肪組織浸潤を認めたが，剥離面は陰性であった．2cm以下の小膵内分泌腫瘍で膵管浸潤を認めたものは，6例の報告しかないが，うち4例は明らかな悪性であった．非機能性膵内分泌腫瘍で主膵管狭窄を伴う場合は，悪性を念頭にリンパ節郭清を伴う膵切除が適応であるが，周囲リンパ節腫大がない場合には腹腔鏡補助下脾合併膵体尾部切除術は適応可能と考えられた．

We present the case of a 10-year-old girl with biliary atresia in whom focal nodular hyperplasia (FNH) of the liver occurred following successful "Kasai" hepatic portoenterostomy at the age of 2 months. Her jaundice completely disappeared a few weeks after the operation. A 4-cm diameter liver tumor in segment IV was found when she was 5-years old. Needle biopsy could not establish a definitive diagnosis. Because the tumor size was not changing, she was conservatively followed by abdominal echo at an outpatient clinic. She showed progressive liver dysfunction and ongoing cirrhosis, and so at the age of 10 years, she received living donor liver transplantation at our institute. The tumor was pathologically diagnosed as a FNH. Though a FNH in biliary atresia patients is extremely rare, there are only two cases reported in the literature; it should be considered in the differential diagnosis for a hepatic nodule during a long follow-up course in patients with biliary atresia.

Prostate derived factor (PDF) is a member of transforming growth factor-β (TGF-β) superfamily proteins involved in differentiation of the prostate epithelium. Proprotein convertases (PCs) such as furin are thought to mediate the processing of TGF-β superfamily. In the present study, we demonstrated for the first time that human prostate cancer cell lines differentially synthesize and secret prostate derived factor (PDF), and that PDF secreted by LNCaP is processed by PCs. Exposure of LNCaP cells to the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (CMK), a synthetic furin-like protease inhibitor, inhibited PDF processing and resulted in the loss of luminal cell phenotype and induction of basal cell phenotype in LNCaP cells as demonstrated by alternations in the expression of cytokeratins 8, 14, 18, and 19, markers of prostate epithelial cell differentiation. These results suggest that proprotein convertases may be involved in the regulation of prostate epithelial cell differentiation, and may be an important target of prostate cancer therapy. J. Cell. Biochem. 88: 394–399, 2003. © 2002 Wiley-Liss, Inc.

The General Rule for Clinical and Pathological Studies on Bladder Cancer (3rd edition) and General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer (2nd edition) were integrated, and the General Rule for Clinical and Pathological Studies on Renal Pelvic, Ureteral, and Bladder Cancer was published in April 2011. For histopathological diagnosis, a modification in line with the World Health Organization/International Urological Pathology 2004 classification is performed. Urothelial carcinoma is divided into non-invasive urothelial carcinoma and invasive urothelial carcinoma. With respect to the tumor grade classification for non-invasive papillary urothelial carcinoma, a two-grade classification, which is divided into low and high grade, is adopted instead of the three-grade classification adopted in the previous General Rule for Clinical and Pathological Studies. With respect to tumor subtyping for invasive urothelial carcinoma, twelve subtypes are adopted in the latest General Rule for Clinical and Pathological Studies. Subtyping also complies with the WHO/ISUP2004 classification. The handling of urothelial carcinoma with squamous, glandular, or trophoblastic differentiation is modified and they are classified in subtypes. Nine rare subtypes are also added. In the subtype classification, subtypes that are required to be differentiated from benign lesions or malignant tumors, involved in treatment selection, or related to the prognosis are included.

Background: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding. Methods: Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections. Results: Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26–3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation. Conclusions: Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

For multiple low-grade malignant tumors located in the pancreatic head and tail, middle-segment-preserving pancreatectomy (MSPP) is sometimes indicated. However, MSPP has rarely been performed laparoscopically. Here we report the first case of laparoscopic MSPP for multiple pancreatic neuroendocrine tumors diagnosed preoperatively under an endoscopic ultrasound-guided fine-needle aspiration biopsy. A 70-year-old man had multiple small tumors located in the pancreatic head, body and tail. Endoscopic ultrasound-guided fine-needle aspiration biopsy with immunohistochemical staining made a definitive diagnosis of a pancreatic neuroendocrine tumor (G1). To preserve the 5-cm pancreas body, we successfully performed laparoscopic MSPP: subtotal stomach-preserving pancreaticoduodenectomy followed by distal pancreatosplenectomy. Pathological examination revealed negative surgical margin after resection. Postoperative course was uneventful, and at 14 months after the operation, the patient remains tumor-free. The patient has discontinued insulin supplement therapy but does use an oral hypoglycemic agent. Laparoscopy-assisted MSPP, with reconstruction through a 6-cm transverse incision, can be safely performed for selected cases of borderline and malignant lesions.

BACKGROUND The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Purpose We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. Patients and methods From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. Results The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. Conclusions Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.

It has been shown in many carcinomas that the proliferation rate and number of argyrophilic nucleolar organizer regions (AgNOR) are associated with tumor aggressiveness. However, in bladder tumor the significance of the correlation between the number of AgNOR and tumor behavior remains controversial. Therefore, it would be helpful if a new technique could be developed that would allow for more accurate AgNOR counting in association with tumor behavior. We established the simultaneous staining technique of AgNOR with Ki-67 labeling to reveal the significance of AgNOR count in superficial bladder tumor.A total of 50 paraffin sections of superficial bladder tumor were stained with AgNOR and Ki-67 (MIB-1). The numbers of AgNORs in proliferating (MIB-1 positive) or resting (MIB-1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed.The AgNOR count in proliferating cells was significantly higher than that in resting cells (p0.01), and the count significantly increased with tumor grade (p0.01). Based on recurrence-free survival analyses the local recurrence rate was significantly higher in patients with high proliferating cell NOR but not for those with resting or whole cells. However, no AgNOR score helped to select patients at high risk for disease progression.Proliferating cell NOR had a predictive value for local recurrence in patients with superficial bladder tumor.

Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed.CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion.Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P0.0001).A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

The number of nucleolar organizer regions (NOR) of human bladder cancers was evaluated at the light- and electron-microscopic level. The average number of argyrophilic NOR (AgNOR), stained by the one-step silver colloid method, was measured in benign and malignant urothelial cells in the human urinary bladder using a light microscope. The average number of nucleolar fibrillar centers (FC) per nucleus was also calculated by quantitative ultrastructural morphometry in the specimens from the same patients. Statistical evaluations revealed that the average number of AgNOR per nucleus was significantly correlated with the elevation of tumor grade and stage (p < 0.05). An average FC number per nucleus also increased in association with tumor grade and stage (p < 0.05). Although the average number of FC was 5.6 times higher than that of AgNOR, the correlation between the average number of FC and AgNOR was statistically significant. In conclusion, these results suggested that the silver staining method was a useful and convenient tool for the evaluation of the differentiation and invasive potential of bladder cancer cells at the light-microscopic level.

OBJECTIVE To investigate the dose intensity of induction chemotherapy and oncological outcomes of metastatic testicular cancer under centralized management through a regional medical network. MATERIALS AND METHODS We retrospectively analyzed the outcomes of 86 metastatic testicular cancer patients who were given induction chemotherapy at Tsukuba University Hospital and four branch hospitals between January 2000 and November 2010. Principally, management of patients with poor-prognosis disease and patients having risk factors for bleomycin, etoposide and cisplatin were referred to Tsukuba University Hospital before chemotherapy. For high-risk groups, etoposide and cisplatin or etoposide, ifosfamide and cisplatin was used as an alternative to bleomycin, etoposide and cisplatin. RESULTS Overall, 56 and 30 patients were treated at Tsukuba University Hospital and branch hospitals, respectively. Forty-seven, 18 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Eighteen of the 21 patients (86%) with poor-prognosis disease were treated at Tsukuba University Hospital from the beginning of induction chemotherapy. Induction chemotherapy with a high relative dose intensity was possible in most patients. The average relative dose intensity of each drug was >0.96. Treatment procedures other than induction chemotherapy were efficiently centralized; 74% of post-chemotherapy surgery and all second-line or subsequent chemotherapies were performed at Tsukuba University Hospital. The 5-year overall survival rates of the good-, intermediate- and poor-prognosis groups were 97, 93 and 84%, respectively. CONCLUSIONS Induction chemotherapy with high relative dose intensity, post-chemotherapy surgery and salvage chemotherapy was accomplished efficiently through centralization of management. Oncological outcomes were excellent, especially in patients with poor-prognosis disease, whose 5-year OS reached 84%.