Dae Wook Hwang

Matched Case-Control Analysis Comparing Laparoscopic and Open Pylorus-preserving Pancreaticoduodenectomy in Patients With Periampullary Tumors.

OBJECTIVES To evaluate the safety, feasibility, and oncologic outcomes of laparoscopic pylorus-preserving pancreaticoduodenectomy (L-PPPD) to treat periampullary tumors. The clinical outcomes of L-PPPD were compared with open pylorus-preserving pancreaticoduodenectomy (O-PPPD). BACKGROUND Despite recent advances in laparoscopic pancreatic surgery, few studies have compared L-PPPD with O-PPPD. The safety, short-term clinical benefits, and oncologic outcomes of L-PPPD remain controversial. METHODS Between January 2007 and December 2012, a total of 2192 patients diagnosed with periampullary tumors were treated with curative resection at our institution. Of these patients, 137 underwent a laparoscopic approach and 2055 an open technique. A retrospective study was performed to evaluate the safety, feasibility, and oncologic outcomes of L-PPPD compared with O-PPPD. RESULTS The mean operation time for the L-PPPD group was longer than for the O-PPPD group (P < 0.001). Estimated blood loss was similar, as was the incidence of complications, such as pancreatic fistula and delayed gastric empting (P > 0.05). The mean number of analgesic injections administered was lower in the L-PPPD group than in the O-PPPD group (P < 0.001), and the mean duration of the postoperative hospital stays was shorter (P < 0.001). The surgical resection margins and the number of lymph nodes in the resected specimens did not differ between the 2 groups, and there was no significant difference in overall survival curves. CONCLUSIONS L-PPPD had the typical advantages of minimally invasive abdominal procedures, such as less pain, shorter hospital stay, and quicker recovery. It is technically safe and feasible, and has favorable oncologic outcomes in comparison with O-PPPD in patients with periampullary tumors.

Alternative lengthening of telomeres in primary pancreatic neuroendocrine tumors is associated with aggressive clinical behavior and poor survival

Purpose: Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations and occurs frequently in pancreatic neuroendocrine tumors (PanNET). Experimental Design: In a Korean cohort of 269 surgically resected primary PanNETs and 19 sporadic microadenomas, ALT status and nuclear ATRX and DAXX protein expression were assessed and compared with clinicopathologic factors. Results: In PanNETs, ALT or loss of ATRX/DAXX nuclear expression was observed in 20.8% and 19.3%, respectively, whereas microadenomas were not altered. ALT-positive PanNETs displayed a significantly higher grade, size, and pT classification (all, P < 0.001). ALT also strongly correlated with lymphovascular (P < 0.001) and perineural invasion (P = 0.001) and the presence of lymph node (P < 0.001) and distant metastases (P = 0.002). Furthermore, patients with ALT-positive primary PanNETs had a shorter recurrence-free survival [HR = 3.38; 95% confidence interval (CI), 1.83–6.27; P < 0.001]. Interestingly, when limiting to patients with distant metastases, those with ALT-positive primary tumors had significantly better overall survival (HR = 0.23; 95% CI, 0.08–0.68; P = 0.008). Similarly, tumors with loss of ATRX/DAXX expression were significantly associated with ALT (P < 0.001), aggressive clinical behavior, and reduced recurrence-free survival (P < 0.001). However, similar to ALT, when limiting to patients with distant metastases, loss of ATRX/DAXX expression was associated with better overall survival (P = 0.003). Conclusions: Both primary ALT-positive and ATRX/DAXX-negative PanNETs are independently associated with aggressive clinicopathologic behavior and displayed reduced recurrence-free survival. In contrast, ALT activation and loss of ATRX/DAXX are both associated with better overall survival in patients with metastases. Therefore, these biomarkers may be used as prognostic markers depending on the context of the disease. Clin Cancer Res; 23(6); 1598–606. ©2016 AACR.

Practical usefulness of minor grooves of the hepatic surface for liver resection.

BACKGROUND/AIMS The clinical relevance of grooves of the hepatic surface has not been clearly identified. The aim of the present study was to examine the association of minor grooves and liver segmentations, and to evaluate the usefulness of grooves for liver resection. METHODOLOGY Between January 2005 and December 2010, 482 patients with hepatic resection for liver disease were included in this study. We performed glissonean pedicle transection methods for hepatic resection to identify sectors or segments of the liver and examined location, size, depth and relationship with intersegmental line of the hepatic grooves. RESULTS Diaphragmatic grooves were located on anatomical border between right lobe and left lobe and within right anterior sector. The minor grooves were more commonly observed in the right lobe than in the left lobe. The minor grooves between segment V and VI, and segment V and VI were easy to perform monosegmentectomy and right anterior sectionectomy on, respectively. These minor grooves were also helpful to determine the resection margin for non-anatomical resection. CONCLUSIONS Minor grooves were often observed in line with sector or segment, or near to inter-segmental or sectorial border. The anatomical knowledge of hepatic grooves including minor type may be of help for hepatobiliary surgeons and radiologists to understand liver segmentation.

Clinicopathologic and prognostic significance of multiple hormone expression in pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) produce variable peptide hormones. The expression status of some hormones has been linked to the biological and clinical behaviors of PanNETs. A total of 226 surgically resected PanNETs were selected. Immunolabeling for peptide hormones was compared with various clinicopathologic factors, including patient survival. Expression of insulin, glucagon-like peptide 1, glucagon, gastrin, somatostatin, and serotonin were observed in 56 (24.8%), 41 (18.1%), 25 (11.1%), 5 (2.2%), 5 (2.2%), and 4 (1.8%) cases, respectively. Expression of 1, 2, and 3 hormones was noted in 70 (31.0%), 28 (12.4%), and 3 (1.3%) cases, respectively; 125 cases (55.3%) were negative for all hormones. PanNETs with insulin and glucagon-like peptide 1 expression were associated with a lower grade, smaller size, lower pT and pN classifications, absence of lymphovascular invasion, and lymph node metastasis and had better survival by univariate analysis, whereas PanNETs with gastrin expression were associated with a higher grade, larger size, higher pT and pN classifications, presence of lymphovascular invasion, and lymph node metastasis and had worse survival. Gastrin expression, increased age, and tumor grade were negative prognostic factors in multivariate analysis. As the number of hormones expressed increased, the survival rate of PanNET patients increased. In summary, PanNET patients showing insulin or glucagon-like peptide 1 expression and increased numbers of expressed hormones had a better survival outcome by univariate analysis, whereas gastrin expression was a negative prognostic indicator in surgically resected PanNET patients.

Branch duct intraductal papillary mucinous neoplasm of the pancreas: single-center experience with 324 patients who underwent surgical resection

Backgrounds/Aims International treatment guidelines for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas have been proposed, for features associated with malignancy and invasiveness. We investigated the clinicopathological characteristics that are predictive of malignancy or invasiveness and disease recurrence. Methods A review of 324 patients with resected and pathologically confirmed BD-IPMN, between March 1997 and December 2013, was conducted. Results There were 144 (44.4%) low grade dysplasia (LGD), 138 (42.6%) intermediate grade dysplasia (IMGD), 17 (5.3%) high grade dysplasia (HGD), and 25 (7.7%) invasive carcinoma (invIPMC) cases. The 5-year survival rates were 98.1% for LGD, 95.3% for IMGD, 100% for HGD, and 71.8% for invIPMC. Through a univariate analysis, the male sex was associated with malignancy, and CA19-9 was related to both malignant and invasive IPMN. The high risk or worrisome features of the international guidelines were associated with both malignant and invasive IPMN: the total bilirubin of the head/uncinate lesion, tumor size, mural nodule, and the size of the main pancreatic duct (MPD). Through a multivariate analysis, the male sex, elevated CA19-9, mural nodule, and dilated MPD diameter were independently correlated with the malignant IPMN. The elevated CA19-9 and dilated MPD diameter were also correlated with invasive carcinoma. The patient age and the initial pathological diagnosis were strongly associated with disease recurrence following surgical resection. Conclusions The high risk or worrisome features in the current treatment guidelines for BD-IPMN are confined to the morphological characteristics of the disease. Patient factors and biological features should also be considered in order to develop optimal therapeutic or surveillance strategies.

The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study

Objectives The objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC). Methods Between April 2004 and December 2011, data on patients undergoing surgical resection for PDAC were reviewed. Genetic status of DPC4 was determined and correlated to recurrence patterns and clinical outcomes. Results Analysis of 641 patients revealed that genetic status of DPC4 was associated with overall survival and was highly correlated with recurrence patterns, as inactivation of the DPC4 gene was the strongest predictor of metastatic recurrence (odds ratio = 4.28). Treatment modalities for recurrent PDAC included chemotherapy alone and concurrent chemotherapy along with local control. For both locoregional and metastatic recurrence, local control resulted in improved survival; however, for groups subdivided according to recurrence patterns and genetic status of DPC4, local control contributed to improved survival in locoregional recurrences of patients with expressed DPC4, while chemotherapy alone was sufficient for others. Conclusions Genetic status of DPC4 contributes to the recurrence patterns following pancreatectomy, and patients with an initially expressed DPC4 gene receive a greater benefit from intensive local control for locoregional recurrence. The DPC4 gene, therefore, may aid the establishment of treatment strategies for initial adjuvant treatment or for recurrent PDAC.

Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors.

Objectives Studies on the expression of somatostatin receptor (SSTR) subtypes in pancreatic neuroendocrine tumors (PNETs) are rare. The aim of this study was to determine the expression of the SSTR subtypes via immunohistochemistry analyses and assess the correlation between SSTR subtype expression and prognosis. Methods We examined 199 patients with PNET who underwent surgical resection between January 1995 and December 2010 at the Asan Medical Center. For all cases, medical records, including demographic data, clinical symptoms, radiological findings, postoperative treatment outcomes, and expression of SSTR subtypes, were carefully reviewed. Results In total, 162 (81.4%) PNETs expressed more than 1 SSTR subtype. Functioning PNET expressed significantly more SSTR subtypes, compared to nonfunctioning PNET. The SSTR2(+) and SSTR5(+) groups had better prognosis than the SSTR2(−) (P = 0.009) and SSTR5(−) groups (P = 0.03), respectively. In the grade 2 PNET of 2010 World Health Organization classification, the SSTR(+) group had better prognosis than SSTR(−) group. Conclusions The expression of SSTR 2 and 5 were related with good prognosis of PNET. In World Health Organization grade 2 PNET, the SSTR(+) group had better prognosis than SSTR(−) group. The SSTR expression(+) by immunohistochemistry might be related with good prognosis of the patients with surgically resected PNET.

Surgical outcomes of multifocal branch duct intraductal papillary mucinous neoplasms of pancreas

Backgrounds/Aims Appropriate management for multifocal branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas is still controversial. This study was intended to reveal surgical outcomes of surgical resection for multifocal BD-IPMNs, with BD-IPMNs in the remnant pancreas. Methods Between January 1995 and December 2013, 699 patients underwent the pancreatic resection due to IPMN of pancreas in our institution. Among them, 37 patients showed multifocal BD-IPMNs. After excluding patients who had BD-IPMNs completely resected, medical records of 22 patients with remained BD-IPMNs in the remnant pancreas were retrospectively reviewed. Results Mean patient age was 65±6.4 years. Types of surgery included central pancreatectomy (n=1), distal pancreatectomy (n=14), and standard pylorus-preserving pancreaticoduodenectomy (n=7). Specimen pathology showed that IPMN was either at low/intermediate-grade dysplasia (n=17) or at high-grade dysplasia (n=2). Three patients had IPMN associated with invasive carcinoma. Their mean follow-up period was 40.4 months. During follow-up, one mortality occurred 35.2 months after the operation which was not associated with IPMN. There was no clinically significant disease progression or recurrence of IPMN in the remnant pancreas during the follow-up period. Conclusions Our results support that we can safely preserve the pancreas parenchyma with multifocal BD-IPMNs. Benign-looking multifocal BD-IPMNs in the remnant pancreas do not affect the survival of patients.

Metastasis of hepatocellular carcinoma to the ovary: a case report and review of the literature.

Metastasis of hepatocellular carcinoma (HCC) to the ovary is notably rare. We present a case of HCC metastasis to the ovary with a review of the literature, which includes only 7 reported cases. A 43-year-old hepatitis B virus carrier was admitted with a right ovarian cystic mass. She had been diagnosed with HCC 2 years prior, for which she underwent transarterial chemoembolization followed by right posterior sectionectomy. Eight months after the hepatectomy, the first intrahepatic recurrence was detected and treated with transarterial chemoembolization. An additional intrahepatic recurrence occurred 12 months after transarterial chemoembolization and was managed with left medial sectionectomy and intra-operative radiofrequency ablation. Over the following 3 months, the patient developed elevated alpha-fetoprotein, and positron emission tomography showed a cystic mass in the right side of the pelvic cavity with focal hypermetabolic activity, which suggested a site of recurrent HCC. An exploratory laparotomy was performed, and a soft, ovoid cystic mass was identified in the right ovary. There was no evidence of metastases in the liver, left ovary, or peritoneum. Because of the absence of tumor on the surface of the ovary and the lack of peritoneal seeding, the mode of metastasis was thought to be hematogenous. Therefore, a right salphingo-oophorectomy was performed. The pathological features showed metastatic HCC with clear resection margins. Although metastasis of HCC to the ovary is very rare, it should be suspected in a female patient with a lower abdominal mass and an elevated serum AFP level in the absence of other demonstrable metastases.

Appraisal of Laparoscopic Distal Pancreatectomy for Left-Sided Pancreatic Cancer: A Large Volume Cohort Study of 152 Consecutive Patients

Background The aim of this study was to appraise the value of laparoscopic distal pancreatectomy (LDP) for left-sided pancreatic cancer based on a large volume cohort study. Methods We reviewed data for all consecutive patients undergoing LDP for left-sided pancreatic cancer at Asan Medical Center (Seoul, Korea) between December 2006 and December 2014. Results A total of 91 male and 61 female patients, with a median age of 62.7 years were included in this study. The median operative duration was 234 minutes. Pathological reports revealed the following: a median tumor size of 3.0 cm (range, 0.4–10.0), T stages (T1 in 7.9%, T2 in 5.3%, T3 in 86.8%, and no T4), the tumor differentiation (well differentiated in 16.4%, moderately differentiated in 75.4%, and poorly differentiated in 8.2%), and R0 resection in 126 patients (82.9%). After pancreatectomy, 96 patients (63.2%) received adjuvant chemotherapy, and the median time to chemotherapy was 30 days. The median length of hospital stay was 8 days (range, 5–31), and the median time to diet resumption was 1 day. Grade B or C postoperative pancreatic fistula occurred in 14 patients (9.2%) and grade II or III complications occurred in 27 (17.7%). The median overall survival was 43.0 months. A Cox proportional hazards model showed that tumor size, N1 stage, combined resection, and incompleteness of planned adjuvant chemotherapy affect patient survival. Conclusions LDP for left-sided pancreatic cancer is reasonable within selected indications. An international consensus on laparoscopic surgery for pancreatic cancer would be desirable and timely.