Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). @*Materials and Methods@#Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. @*Results@#Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. @*Conclusion@#Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. @*Materials and Methods@#This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. @*Results@#Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). @*Conclusion@#Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. @*Materials and Methods@#A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. @*Results@#The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. @*Conclusion@#The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma. @*Materials and Methods@#Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed. @*Results@#The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111). @*Conclusion@#AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma. @*Materials and Methods@#Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed. @*Results@#The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111). @*Conclusion@#AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Prognostic factors predicting survival rate over 10 years of patients with intrahepatic cholangiocarcinoma after hepatic resection

PURPOSE: Hepatic resection is considered as the optimal treatment for intrahepatic cholangiocarcinoma (IHCC); however, the survival rate after resection is low and the analysis of long-term (≥10 years) survivors is rare. This study aims to analyze the clinicopathological factors affecting the long-term survival of patients with IHCC.METHODS: Between January 2003 and December 2012, a single-institution cohort of 429 patients who underwent hepatic resection for IHCC were reviewed retrospectively. Surgical results, recurrence, and survival rates were investigated, and multivariate analyses were performed to identify prognostic factors.RESULTS: The overall 1- , 3- , 5- and 10-year survival rates of patients were 76.5%, 44.1%, 33.3%, and 25.1%, respectively. Multivariate analysis showed that the serum CA 19-9 level (≥38 U/mL) (P < 0.001), lymph node (LN) metastasis (P = 0.001), and lymphovascular invasion (LVI) (P = 0.012) were independent factors associated with overall survival. In particular, CA 19-9 level and histologic type were determined to be independent factors affecting survival for more than 10 years.CONCLUSION: CA 19-9 (≥38 U/mL), LN metastasis, and LVI were identified as independent risk factors for survival after resection of IHCC. CA 19-9 (<38 U/mL) and histologic type were independent factors predicting survival for more than 10 years.

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas

Background@#Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. @*Methods@#We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. @*Results@#A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p<.001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively. @*Conclusions@#The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.

Sarcoma metastasis to the pancreas: experience at a single institution

Background@#Reports of metastatic sarcoma to the pancreas are limited. We reviewed the clinicopathologic characteristics of such cases. @*Methods@#We reviewed 124 cases of metastatic tumors to the pancreas diagnosed at Asan Medical Center between 2000 and 2017. @*Results@#Metastatic tumors to the pancreas consisted of 111 carcinomas (89.5%), 12 sarcomas (9.6%), and one melanoma (0.8%). Primary sarcoma sites were bone (n = 4); brain, lung, and soft tissue (n = 2 for each); and the uterus and pulmonary vein (n = 1 for each). Pathologically, the 12 sarcomas comprised 2 World Health Organization grade III solitary fibrous tumors/hemangiopericytomas, and one case each of synovial sarcoma, malignant solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, intimal sarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, subtype uncertain, and high-grade spindle-cell sarcoma of uncertain type. The median interval between primary cancer diagnosis and pancreatic metastasis was 28.5 months. One case manifested as a solitary pancreatic osteosarcoma metastasis 15 months prior to detection of osteosarcoma in the femur and was initially misdiagnosed as sarcomatoid carcinoma of the pancreas. @*Conclusions@#The metastatic sarcoma should remain a differential diagnosis when spindle-cell malignancy is found in the pancreas, even for solitary lesions or in patients without prior history.

Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with the 7th Staging System / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study was conducted to evaluate the prognostic values of the 7th and 8th American Joint Committee on Cancer (AJCC) staging systems for patients with resected perihilar cholangiocarcinoma (PHCC). @*Materials and Methods@#A total of 348 patients who underwent major hepatectomy for PHCC between 2008 and 2015 were identified from a single center. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index was used to evaluate the prognostic predictability of the 8th AJCC staging system compared with that of the 7th. @*Results@#In the 8th edition, the stratification of each group of T classification improved compared to that in the 7th, as the survival rate of T4 decreased (T2, 31.2%; T3, 13.9%; T4, 15.1%; T1- T2, p=0.260; T2-T3, p=0.001; T3-T4, p=0.996). Both editions showed significant survival differences between each N category, except between N1 and N2 (p=0.063) in 7th edition. Differences of point estimates between the 8th and 7th T and N classification and overall stages were +0.028, +0.006, and +0.039, respectively (T, p=0.005; N, p=0.115; overall stage, p=0.005). In multivariable analysis, posthepatectomy liver failure, T category, N category, distant metastasis, histologic differentiation, intraoperative transfusion, and resection margin status were associated with OS. @*Conclusion@#The prognostic predictability of 8th AJCC staging for PHCC improved slightly, with statistical significance, compared to the 7th edition, but its overall performance is still unsatisfactory.

Validation of the 8th Edition of the American Joint Committee onCancer Staging System for Gallbladder Cancer and Implications forthe Follow-up of Patients without Node Dissection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The 8th edition of gallbladder cancer staging in the American Joint Committee on Cancer(AJCC) staging system changed the T and N categories. @*Materials and Methods@#In order to validate the new staging system, a total of 348 surgically resected gallbladdercancers were grouped based on the 8th edition of the T and N categories and comparedwith patients’ survival. @*Results@#Significant differences were noted between T1b-T2a (p=0.003) and T2b-T3 (p < 0.001)tumors, but not between Tis-T1a, T1a-T1b, and T2a-T2b tumors. However, significant survivaldifferences were observed both by the overall and pair-wise (T1-T2, T2-T3) comparisons(all, p < 0.001) without dividing T1/T2 subcategories. When cases with ! 6 examined lymphnodes were evaluated, significant survival differences were observed among the entire comparison(p < 0.001) and pair-wise comparisons of N0-N1 (p=0.001) and N1-N2 (p=0.039)lesions. When cases without nodal dissection (NX) were additionally compared, significantsurvival differences were observed between patients with N0-NX (p=0.001) and NX-N1(p < 0.001) lesions. @*Conclusion@#The T category in the 8th edition of the AJCC staging system did not completely stratify theprognosis of patients with gallbladder cancer. Modification by eliminating T subcategoriescan better stratify the prognosis. In contrast, the N category clearly determines patients’survival with ! 6 examined lymph nodes. The survival time in patients of gallbladder cancerswithout nodal dissection is between N0 and N1 cases. Therefore, close postoperative followedup is recommended for those patients.

Predictors of early recurrence following a curative resection in patients with a carcinoma of the ampulla of Vater

Purpose@#Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%–50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection. @*Methods@#The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection. @*Results@#There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30–94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year. @*Conclusion@#An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.

Transduodenal ampullectomy for ampullary tumors - single center experience of consecutive 26 patients

PURPOSE: Transduodenal ampullectomy (TDA) has been reported in a limited number of cases and in a small number of case series. The aim of this study was to analyze perioperative and long-term oncological outcomes of patients with ampullary tumors who underwent TDA in a single large-volume center. METHODS: Through a retrospective review of data from 2004 to 2016, we identified 26 patients who underwent TDA at Asan Medical Center. RESULTS: Eleven of 26 patients underwent TDA for T1 and carcinoma in situ (high-grade dysplasia) cancer; these patients are still alive without recurrence. A major in-hospital complication (3.8%) occurred in 1 case, but there was no case of 90-day mortality. In addition, none of the patients was diagnosed as having newly developed diabetes mellitus after TDA. No significant differences were found between open and laparoscopic-TDA in terms of operation time, painkiller use, and hospital stay. CONCLUSION: TDA is a feasible and effective surgical procedure for the treatment of selected patients with ampullary tumors. It is an alternative treatment option in cases of ampullary tumors not amenable to endoscopic papillectomy or pancreaticoduodenectomy.

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. METHODS: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. RESULTS: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. CONCLUSIONS: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in 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.

Prognostic factors associated with early mortality after surgical resection for pancreatic adenocarcinoma

BACKGROUNDS/AIMS: Identifying pancreatic cancer patients at high risk of early mortality following surgical resection for pancreatic cancer is important to make optimal treatment decisions in multidisciplinary setting. The purpose of this study was to identify the factors related to early mortality in patients who underwent pancreatic resection for pancreatic adenocarcinoma. METHODS: We reviewed our institution's experience with all consecutive patients who underwent pancreatectomy for pancreatic adenocarcinoma from January 2000 to December 2010. One thousand patients were eligible for our study. Fifty-three patients who did not meet the study criteria were excluded. Based on 12 months after surgery, patients were divided into early mortality group or the remaining group. We performed logistic regression analysis to identify predictors of early mortality. RESULTS: Among 947 patients who met our study criteria, 302 (31.9%) early mortality (defined as experiencing death within 12 months after surgery) occurred. Multivariate analysis revealed that patient age and surgery time period were statistically significant predictors of early mortality within six months after surgery. Poorly differentiated tumor and adjuvant chemotherapy were statistically significant predictors of early mortality within 12 months after surgery. Total pancreatectomy and lymphovascular invasion were significant (p<0.05) prognostic factors of early mortality within 6 or 12 months after surgery. CONCLUSIONS: We suggest followings to avoid early mortality after pancreatic resection: patients with multiple risk factors related to early mortality after pancreatectomy should be considered for alternative treatment; patient's general condition and surgical technique improvement are important; and adjuvant therapy should be taken into consideration.

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.

Impact of critical pathway implementation on hospital stay and costs in patients undergoing pancreaticoduodenectomy

BACKGROUNDS/AIMS: Recent studies have shown that pancreaticoduodenectomy (PD) can be performed quite safely. Critical pathway (CP) has been one of the key tools used to achieve excellent outcomes in high-quality, high-volume centers. This study was designed to evaluate the impact of CP implementation for PD patients. METHODS: The important components of CP for PD patients include the early start of an oral diet and removal of the abdomen drain following follow-up computed tomography, with the intention of shortening the postoperative hospital stay. The study group (CP group) comprised of 88 patients who underwent pylorus-preserving or classical PD from January 2009 to December 2010. The control group (pre-CP group) was 185 patients who underwent PD between January 2005 and December 2008. RESULTS: The two groups did not show significant differences in demographic profiles and the primary diagnosis. The incidences of overall postoperative complications such as delayed gastric emptying, fistula, and hemorrhage were similar or decreased in the CP group (54% vs. 40.9%). The incidence of clinically significant complications also showed a similar rate (5.4% vs. 4.5%) between the two groups. The nutritional status at discharge and re-admission rates were not different. The CP group showed a significantly shorter postoperative hospital stay (20.2+/-9.2 days vs. 14.9+/-5.1 days, p<0.001) and the total medical costs were also significantly reduced, by 15% (p<0.001). CONCLUSIONS: The results of this study indicated that the implementation of CP for PD patients can decrease the length of hospital stay and reduce medial costs, with maintenance or improvement of patient outcomes. Further investigation is necessary to validate the actual impact of CP for PD through multi-center high-volume studies.

Laparoscopic Versus Open Central Pancreatectomy: Single-institution Comparative Study

PURPOSE: Despite recent advances in laparoscopic pancreatic surgery, few studies have compared laparoscopic central pancreatectomy (LCP) with open central pancreatectomy (OCP). The aim of this study was to compare clinical outcomes between LCP and OCP as a single institutional study. METHODS: During the study period (From January, 1998 to December, 2010), we performed central pancreatectomy in 95 cases. Among them, 26 cases of totally LCP and 55 cases of OCP were compared retrospectively. RESULTS: Benign pancreatic neoplasm was the main indication. The mean operation time for the LCP group (350.2 min) was longer than that for the OCP group (283.4 min). And there was no significant difference in mean actual blood loss (477 ml versus 714 ml, p=0.083) between the LCP and OCP groups. Return to a normal bowel movement and resumption of a liquid diet were achieved 5.5+/-2.6 days after the operation in the LCP group and 6.6+/-2.0 days after the operation in the OCP group (p=0.039). The mean duration of postoperative hospital stay was 13.8 days for the LCP group, which was significantly shorter than the 22.5 days for the OCP group (p=0.015). The overall complication rate was 42.3% (11 cases) in the LCP group and 45.5% (25 cases) in the OCP group (p=0.790). CONCLUSION: Use of LCP for benign or low grade malignant lesions of the pancreatic neck portion is feasible and safe. Compared to the open method, the laparoscopic approach to central pancreatectomy appears to provide advantages of early resumption of a normal diet and reduction of postoperative hospital stay without further complications.

Catheter Embolism during Chemoport Removal

Chemoport is widely used in pediatric surgery field. But various complications can occur during the process of insertion or removal of chemoport. Surgeons must be familiar with the treatment of these complications. We had one catheter cuts off during chemoport removal, become a catheter embolism. Interventional radiologic removal was successful. Verifying the length of removed catheter and careful observation of the catheter tip during removal procedure is important to prevent the possibility of catheter embolus. Radiologic intervention was accessible to remove the retained catheter.