Mee Joo Kang

A Prospective Randomized Controlled Study Comparing Outcomes of Standard Resection and Extended Resection, Including Dissection of the Nerve Plexus and Various Lymph Nodes, in Patients With Pancreatic Head Cancer

Objective:To prospectively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer. Background:Despite randomized controlled trials on the extent of surgery in pancreatic cancer, attempts have been made to perform more extended resections. Methods:A total of 244 patients were enrolled; of these, 200 were randomized to undergo standard resection or extended resection, with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis. We evaluated 167 patients from 7 centers who fulfilled all of the required criteria. Result:Operation time was longer and estimated blood loss was higher in the extended resection group than in the standard resection group, but the R0 resection rate was comparable. The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the standard resection group (33.7 vs 17.3; P < 0.001). The morbidity rate was slightly higher in the extended resection group than in the standard resection group. Two patients in the extended resection group died in hospital. Median survival after R0 resection was similar in the extended resection and standard resection groups (18.0 vs 19.0 months; P = 0.239) regardless of lymph node metastasis. Adjuvant chemoradiation had a positive impact on overall survival. Conclusions:This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)?

Systematic review on the surgical treatment for T1 gallbladder cancer

AIM To evaluate the efficacy of simple and extended cholecystectomy for mucosa (T1a) or muscularis (T1b) gallbladder (GB) cancer. METHODS Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer were searched from MEDLINE (PubMed), Cochrane Library, EMBase, and CancerLit using the search terms of GB, cancer/carcinoma/tumor/neoplasm. RESULTS Twenty-nine out of the 2312 potentially relevant publications met the eligibility criteria. Of the 1266 patients with GB cancer included in the publications, 706 (55.8%) and 560 (44.2%) had T1a and T1b GB cancer, respectively. Simple cholecystectomy for T1a and T1b GB cancer was performed in 590 (83.6%) and 375 (67.0%) patients, respectively (P < 0.01). In most series, the treatment of choice was simple cholecystectomy for T1a GB cancer patients with a 5-year survival rate of 100%. Lymph node metastasis was detected in 10.9% of the T1b GB cancer patients and in 1.8% of the T1a GB cancer patients, respectively (P < 0.01). Eight patients (1.1%) with T1a GB cancer and 52 patients (9.3%) with T1b GB cancer died of recurrent GB cancer (P < 0.01). CONCLUSION Simple cholecystectomy represents the adequate treatment of T1a GB cancer. There is no definite evidence that extended cholecystectomy is advantageous over simple cholecystectomy for T1b GB cancer.

Measurement of pancreatic fat by magnetic resonance imaging: predicting the occurrence of pancreatic fistula after pancreatoduodenectomy.

Objective:The purpose of this study was to determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have higher pancreatic fat levels than matched controls and if so, to investigate whether preoperative dual gradient-echo magnetic resonance (MR) imaging can be used to measure pancreatic fat and predict the development of postoperative pancreatic fistula. Summary Background Data:Pancreatic fistula is a major complication and its most frequently reported risk factors tend to be anatomic features of the pancreatic remnant, such as a soft pancreatic texture. Methods:Between January 2007 and September 2007, a total of 96 cases of pancreatoduodenectomy were performed at Seoul National University Hospital. Of total, 20 patients (20.8%) who developed a pancreatic fistula were carefully matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation with 20 control patients who did not develop a pancreatic fistula. In the pancreatic fistula group, 9 patients (45%) had a grade A fistula and 11 (55%) grade B fistula. Degrees of pancreatic fatty infiltration and fibrosis were assessed quantitatively. In-phase and opposed-phase images were obtained by dual-gradient-echo MR imaging. Percentage decreases in pancreatic signal intensity on opposed-phase images relative to those on in-phase images were calculated and defined as relative signal intensity decreases (RSID). Results:More patients in the pancreatic fistula group had a soft pancreatic texture or a smaller pancreatic duct and total fat and RSID were significantly higher. In soft pancreatic texture group, intralobular, interlobular, and total fat were significantly elevated. Furthermore, pancreatic fat levels were found to be correlated positively with RSID (P = 0.013). RSID was correlated with total pancreatic fat and when an RSID criterion more than 7.032 was used, pancreatic fistula could be predicted as 72.7% sensitivity and 75.9% specificity. Conclusion:Our findings suggest that increased pancreatic fat is a risk factor of postoperative pancreatic fistula. Preoperative measurements of pancreatic fat by MRI offer a noninvasive predicting the occurrence of pancreatic fistula.

Long-term prospective cohort study of patients undergoing pancreatectomy for intraductal papillary mucinous neoplasm of the pancreas: implications for postoperative surveillance.

Objective:To evaluate long-term follow-up results after surgical treatment of intraductal papillary mucinous neoplasm (IPMN) to optimize postoperative surveillance strategies. Background:Little is known about the postoperative natural history of IPMN, especially about long-term follow-up results in patients with benign or noninvasive IPMN. Methods:Long-term follow-up was undertaken in a prospective cohort of 403 consecutive patients who underwent surgical treatment of IPMN at Seoul National University Hospital. Of these, 37 patients with ductal adenocarcinoma arising in IPMN were excluded from the analysis. Results:Of the 366 patients, 82 had low-grade dysplasia, 171 had intermediate-grade dysplasia, 45 had high-grade dysplasia, and 68 had IPMN with associated invasive carcinoma. During a median follow-up of 44.4 months, the overall recurrence rate was 10.7%. Pathologic grade of dysplasia was associated with recurrence rate (P < 0.001). IPMNs involving main duct had higher rate of recurrence (P = 0.021). Of the 298 patients with benign or noninvasive IPMN, 16 (5.4%) had recurrences including distant metastasis. Multivariate analysis revealed that the degree of dysplasia was the most important predictor of recurrence (P < 0.001). The overall 5-year disease-free survival rate was 78.9% and was significantly lower in patients with high-grade dysplasia than in those with low- or intermediate-grade dysplasia (P = 0.045). Conclusions:Pancreatic IPMNs recur in 10.7% of patients. Recurrence is correlated with the degree of dysplasia, and 5.4% of patients with benign or noninvasive IPMN have recurrences including distant metastasis. Thorough postoperative surveillance is needed not only for patients with invasive IPMN but also for those with benign or noninvasive IPMN, especially for patients with high-grade dysplasia.

Percutaneous cholecystostomy for acute cholecystitis in patients with high comorbidity and re-evaluation of treatment efficacy

BACKGROUND In high-risk and unfit-for-surgery patients with acute cholecystitis (AC), treatment options are controversial. Few studies have reported the results of long-term follow-up. This study aimed to evaluate the clinical course of patients after removal of the percutaneous cholecystostomy (PC) catheter in high-risk patients with AC, time interval to relapse, and factors influencing relapse. METHODS From 2000 to 2011, 183 patients with AC underwent PC and catheter removal in Seoul National University Hospital and Boramae Hospital, Korea. Sixty cases were reviewed retrospectively after excluding cases with intended interval cholecystectomy, malignant biliary obstruction, loss to follow-up, and insufficient follow-up information. RESULTS The mean age was 68.6 ± 13.8 years, and the mean Karnofsky performance score was 24.8 ± 9.7. After insertion of a PC catheter, symptom resolution and improvement on imaging were achieved in 95% and 97.9% of patients, respectively. Laboratory values were also improved (P < .01). There was no mortality during admission; 2 patients (3.3%) experienced complications during removal of the PC catheter. Relapse was observed in 7 patients (11.7%) during a median follow-up of 38.1 ± 24.8 months. There were no differences in clinical, laboratory, or imaging findings between relapsing and nonrelapsing patients. Therefore, prediction of relapse was not possible. CONCLUSION Among high-risk patients with AC, 88.3% were managed with PC without relapse within a median follow-up period of 38.1 months, despite radiologically severe AC in some patients. We conclude that a temporary PC can be a first-line treatment for AC without interval cholecystectomy.

Evaluation of clinical meaning of histological subtypes of intraductal papillary mucinous neoplasm of the pancreas.

Objectives Prognostic value of histological subtypes of pancreatic intraductal papillary mucinous neoplasm (IPMN) has been reported to have conflicting results. The authors investigated the clinicopathological characteristics and prognostic significance of the histological subtypes of IPMNs with various degrees of dysplasia. Methods Two hundred thirteen patients with surgically treated pancreatic IPMN at a single tertiary care referral center were included. Pathological slides were thoroughly reviewed by a specialized pathologist. Results Of the 213 patients, 38 low-grade, 97 intermediate-grade, and 18 high-grade dysplasia and 59 IPMNs with an associated invasive carcinoma (invasive IPMN) were identified. Histological subtypes consisted of 135 gastric (63.4%), 38 intestinal (17.8%), 38 pancreatobiliary (17.8%), and 2 oncocytic types (0.9%). Histological subtypes were associated with radiological type (P < 0.001), degree of dysplasia (P < 0.001), and T stage (P < 0.001). The proportions of invasive IPMN were 14.1%, 42.1%, 57.9%, and 100% of gastric, intestinal, pancreatobiliary, and oncocytic types, respectively. Disease-specific survival was not affected by histological subtype in overall patients (P = 0.881). For invasive IPMNs, histological subtypes had a marginal significance on survival (P = 0.050), which lost statistical significance after multivariate analysis (P = 0.341). Conclusions Although histological subtypes are associated with the degree of dysplasia, histological subtypes have limited prognostic value for pancreatic IPMNs.

Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma invasive IPMN versus pancreatic ductal adenocarcinoma-associated IPMN.

Objectives Current version of World Health Organization classification introduced the concept of “intraductal papillary mucinous neoplasm (IPMN) with an associated invasive carcinoma.” The authors investigated the clinicopathologic characteristics and prognosis of this disease category according to tumor morphology and percentage of invasive component. Methods Fifty-nine patients who underwent surgical resection of IPMN with an associated invasive carcinoma at Seoul National University Hospital were subgrouped according to the invasive component of less than 5% (minimally invasive [MI] intraductal papillary mucinous carcinoma [IPMC] [MI-IPMC]), 5%–50% (invasive IPMC [IPMC-I]), and 50% or greater (pancreatic ductal adenocarcinoma [PDAC]-associated IPMN [PDAC-IPMN]). Prognosis was compared with 219 curatively resected conventional PDAC. Results Eleven MI-IPMCs (18.6%), 24 IPMC-Is (40.7%), and 24 PDAC-IPMNs (40.7%) were identified. With the transition from MI-IPMC to IPMC-I and PDAC-IPMN, percentage of advanced T (P < 0.001) or N stage (P = 0.001), expression of S100A4 (P = 0.004), p53 (P = 0.028), and CD24 (P = 0.009) increased; and SMAD4 expression decreased (P < 0.001). The overall 5-year survival rates for MI-IPMC, IPMC-I, and PDAC-IPMN were 80.8%, 59.0%, and 29.3%, respectively (P < 0.001). Pancreatic ductal adenocarcinoma-associated IPMN had poor prognosis compared with MI-IPMC (P = 0.011) or IPMC-I (P = 0.026) but had comparable prognosis with conventional PDAC (P = 0.138). Conclusions Pancreatic ductal adenocarcinoma-associated IPMN has different clinicopathological characteristics compared with the IPMC-I. Intraductal papillary mucinous neoplasm with an associated invasive carcinoma is composed of a wide spectrum of disease.

Pancreatic Steatosis and Fibrosis: Quantitative Assessment with Preoperative Multiparametric MR Imaging

PURPOSE To evaluate the diagnostic performance of multiparametric pancreatic magnetic resonance (MR) imaging, including the T2*-corrected Dixon technique and intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging, in the quantification of pancreatic steatosis and fibrosis, with histologic analysis as the reference standard, and to determine the relationship between MR parameters and postoperative pancreatic fistula. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the informed consent requirement was waived. A total of 165 patients (93 men, 72 women; mean age, 62 years) underwent preoperative 3-T MR imaging and subsequent pancreatectomy (interval, 0-77 days). Fat fractions, IVIM DW imaging parameters (true diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [f]), pancreas-to-muscle signal intensity ratios on unenhanced T1-weighted images, and pancreatic duct sizes were compared with the fat fractions and fibrosis degrees (F0-F3) of specimens. In 95 patients who underwent pancreatoenteric anastomosis, MR parameters were compared between groups with clinically relevant postoperative pancreatic fistula and those without. The relationship between postoperative pancreatic fistula and MR parameters was evaluated by using logistic regression analysis. RESULTS Fat fractions at MR imaging showed a moderate relationship with histologic findings (r = 0.71; 95% confidence interval: 0.63, 0.78). Patients with advanced fibrosis (F2-F3) had lower D*([39.72 ± 13.64] ×10(-3)mm(2)/sec vs [32.50 ± 13.09] ×10(-3)mm(2)/sec [mean ± standard deviation], P = .004), f (29.77% ± 8.51 vs 20.82% ± 8.66, P < .001), and unenhanced T1-weighted signal intensity ratio (1.43 ± 0.26 vs 1.21 ± 0.30, P < .001) than did patients with F0-F1 disease. Clinically relevant fistula developed in 14 (15%) of 95 patients, and f was significantly associated with postoperative pancreatic fistula (odds ratio, 1.17; 95% confidence interval: 1.05, 1.30). CONCLUSION Multiparametric MR imaging of the pancreas, including imaging with the T2*-corrected Dixon technique and IVIM DW imaging, may yield quantitative information regarding pancreatic steatosis and fibrosis, and f was shown to be significantly associated with postoperative pancreatic fistulas.

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients.ResultsIn this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2.ConclusionsWe observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment.

Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma: Invasive IPMN versus pancreas ductal adenocarcinoma-associated IPMN

OBJECTIVES Current version of World Health Organization classification introduced the concept of ‘‘intraductal papillary mucinous neoplasm(IPMN) with an associated invasive carcinoma.’’ The authors investigated the clinicopathologic characteristics and prognosis of this disease category according to tumor morphology and percentage of invasive component. METHODS Fifty-nine patients who underwent surgical resection of IPMN with an associated invasive carcinoma at Seoul National University Hospital were subgrouped according to the invasive component of less than 5% (minimally invasive [MI] intraductal papillary mucinous carcinoma [IPMC] [MI-IPMC]), 5%- 50% (invasive IPMC [IPMC-I]),and 50% or greater (pancreatic ductal adenocarcinoma [PDAC]-associated IPMN [PDAC-IPMN]). Prognosis was compared with 219 curatively resected conventional PDAC. RESULTS Eleven MI-IPMCs (18.6%), 24 IPMC-Is (40.7%), and 24PDAC-IPMNs (40.7%) were identified. With the transition from MIIPMC to IPMC-I and PDAC-IPMN, percentage of advanced T (P G0.001) or N stage (P = 0.001), expression of S100A4 (P = 0.004), p53(P = 0.028), and CD24 (P = 0.009) increased; and SMAD4 expression decreased (P G 0.001). The overall 5-year survival rates for MIIPMC,IPMC-I, and PDAC-IPMN were 80.8%, 59.0%, and 29.3%,respectively (P G 0.001). Pancreatic ductal adenocarcinoma-associated IPMN had poor prognosis compared with MI-IPMC (P = 0.011) or IPMC-I (P = 0.026) but had comparable prognosis with conventional PDAC (P = 0.138). CONCLUSIONS Pancreatic ductal adenocarcinoma-associated IPMN has different clinicopathological characteristics compared with the IPMC-I.Intraductal papillary mucinous neoplasm with an associated invasive carcinoma is composed of a wide spectrum of disease.