Correlation between Angiotensin Inhibitor Administration and Longer Survival in Patients Who Underwent Curative Resection for Pancreatic Cancer

Purpose@#The microenvironment of pancreatic ductal adenocarcinoma (PDAC) with extensive desmoplastic stroma contributes to aggressive cancer behavior. Angiotensin system inhibitors (ASIs) reduce stromal fibrosis and are a promising therapeutic strategy. The purpose of this study was to examine how ASIs affected the oncological results of patients who had their PDAC removed. @*Materials and Methods@#A retrospective assessment was conducted on the clinicopathological and survival data of patients who received curative resection for PDAC at Severance Hospital between January 2012 and December 2019. @*Results@#A total of 410 participants (228 male and 182 female), with a median follow-up period of 12.8 months, were included in this study. Patients were divided into three groups, based on ASI use and history of hypertension: group 1, normotensive and never used ASI (n=210, 51.2%); group 2, ASI non-users with hypertension (n=50, 12.2%); and group 3, ASI users with hypertension (n=150, 36.6%). The three groups did not differ significantly in terms of age, sex, kind of operation, T and N stages, or adjuvant and neoadjuvant therapy. Moreover, there was no discernible difference in disease-free survival between those who used ASI and those who did not (p=0.636). The 5-year overall survival (OS) rates in groups 1, 2, and 3 were 52.6%, 32.3%, and 38.0%, respectively. However, the OS rate of ASI users was remarkably higher than that of non-users (p=0.016). @*Conclusion@#In patients with resected PDAC, ASI is linked to longer survival rates. Furthermore, for individuals with hypertension, ASI in conjunction with conventional chemotherapy may be an easy and successful treatment option.

The Revo-i Robotic Surgical System in Advanced Pancreatic Surgery: A Second Non-Randomized Clinical Trial and Comparative Analysis to the da VinciTM System

Purpose@#Numerous robot-assisted pancreatic surgery are being performed worldwide. This study aimed to evaluate the feasibility and safety of the Revo-i robot system (Meerecompany, Seoul, Republic of Korea) for advanced pancreatic surgery, and also compare this new system with the existing da Vinci TM robot system (Intuitive Surgical, Sunnyvale, CA, USA) in the context of robot-assisted pancreaticoduodenectomy (RPD). @*Materials and Methods@#This study was a one-armed prospective clinical trial that assessed the Revo-i robot system for advanced pancreatic surgery. Ten patients aged 30 to 73 years were enrolled between December 2019 and August 2020. Postoperative outcomes were retrospectively compared with those of the da VinciTM surgical system. From March 2017 to August 2020, a total of 47 patients who underwent RPD were analyzed retrospectively. @*Results@#In the prospective clinical trial, pancreaticoduodenectomy was performed in nine patients and one patient underwent central pancreatectomy. Among the 10 study participants, the incidence of major complications was 0% in hospital stay. There were eight postoperative pancreatic fistula (POPF) biochemical leaks (80%). In the retrospective analysis that compared the Revo-i and da VinciTM robotic systems, 10 patients underwent Revo-i RPD and 37 patients underwent da VinciTM RPD, with no significant differences in complication or POPF incidence rates between the two groups (p=0.695, p=0.317). @*Conclusion@#In this single-arm prospective study with short-term follow-up at a single institution, the Revo-i robotic surgical system was safe and effective for advanced pancreatic surgery. Revo-i RPD is comparable to the da VinciTM RPD and is expected to have wide clinical application.

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis

Background/Aims@#Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. @*Methods@#We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. @*Results@#Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. @*Conclusions@#We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

A Prognostic Impact of Splenectomy in Laparoscopic Distal Pancreatectomy on Benign/Borderline Pancreatic Tumors: A Change of the Era

Purpose@#In the past, spleen preservation during distal pancreatectomy (DP) was preferred; however, more recent studies reported comparable results between splenectomy and spleen preserving. We retrospectively reviewed patients in a single center who underwent laparoscopic DP with/without splenectomy, and evaluated the chronologic changes of surgical outcomes of the two procedures. @*Materials and Methods@#Patients who underwent laparoscopic DP with or without splenectomy due to benign/borderline tumor from 2005 to 2019 were included in this study. We divided this period into Era 1 (2005–2012) and Era 2 (2013–2019), and compared the chronological evolution of surgical outcomes of laparoscopic distal pancreatosplenectomy (LDPS) to those of laparoscopic spleen-preserving distal pancreatectomy (LSpDP), including the long-term postoperative immunologic profiles. @*Results@#A total of 198 cases were included (LSpDP: 80 cases; LDPS: 118 cases). As the period changed from Era 1 to Era 2, the ratio of LSpDP decreased and the surgical outcomes of LDPS improved. In Era 1, LSpDP group showed superior results compared to LDPS group in terms of hospital days and postoperative pancreatic fistula ratio; however, in Era 2, the surgical outcomes showed no statistical differences. No significant differences were observed in all of the immunologic markers. @*Conclusion@#We carefully conclude that during laparoscopic DP, combined splenectomy can be equivalent to spleen preserving in surgical and immunological outcomes, and inevitable splenectomy can be safely conducted.

Initial experiences of robotic SP cholecystectomy:a comparative analysis with robotic Si single-site cholecystectomy

Purpose@#The da Vinci SP robotic surgical system (Intuitive Surgical) offers pure SP with 4 lumens, which accommodates the fully-wristed endoscope and 3 arms with multijoint feature. We herein present our initial experience of the da Vinci SP surgical system in robotic single-site cholecystectomy. @*Methods@#Thirty consecutive patients with a preoperative diagnosis of gallstones and/or chronic cholecystitis who underwent robotic SP cholecystectomy (RSPC) using da Vinci SP surgical system from January to May 2019 were reviewed.The perioperative outcomes were assessed and compared with those performed using Si-robotic single-site surgical system. @*Results@#Mean docking time was 5.2 minutes. The mean actual dissection time was 14.6 minutes while the mean operation time was 75.1 minutes. Postoperative course was unremarkable and patients were discharged after a mean hospital stay of 1.5 days. In comparative analysis, operation time (109.5 ± 30.0 minutes vs. 75.1 ± 17.5 minutes, P = 0.001), docking time (11.9 ± 4.3 minutes vs. 5.2 ± 1.9 minutes, P = 0.001), actual dissection time (34.6 ± 18.4 minutes vs. 14.6 ± 5.1 minutes, P = 0.001), console time (58.7 ± 23.0 minutes vs. 32.4 ± 11.6 minutes, P = 0.001), immediate postoperative pain (4.6 ± 1.3 vs. 3.2 ± 1.0, P = 0.001), and pain prior to discharge (2.0 ± 0.6 vs. 1.4 ± 0.0, P = 0.002) were significantly improved in RSPC. @*Conclusion@#RSPC is feasible, safe, and effective. The perioperative outcomes are better compared with Si-robotic singlesite surgical systems.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Adverse Impact of Intraoperative Conversion on the Postoperative Course Following Laparoscopic Pancreaticoduodenectomy

Purpose@#The aim of the current study was to evaluate the adverse clinical impact of intraoperative conversion during laparoscopic pancreaticoduodenectomy (LPD). @*Materials and Methods@#The medical records of patients who underwent pancreaticoduodenectomy (PD) were retrospectively reviewed. Perioperative clinical variables were compared between patients who underwent converted PD (cPD) and initially planned open PD (OPD) to investigate the clinical impact and predictive factors of intraoperative conversion during LPD. @*Results@#A total of 171 patients were included. Among them, 31 patients (19.3%) were found to have intraoperative conversion during LPD. Failure of progression due to severe adhesion (12 patients, 7%) and major vessel invasion (7 patients, 4%) were the two most frequent reasons for conversion. On multivariate analysis, age [Exp(β)=1.044, p=0.044] and pancreatic texture [Expa(β)=2.431, p=0.039) were found to be independent factors for predicting intraoperative conversion during LPD. In comparative analysis with the OPD group, the cPD group had a longer operation time (516.8 min vs. 449.9 min, p=0.001), higher rate of postoperative hemorrhage (12.1% vs. 0.85%, p=0.008), higher reoperation rate (9.1% vs. 0%, p=0.01), and higher cost (21886.4 USD vs. 17168.9 USD, p=0.018). @*Conclusion@#Intraoperative conversion during LPD can have an adverse clinical impact on the postoperative course following LPD. Appropriate patients selection and improvement of surgical techniques will be crucial for unnecessary intraoperative conversion and safe LPD.

Adverse Impact of Intraoperative Conversion on the Postoperative Course Following Laparoscopic Pancreaticoduodenectomy

Purpose@#The aim of the current study was to evaluate the adverse clinical impact of intraoperative conversion during laparoscopic pancreaticoduodenectomy (LPD). @*Materials and Methods@#The medical records of patients who underwent pancreaticoduodenectomy (PD) were retrospectively reviewed. Perioperative clinical variables were compared between patients who underwent converted PD (cPD) and initially planned open PD (OPD) to investigate the clinical impact and predictive factors of intraoperative conversion during LPD. @*Results@#A total of 171 patients were included. Among them, 31 patients (19.3%) were found to have intraoperative conversion during LPD. Failure of progression due to severe adhesion (12 patients, 7%) and major vessel invasion (7 patients, 4%) were the two most frequent reasons for conversion. On multivariate analysis, age [Exp(β)=1.044, p=0.044] and pancreatic texture [Expa(β)=2.431, p=0.039) were found to be independent factors for predicting intraoperative conversion during LPD. In comparative analysis with the OPD group, the cPD group had a longer operation time (516.8 min vs. 449.9 min, p=0.001), higher rate of postoperative hemorrhage (12.1% vs. 0.85%, p=0.008), higher reoperation rate (9.1% vs. 0%, p=0.01), and higher cost (21886.4 USD vs. 17168.9 USD, p=0.018). @*Conclusion@#Intraoperative conversion during LPD can have an adverse clinical impact on the postoperative course following LPD. Appropriate patients selection and improvement of surgical techniques will be crucial for unnecessary intraoperative conversion and safe LPD.

Laparoscopic pancreaticoduodenectomy with excision of aberrant right hepatic artery after preoperative segmental embolization in mid-bile duct cancer

Laparoscopic pancreaticoduodenectomy has proven to be a safe and effective alternative to open pancreati coduodenectomy with similar oncologic outcomes. Cases including excision of the hepatic artery with or without reconstruction during pancreaticoduodenectomy have been reported for periampullary cancer. Here we present a case of an 82-year-old patient who underwent laparoscopic pancreaticoduodenectomy following preoperative arterial embolization of an aberrant right hepatic artery arising from the superior mesenteric artery.

Laparoscopic pancreaticoduodenectomy in pancreatic ductal adenocarcinoma

Laparoscopic pancreatoduodenectomy (LPD) in pancreatic cancer is primarily criticized for its technical and oncological safety. Although solid evidence has not yet been established, many institutions are performing LPD for pancreatic cancer patients, with continuous efforts to ensure oncologic safety. In this video, we demonstrated a case of standard LPD combined with vascular resection in pancreatic cancer.

Laparoscopic pancreaticoduodenectomy with excision of aberrant right hepatic artery after preoperative segmental embolization in mid-bile duct cancer

Laparoscopic pancreaticoduodenectomy has proven to be a safe and effective alternative to open pancreati coduodenectomy with similar oncologic outcomes. Cases including excision of the hepatic artery with or without reconstruction during pancreaticoduodenectomy have been reported for periampullary cancer. Here we present a case of an 82-year-old patient who underwent laparoscopic pancreaticoduodenectomy following preoperative arterial embolization of an aberrant right hepatic artery arising from the superior mesenteric artery.

Laparoscopic pancreaticoduodenectomy in pancreatic ductal adenocarcinoma

Laparoscopic pancreatoduodenectomy (LPD) in pancreatic cancer is primarily criticized for its technical and oncological safety. Although solid evidence has not yet been established, many institutions are performing LPD for pancreatic cancer patients, with continuous efforts to ensure oncologic safety. In this video, we demonstrated a case of standard LPD combined with vascular resection in pancreatic cancer.

Yonsei Criteria, a Potential Linkage to Intratumoral Foxp3⁺/CD8⁺ Ratio for the Prediction of Oncologic Outcomes in Resected Left-Sided Pancreatic Cancer

PURPOSE: This study sought to investigate associations among Yonsei criteria (tumor confined to the pancreas, intact fascia layer between the distal pancreas and the left adrenal gland and kidney, and tumor located more than 1–2 cm from the celiac axis) and tumor infiltrating lymphocytes in pancreatic cancer.MATERIALS AND METHODS: Patients who underwent curative distal pancreatectomy due to left-sided pancreatic cancer from January 2000 to December 2011 were enrolled. Follow-up was completed September 30, 2015.RESULTS: Fifty patients were enrolled. Having ≥ two metastatic lymph nodes (LNs, p=0.002), intraoperative transfusion (p=0.011), low levels of tumor infiltrating CD8⁺ T-cells (p=0.001), and a high Foxp3⁺/CD8⁺ ratio (p=0.009) were independent risk factors for disease-free survival. Not satisfying the Yonsei criteria (p=0.021), having ≥ two metastatic LNs (p=0.032), low levels of tumor infiltrating CD8⁺ T-cells (p=0.040) and a high Foxp3⁺/CD8⁺ ratio (p=0.032) were associated with unfavorable overall survival. High levels of CA19-9 and not satisfying the Yonsei criteria were significantly associated with a high Foxp3⁺/CD8⁺ ratio [Exp(β)=3.558; 95% confidence inverval: 1.000–12.658; p=0.050].CONCLUSION: Yonsei criteria may be clinically detectable biologic marker with which to predict immunologic status and survival in pancreatic cancer patients.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Minimally Invasive Single-Site Cholecystectomy in Obese Patients: Laparoscopic vs. Robotic

PURPOSE: Laparoscopic cholecystectomy is treatment method for management of benign gallbladder diseases. Further attempts are made to operate single-port laparoscopic cholecystectomy. However, single-port laparoscopic cholecystectomy, the procedure remains technically difficult, especially in obese patient. Recently, a robotic surgical system for minimal invasive surgery was introduced to overcome the limitations of conventional laparoscopic surgery. METHODS: From April 2009 to August 2017, we retrospectively reviewed the medical records of patients with single-site, minimally invasive (laparoscopic and robotic) cholecystectomy with high BMI (>25 kg/m2). We analyzed general characteristics and perioperative outcomes between the single-fulcrum laparoscopic cholecystectomy group and the robotic single-site cholecystectomy (RSSC) group. RESULTS: Operation time (57.56±11.10 vs 98.5±12.28 p<0.001) was significantly longer and postoperative pain score (3.61 vs 5.15 p=0.000) was significantly higher in the robotic single-site cholecystectomy (RSSC) group, but the actual dissection time (25.85±11.09 vs 25.79±13.35 p=0.978) was not significantly different between the two approaches. Iatrogenic gallbladder perforation, (13 vs 6 p=0.005), patients undergoing RSSC showed a significantly smaller amount than did those undergoing single-fulcrum laparoscopic cholecystectomy (SFLC). CONCLUSION: It is difficult to say for certain that RSSC is clearly better than SFLC in obese patients. However, because of the technical convenience and efficiency of surgery with RSSC, RSSC can be practically worthwhile. Further study is mandatory.

Oncologic Outcomes of Extended Lymphadenectomy without Liver Resection for T1/T2 Gallbladder Cancer

PURPOSE: This study provides a standardized operative strategical algorithm that can be applied to patients with T1/T2 gallbladder cancer (GBC). Our aim was to determine the oncologic outcome of radical cholecystectomy with para-aortic lymph node dissection without liver resection in T1/T2 GBC. MATERIALS AND METHODS: From January 2005 to December 2017, 164 patients with GBC underwent operations by a single surgeon at Severance Hospital. A retrospective review was performed for 113 of these patients, who were pathologically determined to be in stages T1 and T2 according to American Joint Committee on Cancer 7th guidelines. RESULTS: Of the 113 patients, 109 underwent curative resection for T1/T2 GBC; four patients who underwent palliative operations without radical cholecystectomies were excluded from further analyses. For all T1b and T2 lesions, radical cholecystectomy with para-aortic lymph node dissection was performed without liver resection. There were four GBC-related mortalities, and 5-year disease-specific survival was 97.0%. The median follow-up was 50 months (range: 5–145 months). In all T stages, the median was not reached for survival analysis. Five-year disease-specific survival for T1a, T1b, and T2 were 100%, 94.1%, and 97.1%, respectively. Five-year disease-free survival for T1a, T1b, and T2 were 100%, 87.0%, and 91.8%, respectively. CONCLUSION: Our results suggest that the current operative protocol can be applied to minimal invasive operations for GBC with similar oncologic outcomes as open approach. For T1/T2 GBC, radical cholecystectomy, including para-aortic lymph node dissection, can be performed safely with favorable oncologic outcomes.

Technical feasibility of da Vinci SP single-port robotic cholecystectomy: a case report

The da Vinci surgical system released its new pure single-port platform, the da Vinci SP, offering improvements and refinements for established robotic single-site procedures. Herein, we present the first case of robotic single-site cholecystectomy using the da Vinci SP system (RSPC) demonstrating its safety and technical feasibility. A 59-year-old female with chronic calculus cholecystitis was admitted for elective RSPC. Docking time took 6 minutes. The patient underwent successful RSPC with a total operation time of 89 minutes. There was no significant intraoperative event. The patient had unremarkable postoperative course. Multijoint instruments, simple docking process, and third-arm functionality are among the RSPC's advantages. Absence of the port for an assistant surgeon can be a hindrance in performing more complicated surgeries. The present case suggests that RSPC is safe and feasible. The promising features and potential application of da Vinci SP in hepatobiliary and pancreas surgery need further study.

Preoperative Metabolic Tumor Volume(2.5) Associated with Early Systemic Metastasis in Resected Pancreatic Cancer: A Transcriptome-Wide Analysis

BACKGROUND/AIMS: ¹⁸F-fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancers. METHODS: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters and PET parameters were evaluated, and transcriptome-wide analysis was performed to identify the oncologic impact and molecular landscape of the metabolic phenotype of resectable pancreatic cancers. RESULTS: Preoperative metabolic tumor volume (MTV)(2.5) was significantly higher in the pN1 group compared to the pN0 group (11.1±11.2 vs 6.5±7.8, p=0.031). Higher MTV(2.5) values (MTV(2.5) ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV(2.5) ≥4.5 compared to those with MTV(2.5) <4.5 (0.12±0.13 vs 0.05±0.08, p=0.001). Disease-specific survival of patients with MTV(2.5) <4.5 was better than that of patients with MTV(2.5) ≥4.5 (mean, 28.8 months; 95% confidence interval [CI], 40.1 to 57.0 vs mean, 32.6 months; 95% CI, 25.5 to 39.7; p=0.026). Patients with MTV(2.5) ≥4.5 who received postoperative adjuvant chemotherapy showed better survival outcomes than patients with MTV(2.5) ≥4.5 who did not receive adjuvant treatment in resected pT3 pancreatic cancers (p<0.001). Transcriptome-wide analysis revealed that tumors with MTV(2.5) ≥4.5 demonstrated significantly different expression of cancer-related genes reflecting aggressive tumor biology. CONCLUSIONS: Resectable pancreatic cancer with high MTV(2.5) is not only associated with lymph node metastasis but also early systemic metastasis. The molecular background of resectable pancreatic cancer with high MTV(2.5) may be associated with aggressive biologic behavior, which might need to be considered when managing resectable pancreatic cancers. Further study is mandatory.

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats

PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.