Eicosapentaenoic acid attenuates obesity-related hepatocellular carcinogenesis.

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity, is an emerging risk factor for hepatocellular carcinoma (HCC). Accumulating evidence has shown that chronic inflammation represents a plausible link between obesity and HCC and that the pro-inflammatory cytokine interleukin (IL)-6 contributes to the development of obesity-related HCC. In the present study, we aimed to examine the therapeutic potential of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), which exerts anti-inflammatory effects. The results showed that the development of carcinogen-induced HCC was significantly less in mice fed a high-fat diet (HFD) supplemented with EPA than in those fed HFD only, suggesting that EPA attenuates the development of obesity-related HCC. Although EPA did not appear to affect obesity-linked inflammation, it suppressed the activation of the pro-tumorigenic IL-6 effector STAT3, contributing to the inhibition of tumor growth. These findings suggest a clinical implication of EPA as a treatment for obesity-related HCC.

Clinicopathological differences between proximal and distal pT3 colon cancer and the clinical significance of the depth of cancer invasion beyond the muscularis propria.

BACKGROUND/AIMS: To investigate differences in clinicopathological features between proximal and distal pT3 colon cancers and to determine whether the depth of the cancer invasion beyond the muscularis propria (DBM) serves as an objective indicator of the depth of tumor invasion in proximal colon cancer and in distal colon cancer. METHODOLOGY: A total of 207 patients who underwent surgery for proximal and distal pT3 colon cancer between 1996 and 2001 were included in the analysis. RESULTS: No differences were noted between proximal and distal cancers in lymph node metastasis, distant metastasis, lymphatic/venous invasion, histological type and curability of surgical resection, although proximal cancer patients were significantly older. High-grade malignancy appeared to be more commonly noted in the proximal colon cancer cases but there was no significant difference in prognosis between proximal and distal cancer patients. CONCLUSIONS: Regarding the correlation between DBM and prognosis, there was a significant decrease in the 5-year survival rate in patients with proximal lesions of DBM 3000µm or more, and patients with distal lesions of DBM 5000µm or more. DBM is thus an objective indicator of depth of tumor invasion for both proximal and distal lesions, a prognostic factor and a guide to determining whether postoperative adjuvant chemotherapy is indicated for pT3 colon cancer cases.

Disseminated Carcinomatosis of Bone Marrow as the Initial Presentation of Intrahepatic Cholangiocarcinoma without Jaundice: An Autopsy Case Report.

Disseminated carcinomatosis of the bone marrow (DCBM) is often accompanied by disseminated intravascular coagulation (DIC) and has a poor prognosis. DCBM develops most frequently in gastric cancer and is rarely associated with intrahepatic cholangiocarcinoma. A 41-year-old man was incidentally found to have DIC on his regular visit for ulcerative colitis and was diagnosed with DCBM with intrahepatic cholangiocarcinoma. He received intensive care, including chemotherapy, but died suddenly from hyperkalemia, possibly due to tumor lysis syndrome (TLS). The autopsy showed the periductal infiltrating type of intrahepatic cholangiocarcinoma and tumor necrosis, possibly due to chemotherapy, indicating the effectiveness of chemotherapy for DCBM with intrahepatic cholangiocarcinoma.

Extralobar sequestration with a pulmonary arterial feeding vessel.

Extralobar sequestrations are rare congenital malformations of the lung. They are usually located between the diaphragm and left lower lobe and receive their blood supply from the aorta. We report a case of extralobar sequestration in an atypical location with a pulmonary arterial feeding vessel. An 18-year-old woman presented with an abnormality on chest X-ray. Chest computed tomography revealed a lung field not communicating with the bronchus between the upper and lower right lung lobes. Three-dimensional reconstruction computed tomography demonstrated a feeding artery from the pulmonary artery draining into the pulmonary vein. We diagnosed her with extralobar sequestration and resected the sequestered lung using video-assisted thoracic surgery. Therefore, three-dimensional reconstruction computed tomography helped identify the abnormal blood vessels, and video-assisted thoracic surgery may be useful in the treatment of extralobar sequestration.

Elderly-Onset Multiple System Atrophy with Lewy Body Pathology: A Case Report.

An 81-year-old woman presented with a 2-year history of progressive dysarthria and gait disturbance. Subsequently, she developed orthostatic hypotension, obstructive sleep apnea, right-sided resting tremor, and rigidity. Together with characteristic findings of imaging studies, she was diagnosed with multiple system atrophy (MSA). Despite progressive dysphagia and repeated choking episodes, the patient elected not to use artificial feeding or tracheostomy. She died suddenly at age 91 after 12 years of illness. The autopsy revealed neuropathological features of both MSA and of Parkinson's disease. The peripheral autonomic ganglia revealed both pre- and postganglionic involvement by synucleinopathy, which may have underscored the sudden death of the patient. The patient survived 10 years after onset, despite the presence of multiple poor prognostic factors in MSA including the onset of old age and early appearance of orthostatic hypotension and falls, in addition to the complication of PD pathology found by autopsy. Multidisciplinary team approach and her preserved cognitive function may have been contributory to the long-term survival.

[Our experience of the treatment with cetuximab for unresectable advanced colorectal cancer].

We report here the experience of the treatment with cetuximab in our department. Thirteen patients were treated with cetuximab. Median age was 65-year-old including 8 males and 5 females. Six cases were treated with single administration, and seven were with CPT-11. Median number of treatment was 13 times. In evaluable 9 cases, partial response (PR) was obtained in 3 cases and stable disease (SD) and progressive disease (PD) were in 2 and 4 cases, so that the response rate and disease control rate were 33% and 56%, respectively. Median survival after initiation of cetuximab was 219 days. Skin toxicity was observed in 91% including only one case with grade 3. We think that it is important to control skin toxicity for a continuation of cetuximab.

[A case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after standard chemotherapy failure].

We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.

[Two cases of colorectal cancer patients with poor performance status who had unresectable liver metastasis effectively treated by cetuximab].

We reported two cases of colorectal cancer patients with EGFR-positive unresectable synchronous liver metastasis effectively treated by cetuximab after the progression of the prior chemotherapy. Case 1: A 49-year-old female with unresectable synchronous liver metastasis from colon cancer received cetuximab monotherapy as fifth-line therapy. Then, abdominal CT showed shrinkage of the liver metastasis (PR) and the performance status was improved from 3 to 0 as upper abdominal pain reduced. Case 2: A 67-year-old female with unresectable liver metastasis from colon cancer received cetuximab with CPT-11 combined therapy as fourth-line therapy. After that, liver metastasis also decreased (PR), and upper abdominal pain and PS were improved from 2 to 0. These two cases of KRAS status on cancer tissue also showed wild-type, and in these cases cetuximab proved effective.

Successful Resection of a Giant Pulmonary Colloid Adenocarcinoma via Median Sternotomy.

We report on a giant pulmonary colloid adenocarcinoma successfully resected using a median sternotomy approach. A 69-year-old woman visited our hospital owing to a giant mass detected on chest radiography. A giant cystic mass measuring 115 × 90 mm was detected in the right upper lung using computed tomography. We suspected mucinous adenocarcinoma and performed right upper lobectomy and mediastinal lymph node dissection with median sternotomy. The surgical field of view for the tumor and superior vena cava was satisfactory, and compression but not invasion of the superior vena cava and chest wall by the tumor was observed. The tumor was pathologically diagnosed as a colloid adenocarcinoma of stage IIIA with pT4N0M0. The postoperative course was uneventful, with no signs of recurrence at one and a half years after operation. Thus, this case demonstrates that for giant lung tumor surgery, median sternotomy is useful and safe for improving the surgical field of view.

Recurrent pericardial effusion with pericardial amyloid deposition: a case report and literature review.

Pericardial amyloidosis is a rare cause of pericardial effusion. Here, we report a case of recurrent pericardial effusion because of pericardial amyloid deposition. The patient was a man in his 40s admitted for pulmonary embolism. During hospitalization, arterial fibrillation and cardiac tamponade were observed, and an initial pericardial puncture was performed. Thereafter, pericardial puncture was repeated nine times over the next two years. Cytological examination of the pericardial effusion suggested malignant mesothelioma. Afterward, pericardial fenestration and partial resection were performed. Intraoperatively, a thickened pericardium and hemorrhagic pericardial effusion were noted. Histologically, the surface of the pericardium was covered by an eosinophilic amorphous material. Congo red and DYLON stains, electron microscopy, and immunohistochemical findings revealed localized amyloidosis composed of an immunoglobulin lambda light chain. Although the patient did not receive further treatment for 5 years postoperatively, his renal and cardiac functions remained within normal limits. Based on these findings, the patient was diagnosed with localized amyloidosis. So far, hemorrhagic pericardial effusion has been reported in few cases with systemic amyloidosis. Because localized immunoglobulin light-chain-derived (AL) amyloidosis may progress to systemic disease (although it is a very rare occurrence), long-term follow-up is necessary to detect recurrence or progression to a systemic form.

Metachronous Thin-Walled Cavity Lung Cancers Exhibiting Variable Histopathology.

We report a case of metachronous thin-walled cavity lung cancers exhibiting variable histopathology. A 70-year-old man visited our hospital because of a thin-walled cavity located in the right upper lobe, detected by chest computed tomography. Right upper lobectomy was performed and a histological diagnosis of squamous cell carcinoma was made. Computed tomography at 7 years posttreatment detected a new thin-walled cavity in the left lower lobe. Histopathology after video-assisted thoracic surgery left S6 segmentectomy revealed adenocarcinoma. Patients with primary lung carcinoma may present with thin-walled cavities; postoperative screening can aid early the detection of metachronous primary lung cancers of variable origin.

Enhancement of the Marginal Area in Colorectal Cancer Liver Metastasis on Computed Tomography Correlates With Microvessel Density and Clinicopathological Factors.

BACKGROUND: Previously, we aimed to predict the effect of bevacizumab in liver metastasis using the ratio of the computed tomography (CT) value for hepatic metastatic lesions in the arterial phase in contrast-enhanced (CE) CT to that on plain CT. However, there is no report on the relation between the CT contrast effect and microvessel density (MVD) in liver metastasis. PATIENTS AND METHODS: Thirty-two patients who underwent liver resection for metastasis from colorectal cancer (excluding neoadjuvant chemotherapy cases) between April 2006 and October 2011 at our Department were analyzed retrospectively. The relation between the CE ratios obtained from the whole tumor or tumor margin and the MVD using the liver metastatic lesion of colorectal cancer were analyzed. It was also examined whether the CE ratios and MVD were related to the clinicopathological factors of the primary tumor. RESULTS: There was a significant correlation between the CE ratios obtained from assessment using the entire tumor and the tumor margin as regions of interest (ROI). Furthermore, there was a significant correlation between the MVD and CE ratios. Cases with lymphatic invasion, N2, N3 nodal status and grade B and C were significantly more often observed in the group with high MVD. In contrast, in the group with high CE using the whole tumor as ROI, cases with grade B or C were significantly fewer. However, the number of hepatic metastasis was significantly higher and the diameter was significantly larger in the group with high CE using the tumor margin as ROI. Moreover, cases with grade B or C were recognized significantly more often. CONCLUSION: The CE ratio correlated with the MVD. The CE ratio using the tumor margin was similar to the MVD in relation to the clinicopathological factors. Taken together, these findings suggest that the CE ratio using the tumor margin as ROI may reflect MVD.

Changes of immunological parameters reflect quality of life-related toxicity during chemotherapy in patients with advanced colorectal cancer.

UNLABELLED: Anticancer drugs may frequently induce host immunosuppression and symptomatic toxicities. Once symptomatic toxicity occurs, the patient's quality-of-life (QOL) is reduced. Since little is known of the relationship between host immunity and the toxicity of chemotherapy, the host immunity before and after chemotherapy was compared to assess whether it is related to symptomatic toxicity during chemotherapy. PATIENTS AND METHODS: Fourteen patients with colorectal cancer underwent leucovorin /5-fluorouracil (LV/5-FU) treatment, or S-1/irinotecan (CPT-11). Host immunity (cytokine production of peripheral blood mononuclear cell (PBMC), serum soluble interleukin-2 receptor (sIL-2R) levels and phenotypic analyses of PBMC were measured before and after the first chemotherapy. RESULTS: An increase of sIL-2R, CD4+CD25+ T-cells and the CD4/8 ratio in patients with symptomatic adverse reactions were found. These changes in the first chemotherapy were significantly different (p = 0.0211, p = 0.0087, p = 0.0234). CONCLUSION: The current study indicated that there are some parameters correlated with toxicity during chemotherapy which effect QOL. In such patients, negative influences on host immunity, such as an increase of sIL-2R and regulatory T-cells, and a decrease of cytotoxic T-cells could occur.

Successful treatment with S-1 plus CPT-11 for lymph node metastasis from colon cancer: report of a case.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo), based on the biochemical modulation of 5-fluorouracil (5-FU). S-1 plus irinotecan (CPT-11) for advanced colorectal cancer as expected showed equally good results as these with CPT-11 plus infusional 5-FU/LV (FOLFIRI regimen). A case of unresectable lymph node metastasis from colon cancer successfully treated with S-1 plus CPT-11 is reported here. A 65-year-old man had metastasis to the lymph nodes in the left supra clavicular region and the superior mesenteric artery. S-1 plus CPT-11 was chosen for the treatment. After 2 courses, since grade 2 toxicity for dysgeusia was observed, S-1 administration was shortened. After 3 courses of the revised regimen, the enlarged lymph nodes disappeared on conventional CT and fluorine-18 fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT) and the case was assessed as a complete response (CR). Because CR was continued by an additional four courses of treatment, the regimen was changed to a single administration of S-1. Although eighteen months have passed since the induction of CR by S-1 plus CPT-11 therapy, no symptoms or findings of relapse have been observed.

[Cancer stromal cells influence on the tumor angiogenic pattern].

Since the progression and metastasis of solid tumors depend on their local microcirculation, we sought to characterize the tumor angiogenesis three-dimensionally in a highly metastatic mouse melanoma model, B16BL6 melanoma injected with Matrigel into syngeneic C57BL/6 mice by using confocal laser scanning microscopy and transmission electron microscopy. We found that B16 melanoma within Matrigel grew significantly quicker than B16 melanoma alone and was accompanied by altered tumor angiogenesis and avascular area. We characterized the unique patterns of avascular area by using confocal laser-scanning microscopy and transmission electron microscopy.

[A prediction of prognosis by A-L score in patients with stage IV colorectal cancer].

We analyzed the relationship between A-L score classified by serum albumin level and lymphocytes/white blood cells ratio and clinicopathological features in patients with Stage IV colorectal cancer. Seventy-nine patients were classified by the A-L score. In lower-scored cases, the populations of elderly patients, patients with emergency operation and patients with poorer PS were increased. Additionally, the 2-year survival rate was decreased as low as A-L score. In the multivariate analysis, the A-L score was independent prognostic factor in Stage IV colorectal cancer.

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer].

Bevacizumab, a humanized monoclonal antibody to VEGF for advanced recurrent colorectal cancer, has been known for complications of gastrointestinal perforation, hemorrhage, thromboembolism and proteinuria, as adverse effects. These findings must be taken care as well as adverse drug reactions (ADR) caused by combination chemotherapy. We here in present a clinical experience in treatment with bevacizumab for unresectable colorectal cancer. Six patients treated with bevacizumab for over two courses until April 2008 were analyzed for this study. PR was obtained in one case with mFOLFOX6. Even though, grade 3 neutropenia was observed in only one case with FOLFIRI, the other cases had grade 2 or less in ADR. In addition, there were no any specific ADRs related with bevacizumab, so we concluded that combination chemotherapy for advanced recurrent colorectal cancer with bevacizumab was well-tolerated.

[Reduction of oxaliplatin-related neurotoxicity by calcium and magnesium infusions].

PURPOSE: Oxaliplatin in combination with infusional 5-fluorouracil/leucovorin (FOLFOX) have emerged as the standard of care in the therapy of advanced-stage colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. We decided to use Ca and Mg for prevention of oxaliplatin-related neurotoxicity with reference to the report of Gamelin et al. METHODS: The subjects were 14 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m(2)) was given intravenously as FOLFOX regimen. All 14 patients received infusions of Ca gluconate and Mg sulfate before and after oxaliplatin. RESULTS: Only 1 patient had grade 3 toxicity (nausea and vomiting). Sensory neuropathy occurred in 8 patients (57.1%). There was no neurotoxicity with functional impairment in this study. Sensory neuropathy hardly occurred before 4 cycles. CONCLUSIONS: Ca/Mg infusions seem to prevent acute oxaliplatin-induced neurotoxic.

[Extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion--a case report].

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.

Well-differentiated adenocarcinoma associated with ulcerative colitis.

OBJECTIVES: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. METHODS AND RESULTS: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. CONCLUSIONS: These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed.