Laparoscopic enucleation of insulinomas.

HYPOTHESIS: Laparoscopic enucleation of insulinomas is safe and effective and is associated with a short hospital stay. DESIGN: Case series identified through retrospective review of medical records. SETTING: University of California, San Francisco Medical Center, a tertiary care referral hospital. PATIENTS: Nine patients with insulinomas that were thought to be suitable for laparoscopic enucleation. INTERVENTION: Laparoscopic enucleation of solitary insulinomas of the pancreas. MAIN OUTCOME MEASURES: Successful enucleation, conversion to open operation, postoperative complications, and duration of hospitalization. RESULTS: Seven of 9 patients had curative laparoscopic enucleations of insulinomas. In the 2 other patients, the laparoscopic approach was converted to an open operation to perform a distal pancreatectomy. All patients were cured. Computed tomography (CT) localized the tumor in 5 of 9 patients; laparoscopic enucleation was successful in all 5. Endoscopic ultrasonography correctly identified the lesions in 2 of 3 patients with nondiagnostic CT scans. Both lesions were successfully enucleated laparoscopically. Postoperative pancreatic fistulas occurred in 7 of 9 patients, but they caused little morbidity. No patient required another operation. Five of 7 patients treated laparoscopically were discharged to home on the first postoperative day. CONCLUSIONS: Laparoscopic enucleation was safe and effective. If the lesion was seen on CT, it could be removed laparoscopically. Endoscopic ultrasonography was useful for identifying lesions in patients whose CT scans were nondiagnostic. Pancreatic fistulas were common, but they resolved spontaneously and produced little morbidity. Laparoscopic enucleation resulted in a short hospitalization and rapid recovery for most patients.

Key factors for successful en bloc endoscopic submucosal dissection of early stage gastric cancer using an insulation-tipped diathermic knife.

BACKGROUND/AIMS: En bloc endoscopic mucosal resection (EMR) is presently considered to be the treatment of choice for endoscopically resectable early stage gastric cancer (EGC). Although a new EMR technique using an insulation-tipped diathermic knife (endoscopic submucosal dissection using an IT knife: IT knife-ESD) is reportedly suitable for en bloc resection, a failure in en bloc resection (piecemeal resection) can occur. We retrospectively analyzed factors affecting the success rate of en bloc resection by IT knife-ESD. METHODOLOGY: A total of 71 gastric lesions were treated by IT knife-ESD. En bloc/piecemeal resection rates were investigated. Twelve potential factors associated with clinicopathological characteristics or procedures were analyzed univariately and multivariately. RESULTS: IT knife-ESD was successfully performed in all 71 lesions. En bloc resection was achieved in 63 lesions (91%), while eight lesions (9%) were removed as two or more fragments (piecemeal resection). The multivariate analysis identified only one independent factor affecting the success rate of en bloc resection: the second-half period of procedure application. The en bloc resection rate was not associated with the tumor location/site, tumor size, specimen size, and ulceration within the tumor. CONCLUSIONS: Much experience with IT knife-ESD may resolve the tumor-related technical difficulties. It is true for this advanced procedure that endoscopist experience is highly likely to be a critical factor for treatment success. We consider that IT knife-ESD for EGC is feasible and safe when performed by experienced endoscopists.

Pancreatic carcinoma that completely obstructs the Wirsung duct without dilatation of the main pancreatic duct.

BACKGROUND AND AIM: Pancreatic carcinomas in which the main pancreatic duct (MPD) is completely obstructed are almost always associated with dilatation of the upstream MPD. However, some carcinomas are not associated with MPD dilatation despite complete MPD obstruction. This paradoxical phenomenon has not been well documented. METHODS: The findings from endoscopic retrograde cholangiopancreatography in 207 cases of pancreatic head carcinomas were analyzed with special reference to this unique type of carcinoma. Twenty-five of the patients were found to exhibit no MPD dilatation on ultrasonography, computed tomography or magnetic resonance imaging. RESULTS: Pancreatography via the major papilla showed complete obstruction of the MPD (112 patients with MPD dilatation and 6 without), stenosis (70 and 10, respectively), or no abnormal findings (0 and 9, respectively). In all six patients with complete MPD obstruction but without upstream MPD dilatation, injection of the minor papilla revealed a non-dilated dorsal pancreatic duct. The size of the obstructive carcinomas with and without MPD dilatation was comparable. CONCLUSIONS: Some (3%) pancreatic head carcinomas are not associated with MPD dilatation despite complete obstruction of the Wirsung duct. In such cases, the Santorini duct drains the dorsal pancreatic duct, completely compensating for the obstructed Wirsung duct. Attention should be paid to this unique type of carcinoma in diagnosing pancreatic head carcinomas.

En bloc endoscopic mucosal resection of a large early stage gastric cancer by combined use of an insulation-tipped diathermic knife and a grasping forceps percutaneously inserted into the gastric lumen.

A new endoscopic mucosal resection using an insulation-tipped diathermic knife (IT knife-EMR) is a promising procedure for en bloc resection of an early stage gastric cancer. However, the use of this procedure for a large lesion on the greater curvature of the gastric middle-upper body is technically difficult. With the help of a grasping forceps percutaneously inserted into the gastric lumen, which allowed traction to be applied to the lesion, a 66-year-old man with a large tumor (49mm in diameter) on the greater curvature of the gastric middle body underwent IT knife-EMR. This approach enabled easy dissection between the submucosa and the muscle layer by the IT knife under direct vision. The lesion was completely removed as a single piece. This new technique, employing IT knife-EMR in cooperation with a percutaneously inserted grasping forceps, could be a potential procedure to make original IT knife-EMR easier. This approach may enhance the utility of original IT knife-EMR for selected tumors, that is, large tumors on the greater curvature of the middle-upper body of the stomach and/or ulcerated tumors. We propose that the present approach may provide an important alternative to laparoscopic intragastric surgery.

Risk factors for acute pancreatitis after endoscopic papillary balloon dilation.

BACKGROUND/AIMS: Although EPBD (endoscopic papillary balloon dilation) may cause acute pancreatitis, risk factors for post-EPBD pancreatitis have not been well described. We retrospectively analyzed risk factors predictive of acute pancreatitis after EPBD. METHODOLOGY: A total of 101 patients underwent EPBD for choledocholithiasis. Post-EPBD acute pancreatitis was investigated. Nineteen potential risk factors, related to clinical characteristics or procedures, were retrospectively analyzed univariately and multivariately. RESULTS: Bile duct clearance was achieved in 96 patients. Serum amylase was elevated after EPBD in 69 patients. Early complications occurred in 11 patients (11%); 5 had minimal (pain persisting for only 12-24 hours) and 6 mild (requiring 1-3 days of treatment) pancreatitis. These 11 patients showed at least a three-fold elevation of serum amylase. Multivariate analysis identified two independent risk factors for pancreatitis (prior history of acute pancreatitis, and bile duct diameter < or = 9 mm). The risk for post-EPBD pancreatitis was not associated with young age, pre-EPBD hyperamylasemia, large or multiple stones, periampullary diverticulum, pancreatic contrast injection, mechanical lithotripsy or residual stones. CONCLUSIONS: Acute pancreatitis, usually mild or minimal, can be anticipated after EPBD for bile duct stones in approximately 10% of patients. In those with previous pancreatitis or a non-dilated bile duct, special care is necessary given the high incidence of pancreatitis.

Laminin-5 gamma 2 chain and matrix metalloproteinase-2 may trigger colorectal carcinoma invasiveness through formation of budding tumor cells.

UNLABELLED: Tumor budding has been reported to be significantly associated with lymph node or distant metastasis in colorectal carcinomas. We attempted to elucidate the contributing factors for the formation of budding tumor cells. PATIENTS AND METHODS: Fifty T1 colorectal carcinomas were immunostained using several antibodies against adhesion-related molecules, and the associations between tumor budding and clinicopathological factors were examined. RESULTS: Univariate analysis revealed that predominant histology, lymphatic permeation, depth of invasion, width of invasion, CD44 variant 6 expression, laminin-5 gamma 2 chain expression and stromal MMP-2 expression were associated with tumor budding. Multivariate analysis showed that lymphatic permeation, laminin-5 gamma 2 chain expression and stromal MMP-2 expression were independently and significantly associated with tumor budding. Furthermore, laminin-5 gamma 2 chain and stromal MMP-2 expression patterns were significantly associated with locoregional failure. CONCLUSION: These results suggest that laminin-5 gamma 2 chain and MMP-2 may contribute synergistically to the formation of budding tumor cells.

Matrix metalloproteinases may contribute compensationally to tumor invasion in T1 colorectal carcinomas.

BACKGROUND: Few investigators have focused on possible interactions among several MMPs collectively. MATERIALS AND METHODS: Immunostaining for MMP-7, MMP-2 and MT1-MMP was performed on 51 early invasive (T1) colorectal carcinomas, and correlations between the expressions of pairs of MMPs were examined. RESULTS: MMP-7 expression was positive at the invasive front in 18 (35%) out of 51 tumors. Cytoplasmic MMP-2 expression was positive in 20(39%) out of 51 tumors, whereas its expression in the stroma was positive in 17(33%) out of 51 tumors. MT1-MMP was localized predominantly in the tumor cell cytoplasm in 14 (27%) out of 51 tumors. There was an inverse correlation between MMP-7 and cytoplasmic MMP-2 expression with marginal significance (p = 0.06), and between MMP-7 and MT1-MMP expression with statistical significance (p = 0.01). The association between cytoplasmic MMP-2 and MT1-MMP expression was statistically significant (p = 0.0004). CONCLUSION: MMP-7 and MMP-2 or MT1-MMP may contribute compensationally to tumor invasion and metastasis in T1 colorectal carcinomas.

Coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomas.

We attempted to examine the correlation between matrilysin and laminin-5 gamma2 chain expression with reference to the number of dedifferentiation units along the entire invasive front (tumor budding). Immunostaining for hMMP-7 and laminin-5 gamma2 chain was performed in 50 T1 colorectal carcinomas, and immunoreactivity was evaluated at the invasive front of the tumor. On hematoxylin-eosin sections, the number of tumor budding was counted. The localization of matrilysin tended to be widespread compared with that of laminin-5 gamma2 chain. Matrilysin and laminin-5 gamma2 chain expression were positive in 28 (56%) and 15 (30%) tumors respectively. There was a significant correlation between matrilysin and laminin-5 gamma2 chain expression (P = 0.02). Matrilysin(+)/laminin-5 gamma2 chain(+) tumors had a significantly greater amount of tumor budding than matrilysin(-)/laminin-5 gamma2 chain(-) tumors (P = 0.003) or matrilysin(+)/laminin-5 gamma2 chain(-) tumors (P = 0.03). In conclusions, coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomas.

Predictive factors for acute pancreatitis and hyperamylasemia after endoscopic papillary balloon dilation.

BACKGROUND: Although endoscopic papillary balloon dilation may result in acute pancreatitis or hyperamylasemia, the risk factors for these complications have not been well documented. Risk factors predictive of acute pancreatitis and hyperamylasemia after endoscopic papillary balloon dilation were retrospectively analyzed. METHODS: In 118 patients who underwent endoscopic papillary balloon dilation for choledocholithiasis, postendoscopic papillary balloon dilation acute pancreatitis and hyperamylasemia (at least 3-fold elevation) were investigated. A multivariate analysis was conducted for 20 potential risk factors related to clinical and procedure characteristics. RESULTS: Bile duct clearance was achieved in 113 patients. Early complications in the form of mild pancreatitis occurred in 7 patients (6%). Multivariate analysis identified history of acute pancreatitis as the only risk factor for postendoscopic papillary balloon dilation pancreatitis. Postendoscopic papillary balloon dilation hyperamylasemia occurred in 30 patients (25%). Multivariate analysis identified 4 independent risk factors for hyperamylasemia: an age of 60 years or less, previous pancreatitis, bile duct diameter 9 mm or less, and difficult bile duct cannulation. CONCLUSIONS: Endoscopic papillary balloon dilation is associated with a relatively low occurrence (6%) of pancreatitis but a high frequency (25%) of hyperamylasemia. The latter may represent pancreatic irritation or latent pancreatic injury. Particular care is necessary when endoscopic papillary balloon dilation is performed in younger patients, those with a history of pancreatitis, patients with a nondilated bile duct, and when cannulation is difficult.

Laminin-5 gamma2 chain expression as a possible determinant of tumor aggressiveness in T1 colorectal carcinomas.

This study was undertaken to clarify the associations between laminin-5 y2 chain expression, and tumor budding and lymph node metastasis or local recurrence (locoregional failure) of 50 T1 colorectal carcinomas immunohistochemically. Fifteen (30%) of 50 lesions were positive for laminin-5 gamma2 chain expression. By univariate analysis, less histological differentiation (P = 0.02), nonpolypoid growth pattern (P = 0.03) and tumorbudding (P < 0.001) were associated with laminin-5 gamma2 chain positivity. By multivariate analysis, tumor budding alone was significantly associated with laminin-5 gamma2 chain positivity (P = 0.006), and correlation between nonpolypoid growth pattern and laminin-5 gamma2 chain positivity lost its significance (P = 0.09). Tumor budding (P = 0.004) and laminin-5 gamma2 chain expression (P = 0.001) were significantly associated with locoregional failure. Laminin-5 gamma2 chain expression may contribute to the formation of budding tumor cells at the invasive front, and immunostaining of this adhesion molecule may be useful in identifying high-risk patients for locoregional failure in T1 colorectal carcinomas.

Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas.

BACKGROUND: The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial. METHODS: In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitt's classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, alpha-catenin, beta-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically. RESULTS: By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear beta-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear beta-catenin and CD44 variant 6, and locoregional failure was marginally significant ( P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous alpha-catenin expression were marginally significant ( P = 0.06; P= 0.08), whereas, a relative grading of submucosal invasion was not significant ( P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding ( P = 0.005; P < 0.001). CONCLUSIONS: These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas.

High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its potential use in the diagnosis of liver neoplasms.

BACKGROUND: An increased level of high mobility group A (HMGA) gene/protein expression has been demonstrated to be associated with many human neoplasms originating from a variety of tissues. However, HMGA1 expression has not yet been studied in hepatic tumors. In this study, we analyzed HMGA1 expression in hepatic primary and metastatic tumors in order to verify whether determination of the HMGA1 expression level could provide any diagnostic advantages in the pathological diagnosis of hepatic tumors. METHODS: Twenty samples of hepatocellular carcinoma, 5 samples of intrahepatic cholangiocarcinoma, and 21 samples of metastatic adenocarcinoma to the liver (15 metastatic tumors from colorectal carcinoma and 6 metastatic tumors from pancreatic carcinoma) were analyzed immunohistochemically using an HMGA1-specific antibody. RESULTS: While no significant nuclear immunoreactivity was found in hepatocytes of non-neoplastic liver tissue, 40% (2/5) of intrahepatic cholangiocarcinomas, 53.3% (8/15) of metastatic lesions from colorectal carcinoma, and 100% (6/6) of metastatic lesions from pancreatic carcinoma showed positive immunoreactivity. In contrast, all 20 samples of hepatocellular carcinoma were negative for HMGA1 nuclear immunoreactivity. Thus, hepatocellular carcinoma represents the first case of malignant neoplasia in which HMGA1 expression is not induced, which presents a striking contrast to several previous studies demonstrating the significance of increased HMGA gene/protein levels in carcinogenesis and/or tumor progression. CONCLUSIONS: Based on these findings, we conclude that the HMGA1 protein level could serve as a potential diagnostic marker that may enable the differential diagnosis between hepatocellular carcinoma and intrahepatic cholangiocarcinoma or metastatic adenocarcinoma to the liver.

Diagnostic significance of high mobility group I(Y) protein expression in intraductal papillary mucinous tumors of the pancreas.

INTRODUCTION: Overexpression of the high mobility group I(Y), [HMGI(Y)], gene/proteins has been demonstrated in many types of human malignancies, suggesting that HMGI(Y) may play a vital role in the oncogenic transformation of cells. AIMS: To analyze HMGI(Y) expression in intraductal papillary mucinous tumor (IPMT) of the pancreas to verify whether determination of the HMGI(Y) expression level could provide any diagnostic advantages in the pathological diagnosis of IPMT. METHODOLOGY: Thirty-three different lesions from 25 patients with IPMT, including 20 with mild dysplasia, 7 with moderate dysplasia, and 6 with carcinoma, were analyzed immunohistochemically with use of an HMGI(Y)-specific antibody. RESULTS: Immunohistochemical analysis revealed that, although no significant immunoreactivity was found in cases of normal pancreatic duct or mild dysplasia, 28.6% (2/7) of moderate dysplasia showed multifocal immunoreactivity with moderate intensity. In contrast, in 50% (3/6) of the cases of carcinoma, intense multifocal or diffuse immunoreactivity occurred, almost equivalent to that observed in cases of duct cell carcinoma, whereas in the remaining 3 cases of carcinoma only a faint focal immunoreactivity occurred. Histologic examination revealed that these HMGI(Y)-positive carcinomas had an invasive growth pattern, whereas the HMGI(Y)-negative carcinomas were either carcinomas in situ or tumors with minimal invasion. Thus, an increased expression level of HMGI(Y) proteins was closely associated with the malignant phenotype in IPMT. CONCLUSION: On the basis of these findings, we propose that HMGI(Y) proteins could play an important role(s) in a multistage process of carcinogenesis of IPMT and that the HMGI(Y) protein level could serve as a potential diagnostic marker, which may enable the identification of tumor cells with potential to be biologically malignant.

Differential diagnosis of benign versus malignant nonfunctioning islet cell tumors of the pancreas: the roles of EUS and ERCP.

BACKGROUND: Differentiation between benign and malignant nonfunctioning islet cell tumors of the pancreas before surgery is often difficult. The roles of EUS and ERCP were evaluated in the differential diagnosis of these tumors. METHODS: Seven patients with histologically confirmed nonfunctioning islet cell tumors (4 benign, 3 malignant) underwent EUS and ERCP. OBSERVATIONS: EUS demonstrated a homogeneous hypoechoic mass or a hypoechoic mass with a regular central echogenic area in the 4 cases of benign tumor, and a hypoechoic mass with an irregular central echogenic area in all 3 cases of malignant tumor. The irregular central echogenic area corresponded to severe hemorrhage, necrosis, or fibrosis with hyalinosis (hyaline degeneration) on pathologic examination. ERCP demonstrated displacement or complete obstruction (because of ductal invasion) of the main pancreatic duct in 2 patients with malignant tumors and no abnormalities in the other 5 cases. CONCLUSIONS: In patients with nonfunctioning islet cell tumors, a hypoechoic mass with an irregular central echogenic area on EUS or complete obstruction of the main pancreatic duct on ERCP suggests malignancy.

Cavernous Pancreatic Ductal Ectasia with Smooth Muscle Proliferation Causing Recurrent Acute Pancreatitis.

Pancreatic cystic lesions have various etiologies,including pseudocyst (inflammatory cyst), retentioncyst, congenital cyst, and neoplastic cyst (1).Recently, we experienced a case with a uniquepancreatic cyst-like lesion causing recurrent acutepancreatitis. This patient had multiple cystic dilatations of branch pancreatic ducts surrounded by proliferationof smooth muscle tissue, with neither neoplastic nor inflammatory changes. To our knowledge, there are no previous reports of such a case.