Duck Jong Han

Treatment Guidelines for Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: When Can We Operate or Observe?

BackgroundThe objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN.MethodsWe retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea.ResultsOf 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor ≤2 cm without a mural nodule was 9.2%, for a tumor of ≤2 cm plus a mural nodule was 25%, and for other conditions such as tumor >2 cm, >25%.ConclusionsMany branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of ≤2 cm without a mural nodule.

Single-center experience of laparoscopic left pancreatic resection in 359 consecutive patients: changing the surgical paradigm of left pancreatic resection

AbstractBackgroundLaparoscopic distal pancreatectomy (LDP) is increasingly performed for lesions of the body and tail of the pancreas. We analyzed the clinical characteristics of the largest series of patients to date who underwent LDP at a single center, as well as their outcomes, to reassess the surgical paradigm for left pancreatic resection.MethodsWe retrospectively reviewed the records of 359 patients who underwent LDP at Asan Medical Center, Seoul, Korea, for pancreatic neoplasms between March 2005 and December 2010.ResultsOf the 359 patients, 323 (90%) had benign or low-grade malignant neoplasms and 36 (10%) had malignancies. The most common diagnosis was intraductal papillary mucinous neoplasm (IPMN) in 72 patients (21.2%). There were 24 patients (6.7%) with pancreatic ductal adenocarcinoma (PDAC). We found that 178 patients (49.6%) underwent spleen-preserving LDP (SP-LDP): 150 (84.3%) by main splenic vessel preservation, and 28 (15.7%) supported by short gastric and gastroepiploic vessels (Warshaw technique). Postoperative complications occurred in 43 (12%) patients, including 25 (7%) with pancreatic fistula (ISGPF grade B, C), but there was no death. Median operative time was 195 (range, 78–480) min, and median postoperative hospital stay was 8 (range, 4–37) days. The proportion of patients with pancreatic lesions who underwent LDP increased from 8.6% in 2005 to 66.9% in 2010. Kaplan–Meier analysis showed that the 1- and 2-year overall survival rates in the 24 patients with PDAC were 85.2% each.ConclusionsLDP is feasible, safe, and effective for the treatment of benign and low-grade malignant lesions of the pancreas. The increased use of LDP for left-sided pancreatic lesions, including malignant lesions, represents a paradigm shift from open distal pancreatectomy.

Multicenter Analysis of Clinicopathologic Features of Intraductal Papillary Mucinous Tumor of the Pancreas: Is It Possible to Predict the Malignancy Before Surgery?

BackgroundDespite recently increasing numbers of reports on intraductal papillary mucinous tumors (IPMTs), difficulties still remain in terms of diagnosis, treatment, and prognosis. The purpose of this multicenter study was to evaluate the clinicopathologic features of IPMT in Korea and to suggest predictive criteria for malignancy in IPMT.MethodsWe retrospectively reviewed the clinicopathologic data of 208 patients who underwent operations for IPMT between 1993 and 2002 at 28 institutes in Korea.ResultsOf the 208 patients (mean age, 61 years), 147 were men and 61 were women. A total of 124 patients underwent pancreatoduodenectomy, 42 underwent distal pancreatectomy, 17 underwent total pancreatectomy, and 25 underwent limited pancreatic resection. There were 128 benign cases (adenoma, n = 62; borderline, n = 66) and 80 malignant cases (noninvasive, n = 29; invasive, n = 51). A significant difference in 5-year survival was observed between the benign and malignant groups (92.6% vs. 65.3%; P = .006). Of the six factors (age, location, duct dilatation, mural nodule, main duct type, and tumor size) that showed statistical differences by univariate analysis between the benign and malignant groups, three were significant by multivariate analysis—namely, mural nodule (P = .009), tumor size (P = .023), and a dilated duct size (P = .010).ConclusionsA significant proportion of IPMTs are malignant, although the overall prognosis of IPMT is superior to that of ordinary pancreatic cancer. Radical surgery is recommended for IPMT with the predictors of malignancy: mural nodule, tumor size (⩾30 mm), and dilated duct size (⩾12 mm).

Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma

BACKGROUND To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma (LAPC). METHODS Patients with histologically confirmed LAPC were given 3-6 cycles of fixed-dose rate gemcitabine/capecitabine every 3 weeks. At the end of chemotherapy, patients were restaged and underwent surgery if the disease was not classified as unresectable. Our institutional criteria were used to classify respectability, which was recategorized on the basis of National Comprehensive Cancer Network (NCCN) criteria retroactively. The primary end point was rate of microscopic curative resection. RESULTS Forty-three eligible patients (18 with borderline resectable disease and 25 with unresectable disease on the basis of NCCN criteria) were enrolled. The radiologic response rate was 18.6%. Grade three or worse adverse events were mainly hand-foot syndrome (11%), and there were no grade four adverse events. Surgery was performed in 17 patients (39.5%); pathologic curative resection (R0) was achieved in 14 patients (32.5%) among total 43 patients, and 82.3% (14/17) among the 17 resected patients. With 43-month follow-up, the median overall was 16.6 months with a median progression-free survival of 10.0 months. Median overall survival was 23.1 months in patients who underwent surgery and 13.2 months in patients who could not complete the surgery (P = .017). CONCLUSION A subset of patients with borderline or unresectable pancreatic cancer could be performed curative tumor resection after neoadjuvant chemotherapy. Some patients might be benefit on survival from neoadjuvant chemotherapy after surgical resection.

Intraductal papillary mucinous neoplasm of the pancreas: clinical characteristics and treatment outcomes of 118 consecutive patients from a single center

BACKGROUND/PURPOSE Appropriate surgical treatment strategies based on clinicopathological findings are unavailable for intraductal papillary mucinous neoplasm (IPMN) of the pancreas. We investigated the clinical features of pancreatic IPMN in a single-center database in order to design an optimal surgical strategy. METHODS The medical records of 118 consecutive patients who had undergone surgical resection between August 1994 and December 2004, in whom IPMN was histologically confirmed, were reviewed retrospectively for radiological and pathological findings. RESULTS Most of the invasive carcinomas in these patients were detected as the main-duct type (88.5%). The type of tumor (main-duct type vs branched-duct type), the tumor size, and the dilated duct size were significant predictive factors associated with malignancy. The relative risk of malignancy was greatest at 13-mm or more ductal dilation in the main-duct type (Odds ratio, 4.1), at 35-mm or more tumor size (Odds ratio, 7.6), and for main-duct type (Odds ratio, 3.9). Major pancreatic resections such as total pancreatectomy and pancreatoduodenectomy were performed in 14.5% and 69% of the patients, respectively. There was a 19.5% rate of incomplete resection, with these patients having a positive resection margin. However, significant recurrence did not occur in patients with a benign IPMN lesion which remained at the resection margin. The overall postoperative survival rate at 5 years was 98.2% for benign IPMN and 65.3% for malignant IPMN. CONCLUSIONS Function-preserving strategies, based on the clinical status of the patient, are necessary in order to avoid possible severe metabolic complications following extended pancreatectomy in patients with benign IPMN because of the low recurrence rate and good prognosis of this entity, irrespective of margin status.

Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence.

Background. Lamivudine has been reported to be able to stabilize liver enzyme and hepatitis B virus (HBV) replication with recurrent hepatitis that has been regarded as a frequent and major risk factor for hepatic dysfunction and chronic liver disease in renal transplant recipients. Because large number of hepatitis antigenemia patients among renal transplant patients experience recurrent hepatic dysfunction with HBV recurrence and permanent histological deterioration, preemptive or primary prophylactic use of lamivudine before transplantation may be more beneficial than a trial for the treatment of advanced hepatic dysfunction. Methods. We conducted a double arm study to compare the efficacy of lamivudine between the preemptive (HBV DNA positive) or prophylactic (HBV DNA negative) trial for the maintenance of stable liver function (n=10) and the trial for the salvage of advanced hepatic dysfunction developed after renal transplantation (n=6) in hepatitis B viremia carrier renal transplant recipients. Results. Hepatic dysfunction with recurrent HBV antigenemia developed in 11 of 36 (30.6%) hepatitis antigenemia patients with a mean duration of 8.4 months (range 5–19.4 months). In six patients treated with lamivudine after hepatic dysfunction from recurrent hepatitis B viremia, serum AST and ALT level normalized within 1 month and HBV-DNA disappeared in all cases. HBV-DNA, however, reappeared in three (50%) without any discontinuation of lamivudine. Liver biopsy revealed recurrent chronic active hepatitis with severe activity of fibrosis in four cases, cholestatic fibrosing hepatitis in one, and permanent cirrhotic change in one. In seven patients who had preemptive lamivudine treatment at 9, 6, 2, 2, 1, 0, 0 month before the transplantation, HBV-DNA had converted to negative with a mean follow up of 1.2 months (range 1–2 month) in all case. Three patients who had prophylactic trials with lamivudine have all remained HBV-DNA negative. The recurrence rate of HBV viremia in the preemptive or prophylactic lamivudine treated group is 10.0% (1/10), which is significantly lower than that (42.3%, 11/25) in the nonlamivudine-treated group. The re-recurrence rate of HBV viremia was significantly higher (3/6, 50.0%) in the reactive lamivudine treated group than in prophylactic or preemptive group (1/10, 10%). Conclusion. Although lamivudine treatment after hepatic dysfunction can be a sound conventional treatment modality, this preliminary study may suggest that preemptive or prophylactic trial of lamivudine before hepatic dysfunction might be a more effective strategy for prevention of permanent histological deterioration and recurrence of hepatitis B viremia.

Solid pseudopapillary tumor of the pancreas: Can malignancy be predicted?

BACKGROUND The objective of this study was to examine the clinicopathologic characteristics of solid pseudopapillary tumors (SPTs) of the pancreas, including the risk factors for disease recurrence and their effects on survival. METHODS The medical records of 114 patients who underwent surgery for a pathologically confirmed SPT between January 1995 and December 2007 were reviewed retrospectively. RESULTS Of the 114 patients, 98 (86.9%) were female, and the median age was 36 years (range, 11-75). All 114 patients underwent curative intent surgery and 13 (11.4%) underwent laparoscopic surgery. Of the 114 patients, 26 (22.8%) had solid pseudopapillary carcinoma (SPC). There were no differences in any clinical factors between the benign SPT and SPC groups; however, the only 4 recurrences identified were in the SPC group. After follow-up ranging from 11 to 177 months, all 114 patients were alive, with only 4 showing evidence of recurrence. Recurrence was observed in young patients with metastasis at first operation, invasion of an adjacent organ, and a large mass (≥13 cm). CONCLUSION Adequate operative resection including laparoscopic surgery is the mainstay of treatment for SPT. Although statistically significant risk factors for recurrence cannot be determined, tumor metastasis at the first operation, invasion of adjacent organ, large tumor size, young patient age, tumor rupture, and inadequate resection may increase the risk of recurrence. Our results demonstrate that long-term survival could be achieved by aggressive operative resection and interventional treatment of recurrent disease.

Treatment of chronic hepatitis B with lamivudine in renal transplant recipients

BACKGROUND Lamivudine is a potent inhibitor of hepatitis B virus replication. Little has been reported about the efficacy and safety of lamivudine in the treatment of chronic hepatitis B in the setting of renal transplantation. METHODS Two patients were treated for chronic hepatitis B with lamivudine and subsequently underwent renal transplantation. Four other patients were treated with lamivudine for reactivation of hepatitis B after renal transplantation. Chronic hepatitis B was proven histologically in all the patients. The doses of lamivudine ranged from 100 to 150 mg/day. Hepatic enzyme and viral markers were monitored. RESULTS Lamivudine was well tolerated for a median duration of 8 months (range, 4-14 months) without significant side effects. Viral replication was suppressed, as evidenced by negative conversion of serum hepatitis B virus DNA in all the patients. Hepatic enzyme was also normalized. Modification of doses of immunosuppressant regimen was not required in using lamivudine in all patients. One patient experienced acute rejection and responded to solumedrol pulse therapy with normalization of graft function. Normal graft function was maintained in other patients while they were treated with lamivudine. CONCLUSION Lamivudine was a safe and effective therapy for activated hepatitis B in renal transplant recipients in the short term.

Tacrolimus Concentrations in Relation to CYP3A and ABCB1 Polymorphisms Among Solid Organ Transplant Recipients in Korea

Background. Cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P-gp) affect the bioavailability of tacrolimus, the most commonly used immunosuppressive agent in organ transplant recipients. We have determined the genotypic frequencies of the CYP3A and ATP-binding cassette sub-family B member 1 (ABCB1) genes, which encode the CYP3A and P-gp proteins, respectively, in Korean organ transplant recipients and donors, and have assessed the influence of CYP3A and ABCB1 polymorphisms on tacrolimus concentrations. Methods. Using chip-based MALDI-TOF mass spectrometry, 506 solid organ transplant recipients and 62 corresponding of liver transplant donors were genotyped for CYP3A4*6, CYP3A4*18, CYP3A5*3, CYP3A5P1*3, ABCB1 c.2677G>A/T, and ABCB1 c.3435C>T alleles, and their steady-state blood concentrations of tacrolimus were measured. Results. Frequencies of variant alleles among the transplant recipients were CYP3A5*3 76.8%, CYP3A5P1*3 75.9%, ABCB1 c.2677A/T 52.8%, ABCB1 c.3435T 36.9%, CYP3A4*18 1.9%, and CYP3A4*6 0.3%. The CYP3A5P1*3 allele was strongly linked to the CYP3A5*3 allele (r2=0.816). Patients with the CYP3A5*3 and CYP3A5P1*3 alleles showed higher blood tacrolimus concentrations per adjusted dose ratio than did patients with wild-type alleles, among both liver transplant donors and renal transplant recipients. Conclusion. The CYP3A5 genotype of the liver is considered to show the most important association with tacrolimus concentrations. Ultimately, genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing solid organ transplantation.

Validation of the 2012 International Consensus Guidelines Using Computed Tomography and Magnetic Resonance Imaging: Branch Duct and Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Objective:To validate the 2012 guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas and to compare diagnostic performances of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiating malignant from benign IPMN. Background:As IPMN has variable risks of malignancy and management of this entity is closely related to its malignant potential, it is important to predict risks of IPMN malignancy. Methods:This retrospective study included 158 patients with surgically confirmed IPMN of the pancreas who underwent both preoperative CT and MRI. Two radiologists evaluated the “high-risk stigmata” and “worrisome features” of the 2012 guidelines for branch duct (BD)-IPMN and main duct (MD)-IPMN. Univariate and multivariable analyses were used to identify significant predictors of malignancy in IPMN. The diagnostic performance was compared between CT and MRI. Results:Malignant IPMN was seen in 8 of 60 patients (13.3%) with BD-IPMN and 44 of 98 patients (44.9%) with MD-IPMN. Presence of mural nodule was the most important predictor in BD-IPMN and MD-IPMN (odds ratios, 9.2 and 7.6, respectively, P = 0.01 on CT; and odds ratios, 5.7 and 13.3, respectively, P ⩽ 0.04 on MRI), whereas mural nodule size and lymphadenopathy were significant only in MD-IPMN (P < 0.05). The diagnostic performance of CT and MRI for significant findings was not statistically different in both types of IPMN (P > 0.34). Conclusions:The presence of mural nodule was the most important predictor of malignancy in both types of IPMN. Mural nodule size and lymphadenopathy were also significant predictors in MD-IPMN. Computed tomography and MRI showed similar diagnostic performances for differentiating malignant from benign IPMN.