Masakazu Ikenaga

High Incidence of Thrombosis of the Portal Venous System After Laparoscopic Splenectomy: A Prospective Study With Contrast-Enhanced CT Scan

Objective:The aims of this prospective study were to investigate the true incidence of portal or splenic vein thrombosis (PSVT) after elective laparoscopic splenectomy using contrast-enhanced computed tomography (CT) scan, and outcome of anticoagulant therapy for PSVT. Summary Background Data:Although rare, thrombosis of the portal venous system is considered a possible cause of death after splenectomy. The reported incidence of ultrasonographically detected PSVT after elective open splenectomy ranges from 6.3% to 10%. Methods:Twenty-two patients underwent laparoscopic splenectomy (LS group), and 21 patients underwent open splenectomy (OS group). Preoperative and postoperative helical CT with contrast were obtained in all patients, and the extent of thrombosis was investigated. Prothrombotic disorder was also determined. Results:PSVT occurred in 12 (55%) patients of the LS group, but in only 4 (19%) of the OS group. The difference was significant (P = 0.03). Clinical symptoms appeared in 4 of the 12 LS patients. Thrombosis occurred in the intrahepatic portal vein (n = 9), extrahepatic portal vein (n = 2), mesenteric veins (n = 1), proximal splenic vein (n = 4), and distal splenic vein (n = 8). Prothrombotic disorder was diagnosed in 1 patient. Anticoagulant therapy was initiated once the diagnosis was established, and complete recanalization, except for distal splenic vein, was observed without any adverse event. Patients with splenomegaly were at high risk of PSVT. Conclusions:PSVT is a more frequent complication of laparoscopic splenectomy than previously reported but can be treated safely following early detection by CT with contrast.

Comparative Detection of Lymph Node Micrometastases of Stage II Colorectal Cancer by Reverse Transcriptase Polymerase Chain Reaction and Immunohistochemistry

PURPOSE Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application. PATIENTS AND METHODS Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis. RESULTS Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR-negative, with respect to both disease-free and overall survival (P =.027 and.015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohns-like lymphoid reaction were both independent prognostic factors. CONCLUSION Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.

Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

We examined the RNA content of the gene encoding angiopoietin (Ang)‐2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse‐transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang‐2 protein expression. Tie‐2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang‐2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P = .002). Western blot analysis suggested that expression of Ang‐1, Ang‐2, Tie‐2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang‐2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang‐2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver. (HEPATOLOGY 2004;39:528–539.)

Fusion Image of Positron Emission Tomography and Computed Tomography for the Diagnosis of Local Recurrence of Rectal Cancer

BackgroundThe aim of this study was to evaluate the clinical and therapeutic value of digital fusion image (FI) of positron emission tomography (PET) using 18F-fluorodeoxy glucose and computed tomography (CT) in patients who were suspected of having a local recurrence of rectal cancer.MethodsForty-two patients (32 men and 10 women; mean age, 61.4 years, range, 40–79 years) with a suspicion of local recurrence after curative resection of rectal cancer were prospectively recruited and underwent 18F-fluorodeoxy glucose-PET and CT. The FI was reconstructed with a commercially available digital software program, T-B Fusion. Wilcoxon signed rank test was used to compare FI with CT alone or PET alone.ResultsFI yielded a correct diagnosis in 39 (93%) of 42 patients, whereas CT alone and PET alone did so in 33 (79%) and 37 (88%) patients, respectively. FI had better diagnostic accuracy than CT alone (P = .0138) and PET alone (P = .0156). Overall, FI altered patient management in 11 (26.2%) patients on the basis of additional information, including differentiation of the tumor from the postoperative scar in 6 patients, exact anatomical location in 3 patients, and both in 2 patients.ConclusionsFI has a potential clinical value in the treatment of suspected local recurrence of rectal cancer.

A Multicenter Prospective Study of Surgical Audit Systems

Objective:This study was undertaken to evaluate a modified form of Estimation of Physiologic Ability and Surgical Stress (E-PASS) for surgical audit comparing with other existing models. Background:Although several scoring systems have been devised for surgical audit, no nation-wide survey has been performed yet. Methods:We modified our previous E-PASS surgical audit system by computing the weights of 41 procedures, using data from 4925 patients who underwent elective digestive surgery, designated it as mE-PASS. Subsequently, a prospective cohort study was conducted in 43 national hospitals in Japan from April 1, 2005, to April 8, 2007. Variables for the E-PASS and American Society of Anesthesiologists (ASA) status-based model were collected for 5272 surgically treated patients. Of the 5272 patients, we also collected data for the Portsmouth modification of Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) in 3128 patients. The area under the receiver operative characteristic curve (AUC) was used to evaluate discrimination performance to detect in-hospital mortality. The ratio of observed to estimated in-hospital mortality rates (OE ratio) was defined as a measure of quality. Results:The numbers of variables required were 10 for E-PASS, 7 for mE-PASS, 20 for P-POSSUM, and 4 for the ASA status-based model. The AUC (95% confidence interval) values were 0.86 (0.79–0.93) for E-PASS, 0.86 (0.79–0.92) for mE-PASS, 0.81 (0.75–0.88) for P-POSSUM, and 0.73 (0.63–0.83) for the ASA status-based model. The OE ratios for mE-PASS among large-volume hospitals significantly correlated with those for E-PASS (R = 0.93, N = 9, P = 0.00026), P-POSSUM (R = 0.96, N = 6, P = 0.0021), and ASA status-based model (R = 0.83, N = 9, P = 0.0051). Conclusion:Because of its features of easy use, accuracy, and generalizability, mE-PASS is a candidate for a nation-wide survey.

Molecular analysis of diminutive, flat, depressed colorectal lesions: are they precursors of polypoid adenoma or early stage carcinoma?

BACKGROUND The diminutive, flat depressed colorectal lesion is a possible precursor of early stage carcinoma. However, the significance of this lesion in colon carcinogenesis remains unclear. METHODS Eighty-one diminutive flat lesions (<5 mm diameter) with a central depression (DPdep) were resected colonoscopically and their molecular characteristics were investigated. In parallel, 68 diminutive polyps (<5 mm diameter) with a polypoid growth pattern but no depression (DPpo) were analyzed as controls. After histopathologic diagnosis, only neoplastic tissues were stained by immunohistochemistry for p53 gene and cyclooxygenase 2 (COX-2) and the proliferation marker, Ki-67. Mutation of the K-ras gene was analyzed with the polymerase chain reaction-restriction fragment length polymorphism method by using DNA from microdissected tissue in paraffin sections. RESULTS Seventy-nine of 81 DPdep and 35 of 68 DPpo were diagnosed as neoplastic. Mild, moderate, and severe dysplasia were found in, respectively, 56, 15, and 8 DPdep polyps, and in 34, 1, and 0 DPpo polyps. Thus, DPdep were more likely to be neoplastic and to exhibit moderate and severe dysplasia compared with DPpo (p < 0.0001). No DPdep or DPpo was positive for the p53 protein. The proportion of specimens with K-ras codon 12 mutation was 13.4% in diminutive polyps (DP), and tended to be lower in DPdep (8.6%) than in DPpo (25.0%) (p = 0.073). The median (interquartile range) of the Ki-67 index of DPdep tended to be lower than that of DPpo (respectively, 0.0 [0.0-5.9] vs. 4.5 [0.0-17.1]; p = 0.0281). COX-2 overexpression was observed in 12 of 77 (15.6%) DP and there was no significant difference between DPdep (3 of 23, 13.0%) and DPpo (9 of 54, 16.7%). CONCLUSION Diminutive, flat, depressed lesions in this study had low rates of the genetic alterations associated with malignant progression. This indicates that either a different neoplastic mechanism is operative or that these lesions have a lower malignant potential than indicated by their histopathologic features.

Value of general surgical risk models for predicting postoperative liver failure and mortality following liver surgery.

This study evaluated the ability of general surgical models to predict postoperative morbidity and mortality in liver surgery.

Effect of Preoperative Immunonutrition on Body Composition in Patients Undergoing Abdominal Cancer Surgery

PurposePreoperative immunonutrition may induce changes that modulate stress responses and improve the outcome of patients undergoing abdominal cancer surgery. We evaluated the effectiveness of preoperative immunonutrition using an immune-enhancing diet product called Impact.MethodsForty patients aged 20–75 years, who were scheduled to undergo abdominal cancer surgery, were given Impact for 5 days preoperatively, at 1000 ml/day, in addition to a regular diet. We took various measurements before and after Impact administration.ResultsAll but two patients tolerated a daily intake >900 ml (mean: 924 ml). The serum retinol-binding protein level increased from 3.21 to 3.76 mg/dl and the arginine level increased from 91.9 to 112.0 mmol/ml after Impact intake. The urinary excretion of uracil increased significantly, from 57.6 to 88.9 mmol/g creatinine, as did the content of n-3 fatty acids and the n-3/n-6 ratio in membrane phospholipids from the white blood cells. These changes were not observed in the two patients who did not tolerate Impact. There was no significant improvement in clinical outcome.ConclusionsPreoperative immunonutrition was well tolerated by cancer patients. It induced structural changes in the white blood cell membranes and increased the body store of arginine and nucleotides. These effects may modulate the response to surgical stress.

An icteric type hepatocellular carcinoma with no detectable tumor in the liver: report of a case.

A 70-year-old man was admitted to our hospital with obstructive jaundice. Computed tomography revealed a tumor in the left intrahepatic bile duct extending to the common bile duct without any significant lesions in the liver. Cholangiography showed a filling defect due to an intraductal tumor. Cytology of the bile juice was negative and tumor markers were carcinoembryonic antigen 5.7 ng/ml, carbohydrate antigen 19-9 49 U/ml, α-fetoprotein 9 ng/dl, and PIVKA-II 19 200 AU/ml. With a preoperative diagnosis of hilar bile duct carcinoma, a laparotomy was performed. The common bile duct was filled with a tumor and it extended into the bilateral intrahepatic bile ducts. The intraductal tumor was removed together with the extrahepatic bile ducts. An intraoperative histological examination of the tumor showed a well-differentiated hepatocellular carcinoma. No lesions were detected in the liver by ultrasonography, palpation during the operation, or a computed tomography scan after the operation. At 1 year postoperatively, no recurrence has been seen in this patient.

Cancer Stem-like Properties in Colorectal Cancer Cells with Low Proteasome Activity.

Purpose: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs. Experimental Design: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs. LPACs were isolated by flow cytometry. Treatment resistance (radio- and chemotherapy) and the capacity of LPACs to act as CSCs were analyzed. Microarray analysis was performed to reveal genes related to treatment resistance. The prognostic impact of potent genes was examined in 190 patients with colorectal cancer. Results: LPACs had a significantly increased capacity for radioresistance and chemoresistance (5-fluorouracil and oxaliplatin), significantly lower reactive oxygen species activity, and significantly increased sphere formation capacity compared with non-LPACs. The number of cells in the G0–G1 phase was significantly higher among LPACs. Subcutaneous injection of as few as 20 LPACs led to tumor formation in immunologically incompetent mice. Microarray analysis revealed that the expression of EP300-interacting inhibitor of differentiation 3 (EID3) was significantly increased in LPACs. In vitro assay revealed that EID3 positively controlled cell proliferation and treatment resistance. The high expression of EID3 was an adverse prognostic indicator in patients with colorectal cancer (P = 0.0400). Conclusions: LPACs have characteristic treatment resistance and act as CSCs in colorectal cancer. In addition, EID3 is one of the potential regulators of treatment resistance in colorectal cancer and may be a potential therapeutic target. Clin Cancer Res; 22(21); 5277–86. ©2016 AACR.