The Efficacy of Imatinib Mesylate in the Treatment of a Rare Lytic Bone Lesion Caused by Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia: A Case Report.

CASE: We report a patient with hypereosinophilia-associated massive osteolytic lesion of the sacrum who was admitted to our hospital. Genetic analysis revealed that atypical eosinophilic cells were positive for FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) fusion gene. Treatment was initiated with oral administration of imatinib mesylate. The patient responded rapidly to this medication with a marked reduction in eosinophilia both from the peripheral blood and FIP1L1-PDGFRA fusion gene in the bone marrow within 2 weeks, followed by gradual osteosclerotic repair of the sacrum. CONCLUSIONS: This case study found that the drug imatinib proved very effective in the treatment of this rare condition.

[A case of liver metastasis 11 years after resection of a gastrointestinal stromal tumor of the duodenum].

A 77-year-old Japanese man with a gastrointestinal stromal tumor (GIST) had undergone a duodenectomy 11 years prior. At that time, he had an incidentally detected left renal cell carcinoma, for which he underwent a nephrectomy and was followed-up at our institution. Twenty-four months after the nephrectomy, a 13-mm low-density mass was found on abdominal computed tomography (CT). Contrast-enhanced ultrasonography indicated an irregular hyperenhancement in the vascular phase and a defect on the post-vascular image. A tumor biopsy for differential diagnosis revealed that the tumor was a GIST. Since positron emission tomography-CT and capsule endoscopy revealed no evidence of a primary lesion, we performed a partial hepatectomy without adjuvant treatment. Microscopic examination revealed that the tumor consisted of uniform spindle cells with a fascicular growth pattern. Immunohistochemical examination revealed c-kit and CD34 expressions, similar to those found in the resected duodenal GIST specimen 11 years prior. We diagnosed metastatic liver tumor from the duodenal GIST resected 11 years prior. The patient remains alive without disease recurrence 24 months after the hepatectomy. Long-term surveillance is required after resection of a high-risk primary GIST.

[Multiple hepatic sclerosed hemangiomas that are difficult to diagnose preoperatively:a case report].

An 83-year-old woman was admitted to our hospital because of a space-occupying lesion (SOL) in the liver. Enhanced computed tomography (CT) showed a nodule measuring 20mm in size in the posterosuperior segment of the right hepatic lobe (S7) and another nodule measuring 14mm in size in the anterosuperior segment of the right hepatic lobe (S8). The margins of these nodules showed faint enhancement in the arterial phase and presented as low-density areas in the equilibrium phase. The S8 SOL could not be easily identified using ultrasonography (US). However, the S7 SOL could be clearly identified as a nodule accompanying the marginal enhancement in the early vascular phase and a defect in the late vascular phase using contrast-enhanced US. On gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, both nodules were described as low-intensity lesions in the T1 phase, high-intensity lesions in the T2 phase, faint high-intensity diffusion-weighted images, and clear low-intensity lesions in the hepatobiliary phase. On positron-emission CT, there was no uptake of 18F-fluorodeoxyglucose in these nodules. Hepatectomy was performed because we were unable to rule out a malignant tumor. Histopathologically, these lesions demonstrated collapsed vascular spaces against a background of rich paucicellular fibrous stroma and were diagnosed as sclerosed hemangiomas. The occurrence of multiple sclerosed hemangiomas is rare and often difficult to diagnose because of variable findings on imaging studies. We report a case of multiple hepatic sclerosed hemangiomas, which was difficult to diagnose preoperatively. Moreover, we have reviewed the literature, particularly with respect to the relevant imaging findings.

Clinical significance of sIL-2R levels in B-cell lymphomas.

Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.

Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm.

BACKGROUND: Hepatocellular carcinoma (HCC) ≤ 2 cm in diameter is considered to have a low potential for malignancy. METHODS: A retrospective review was undertaken of 149 patients with primary solitary HCC ≤ 2 cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC ≤ 2 cm accompanied by MI was compared to that of patients with HCC ≤ 2 cm without MI. RESULTS: Forty-three patients with HCC ≤ 2 cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-γ-carboxy prothrombin (DCP) >100 mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC ≤ 2 cm with MI (3 year 44%) were significantly worse than those for HCC ≤ 2 cm without MI (3 year 72%). This disadvantage of disease-free survival rate of patients with HCC ≤ 2 cm with MI could be dissolved by hepatic resection with a wide tumor margin of ≥ 5 mm (P = 0.04). CONCLUSIONS: Even in cases of HCC ≤ 2 cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (>100 mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.

A case of spindle cell type anaplastic carcinoma of the pancreas -review of Japanese case report-.

We present a case of spindle cell type anaplastic carcinoma of the pancreas in a 63-year-old woman. A pancreatic mass was incidentally detected by routine abdominal ultrasonography examination for her hepatitis B infection, and she was admitted to our hospital for further examination. Computed tomography revealed a hypo-vascular mass measuring 25mm in maximal dimension at the pancreas body. Endoscopic ultrasonography showed a hypoechoic mass as the pancreas body and a swollen lymph node near the tumor. Endoscopic retrograde pancreatography revealed disruption of the main pancreatic duct, and carcinoma cells were detected in pancreatic juice obtained via an endoscopic nasopancreatic drainage tube. We diagnosed this case as an invasive ductal adenocarcinoma of the pancreas body, therefore the distal pancreatectomy with splenectomy (D1+α) was performed. The histopathological diagnosis for this case was a "spindle cell type anaplastic carcinoma of the pancreas". The patient has remained well with no evidence of recurrence for 9 months since her operation.

[A study of the usefulness of pancreatic juice cytology obtained via an endoscopic nasal pancreatic drainage (ENPD) tube].

We studied the usefulness of pancreatic juice cytology obtained via an indwelling endoscopic nasal pancreatic drainage (ENPD) tube. In general, cytology was performed three times. The sensitivity was 0.35 on the first time and 0.59 after three times (p<0.01). The sensitivity in relation to tumor size of pancreatic cancer was 0.77 for Tis (3 cases) and TS1 (10 cases), 0.76 for TS2 (29 cases), 0.56 for TS3 (9 cases) and 0 for TS4 (4 cases). A significant difference of p=0.01 was recognized among the 4 groups, and the sensitivity for small tumors was higher than that for large tumors. The pancreatic juice can be obtained repeatedly via the ENPD tube and that contributes to improving the diagnostic accuracy. It is useful as a definitive diagnosis method in early stage pancreatic cancer because it is easier to detect positive results in smaller tumor, furthermore, it is possible to diagnose carcinoma in situ.

Gastric carcinoma with protein-losing gastroenteropathy: report of a case.

This report describes the successful treatment of a case of true gastric cancer presenting as protein-losing gastroenteropathy. A 58-year-old Japanese male presented gastric carcinoma. His serum albumin and total protein levels were 1.8 and 4.2 g/dl, respectively. He was diagnosed with gastric cancer with protein-losing gastroenteropathy based on (99m)Tc-human serum albumin scintigraphy. The patient underwent a total gastrectomy following neoadjuvant chemotherapy. There are 23 detailed case reports of gastric carcinoma with protein-losing gastroenteropathy. Most of these cases had large villous or cauliflower-like gastric tumors that were defined as papillary or well differentiated adenocarcinoma. Gastric cancer with protein-losing gastroenteropathy is extremely rare, but it can easily be diagnosed if the villous or cauliflower-like features are well defined.

Prognostic re-evaluation of peritoneal lavage cytology in Japanese patients with gastric carcinoma.

BACKGROUND/AIMS: The aim of the present study was to re-evaluate CY(+) with gastric carcinoma in Japanese patients to identify the characteristics that might distinguish patients with a poor prognosis from those with an intermediate prognosis among CY(+) patients. METHODOLOGY: CY(+) was found in 56 of 566 patients (9.9%) who had undergone surgery for gastric carcinoma between January 2000 and December 2006. The 56 patients with CY(+) were classified into four groups: group A, P(-)CY(+) (n = 10); group B, P1CY (+) (n = 10); group C, P2,3CY(+) (n = 18); group D, other (n = 18). RESULTS: The 5-year survival of all patients with CY(+) was 12%. A multivariate analysis demonstrated serosal invasion, lymph node metastasis, and CY(+) to be independent prognostic factors. However, the 5-year survival in group A was 30%. The prognosis of group A patients was significantly better than that of patients in any other group (Groups B, C, D; p < 0.02). Sites of the recurrence in group A were located only in the peritoneum but the lymph nodes, etc. CONCLUSIONS: Gastric carcinoma with CY(+) has a poor prognosis because it is associated with non-curative factors, peritoneal dissemination, and liver or lymph nodes metastases. However, a small subpopulation of patients with P(-)CY(+) showed an intermediate prognosis.

Surgically resected hepatocellular carcinomas in patients with non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Surgically resected hepatocellular carcinomas (HCC) in patients with non-alcoholic steatohepatitis (NASH) have rarely been described and the clinicopathological characteristics of HCC and non-cancerous liver tissue are still obscure. METHODOLOGY: From 1997 to 2004, 242 patients with HCC underwent hepatic resection at the Hiroshima Red Cross Hospital and Atomic Bomb Survivors' Hospital. Among this group, the diagnosis of NASH was made in 3 patients. RESULTS: All 3 patients with HCC had cirrhosis. The tumor cells contained Mallory bodies and fat. The non-cancerous areas showed nodular regeneration with fatty changes, ballooning degeneration, and mild inflammatory infiltrates, as well as perivenular and perisinusoidal fibrosis. CONCLUSIONS: Patients with NASH and cirrhosis may progress to HCC, and careful follow-up based on tumor markers and imaging modalities, is essential to detect resectable HCC in patients with NASH and cirrhosis.

Impact of obesity on the surgical outcome following repeat hepatic resection in Japanese patients with recurrent hepatocellular carcinoma.

AIM: To evaluate the impact of obesity on the posto-perative outcome after hepatic resection in patients with hepatocellular carcinoma (HCC). METHODS: Data from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC were studied. We compared the surgical outcomes between the non-obese group (body mass index: BMI < 25 kg/m(2)) and the obese group (BMI > or = 25 kg/m(2)). RESULTS: Following curative hepatectomy in patients with primary HCC, the incidence of postoperative complications and the long-term prognosis in the non-obese group (n = 240) were comparable to those in the obese group (n = 88). Among patients with recurrent HCC, the incidence of postoperative complications after repeat hepatectomy was not significantly different between the non-obese group (n = 44) and the obese group (n = 16). However, patients in the obese group showed a significantly poorer long-term prognosis than those in the non-obese group (P < 0.05, five-year survival rate; 51.9% and 92.0%, respectively). CONCLUSION: Obesity alone may not have an adverse effect on the surgical outcomes of patients with primary HCC. However, greater caution seems to be required when planning a repeat hepatectomy for obese patients with recurrent HCC.

Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case.

Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the c-kit receptor gene, which are targets for imatinib mesylate. However, imatinib resistance is an increasing clinical problem. We herein present such a case with a recurrent GIST, in association with the development of a secondary mutation in the c-kit gene. A 67-year-old man, who had a GIST of the stomach with multiple liver metastases, underwent a partial gastrectomy, distal pancreatectomy, and partial hepatectomy. After surgery, he was treated with imatinib. However, during the approximately 4-year treatment period, a recurrence of the GIST in the liver was detected, for which a partial hepatectomy was again performed. The primary GIST constitutively had a deletion mutation in exon 11. In addition, the recurrent hepatic tumor developed a secondary point mutation (Val654Ala) in exon 13, which may be responsible for the imatinib resistance.

[A case of systemic amyloidosis treated by chemotherapy with autologous peripheral blood stem cell transplantation].

A 67-year-old woman was admitted to our hospital because of breathlessness. Systemic amyloidosis had been diagnosed 5 years previously. Her chest X-ray film showed multiple nodules in both lung fields. Chest computed tomography (CT) revealed some of the nodules had calcifications. Bronchoscopy demonstrated amyloid deposits in the bronchial walls. The serum titer of anti-SS-A antibody was high. Results of both the Schirmer Test and the Rose-Bengal Test were positive. The final diagnosis was systemic amyloidosis with Sjögren's syndrome. She was treated by chemotherapy using high dose melphalan with autologous peripheral blood stem cell transplantation (PBSCT). It was obvious that her chest X-ray film findings and bronchoscopic findings had improved 9 months after high dose chemotherapy with PBSCT. The disappearance of M protein and improvement of thirst, a symptom of Sjögren's syndrome, were also observed.

[A case of natural killer cell lymphoma with high adenosine deaminase level in pleural effusion].

A 61-year-old man was admitted to our hospital with cough, breathlessness, anorexia and chest pain. Chest radiograph showed right pleural effusion and also a chest CT scan showed right pleural effusion with thickening of the right visceral pleura, pericardial effusion and a liver tumor. The pleural effusion was slightly bloody and exudative. The adenosine deaminase (ADA) level in the pleural effusion was elevated. Because the cytological examintion of the pleural effusion showed no malignancy, we diagnosed pleuritis tuberculosa. The serum-soluble interleukin-2 receptor level was also elevated. His general condition worsened in spite of the chemotherapy with antibiotics and antituberculous drugs. We finally diagnosed the case as natural killer (NK) cell lymphoma from CT-guided needle biopsy just before death, and necropsy. In this case, the high level of ADA in the pleural effusion suggested lymphoma.

[Case of pulmonary carcinosarcoma and a summary of 17 cases reported in Japan].

The patient was a 69-year-old man who complained of dyspnea and severe general fatigue. Chest CT showed a large tumor (6 x 5 cm) in the left S3 together with left pleural effusion. Despite pleurodesis and chemotherapy, he died 1.5 months after admission. At autopsy, a final diagnosis of pulmonary carcinosarcoma was obtained. We have summarized 17 cases of pulmonary carcinosarcoma reported in Japan. All patients were men, and had an average age of 68 years. The majority of the patients were heavy smokers. Death was reported in 70% of cases, the median survival period being 5 months, whereas the patients reported as living had operable cases of T2 tumor without distant metastatic lesions.

[A case of primary pulmonary leiomyosarcoma with history of pneumonia 5 years before].

A 35-year-old woman with past history of pneumonia in the right lung field 5 years before was admitted to our hospital because of fever and cough. Chest radiographs showed a pulmonary tumor with atelectasis of the right lower lung. Chest CT also revealed a round clear-edged tumor at the right S6 with atelectasis of the right lower lung lobe. Bronchoscopic findings showed a yellowish endobronchial tumor in the right truncus intermedius, which proved to be leiomyosarcoma. We could not find any other malignant lesion, and therefore, on a diagnosis of primary pulmonary leiomyosarcoma, right middle and lower lobectomy was performed with lymph node excision. Retrospective examination of the chest radiographs revealed not only that the original region of the leiomyosarcoma seemed to be near the site of the earlier pneumonia, but also that the atelectasis-like findings 2 years before were similar to the findings on this admission. It was reported that, if an operation could not be performed at an early stage, the prognosis might be poor. In the follow-up of the abnormal chest radiographic findings, the clinic physician should observe the symptoms from the same viewpoint as hospital doctors. It is important to keep an active relationship between clinic and hospital. We might have reached our final diagnosis earlier if we had been more active in seeking an examination for abnormal chest radiographic findings, without attaching too much importance to the patient's age.

[A case of severe pneumoconiosis with synchronous triple lung cancer].

A 70-year-old man who had worked in a stonepit for about fifty years was admitted to our hospital for detailed examination of the signs of pneumoconiosis (3/3, q) and a nodular shadow in the right upper lung field. Under a clinical diagnosis of lung cancer complicated with pneumoconiosis, right upper lobectomy with a right S6 resection was performed. Pathological examination revealed moderately differentiated adenocarcinoma of the right S2, well-differentiated adenocarcinoma of the right S6, and a squamous cell carcinoma of the right S1 which was not detected by chest CT. In addition to the difficulty of diagnosing lung cancer in a patient with severe pneumoconiosis, treatment for lung cancer may be limited by the poor pulmonary function that results from pneumoconiosis. Although the labor administration's decision that lung cancer patients with concomitant pneumoconiosis deserve compensation can be evaluated as a good one, the study of the relationship between pneumoconiosis and lung cancer needs further study through follow-up examination of pneumoconiosis cases.