Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma.

BACKGROUND: The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). METHODS: From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. RESULTS: The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (p = 0.002), nodal involvement (p < 0.001), poor differentiation (p < 0.001), perineural and lymphovascular invasion (p < 0.001), and pancreatobiliary or mixed subtype (p < 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (p = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (p < 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; p < 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. CONCLUSION: FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.

The effects of sarcopenia and sarcopenic obesity after pancreaticoduodenectomy in patients with pancreatic head cancer.

BACKGROUND: Recently, several studies have reported that sarcopenia and sarcopenic obesity (SO) could worsen postoperative complications after PD. This study aims to evaluate the effects of preoperative sarcopenia and SO following PD in pancreatic head cancer (PHD). METHODS: Preoperative sarcopenia and SO were assessed in 548 patients undergoing PD for PHC at Samsung Medical Centre between 2007 and 2016. The visceral adipose tissue-to-skeletal muscle ratio was calculated from cross-sectional visceral fat and muscle areas on preoperative CT images. The overall survival (OS) and rate of clinically relevant postoperative pancreatic fistula (CR-POPF) among postoperative complications were extracted from prospectively maintained databases. RESULTS: Preoperative sarcopenia was present in 252 patients (45.9%). The 5-year survival rates of patients with non-sarcopenia and sarcopenia were 28.4% and 23.4% (p = 0.046). Preoperative SO was present in 202 patients (36.9%). After multivariable analysis, the presence of SO was the only independent risk factor for CR-POPF (p = 0.018). CONCLUSION: Sarcopenia can be a risk factor affecting decreased OS after PD in patients with PHC. SO is the only predictive factor for CR-POPF after PD in patients with PHC. More observational studies are needed to evaluate the effects of sarcopenia and SO on survival after PD.

Nomogram for predicting postoperative pancreatic fistula.

BACKGROUND: Previous studies analyzed risk factors for postoperative pancreatic fistula (POPF) and developed risk prediction tool using scoring system. However, no study has built a nomogram based on individual risk factors. This study aimed to evaluate individual risks of POPF and propose a nomogram for predicting POPF. METHODS: From 2007 to 2016, medical records of 1771 patients undergoing pancreaticoduodenctomy were reviewed retrospectively. Variables with p < 0.05 in multivariate logistic regression analysis were included in the nomogram. Internal performance validation was executed using a repeated cross validation method. RESULTS: Of 1771 patients, 222 (12.5%) experienced POPF. In multivariable analysis, sex (p = 0.004), body mass index (BMI) (p < 0.001), ASA score (p = 0.039), preoperative albumin (p = 0.035), pancreatic duct diameter (p = 0.002), and location of tumor (p < 0.001) were identified as independent predictors for POPF. Based on these six variables, a POPF nomogram was developed. The area under the curve (AUC) estimated from the receiver operating characteristic (ROC) graph was 0.709 in the train set and 0.652 in the test set. CONCLUSIONS: A POPF nomogram was developed. This nomogram may be useful for selecting patients who need more intensified therapy and establishing customized treatment strategy.

Left lobe living donor liver transplantation using the resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (RAPID) procedure in cirrhotic patients: First case report in Korea.

In liver transplantation, the primary concern is to ensure an adequate future liver remnant (FLR) volume for the donor, while selecting a graft of sufficient size for the recipient. The living donor-resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (LD-RAPID) procedure offers a potential solution to expand the donor pool for living donor liver transplantation (LDLT). We report the first case involving a cirrhotic patient with autoimmune hepatitis and hepatocellular carcinoma, who underwent left lobe LDLT using the LD-RAPID procedure. The living liver donor (LLD) underwent a laparoscopic left hepatectomy, including middle hepatic vein. The resection on the recipient side was an extended left hepatectomy, including the middle hepatic vein orifice and caudate lobe. At postoperative day 7, a computed tomography scan showed hypertrophy of the left graft from 320 g to 465 mL (i.e., a 45.3% increase in graft volume body weight ratio from 0.60% to 0.77%). After a 7-day interval, the diseased right lobe was removed in the second stage surgery. The LD-RAPID procedure using left lobe graft allows for the use of a small liver graft or small FLR volume in LLD in LDLT, which expands the donor pool to minimize the risk to LLD by enabling the donation of a smaller liver portion.

Comparison between percutaneous transhepatic gallbladder drainage and upfront laparoscopic cholecystectomy in patients with moderate-to-severe acute cholecystitis: a propensity score-matched analysis.

Purpose: In the Tokyo Guidelines 2018 (TG18), emergency laparoscopic cholecystectomy is recognized as a crucial early treatment option for acute cholecystitis. However, early laparoscopic intervention in patients with moderate-to-severe acute cholecystitis or those with severe comorbidities may increase the risk of complications. Therefore, in the present study, we investigated the association between early laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) in moderate-to-severe acute cholecystitis patients. Methods: We retrospectively analyzed 835 TG18 grade II or III acute cholecystitis patients who underwent laparoscopic cholecystectomy at 4 tertiary medical centers in the Republic of Korea. Patients were classified into 2 groups according to whether PTGBD was performed before surgery, and their short-term postoperative outcomes were analyzed retrospectively. Results: The patients were divided into 2 groups, and 1:1 propensity score matching was conducted to establish the PTGBD group (n = 201) and the early laparoscopic cholecystectomy group (n = 201). The PTGBD group experienced significantly higher rates of preoperative systemic inflammatory response syndrome (24.9% vs. 6.5%, P < 0.001), pneumonia (7.5% vs. 3.0%, P = 0.045), and cardiac disease (67.2% vs. 57.7%, P = 0.041) than the early operation group. However, there was no difference in biliary complication (hazard ratio, 1.103; 95% confidence interval, 0.519-2.343; P = 0.799) between the PTGBD group and early laparoscopic cholecystectomy group. Conclusion: In most cases of moderate-to-severe cholecystitis, early laparoscopic cholecystectomy was relatively feasible. However, PTGBD should be considered if patients have the risk factor of underlying disease when experiencing general anesthesia.

Adverse Effects of Sarcopenic Obesity on Postoperative Complications after Major Hepatectomy in Patients with Hilar Cholangiocarcinoma.

Sarcopenic obesity (SO), which is defined as a high ratio of visceral adipose tissue to skeletal muscle, is a well-known risk factor for post-hepatectomy outcomes in patients with hepatocellular carcinoma. However, few studies have evaluated the effect of SO on postoperative outcomes in patients with hilar cholangiocarcinoma (CCC). This retrospective study aimed to evaluate the effect of preoperative SO on postoperative outcomes in patients with hilar CCC following major hepatectomy. Preoperative SO was assessed in 328 patients undergoing hepatectomy for hilar CCC at three institutions between 2006 and 2016. SO was calculated from cross-sectional visceral fat and muscle area displayed on preoperative CT imaging. Preoperative SO was present in 98 patients (29.9%). The major complication rate in patients with SO was higher than in those without SO (54.1% vs. 37.0%, p = 0.004). Additionally, postoperative hospital stays were prolonged in patients with SO (18.5 vs. 16.5 days, p = 0.038). After multivariable analysis, SO was identified as an independent risk factor for major complications after hepatectomy in hilar CCC patients (OR = 0.866, 95% CI: 1.148-3.034, p = 0.012). Careful postoperative management is needed after major hepatectomy in hilar CCC patients with SO.

Clinical outcomes of pancreaticoduodenectomy for pancreatic ductal adenocarcinoma depending on preservation or resection of pylorus.

BACKGROUNDS/AIMS: The comparative effectiveness of pylorus-resecting pancreaticoduodenectomy (PRPD) and pylorus- preserving pancreaticoduodenectomy (PPPD) in pancreatic head cancer is still disputed. The aim of this study was to analyze the data obtained from a large, single center with PPPD compared with PRPD in terms of postoperative outcomes, including blood glucose levels and survival in patients with pancreatic head cancer. METHODS: Between January 2007 and December 2016, a total of 556 patients with pancreatic head cancer underwent either PPPD or PRPD. We analyzed the clinicopathologic data to assess short- and long-term outcomes retrospectively. RESULTS: For underlying disease, patients with DM in PPPD were fewer than in PRPD (33.0% vs. 46.2%, p=0.002). The median value of CA19-9 was significantly higher in PRPD than in PPPD (129.36 vs. 86.47, p=0.037). The incidence of Clavien-Dindo grade III to V major complications in PPPD was significantly higher than in PRPD (20.4% vs. 13.4%, p=0.032). Resection of pylorus was shown to reduce complications in univariate and multivariate analyses (p=0.032 and = 0.021, respectively). The 5-year survival rates were 27.6% in the PPPD group and 22.4% in the PRPD group (p=0.015). CONCLUSIONS: The results of PPPD and PRPD showed no significant differences from those reported conventionally in previous studies. Although further well-designed studies are needed, it is more important to select the range of surgical resection for the patient's disease regardless of resection of pylorus.

Predictive Nomogram for Early Recurrence after Pancreatectomy in Resectable Pancreatic Cancer: Risk Classification Using Preoperative Clinicopathologic Factors.

The survival of patients with pancreatic ductal adenocarcinoma (PDAC) is closely related to recurrence. It is necessary to classify the risk factors for early recurrence and to develop a tool for predicting the initial outcome after surgery. Among patients with resected resectable PDAC at Samsung Medical Center (Seoul, Korea) between January 2007 and December 2016, 631 patients were classified as the training set. Analyses identifying preoperative factors affecting early recurrence after surgery were performed. When the p-value estimated from univariable Cox's proportional hazard regression analysis was <0.05, the variables were included in multivariable analysis and used for establishing the nomogram. The established nomogram predicted the probability of early recurrence within 12 months after surgery in resectable PDAC. One thousand bootstrap resamplings were used to validate the nomogram. The concordance index was 0.665 (95% confidence interval [CI], 0.637-0.695), and the incremental area under the curve was 0.655 (95% CI, 0.631-0.682). We developed a web-based calculator, and the nomogram is freely available at http://pdac.smchbp.org/. This is the first nomogram to predict early recurrence after surgery for resectable PDAC in the preoperative setting, providing a method to allow proceeding to treatment customized according to the risk of individual patients.

Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer.

BACKGROUND: Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. METHODS: From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). RESULTS: The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). CONCLUSIONS: It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.

Risk prediction platform for pancreatic fistula after pancreatoduodenectomy using artificial intelligence.

BACKGROUND: Despite advancements in operative technique and improvements in postoperative managements, postoperative pancreatic fistula (POPF) is a life-threatening complication following pancreatoduodenectomy (PD). There are some reports to predict POPF preoperatively or intraoperatively, but the accuracy of those is questionable. Artificial intelligence (AI) technology is being actively used in the medical field, but few studies have reported applying it to outcomes after PD. AIM: To develop a risk prediction platform for POPF using an AI model. METHODS: Medical records were reviewed from 1769 patients at Samsung Medical Center who underwent PD from 2007 to 2016. A total of 38 variables were inserted into AI-driven algorithms. The algorithms tested to make the risk prediction platform were random forest (RF) and a neural network (NN) with or without recursive feature elimination (RFE). The median imputation method was used for missing values. The area under the curve (AUC) was calculated to examine the discriminative power of algorithm for POPF prediction. RESULTS: The number of POPFs was 221 (12.5%) according to the International Study Group of Pancreatic Fistula definition 2016. After median imputation, AUCs using 38 variables were 0.68 ± 0.02 with RF and 0.71 ± 0.02 with NN. The maximal AUC using NN with RFE was 0.74. Sixteen risk factors for POPF were identified by AI algorithm: Pancreatic duct diameter, body mass index, preoperative serum albumin, lipase level, amount of intraoperative fluid infusion, age, platelet count, extrapancreatic location of tumor, combined venous resection, co-existing pancreatitis, neoadjuvant radiotherapy, American Society of Anesthesiologists' score, sex, soft texture of the pancreas, underlying heart disease, and preoperative endoscopic biliary decompression. We developed a web-based POPF prediction platform, and this application is freely available at http://popfrisk.smchbp.org. CONCLUSION: This study is the first to predict POPF with multiple risk factors using AI. This platform is reliable (AUC 0.74), so it could be used to select patients who need especially intense therapy and to preoperatively establish an effective treatment strategy.

Validation of original and alternative fistula risk scores in postoperative pancreatic fistula.

BACKGROUND: In 2013, the fistula risk score (FRS) was developed to assess the risk of clinically relevant postoperative pancreatic fistula (CR-POPF). In 2017, the alternative FRS (a-FRS) was proposed. The purpose of this study was to validate the original FRS (o-FRS) and a-FRS for CR-POPF in pancreaticoduodenectomy (PD). METHODS: From January 2007 to December 2016, 1,771 patients underwent PD for periampullary cancers. POPF was defined and classified according to the 2016 International Study Group for Pancreatic Fistula. All data were reviewed retrospectively. RESULTS: Pathologic diagnosis other than ductal adenocarcinoma (P < 0.001), pancreas duct diameter (P < 0.001), and body mass index (P < 0.001) were independent risk factors for CR-POPF. Pancreatic texture (P = 0.534) and estimated blood loss (P = 0.827) were not associated with CR-POPF. The CR-POPF incidence increased with increasing o-FRS score (P < 0.001), and also increased statistically significantly with increasing a-FRS in the higher risk group (P < 0.001). However, the correlations differed. The area under the curve was 0.629 for o-FRS and 0.622 for a-FRS. CONCLUSIONS: Both o-FRS and a-FRS might reflect CR-POPF incidence, but some risk factors had no or low statistical significance. Further research is needed to revise the FRS.

Optimal timing of pancreaticoduodenectomy following preoperative biliary drainage considering major morbidity and postoperative survival.

BACKGROUND: The present study aimed to determine the optimal timing of pancreaticoduodenectomy (PD) following preoperative biliary drainage (PBD) with consideration of postoperative morbidity and survival. METHODS: Between January 2007 and December 2015, consecutive 1,568 patients underwent PD at a single institution. Their data were reviewed retrospectively. RESULTS: Of all, 831 patients underwent PBD. The mean duration between drainage and surgery was 16.9 days. Regarding postoperative outcomes, length of hospital stay was longer in the drainage group (P = 0.028). Postoperative pancreatic fistula was not significantly different between the non-drainage and drainage groups (P = 0.162), but major complications occurred more frequently in the drainage group (P = 0.002). Multivariable analysis showed major complications occurred significantly at third and fourth weeks (odds ratios 1.863 and 2.523) after PBD, whereas early surgery performed in the first 2 weeks did not noticeably increase postoperative complications. In multivariable survival comparison, weekly interval beyond 6 weeks was associated with poor survival in those with pancreatic cancer, while patients with bile duct cancer operated on at the fourth week showed worse prognosis. CONCLUSIONS: Early surgery that reduces the operative delay after PBD may improve both short- and long-term postoperative outcomes in cancer patients undergoing PBD.

Subtype of intraductal papillary mucinous neoplasm of the pancreas is important to the development of metachronous high-risk lesions after pancreatectomy.

BACKGROUNDS/AIMS: Although intraductal papillary mucinous neoplasm (IPMN) has showed a favorable prognosis compared to pancreatic ductal adenocarcinoma, its recurrence patterns have somewhat questionable in detail. After partial pancreatectomy for IPMN, the evaluation for risk of metachronous occurrence of high-risk lesions (HRL) in the residual pancreas is important to establish a postoperative surveillance modality and duration of follow-up. This study aimed to evaluate the factors that may predict the metachronous occurrence of HRL in the remnant pancreas after surgery of the IPMN. METHODS: From 2005 to 2016, clinicopathologic and surveillance data for 346 consecutive patients who underwent surgical resection for IPMN were reviewed retrospectively. Histologic subtype was classified as gastric, intestinal, pancreato-biliary, or oncocytic type. RESULTS: All of IPMN were classified as main duct (n=64, 18.5%), branch duct (n=171, 49.4%), and mixed type (n=111, 32.1%). Forty-eight patients (13.9%) experienced recurrence during follow-up. Among these, 9 patients (2.6%) were identified to metachronous development of HRL in the remnant pancreas. After multivariate analysis, high-grade dysplasia (HGD) or invasive carcinoma (IC) compared to low- or intermediate dysplasia was only independent risk factor for recurrence (HR 3.688, 95% CI 2.124- 12.524, p=0.009). The independent risk factors for metachronous development were HGD/IC (HR 8.414, 95% CI 4.310- 16.426, p=0.001), and intestinal/pancreato-biliary subtype compared to gastric subtype (HR 7.874, 95% CI 3.650- 27.027, p=0.010). CONCLUSIONS: Patients with high-grade dysplasia or invasive carcinoma, and with intestinal or pancreatobiliary subtype should undergo close, long-term surveillance of the remnant pancreas after initial resection.