Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

BACKGROUND: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. METHODS: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. RESULTS: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. CONCLUSION: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.

Risk Factors for Recurrence in Pancreatic Neuroendocrine Tumor and Size as a Surrogate in Determining the Treatment Strategy: A Korean Nationwide Study.

INTRODUCTION: The prognostic factors of pancreatic neuroendocrine tumor (PNET) are unclear, and the treatment guidelines are insufficient. This study aimed to suggest a treatment algorithm for PNET based on risk factors for recurrence in a large cohort. METHODS: Data of 918 patients who underwent curative intent surgery for PNET were collected from 14 tertiary centers. Risk factors for recurrence and survival analyses were performed. RESULTS: The 5-year disease-free survival (DFS) rate was 86.5%. Risk factors for recurrence included margin status (R1, hazard ratio [HR] 2.438; R2, HR 3.721), 2010 WHO grade (G2, HR 3.864; G3, HR 7.352), and N category (N1, HR 2.273). A size of 2 cm was significant in the univariate analysis (HR 8.511) but not in the multivariate analysis (p = 0.407). Tumor size was not a risk factor for recurrence, but strongly reflected 2010 WHO grade and lymph node (LN) status. Tumors ≤2 cm had lower 2010 WHO grade, less LN metastasis (p < 0.001), and significantly longer 5-year DFS (77.9 vs. 98.2%, p < 0.001) than tumors >2 cm. The clinicopathologic features of tumors <1 and 1-2 cm were similar. However, the LN metastasis rate was 10.3% in 1-2-cm sized tumors and recurrence occurred in 3.0%. Tumors <1 cm in size did not have any LN metastasis or recurrence. DISCUSSION/CONCLUSION: Radical surgery is needed in suspected LN metastasis or G3 PNET or tumors >2 cm. Surveillance for <1-cm PNETs should be sufficient. Tumors sized 1-2 cm require limited surgery with LN resection, but should be converted to radical surgery in cases of doubtful margins or LN metastasis.

Prognostic Prediction Models for Resection of Large Hepatocellular Carcinoma: A Korean Multicenter Study.

BACKGROUND: We developed a prognostic prediction model (PPM) using 4 factors for hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin, and tumor volume (TV) (ADV score) is a surrogate marker for post-resection prognosis. This study intended to validate the predictive power of 4-factor PPM and to develop new ADV score-based PPM. METHODS: A total of 526 patients who underwent HR for solitary HCC ≥ 8 cm were selected from 9 Korean institutions between 2008 and 2014. RESULTS: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively. Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and 70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor recurrence and patient survival included AFP ≥ 100 ng/mL, hypermetabolic FDG-positron emission tomography (PET), microvascular invasion and satellite nodules, which comprised 4 factors of the PPM. Five subgroups based on the number of involved risk factors exhibited significant differences in tumor recurrence and patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster prognostic analysis. Patient grouping according to combination of ADV7log and FDG-PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence and patient survival, comparable to those of the 4-factor PPM. CONCLUSIONS: Two PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of early HCC recurrence and long-term survival outcomes in patients who underwent HR for large HCC. We believe that these PPMs can guide surgical treatment for large HCCs from preoperative HR planning to post-resection follow-up.

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post-hepatectomy liver failure.

OBJECTIVES: The actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15). METHODS: Medical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi-hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established. RESULTS: In patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R(2) = 0.499 versus R(2) = 0.239). Post-hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity. CONCLUSIONS: Regardless of ICG R15, an sFLR of ≥ 25% in patients without cirrhosis, and an sFLR of ≥ 25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy.

Prognostic factors for survival after curative resection of distal cholangiocarcinoma: perineural invasion and lymphovascular invasion.

PURPOSE: The purpose of this study was to elucidate the prognostic factors for distal cholangiocarcinoma after curative resection, and to assess the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) as prognostic factors. METHODS: A retrospective analysis of 91 patients who underwent radical surgery for distal cholangiocarcinoma between March 2004 and October 2011 was performed. We analyzed the survival rate and prognostic factors affecting the survival. RESULTS: The overall 1-, 3- and 5-year survival rates were 84.1, 49.7 and 38.9 %, respectively. In the univariate analysis, the prognostic factors influencing the survival were the histological differentiation, lymph node (LN) involvement and TNM stage. In the multivariate analysis, LN metastasis was the only independent prognostic factor. Although patients with PNI tended to show poorer survival, it was not a statistically significant factor (3- and 5-year OS; 62.0 and 54.6 % vs. 42.8 and 30.9 %, P = 0.166). In the patients with a total lymph node count (TLNC) of 11 or less, PNI was a significant prognostic factor; however, it was not a significant factor in the patients with a TLNC over 11. Overall, the LVI had no influence on the patient survival. CONCLUSIONS: LN metastasis was the only significant prognostic factor after the curative resection of distal cholangiocarcinoma. In cases where adequate dissection was performed, it appeared that the PNI and LVI had no influence on the survival.

Sclerosing angiomatoid nodular transformation of the spleen related to IgG4-associated disease: report of a case.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare benign vascular mass, with fewer than 100 cases documented. It is generally recognized as a vascular lesion that develops in the red pulp of the spleen; however, its pathogenesis is not clearly defined. We report a case of SANT of the spleen, which presents evidence to support the hypothesis that this disease entity is associated with IgG4-associated disease. Microscopically, the tumor was composed of multiple vascular structures separated by fibrous connective tissue and immunohistochemical examination revealed positive staining for CD31, CD34, factor VIII, and IgG4. Further research based on large number of cases is warranted to clarify the pathogenesis of this tumor.

Pancreatic arteriovenous malformation treated with transcatheter arterial embolization: Two case reports and review of literature.

BACKGROUND: Various treatment methods are available for the treatment of pancreatic arteriovenous malformation (P-AVM); however, there are no established treatment options for asymptomatic P-AVM. CASE SUMMARY: A 47-year-old and a 50-year-old male patients sought treatment for P-AVM in the pancreas, which was incidentally detected during routine abdominal computed tomography and magnetic resonance imaging conducted as part of a health check-up. They underwent transcatheter arterial embolization (TAE), and over the course of a 9-year follow-up period, the AVM did not worsen and was asymptomatic. CONCLUSION: TAE can be considered as an alternative treatment option for P-AVM in selective cases where patients are asymptomatic or have a high surgical risk.

Pancreatic metastasis from papillary thyroid cancer: a case report and literature review.

Pancreatic metastasis from papillary thyroid cancer (PTC) is extremely rare; only 18 cases have been reported in the literature. However, several reviews have highlighted similar characteristics between metastatic and primary pancreatic tumors. The patient was a 51-year-old male with a history of total thyroidectomy, modified radical neck dissection, and radioactive iodine ablation for PTC in 2014. Nodules suspected of metastasis were found in both lungs on chest computed tomography (CT). However, after 6 months, a follow-up chest CT showed no increase in size; thus, a follow-up observation was planned. Six years after his initial diagnosis, abdominal CT and pancreas magnetic resonance imaging revealed a 4.7 cm cystic mass with a 2.5 cm enhancing mural nodule in the pancreas tail. We diagnosed the pancreatic lesion as either metastatic cancer or primary pancreas cancer. The patient underwent distal pancreato-splenectomy. After surgery, the pathological report revealed that the mass was metastatic PTC. Pancreatic metastasis from PTC indicates an advanced tumor stage and poor prognosis. However, pancreatectomy can increase the survival rate when the lesion is completely resectable. Therefore, surgical resection should be considered as a treatment for pancreatic metastasis from PTC.

Carcinosarcoma of the gallbladder: report of two cases.

Adenocarcinoma is the predominant histological type of carcinoma of the gallbladder, accounting for more than 80% of all gallbladder carcinomas. In contrast, carcinosarcoma of the gallbladder is an extremely atypical subset of gallbladder malignancies. It is characterized by the presence of both epithelial and mesenchymal components. Currently, fewer than 100 cases have been reported in the English literature. Therefore, knowledge and experience regarding this disease are limited. Recently, we experienced two cases of gallbladder carcinosarcoma, which were diagnosed as gallbladder carcinoma based on the preoperative clinical and radiological examinations. Cholecystectomies were performed in both cases, and the malignant tumor cells included carcinomatous and sarcomatous components histologically. The final pathological diagnoses were carcinosarcoma of the gallbladder. We herein report these two cases of gallbladder carcinosarcoma and review the previous pertinent literature.

Primary extragastrointestinal stromal tumor arising in the pancreas: report of a case.

Primary extragastrointestinal stromal tumors (EGISTs) arising in the pancreas are extremely rare, with only ten cases documented to our knowledge. We report a further case of EGIST of the pancreas. The patient was a 55-year-old man who presented with postprandial abdominal discomfort. Abdominal computed tomography and magnetic resonance imaging showed a lobulated heterogenous enhancing mass, 11 cm in diameter, in the abdominal cavity. No regional lymphadenopathy, ascites, or metastasis was seen radiologically. There was no obvious lesion in the stomach or small intestine. The initial diagnosis was a solid pseudopapillary tumor or serous cystic neoplasm. The patient underwent distal pancreatectomy with splenectomy. Microscopically, the tumor consisted of spindle cells arranged in short fascicles. Mitotic figures were seen in 7/50 high-power fields. Immunohistochemical examination revealed strongly positive staining for CD117. Based on these findings, the final pathologic diagnosis was a primary EGIST of the pancreas. This case consolidates the possibility that this rare tumor can involve the pancreas as a primary site and should be included in the differential diagnosis of cystic lesions in this site.

The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study.

Backgrounds/Aims: The goal of the present study was to evaluate the prognostic value of lymph node ratio (LNR) in distal cholangiocarcinoma (DCC) after curative intended surgery. Methods: Clinicopathological data of 162 DCC patients who underwent radical intended surgery between 2012 and 2020 were analyzed retrospectively. Prognostic factors related to overall survival (OS) and disease-free survival (DFS) were evaluated. Results: Median OS time and DFS time were 41 and 29 months, and 5-year OS rate and DFS rate were 44.7% and 38.1%, respectively. In the univariate analysis, significant prognostic factors for OS were histologic differentiation, American Joint Committee on Cancer (AJCC) stage, positive lymph node count, LNR, R1 resection, and perineural invasion. Preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, infiltrative type, histologic differentiation, AJCC stage, positive lymph node count, LNR, R1 resection, perineural invasion, and lymph-vascular invasion were significant prognostic factors for DFS in the univariate analysis. In the multivariate analysis, histologic differentiation, R1 resection, and LNR were the independent prognostic factors for both OS and DFS. The LNR ≥ 0.2 group had a significantly poor prognosis in terms of OS (hazard ratio, 3.915; p = 0.002) and DFS (hazard ratio, 5.840; p < 0.001). Conclusions: LNR has significant value as a prognostic factor of DCC related to OS and DFS. LNR has the potential to be used as a modified staging system with furthermore studies.

Comparison of laparoscopic and open colorectal resections for patients undergoing simultaneous R0 resection for liver metastases.

BACKGROUND: The role of laparoscopic colorectal resection for patients undergoing a simultaneous operation for liver metastases had not been established. This study compared the outcomes between laparoscopic and open colorectal resections for patients undergoing simultaneous surgery for liver metastases. METHODS: This study reviewed 40 consecutive patients undergoing simultaneous R0 resection of synchronous liver metastases between January 2003 and August 2008. In the study, 20 patients who underwent laparoscopic colorectal resection were matched with 20 patients who had an open approach. All available clinicopathologic variables possibly associated with outcome were compared. RESULTS: The laparoscopic and open groups had similar demographics. No patient undergoing the laparoscopic procedure experienced conversion to the open technique. No postoperative mortality occurred in either group. The estimated blood loss was significantly lower in the laparoscopic group than in the open group. Although the operating time in the laparoscopic group was significantly longer (358 vs. 278 min; p = 0.004), the patients in this group had bowel function return 1 day sooner on the average than those in the open group. No significant differences in postoperative complications were observed between the groups. The overall survival was 58.7% at 3 years and 49.2% at 5 years. The 3-year overall survival rate in the laparoscopic group was not significantly different from that in the open group (52.8 vs. 61.0%; p = 0.713). CONCLUSIONS: Laparoscopic colorectal resection with simultaneous resection of liver metastases has an outcome similar to that for an open approach but some short-term advantages.

Clinical features and surgical outcome of solid pseudopapillary tumor of the pancreas: 30 consecutive clinical cases.

BACKGROUND/AIM: This study examined the clinical characteristics and surgical outcomes of solid pseudopapillary tumors of the pancreas (SPT). METHODOLOGY: Cases of SPT encountered in our hospital between January 1994 and December 2009 were reviewed retrospectively. The clinicopathological factors in the benign and malignant cases were compared to determine what features of the tumor could suggest malignant potential. RESULTS: Thirty patients with SPT were identified: 26 females and 4 males with a average age of 30.5 years (range 9-66). The median size of the tumors was 6.2cm (range 1.25 to 15.0). Tumors were located in the head (50%), neck (3.3%), body (16.7%) and tail (30%) of the pancreas. Surgical procedures included a local tumor resection (10 cases) or radical resection, such as a pancreaticoduodenectomy (6 cases), central pancreatectomy (1 case) or distal pancreatectomy (13 cases). There was no recurrence after the surgical resection. All patients were alive at a median follow-up of 58 months (range 6 to 187). Among the clinico-pathological factors, the presence of calcification was associated with the malignant potential (OR=16.000, 95% CI=1.451-176.451, p=0.024). CONCLUSIONS: SPT is a less aggressive pancreatic neoplasm that differs from other pancreatic cancers. The prognosis is favorable after a surgical resection. The presence of calcification is a predictive factor for a malignant SPT.

Undifferentiated embryonal sarcoma of the liver presenting as a hemorrhagic cystic tumor in an adult.

BACKGROUND: Undifferentiated embryonal sarcoma (UES) of the liver is a rare, highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years of age). Only a few cases have been reported in adults, accounting for less than 1% of all primary liver neoplasms. METHODS: A 47-year-old woman presented with a palpable mass in the left upper abdomen. Magnetic resonance imaging revealed a 12x10 cm cystic mass with hemorrhage in the left lateral segment of the liver. The initial impression was a hemorrhagic cystic tumor of the liver. The patient underwent a left lateral sectionectomy of the liver. Histopathology and immunohistochemistry helped make a diagnosis of UES. RESULTS: The patient recovered uneventfully and received systemic chemotherapy. Radiologic examination for follow-up revealed a metastatic lesion in the lumbar spine (L5). She was subjected to radiotherapy at the lumbar spine. She survived 48 months. CONCLUSION: Although hepatic cyst as UES of the liver is difficult to diagnose because of its rarity in adults and lack of specific findings, it should be considered in a differential diagnosis.

Gallbladder paraganglioma with hemorrhage: A case report and literature review.

Gallbladder paraganglioma (GP) is a rare tumor, with only 12 cases reported in the literature to date. Due to its rarity, clinical information of GP is insufficient. We present a case of GP in a 48-year-old female along with a literature review of all GP cases described to date. A 48-year-old female presented with intermittent right upper abdominal pain. Preoperative imaging revealed a hematoma in the gallbladder lumen without any definite etiology. Laparoscopic cholecystectomy was performed. Gross examination of the gallbladder revealed multiple small stones and a large hematoma as well as a 1.6-cm-sized polypoid mass at the gallbladder fundus. Microscopic study of the polypoid mass showed a zellballen appearance. Immunohistochemical analysis revealed that the mass was positive for synaptophysin, CD56, and chromogranin, suggesting GP. GP is difficult to diagnose because of non-specific clinical findings. Almost all GP cases are diagnosed based on histologic findings after cholecystectomy. Simple cholecystectomy was performed as a treatment in all reported cases of GP, including our case. There was no postoperative tumor recurrence or metastasis after surgery.

Comparison of Oncologic Outcomes between Transduodenal Ampullectomy and Pancreatoduodenectomy in Ampulla of Vater Cancer: Korean Multicenter Study.

This study used multicenter data to compare the oncological safety of transduodenal ampullectomy (TDA) with that of pylorus-preserving pancreatoduodenectomy (PPPD) in early ampulla of Vater (AoV) cancer. Data for patients who underwent surgical resection for AoV cancer (pTis-T2 stage) from January 2000 to September 2019 were collected from 15 institutions. The clinicopathologic characteristics and survival outcomes were compared between the PPPD and TDA groups. A total of 486 patients were enrolled (PPPD, 418; TDA, 68). The oncologic behavior in the PPPD group was more aggressive than that in the TDA group at all T stages: larger tumor size (p = 0.034), advanced T stage (p < 0.001), aggressive cell differentiation (p < 0.001), and more lymphovascular invasion (p = 0.002). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the two groups when considering all T stages or only the Tis+T1 group. Among T1 patients, PPPD produced significantly better DFS (PPPD vs. TDA, 84.8% vs. 66.6%, p = 0.040) and superior OS (PPPD vs. TDA, 89.1% vs. 68.0%, p = 0.056) than TDA. Lymph node dissection (LND) in the TDA group did not affect DFS or OS (TDA + LND vs. TDA-only, DFS, p = 0.784; OS, p = 0.870). In conclusion, PPPD should be the standard procedure for early AoV cancer.

Feasibility of Laparoscopic Right Posterior Sectionectomy for Malignant Lesion Compared to Open Right Posterior Sectionectomy: Retrospective, Single Center Study.

Purpose: We aimed to compare the operative outcomes of laparoscopic right posterior sectionectomy (RPS) and open RPS and evaluate the feasibility of laparoscopic RPS. Methods: From January 2009 to December 2017, laparoscopic liver resections were performed in 235 patients at Chonnam National University Hwasun Hospital, South Korea. We retrospectively analyzed the clinical data of 16 patients who underwent laparoscopic RPS and compared the outcomes with those who underwent open RPS (n=17). Results: The laparoscopic group had a mean tumor size of 3.82±1.73 cm (open group [OG]; 4.18±2.07 cm, p=0.596), mean tumor-free margin of 10.44±9.69 mm (OG; 10.06±10.62 mm, p=0.657), mean operation time of 412.2±102.2 min (OG; 275.0±60.5, p<0.001), mean estimated blood loss of 339.4±248.3 ml (OG; 236.4±102.7 ml, p=0.631), mean postoperative hospital stay of 11.63±2.58 days (OG; 14.71±4.69 days, p=0.027), and mean postoperative peaks of aspartate aminotransferase, alanine aminotransferase, total bilirubin, and prothrombin time of 545 mg/dl, 538 mg/dl, 1.39 mg/dl, 1.41 international normalized ratio (OG; 237 (p<0.001), 216 (p<0.001), 1.52 (p=0.817), and 1.45 (p=0.468)), respectively. There were no deaths or major complications in ether group. There were no cases of open conversion. Laparoscopic RPS was associated with a shorter hospital stay, prolonged operation time and lower complication rate. With long-term prognosis, no difference was found in overall survival rate and disease-free survival rate between the two groups. Conclusion: Laparoscopic RPS can be performed, but the problems of long operative time and decrease in liver function should be resolved.

Comparison of laparoscopic versus open distal pancreatectomy for benign, pre-malignant, and low grade malignant pancreatic tumors.

BACKGROUNDS/AIMS: The purpose of this study is to demonstrate that laparoscopic distal pancreatectomy in benign disease is is safer and more favorable to patients than open distal pancreatectomy. METHODS: We retrospectively reviewed data of 150 patients who underwent laparoscopic (n=69) or open (=81) distal pancreatectomy at a double institutes from 2008 to 2018. We reviewed each patient's history for age, sex, pathologic diagnosis. Specific outcomes that were included hospital stay, operative time (in minutes), operative blood loss (in milliliters), 30-daymajormorbidity and mortality (Clavian-Dindo classification), pancreatic leak rate (grade of leak A, B, or C), pancreatic hemorrhage. RESULTS: From 2008 to 2018, there were 150 patients underwent distal pancreatectomy with or without splenectomy for benign pancreatic disease. 81 patients underwent open and 69 patients underwent laparoscopic distal pancreatectomy (LDP) Intra-operative estimated blood loss was significantly lower in the LDP group than in the OPD group (200 vs. 400 ml p<0.01). There was no difference in blood transfusion between the two groups. There was a significant difference in the resection method between the two groups (p<0.01) and there was a significant difference in the use of mesh for prevention of postoperative pancreatic fistula (POPF) (53 vs. 34 p<0.01). There was no significant difference in incidence of POPF (15.9% in LDP vs 7.4% in ODP, p=0.235) between the two groups, morbidity rate between the two groups (18 vs. 30 p=0.152), post - pancreatectomy hemorrhage, wound infection, hospital stay and readmission. CONCLUSIONS: LDP showed there was no difference in the occurrence of POPF, complication and hospital stay. In contrast, intra-operative blood loss was significantly lower in the LDP group than in the ODP group, and LDP was also significantly better in the view point of the feeding advance. In other words, LDP is safer and more favorable to patients than ODP.

Methanol extract of Elaeagnus glabra, a Korean medicinal plant, inhibits HT1080 tumor cell invasion.

Elaeagnus glabra (Thunb.), an evergreen shrub with alternate leaves, has been used as a medicinal plant in Korea. Since many plant-derived molecules have inhibitory effects on tumor cell invasion, primarily via suppression of the activity of matrix metalloproteinases (MMPs), we investigated the effect of the methanol extract of E. glabra on tumor cell invasion. The invasiveness of HT1080 human fibrosarcoma cells were reduced in a dose-dependent manner following 24 h treatment of up to 200 microg/ml of the E. glabra extract, at which concentration no cytotoxicity occurred. Furthermore, gelatinolytic activities, and the protein and mRNA levels of MMP-2 and MMP-9 were also suppressed with increasing concentrations of the extract. Given that MMP-2 and MMP-9 are instrumental in tumor cell invasion, it is very likely that the reduction in tumor cell invasion by E. glabra extract is a consequence, at least in part, of suppressed expression of both MMP-2 and MMP-9. Isolation of a molecule(s) responsible for the extract inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

Synchronous Gastrointestinal Stromal Tumor and Ampullary Neuroendocrine Tumor in Association with Neurofibromatosis Type 1: A Report of Three Cases.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disorder. The pathogenesis of NF1 is suggested to be an alteration of the NF-1 gene, which normally functions as a tumor suppressor. A mutation of NF-1 causes the development of viable tumors in various sites. On the other hand, the synchronous manifestation of a gastrointestinal stromal tumor (GIST) and neuroendocrine tumor (NET) in the background of NF1 is extremely rare. This paper reports three cases treated with surgical intervention along with the long-term follow-up results. Three patients showed synchronous ampullary NET and GIST in association with NF1 supported by postoperative histopathologic analysis. Surgical treatments, such as pancreatoduodenectomy and local excision were applied. No recurrence occurred during the postoperative follow-up period of 10, 9, and 2.7 years. Synchronous GIST and NET in the background of NF1 is extremely rare, but the possible coexistence of other tumors in NF1 patients is relatively higher than that in the general population. Furthermore, both NETs and GISTs occurring in NF1 patients tend to be smaller in size compared to that in the general population. Therefore, when NF1 patients present with vague abdominal discomfort, close attention must be paid to identifying the coexistence of other neoplasms.