Prognostic Effect of Liver Resection in Extended Cholecystectomy for T2 Gallbladder Cancer Revisited: A Retrospective Cohort Study With Propensity Score-matched Analysis.

OBJECTIVE: This study aimed to evaluate the effect of liver resection on the prognosis of T2 gallbladder cancer (GBC). BACKGROUND: Although extended cholecystectomy [lymph node dissection (LND) + liver resection] is recommended for T2 GBC, recent studies have shown that liver resection does not improve survival outcomes relative to LND alone. METHODS: Patients with pT2 GBC who underwent extended cholecystectomy as an initial procedure and did not reoperation after cholecystectomy at 3 tertiary referral hospitals between January 2010 and December 2020 were analyzed. Extended cholecystectomy was defined as either LND with liver resection (LND+L group) or LND only (LND group). We conducted 2:1 propensity score matching to compare the survival outcomes of the groups. RESULTS: Of the 197 patients enrolled, 100 patients from the LND+L group and 50 from the LND group were successfully matched. The LND+L group experienced greater estimated blood loss ( P <0.001) and a longer postoperative hospital stay ( P =0.047). There was no significant difference in the 5-year disease-free survival (DFS) of the 2 groups (82.7% vs 77.9%, respectively, P =0.376). A subgroup analysis showed that the 5-year DFS was similar in the 2 groups in both T substages (T2a: 77.8% vs 81.8%, respectively, P =0.988; T2b: 88.1% vs 71.5%, respectively, P =0.196). In a multivariable analysis, lymph node metastasis [hazard ratio (HR) 4.80, P =0.006] and perineural invasion (HR 2.61, P =0.047) were independent risk factors for DFS; liver resection was not a prognostic factor (HR 0.68, P =0.381). CONCLUSIONS: Extended cholecystectomy including LND without liver resection may be a reasonable treatment option for selected T2 GBC patients.

Suggested use of empirical antibiotics in acute cholecystitis based on bile microbiology and antibiotic susceptibility.

BACKGROUND: Bacterial infection is common in acute cholecystitis (AC). To identify appropriate empirical antibiotics, we investigated AC-associated microorganisms and their susceptibilities to antibiotics. We also compared preoperative clinical findings of patients grouped according to specific microorganisms. METHODS: Patients who underwent laparoscopic cholecystectomy for AC between 2018 and 2019 were enrolled. Bile cultures and antibiotic susceptibility tests were performed, and clinical findings of patients were noted. RESULTS: A total of 282 patients were enrolled (147 culture-positive and 135 culture-negative). The most frequent microorganisms were Escherichia (n = 53, 32.7%), Enterococcus (n = 37, 22.8%), Klebsiella (n = 28, 17.3%), and Enterobacter (n = 18, 11.1%). For Gram-negative microorganisms, second-generation cephalosporin (cefotetan: 96.2%) was more effective than third-generation cephalosporin (cefotaxime: 69.8%). Vancomycin and teicoplanin (83.8%) were the most effective antibiotics for Enterococcus. Patients with Enterococcus had higher rates of CBD stones (51.4%, p = 0.001) and biliary drainage (81.1%, p = 0.002), as well as higher levels of liver enzymes, than patients with other microorganisms. Patients with ESBL-producing bacteria had higher rates of CBD stones (36.0% vs. 6.8%, p = 0.001) and biliary drainage (64.0% vs. 32.4%, p = 0.005) than those without. DISCUSSION: Preoperative clinical findings of AC are related to microorganisms in bile samples. Periodic antibiotic susceptibility tests should be conducted to select appropriate empirical antibiotics.

The diagnostic and prognostic values of inflammatory markers in intraductal papillary mucinous neoplasm.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an broad-spectrum disease from benign to malignant. Inflammatory markers are known as prognostic predictors in various diseases. The purpose of this study was to determine the predictive value of inflammatory markers for prognosis in IPMN. METHODS: From April 1995 to December 2016, patients who underwent pancreatectomy with pathologically confirmed IPMN at four tertiary centers were enrolled. Patients with a history of pancreatitis or cholangitis, and other malignancies were excluded. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and advanced lung cancer inflammation index (ALI) were calculated. RESULTS: Of all, ninety-eight patients (26.8%) were diagnosed as invasive IPMN. The NLR and PLR were significantly elevated in invasive IPMN than in non-invasive disease (2.0 vs 1.8, p = 0.004; 117.1 vs 107.4, p = 0.009, respectively). ALI was significantly higher in non-invasive IPMN than in invasive disease (58.1 vs 45.9, p < 0.001). In multivariate analysis, only NLR showed significant association among the inflammatory markers studied (p = 0.044). In invasive IPMN, the five-year recurrence-free survival rate for NLR less than 3.5 was superior to the rest (59.1 vs 42.2, p = 0.023). CONCLUSION: NLR may help to rightly select IPMN patients who will require surgery and may serve as a useful prognostic factor.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Clinical outcomes of minimally invasive (laparoscopic and robotic) versus open extended cholecystectomy: A multicenter propensity score matched study.

BACKGROUND: This multicenter study aimed to compare the clinical outcomes of minimally invasive extended cholecystectomy (MI-EC) versus open EC (O-EC) for patients with gallbladder cancer (GBC). METHODS: Patients who underwent EC (cholecystectomy, wedge resection of the liver bed, and regional lymphadenectomy) for GBC between 2010 and 2020 in three centers were included in the study. The clinicopathological data were compared after propensity score matching. Additional subgroup analysis on laparoscopic and robotic EC (L-EC and R-EC) was performed. RESULTS: A total of 377 patients were included: 308 for O-EC and 69 for MI-EC, respectively. The MI-EC group had a longer operative time (188.9 vs. 238.1 min, p < .001) and shorter hospital stay (9.0 vs. 7.2 days, p = .007), although no differences were found in operative blood loss, complication rate and survival outcome. In subgroup analysis, L-EC patients had a longer operative time (264.4 vs. 202.0 min, p = .001), compared to R-EC patients with comparable perioperative and survival outcomes. CONCLUSION: Although patients with MI-EC had a longer operation time and higher medical costs, the advantages were enhanced recovery with comparable short- and long-term outcomes. The operation time was less for R-EC patients than for L-EC patients, though the high cost still remains. The surgery type for EC can be selected according to the patient's condition, social status and surgeon's preference.

Comparison of various methods of vessel ligation: what is the safest method?

BACKGROUND: Recently, various hemostatic devices, such as metal or plastic clips, ultrasonic coagulating shears, and electrothermal bipolar vessel sealer, have been widely applied during an operation. The purpose of this study was to analyze the mechanical, histological, and biochemical differences of vessels sealed with various hemostatic devices. METHODS: Thirty New Zealand White rabbits were randomly allocated into five groups, and short gastric vessels were ligated with metal clip, plastic clip, Harmonic Ace, LigaSure, or tie ligation. These vessels were harvested 3 days after operation and histologically analyzed at the site of ligation (proximal) and 5 mm from it (distal). Perivascular fibrosis was assessed on a score of mild to severe according to the severity. Inducible and endothelial nitric oxide synthase (iNOS and eNOS) mRNA expressions were measured quantitatively by real-time PCR at the sites of ligation. Abdominal aorta and inferior vena cava also were harvested and divided with each tool, and bursting pressures were measured. RESULTS: Bursting pressures were measured in 164 arteries and 141 veins. LigaSure showed significantly lower bursting pressures in arteries (p < 0.001), and plastic clip showed significantly lower bursting pressures in veins (p < 0.001). There was a negative relationship between outer diameters and bursting pressures in both the arteries (rho = -0.505, p < 0.001) and the veins (rho = -0.106, p = 0.24). The degree of perivascular fibrosis was not statistically different in either the proximal (p = 0.447) or distal (p = 0.381) sites. The expressions of iNOS and eNOS were significantly lower in the LS group (p < 0.001, and p < 0.001, respectively). CONCLUSIONS: There might be no clinical limitations when applying various hemostatic devices to small vessels under physiologic blood pressures. There were no acute histological differences between the hemostatic devices. However, LS showed the lowest iNOS and eNOS expressions, which might be due to thermal injuries of the whole vessel wall.

Incidence of bactibilia and related factors in patients who undergo cholecystectomy.

Purpose: In general, bile is normally sterile. However, there are reports bactibilia may occur in certain instances, though the causal factors are unclear. We analyzed possible preoperative predictors of bactibilia upon cholecystectomy. Methods: Bile samples were collected during cholecystectomies from November 2018 to November 2019. A total of 428 open or laparoscopic cholecystectomies were performed. Preoperative, intraoperative, and postoperative variables were compared between the culture-positive and culture-negative groups. Results: One hundred fifty-seven patients (36.7%) were culture-positive. Gram-negative bacteria (95 [61.0%]) were more common. Escherichia coli (38 [40.0%]) and Enterobacter (22 [23.2%]) were the most common species. In univariate analysis, age of ≥70 years (P < 0.001), male sex (P < 0.001), high American Society of Anesthesiologists physical status grades (P = 0.001), diabetes mellitus (P = 0.002), jaundice (P = 0.007), high Tokyo Guideline grades (P = 0.008), percutaneous transhepatic gallbladder drainage (PTGBD; P < 0.001), endoscopic retrograde cholangiopancreatography (ERCP; P < 0.001) were identified as a risk factors for bactibilia. In multivariate analysis, age of ≥70 years (hazard ratio [HR], 2.874; 95% confidence interval [CI], 1.769-4.670; P = 0.001), ERCP (HR, 9.001; 95% CI, 4.833-16.75; P < 0.001), and PTGBD (HR, 2.866; 95% CI, 1.440-4.901; P = 0.002) were independent risk factors for bactibilia. Conclusion: Among patients who underwent cholecystectomy, those who were elderly, symptomatic, and underwent preoperative drainage were more likely to have bactibilia. In such cases, surgeons should take care to prevent bile leakage during surgery and consider administering appropriate antibiotics.

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.

Features of T1 pancreatic cancer and validation of the eighth edition AJCC staging system definition using a Korean-Japanese joint cohort and the SEER database.

BACKGROUND/PURPOSE: Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition. METHOD: Data from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p < .001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database. CONCLUSION: Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.

Clinicopathologic analysis of surgically proven intraductal papillary mucinous neoplasms of the pancreas in SNUH: a 15-year experience at a single academic institution.

PURPOSE: The clinical importance of intraductal papillary mucinous neoplasm of the pancreas (IPMN) has been increasing with a large number of newly diagnosed IPMN. This study was designed to explore the characteristics of resected IPMN and to determine the predictive factors for malignant and invasive IPMN. METHODS: Retrospective review of a prospectively collected database was performed on 187 consecutive patients following IPMN surgery between 1994 and 2008 at a tertiary institute. The main duct type IPMN was radiologically defined as main pancreatic duct dilation >5 mm rather than previously defined ≥10 mm. RESULTS: The morphologic types of IPMN included 28 main duct (IPMN-M, 15.0%), 118 branch duct (IPMN-Br, 63.1%), and 41 mixed (IPMN-Mixed, 21.9%) IPMNs. There were 23 patients with adenoma, 106 borderline atypia, 15 carcinoma in situ, and 43 invasive carcinoma. Sixty-nine extrapancreatic malignancies were diagnosed in 61 (32.6%) patients. Based on multivariate analysis, IPMN-M was statistically significant predictor of malignancy/invasiveness (p = 0.013/p = 0.028). In patients with IPMN-Br, the presence of mural nodule was a predictive factor for malignancy/invasiveness (p = 0.005/p = 0.002). In patients with IPMN-Mixed, mural nodule (p = 0.038/p = 0.047) and wall thickening (>2 mm, p = 0.015/p = 0.046) were risk factor for malignancy/invasiveness and elevated CA19-9 (p = 0.046) for invasiveness. CONCLUSIONS: The main pancreatic duct diameter (>5 mm) is a significant predictor for malignancy and invasiveness. Therefore, IPMN patients with main pancreatic duct dilatation (>5 mm) should be considered surgical resection. Mural nodule is the indicator of surgery in IPMN-Br and IPMN-Mixed. In case of IPMN-Mixed with wall thickening or elevated serum CA19-9, surgical resection is recommended.

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.

Development of Nomograms for Predicting Prognosis of Pancreatic Cancer after Pancreatectomy: A Multicenter Study.

Surgical resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Currently, the TNM classification system is considered the standard for predicting prognosis after surgery. However, the prognostic accuracy of the system remains limited. This study aimed to develop new predictive nomograms for resected PDAC. The clinicopathological data of patients who underwent surgery for PDAC between 2006 and 2015 at five major institutions were retrospectively reviewed; 885 patients were included in the analysis. Cox regression analysis was performed to investigate prognostic factors for recurrence and survival, and statistically significant factors were used for creating nomograms. The nomogram for predicting recurrence-free survival included nine factors: sarcopenic obesity, elevated carbohydrate antigen 19-9, platelet-to-lymphocyte ratio, preoperatively-identified arterial abutment, estimated blood loss (EBL), tumor differentiation, size, lymph node ratio, and tumor necrosis. The nomogram for predicting overall survival included 10 variables: age, underlying liver disease, chronic kidney disease, preoperatively found portal vein invasion, portal vein resection, EBL, tumor differentiation, size, lymph node metastasis, and tumor necrosis. The time-dependent area under the receiver operating characteristic curve for both nomograms exceeded 0.70. Nomograms were developed for predicting survival after resection of PDAC, and the platforms showed fair predictive performance. These new comprehensive nomograms provide information on disease status and are useful for determining further treatment for PDAC patients.

Development and external validation of a nomogram with inflammatory markers for predicting invasiveness of intraductal papillary mucinous neoplasm of pancreas.

ABSTRACT: Recent studies have reported that inflammatory markers, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and advanced lung cancer inflammation index, are associated with invasiveness of intraductal papillary mucinous neoplasm (IPMN). This study aimed to develop and validate a new nomogram that includes inflammatory markers for predicting the invasiveness of IPMN.The data of 365 patients who underwent surgical resection for IPMN at 4 centers between 1995 and 2016 were retrospectively reviewed to develop a new nomogram. For external validation, a separate patient cohort was used. The predictive ability of the nomogram was evaluated using the area under the receiver operating characteristic curve.The new nomogram was developed using the following variables which were identified as risk factors for invasive IPMN: body mass index, preoperative serum bilirubin level, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, main duct type, presence of solid portion, and tumor size. After external validation, the area under the curve value was 0.649 (95% CI: 0.578-0.720, P < .001).To the best of our knowledge, this study is the first to predict and externally validate the invasiveness in IPMN using inflammatory markers. Further research is necessary to improve predictability of the model for selecting patients for surgical resection.

External validation of risk prediction platforms for pancreatic fistula after pancreatoduodenectomy using nomograms and artificial intelligence.

Purpose: Postoperative pancreatic fistula (POPF) is a life-threatening complication following pancreatoduodenectomy (PD). We previously developed nomogram- and artificial intelligence (AI)-based risk prediction platforms for POPF after PD. This study aims to externally validate these platforms. Methods: Between January 2007 and December 2016, a total of 1,576 patients who underwent PD in Seoul National University Hospital, Ilsan Paik Hospital, and Boramae Medical Center were retrospectively reviewed. The individual risk scores for POPF were calculated using each platform by Samsung Medical Center. The predictive ability was evaluated using a receiver operating characteristic curve and the area under the curve (AUC). The optimal predictive value was obtained via backward elimination in accordance with the results from the AI development process. Results: The AUC of the nomogram after external validation was 0.679 (P < 0.001). The values of AUC after backward elimination in the AI model varied from 0.585 to 0.672. A total of 13 risk factors represented the maximal AUC of 0.672 (P < 0.001). Conclusion: We performed external validation of previously developed platforms for predicting POPF. Further research is needed to investigate other potential risk factors and thereby improve the predictability of the platform.

Comparison of Short-Term Surgical Outcomes According to Immediately Postoperative Serum Glucose Level in Non-Diabetic Pancreatic Resection Patients.

The adequate regulation of postoperative serum glucose level (SGL) is widely accepted; however, the effects for non-diabetic patients who underwent major pancreatic surgery have not yet been established. We discerned the relevance of the immediately postoperative SGL to short-term postoperative outcomes from major pancreatic surgery in non-diabetic patients. Between January 2007 and December 2016, 2259 non-diabetic patients underwent major pancreatic surgery at four tertiary medical centers in Republic of Korea. Based on a SGL of 200 mg/dL, patients were classified into two groups by averaging the results of four SGL tests taken on the first day after surgery, and their short-term postoperative outcomes were analyzed. A 1:1 propensity score matching method was conducted to establish the high SGL group (n = 568) and the normal SGL group (n = 568). The high SGL group experienced a significantly higher rate of level C complications in the Clavien-Dindo classification (CDc) than the normal SGL group (24.1% vs. 16.5%, p = 0.002). Additionally, an SGL of more than 200 mg/dL was associated with a significantly high risk of complications above level C CDc after adjusting for other risk factors (hazard ratio = 1.324, 95% confidence interval = 1.048-1.672, p = 0.019). The regulation of SGL of less than 200 mg/dL in non-diabetic patients early after major pancreatic surgery could be helpful for reducing postoperative complications.

Analysis of prognostic factors and a proposed new classification for invasive papillary mucinous neoplasms.

BACKGROUND: The characteristics of invasive type-intraductal papillary mucinous neoplasm (invasive IPMN) have not been fully explored due to limited reports. Furthermore, a straightforward method is needed to describe its aggressiveness. The purpose of this study was to investigate prognostic factors and to examine the clinical significance of percentage pancreatic volume occupied by the invasive component in invasive IPMN. METHODS: Of 217 patients who underwent surgical resection with a diagnosis of IPMN between 2001 and 2008, 41 had invasive IPMC. We serially sectioned pancreatic parenchyma at 5-7-mm intervals. Whole slides were reviewed by a pancreas-biliary tract special pathologist, who determined the percentage pancreatic volumes occupied by the invasive components (IC%) in whole IPMN lesions. RESULTS: By multivariate analysis, perineural invasion, metastasis, AJCC stage, and invasive component percentage (IC%) significantly predicted prognosis. IC% was found to be significantly associated with survival. Patients with an IC% <10 had a 3-year survival rate (YSR) of 100%, whereas patients with an IC% >50% had a 3 YSR of 36.5% and those with an IC% of 10-50% had a 3 YSR of 71.4% (p = 0.041). CONCLUSIONS: In addition to conventional prognostic factors, such as AJCC stage and perineural invasion, the percentage of pancreatic volume occupied by the invasive component (IC%) appears to be an important prognostic factor in invasive IPMN. The concept of IC% is straightforward, semiquantitative, and objective, and offers a means of determining tumor aggressiveness; hence, it could be a means of classifying invasive IPMN.

Determination of malignant and invasive predictors in branch duct type intraductal papillary mucinous neoplasms of the pancreas: a suggested scoring formula.

Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP).

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

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

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

Comparison of the long-term outcomes of uncinate process cancer and non-uncinate process pancreas head cancer: poor prognosis accompanied by early locoregional recurrence.

PURPOSE: The embryologic and anatomic peculiarity of the uncinate process may result in distinct clinical features, but few studies have addressed the uncinate process cancer. The purpose of this study was to compare the clinicopathologic characteristics and identify the prognostic factors that affect the survival and recurrence of pancreatic head cancer by tumor location. METHODS: Between January 2002 and December 2008, 453 patients (161 with uncinate and 292 with non-uncinate process cancer) were treated for pancreatic head cancer. Clinicopathologic variables were analyzed by tumor location. RESULTS: Invasion into the superior mesenteric artery (SMA) occurred more frequently (p < 0.001), and overall resectability (p = 0.003), curative resection (p < 0.001), and R0 resection rates (22.3% vs 35.6%; p = 0.003) were lower for uncinate process cancer. Furthermore, overall survival after R0 resection was lower for uncinate process cancer (median 21 vs 26 months; p = 0.018), and this was accompanied by more frequent (p = 0.038) and earlier (median 13 vs 52 months; p < 0.001) locoregional recurrence. Concurrent chemoradiation increased overall (median, 26 vs 13 months; p < 0.001) and disease-free survival (median, 15 vs 6 months; p < 0.001) of uncinate and non-uncinate process cancer, respectively, after curative-intended resection. CONCLUSION: In uncinate process cancer, frequent invasion into the SMA led to lower resectability. Furthermore, lower survival after R0 resection was accompanied with frequent and early locoregional recurrence. Strategies to improve surgical and perioperative locoregional control are required for uncinate process cancer.