Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS.

Correlation between apparent diffusion coefficients on diffusion-weighted MRI and standardized uptake value on FDG-PET/CT in pancreatic adenocarcinoma.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (PET/CT) is increasingly recognized as important for assessing tumor malignancy in oncology. Apparent diffusion coefficient (ADC) and standardized uptake value (SUV) are negatively correlated in some types of cancer based on tumor aggressiveness. PURPOSE: To evaluate relationships between ADC of magnetic resonance imaging and SUV of PET/CT in pancreatic adenocarcinomas. MATERIAL AND METHODS: Twenty-nine patients histopathologically diagnosed with pancreatic adenocarcinomas were evaluated. ADC maps were generated from 3 T-MRI using b values (b = 0, 800 s/mm(2)). PET/CT was performed 60 min after intravenous injection of FDG (3.7 MBq/kg). The margins of tumors on DW-MRI and PET/CT were assessed to measure ADC and SUV of tumor appropriately. For tumors considered well-marginated, minimal and mean ADC as well as maximal and mean SUV were measured. The correlation of ADC and SUV were statistically evaluated and survival period stratified on ADC and SUV also evaluated. RESULTS: Twenty-two tumors on DW-MRI and 25 on PET/CT were deemed well-marginated. Minimal ADC was significantly and negatively correlated with maximal and mean SUV (r = -0.61, P = 0.0040; r = -0.66, P = 0.0015), and mean ADC also showed significantly and negatively correlation with maximal and mean SUV (r = -0.50, P = 0.024; r = -0.54, P = 0.012). There was no significant difference on overall survival stratified on ADC and SUV. CONCLUSION: ADC and SUV were significantly correlated in pancreatic adenocarcinomas, although no significant findings were observed in overall survival.

Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection.

BACKGROUND/AIMS: A soft-coagulation system (SCS) was introduced as an effective device to reduce blood loss in hepatectomy. Here we evaluated the efficacy of a two-surgeon technique using precoagulation by an SCS and the Cavitron Ultrasonic Surgical Aspirator (CUSA) for liver transection. METHODOLOGY: The 163 patients with liver tumors were divided into two groups (conventional group and two-surgeon group). Liver transection was conducted using saline-coupled bipolar electrocautery and CUSA in 102 patients (conventional group). In 61 patients (the two-surgeon group), a two-surgeon technique using precoagulation by an SCS and CUSA for liver resection was performed. RESULTS: The median blood loss was significantly less in the two-surgeon group compared to the conventional group (354.8 mL vs. 557.8 mL, respec tively: p = 0.0011). The postoperative hospital stay was significantly shorter in the two-surgeon group compared to the conventional group (12.7 days vs. 15.5 days, p = 0.0035). CONCLUSIONS: The two-surgeon technique using precoagulation by an SCS and CUSA was significantly reduced blood loss during liver transection, and associated with low morbidity and mortality. This technique may be useful for many hepatobiliary surgeons.

Clinical significance of surgical resection of metastatic lymph nodes from hepatocellular carcinoma.

PURPOSE: The clinical significance of the surgical resection of metastatic lymph nodes (LN) from patients with hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to evaluate the significance of the surgical resection of LN metastasis of HCC. METHODS: Among 961 patients who underwent surgical resection for HCC in our hospital, LN metastasis was identified in 38 patients. In these patients, the metastatic LN were removed completely in 22 patients (complete removal group), and incompletely or not removed in 16 patients (control group). The long-term prognosis after LN metastasis was compared between the two groups. RESULTS: The overall survival rate after LN metastasis was significantly better in the complete removal group (1-, 3- and 5-year: 71.2, 58.0 and 49.7%, respectively) than in the control group (45.9, 23.0 and 15.3%, respectively, p = 0.0477). LN metastasis was not the cause of death in any of the patients in the complete removal group, whereas it was a cause in some patients in the control group. No local LN recurrence was identified in the complete removal group. CONCLUSIONS: The present results suggest that the complete removal of metastatic LN from HCC is clinically beneficial in selected patients.

Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast cancer patients treated with taxane and anthracycline.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is one of the standard care regimens for patients with resectable early-stage breast cancer. It would be advantageous to determine the chemosensitivity of tumors before initiating NAC. One of the parameters potentially compromising such chemosensitivity would be a hypoxic microenvironment of cancer cells. The aim of this study was thus to clarify the correlation between expression of the hypoxic marker carbonic anhydrase-9 (CA9) and chemosensitivity to NAC as well as prognosis of breast cancer patients. METHODS: A total of 102 patients with resectable early-stage breast cancer was treated with NAC consisting of FEC (5-fluorouracil, epirubicin, and cyclophosphamide) followed by weekly paclitaxel before surgery. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity to NAC and the prognostic potential of CA9 expression were evaluated by immunohistochemistry. RESULTS: CA9 positivity was detected in the CNB specimens from 47 (46%) of 102 patients. The CA9 expression in CNB specimens was significantly correlated with pathological response, lymph node metastasis, and lymph-vascular invasion. Multivariate analysis revealed that the CA9 expression in CNB specimens was an independent predictive factor for pathological response. The Kaplan-Meier survival curve revealed a significant negative correlation (p=0.013) between the disease-free survival (DFS) and the CA 9 expression in resected tissues after NAC. Multivariate regression analyses indicated that the CA9 expression in resected tissues was an independent prognostic factor for DFS. CONCLUSIONS: CA9 expression in CNB specimens is a useful marker for predicting chemosensitivity, and CA9 expression in resected tissue is prognostic of DFS in patients with resectable early-stage breast cancer treated by sequential FEC and weekly paclitaxel prior to resection.

Incidence of abnormal retropharyngeal lymph nodes in sinonasal malignancies among adults.

INTRODUCTION: The aim of this study is to investigate the relationship between abnormal retropharyngeal lymph nodes (RPLNs) and sinonasal malignancies among adults. METHODS: Magnetic resonance and computed tomography images from 89 patients over 20 years old who were all histopathologically confirmed to have sinonasal malignancies from September 2001 to April 2014 were assessed retrospectively. Abnormal RPLNs were determined as those >5 mm in shortest axis or showing heterogeneous enhancement on axial images. Locations of sinonasal malignancies were categorized using the anterior border of the pterygopalatine fossa as a boundary: (a) anterior lesions, only present anterior to the boundary, or (b) posterior lesions, present or extending posterior to the boundary. Fisher's exact test was used for the analysis of the relationship between frequency of abnormal RPLNs and lesion location. RESULTS: Abnormal RPLNs were present in 13 of 89 patients (15%), including 6 of 41 squamous cell carcinomas (15%), 4 of 24 malignant lymphomas (17%), 3 of 5 olfactory neuroblastomas (60%), and 0 of 19 others (0%). Four of the 39 patients (10%) with anterior lesions showed abnormal RPLNs, compared to 9 of 50 patients (18%) with posterior lesions. No significant difference in frequency of abnormal RPLNs was apparent between anterior and posterior lesions (P = 0.37). CONCLUSIONS: In primary sinonasal malignancies among adults, the highest incidence of abnormal RPLNs was seen with olfactory neuroblastoma. The frequency of abnormal RPLNs was unaffected by the location of sinonasal malignancies among adults.

MUC1 and HER2 might be associated with invasive phenotype of intraductal papillary mucinous neoplasm.

BACKGROUND/AIMS: The purpose of this study was to clarify the biomarkers which distinguish invasive Intraductal papillary mucinous neoplasms (IPMNs) from noninvasive IPMNs. METHODOLOGY: In tumor specimens from sixty patients with IPMNs (42 noninvasive IPMNs and 18 invasive IPMNs) who underwent surgical resection at our institute, we analyzed the correlation between the immunohistochemical expression level of MUC1, MUC2, MUC4, MUC5AC, p53, VEGFR2, HER2, and HER3. RESULTS: The 5-year survival rate was 100% in noninvasive IPMNs, while that of invasive IPMNs was only 36.5%. MUC1, MUC4, HER2 and HER3 were significantly associated with invasive IPMNs in univariate analysis. Multivariate analysis revealed that MUC1 and HER2 were significantly associated with invasive IPMNs. The 5-year survival of IPMN patients with either MUC1-positive and/or HER2-positive (54.5%) is significantly poorer than that of IPMN patients with MUC1 negative and HER2 negative (100%). CONCLUSIONS: MUC1 and HER2 might be closely associated with invasive phenotype of IPMNs.

Histologically proven hepatocellular carcinoma associated with burned-out nonalcoholic steatohepatitis.

A 64-year-old Japanese man was referred to our hospital because of liver dysfunction. He had no history of alcohol intake, diabetes, hypertension, and hyperlipidemia, and he was negative for hepatitis viral markers. His body mass index was 30.6 kg/m2. Homeostasis model assessment of insulin resistance was 6.1. Liver biopsy revealed mild steatosis, moderate inflammation, ballooning degeneration, and portal fibrosis with bridging fibrosis; on the basis of these findings, the diagnosis of nonalcoholic steatohepatitis was made. Thereafter, follow-up imaging study was performed every 4 months. At 16 months after liver biopsy, a 3 cm hepatic lesion was detected in the right hepatic lobe by computed tomography. Dynamic computed tomography revealed a hepatic tumor enhanced with contrast medium during the arterial phase and a low-density area during the portal phase. Based on the diagnosis of hepatocellular carcinoma, partial hepatectomy was performed. Histological examination revealed a moderately differentiated hepatocellular carcinoma accompanied by liver cirrhosis without steatosis or ballooning degeneration. Finally, the patient was diagnosed with hepatocellular carcinoma arising from burned-out nonalcoholic steatohepatitis.

IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma.

Insulin-like growth factor-binding protein 7 (IGFBP7) functions in several cellular processes including proliferation, senescence and apoptosis. This study analyzed IGFBP7 function in hepatocellular carcinoma (HCC) cells by gene manipulation and investigated the prognostic significance of IGFBP7 expression in clinical HCC samples. In this study, we investigated changes in malignant potential such as cell growth and invasiveness in an HCC cell line, PLC/PRF/5, after transfection with shRNA against IGFBP7. The extent of apoptosis and cell cycle progression were examined after the transfection. The correlation between immunohistochemically determined IGFBP7 expression and long-term postoperative prognosis after curative resection was also investigated in clinical HCC specimens obtained from 104 patients. PLC/PRF/5 cells transfected with shRNA against IGFBP7 showed significantly more rapid growth and stronger invasiveness than control cells. Annexin V assays showed that the IGFBP7-depleted cells were significantly more resistant to apoptosis than the control cells, and showed decreased expression of cleaved caspase-3 and PARP. Cell cycle progression was more rapid in the IGFBP7-suppressed cells. In clinical HCC specimens, IGFBP7 expression was judged as positive in 67 patients (64.4%) and negative in the remaining 37 patients (35.6%). The IGFBP7 downregulation correlated significantly with poor postoperative prognosis, and IGFBP7 status was identified as an independent significant prognostic factor. Our results indicated that IGFBP7 expression correlated significantly with the malignant potential in HCC cells, suggesting that the expression could be a useful prognostic marker for HCC.

Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice.

Cytoglobin (Cygb) is a recently discovered vertebrate globin with molecular characteristics that are similar to myoglobin. To study the biological function of Cygb in vivo, we generated Cygb knockout mice and investigated their susceptibility to N,N-diethylnitrosamine (DEN)-induced tumorigenesis. Four-week-old male mice were administered DEN in drinking water at a dose of 25 ppm for 25 weeks or 0.05 ppm for 36 weeks. Cygb deficiency promoted the DEN-induced development of liver and lung tumors. All Cygb(+/-) and Cygb(-/-) mice treated with 25-ppm DEN exhibited liver tumors, compared with 44.4% of their wild-type counterparts. Lung tumors were present only in Cygb-deficient mice. More than 40% of Cygb(-/-) mice developed liver and lung tumors at the nontoxic dose of DEN (0.05 ppm), which did not induce tumors in wild-type mice. Cygb loss was associated with increased cancer cell proliferation, elevated extracellular signal-regulated kinase and Akt activation, overexpression of IL-1ß, IL-6, Tnfα, and Tgfß3 mRNAs, and hepatic collagen accumulation. Cygb-deficient mice also exhibited increased nitrotyrosine formation and dysregulated expression of cancer-related genes (cyclin D2, p53, Pak1, Src, Cdkn2a, and Cebpa). These results suggest that Cygb deficiency induces susceptibility to cancer development in the liver and lungs of mice exposed to DEN. Thus, globins such as Cygb will shed new light on the biological features of organ carcinogenesis.

Hypervascular hepatocellular carcinomas: detection with gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT.

OBJECTIVES: To retrospectively compare the accuracy of detection of hypervascular hepatocellular carcinoma (HCC) by multiphasic multidetector CT and by gadoxetate disodium-enhanced MR imaging. METHODS: After ethical approval, we analysed a total of 73 hypervascular HCC lesions from 31 patients suspected of having HCC, who underwent both gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT. Five blinded observers independently reviewed CT images, as well as dynamic MR images alone and combined with hepatobiliary phase MR images. Diagnostic accuracy (Az values), sensitivities and positive predictive values were compared by using the Scheffe post hoc test. RESULTS: The mean Az value for dynamic and hepatobiliary phase MR combined (0.81) or dynamic MR images alone (0.78) was significantly higher than that for CT images (0.67, P < 0.001, 0.005, respectively). The mean sensitivity of the combined MR images (0.67) was significantly higher than that of dynamic MR alone (0.52, P < 0.05) or CT images (0.44, P < 0.05). The mean positive predictive values were 0.96, 0.95 and 0.94, for CT, dynamic MR alone and combined MR images, respectively. CONCLUSIONS: Compared with multiphasic multidetector CT, gadoxetate disodium-enhanced MR imaging combining dynamic and hepatobiliary phase images results in significantly improved sensitivity and diagnostic accuracy for detection of hypervascular HCC. KEY POINTS: Gadoxetate disodium is a new liver-specific MR imaging contrast agent. Gadoxetate disodium-enhanced MRI helps the assessment of patients with liver disease. It showed high diagnostic accuracy for the detection of hepatocellular carcinoma.

Arterial stimulation and venous sampling for glucagonomas of the pancreas.

BACKGROUND/AIMS: Arterial stimulation and venous sampling (ASVS) is a catheter-based diagnostic technique used to identify the localization of an insulinoma or gastrinoma. The aim of this study was to clarify the clinical significance of ASVS for glucagonomas. METHODOLOGY: Eight patients with pancreatic hypervascular tumors and elevated serum glucagon levels in the peripheral blood were enrolled. Pancreatic angiography was performed and a bolus dose of calcium was injected into a suitable artery. Hepatic venous blood samples were then obtained to measure concentrations of glucagon and insulin. All patients underwent surgical resection, and the resected specimens were investigated immunohistochemically. RESULTS: Compared to insulin, the glucagon levels stabilized after calcium stimulation in four patients, with a 1.2-fold increase or decrease. In the remaining four patients, there was a 1.6- to 5.8-fold increase in glucagon levels. The peak value of glucagon was observed at 90s or 120s which was slower than the insulin peak observed in patients with insulinoma. The patients with elevated glucagon levels during ASVS exhibited positive immunostaining of glucagon in resected specimens. CONCLUSIONS: Increase in glucagon after calcium stimulation was observed in patients with glucagonomas. ASVS for glucagonomas may be useful in determining the most suitable surgical procedure.

[A patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy who responded completely to S-1 therapy followed by open gastrectomy].

We report a rare case of a patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy, who responded completely to S-1 therapy followed by open gastrectomy. A 72-year-old man with a chief complaint of occult blood in the feces was referred to our hospital and was diagnosed with rectal cancer by colonoscopy. In addition, we found concomitant gastric cancer by gastrointestinal fiberscopy. Abdominal plain computed tomography showed no liver metastasis. In August 2010, we performed laparoscopic resection of the rectal cancer. However, at the time of discharge, abdominal enhanced computed tomography showed multiple liver metastases. Then, we administered 4 courses of S-1 therapy. In December 2010, abdominal enhanced computed tomography showed no liver metastasis. In March 2011, because no other lesion without residual gastric cancer was detected, the patient underwent gastrectomy followed by S-1 therapy. As of January 2012, the patient is alive and disease free. S-1 therapy with laparoscopic resection for rectal cancer and gastrectomy may help prolong the survival of patients with multiple liver metastases of gastric and rectal cancers.

[Day surgery of early breast cancer treated with breast-conserving operation following sentinel lymph node navigation biopsy under local anesthesia].

In the early stages of breast cancer when axillary lymph node dissection is avoidable, we performed same day surgery with a breast-conserving operation following sentinel lymph node navigation biopsy under local anesthesia. Initial sentinel lymph node biopsy under local anesthesia is performed to avoid false-negative sentinel lymph node metastasis. Resected sentinel lymph nodes were examined in fixed sections by hematoxylin-eosin staining and immunohistochemistry. The enrolled subjects were 20 patients with breast cancer whose diagnoses were confirmed before treatment. Two (10.0%) patients had metastasis.

[Four cases of meningeal metastasis originating from breast cancer].

Carcinomatous meningitis due to breast cancer is comparatively rare in Japan. Here, we report 4 cases of carcinomatous meningitis due to breast cancer. Meningeal metastasis was present in only 1 of the 4 cases, and the other 3 cases were associated with brain metastasis. Meningeal metastasis frequently causes symptoms associated with intracranial hypertension. Gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid cytology were useful for the diagnosis of meningeal metastasis. Multidisciplinary therapy, such as radiation and chemotherapy, was performed. Two of the 4 patients were treated with combined intrathecal administration of methotrexate and whole brain radiation. The quality of life was improved by multidisciplinary therapy.

[Needle biopsy using a Monopty Biopsy Instrument for the accurate diagnosis of thyroid cancer].

Aspiration biopsy cytology (ABC) is commonly performed for the diagnosis of thyroid tumor. Because ABC may not provide sufficient tissue for pathological diagnosis, we performed needle biopsy using a Monopty Biopsy Instrument for the accurate diagnosis of thyroid cancer. Furthermore, it is difficult to safely perform a core needle biopsy (CNB) for the diagnosis of breast cancer in the thyroid gland region. In this study, we evaluated the feasibility of using a Monopty Biopsy Instrument as an alternative to conventional ABC or CNB for the biopsy-based diagnosis of thyroid cancer. Twenty patients with clinically suspected thyroid cancer were enrolled, and all patients were thoroughly examined. Seven cases of thyroid cancer were diagnosed, of which 5 cases were papillary carcinoma and 2 were undifferentiated carcinoma.

Cardiac metastasis of lung cancer presented as mimicking ST-elevation myocardial infarction with reciprocal electrocardiographic changes.

We report the case of a patient with metastatic cardiac tumor who presented with chest pain and electrocardiographic changes mimicking acute inferior myocardial infarction. An 84-year-old man who had undergone lung cancer surgery one year earlier was referred to emergency outpatient visit because of chest pain. His 12-lead electrocardiography (ECG) showed ST-segment elevation in the inferior leads with reciprocal ST-segment depression in the precordial and lateral leads, which was initially interpreted as inferior acute myocardial infarction. By emergency coronary angiography, however, there was no significant stenosis or occlusion in the right coronary artery or the left circumflex artery. In echocardiographic examinations after admission, a large mass was found in the area corresponding to the infero-posterior wall of the left ventricle, which had been detected only by positron emission tomography with computed tomography six months earlier. He died one month after admission. Pathological autopsy revealed a tumor of 8 × 5 cm size in the myocardium of the posterior to inferior wall of the left ventricle, and diagnosed as cardiac metastasis from lung cancer. ECG changes with ST-segment elevation, in particular persistent ST-elevation in the absence of Q waves, can be a sign for tumor invasion of the heart. Learning objective: It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents with acute myocardial infarction-like electrocardiography findings. Besides, in this case, positron emission tomography with computed tomography (PET-CT) had detected an abnormal accumulation in the left ventricle earlier than when the tumor was pointed out by echocardiography. Multimodality imaging including PET-CT could help physicians to make the early and accurate diagnosis of metastatic cardiac tumor.

A case of renal cell carcinoma with late recurrence in the bilateral hilar lymph nodes twenty years after surgery.

Renal cell carcinoma (RCC) is a common malignancy with a high recurrence rate. However, brain and bilateral hilar lymph node (BHL) relapse is rare. A 65-year-old man with a chief complaint of hemosputum visited the primary care clinic. Computed tomography revealed BHL enlargement. Histopathological examination of biopsy specimens from the left lingular bronchus revealed RCC. This finding was similar to that of a left nephrectomy specimen of RCC observed 20 years ago. If patients have a medical history of RCC, physicians should consider the possibility of RCC recurrence, regardless of the number of years relapsed postoperatively.

Computed tomography and magnetic resonance imaging appearance of prolactinoma with spheroid-type amyloid deposition.

We report a rare case of prolactinoma with deposition of amyloid and calcifications. Magnetic resonance imaging and/or computed tomography findings have been described in only a few cases. Possible mechanisms of amyloid deposition and calcification were discussed, and literatures were reviewed. In pituitary adenomas, particularly in prolactinomas, amyloid deposits should be included in the differential diagnosis, when hypointense areas are noted on T2-weighted images. Stippled calcifications in the tumor seem to be another characteristic finding.

[Membranous nephropathy with nephrotic syndrome developed after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia].

A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.