Inhibition of the Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer.

This study aims to elucidate the cellular mechanisms behind the secretion of complement factor B (CFB), known for its dual roles as an early biomarker for pancreatic ductal adenocarcinoma (PDAC) and as the initial substrate for the alternative complement pathway (ACP). Using parallel reaction monitoring analysis, we confirmed a consistent ∼2-fold increase in CFB expression in PDAC patients compared with that in both healthy donors (HD) and chronic pancreatitis (CP) patients. Elevated ACP activity was observed in CP and other benign conditions compared with that in HD and PDAC patients, suggesting a functional link between ACP and PDAC. Protein-protein interaction analyses involving key complement proteins and their regulatory factors were conducted using blood samples from PDAC patients and cultured cell lines. Our findings revealed a complex control system governing the ACP and its regulatory factors, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, adrenomedullin (AM), and complement factor H (CFH). Particularly, AM emerged as a crucial player in CFB secretion, activating CFH and promoting its predominant binding to C3b over CFB. Mechanistically, our data suggest that the KRAS mutation stimulates AM expression, enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction conferred greater affinity for C3b over CFB, potentially suppressing the ACP cascade. This sequence of events likely culminated in the preferential release of ductal CFB into plasma during the early stages of PDAC. (Data set ID PXD047043.).

Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer.

BACKGROUND: The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography-a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer. METHODS: Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information. RESULTS: Total RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II. CONCLUSIONS: MAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.

Minimally invasive pancreatoduodenectomy by junior surgeon: Initial experience of the next generation.

BACKGROUND: Several guidelines exist for minimally invasive pancreatoduodenectomy (MIPD) regarding its prerequisites and learning curve. However, these guidelines are based on the experience of the pioneers of MIPD; minimal data exist on the experience of the next generation of surgeons. The aim of this study was to compare the two surgeon types (veteran and junior) for MIPD in terms of immediate postoperative outcomes. METHODS: The postoperative outcomes of 22 patients who underwent robot-assisted pancreatoduodenectomy (RAPD) by a junior surgeon from July 2021 to December 2022 were retrospectively reviewed. The outcomes were compared with the initial postoperative outcomes and the contemporary postoperative outcomes of RAPD by a veteran surgeon. RESULTS: In comparing the initial outcomes between the two surgeon types, the veteran surgeons showed a shorter operation time (junior surgeon vs. veteran surgeon: 606 ± 89 vs. 467 ± 77 min, p < 0.001). However, there was no significant difference in terms of postoperative outcomes, such as blood loss (300 [200-600] ml. vs. 200 [100-500] ml, p = 0.208), major complications (≥CDC IIIa: 4 (18.2%) vs. 4 (18.2%), p = 1.000), postoperative pancreatic fistula (POPF; ≥ISGPF Grade B: 2 (9.1%) vs. 3 (13.6%), p > 0.999), and length of hospital stay (18.0 ± 8.9 days vs. 18.3 ± 7.9 days, p = 0.915), between the two surgeon types. In addition, in a comparison of the contemporary outcomes, there was no significant difference in terms of postoperative outcome (complications: 4 (18.2%) vs 11 (11.1%), p = 0.580; POPF: 2 (9.1%) vs. 3 (3.0%), p = 0.484; length of hospital stay: 18.0 ± 8.9 vs. 15.0 ± 6.5 days, p = 0.065). CONCLUSION: The initial outcomes of MIPD by a well-trained junior surgeon were found to be comparable to those of MIPD by a veteran surgeon.

Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) represent 1-2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. METHODS: This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. RESULTS: Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. CONCLUSION: This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.

Preoperative Fistula Risk Prediction Using Computed Tomography Image Before Pancreatoduodenectomy.

BACKGROUND: Although many formulas for predicting postoperative pancreatic fistula (POPF) have been introduced, POPF is generally predicted during pancreatic surgery due to pancreatic texture. This study was designed to verify the correlation between Hounsfield units (HU) and pancreatic texture and to suggest a fistula risk score (FRS) that can be used before surgery. METHODS: Data from 545 patients who underwent pancreatoduodenectomy for malignant disease between January 2008 and December 2019 were retrospectively reviewed. The HU level of the pancreas was measured, and odds ratio (OR) of the HU for POPF was analyzed. Additionally, the assessed HU was compared with the pancreatic texture (soft vs. hard) and calculated cutoff level. Finally, the preoperatively chosen pancreatic texture according to HU level was applied to the FRS formula (preoperative-FRS: p-FRS), and the results were compared with a previously reported FRS formula (updated alternative-FRS: ua-FRS). RESULTS: The Hounsfield unit levels were correlated with clinically relevant POPF (CR-POPF) (odds ratio [OR]: 1.04 (1.01-1.07), p = 0.015). In the receiver operating characteristic curve, the HU showed significant prediction potential for pancreatic texture (area under the curve [AUC]: 0.744, p < 0.001). The p-FRS also showed acceptable results in predicting CR-POPF (AUC = 0.702, p < 0.001). There was no statistically significant difference in the DeLong's test compared with the ua-FRS (p = 0.314). In the Hosmer-Lemeshow test, observed probabilities were correlated with predicted probabilities (p = 0.596). CONCLUSIONS: The HU level on preoperative computed tomography (CT) is a predictive factor for POPF and could represent for pancreatic texture.

Multidimensional Nomogram to Predict Postoperative Pancreatic Fistula after Minimally Invasive Pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is an inherently severe risk of pancreatic resection. Previous research has proposed models that identify risk factors and predict CR-POPF, although these are rarely applicable to minimally invasive pancreaticoduodenectomy (MIPD). This study aimed to evaluate the individual risks of CR-POPF and to propose a nomogram for predicting POPF in MIPD. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 429 patients who underwent MIPD. In the multivariate analysis, the Akaike information criterion stepwise logistic regression method was used to select the final model to develop the nomogram. RESULTS: Of 429 patients, 53 (12.4%) experienced CR-POPF. On multivariate analysis, pancreatic texture (p = 0.001), open conversion (p = 0.008), intraoperative transfusion (p = 0.011), and pathology (p = 0.048) were identified as independent predictors of CR-POPF. The nomogram was developed based on patient, pancreatic, operative, and surgeon factors by using the following four additional clinical factors as variables: American Society of Anesthesiologists class ≥ III, size of pancreatic duct, type of surgical approach, and < 40 cases of MIPD experience. CONCLUSIONS: A multidimensional nomogram was developed to predict CR-POPF after MIPD. This nomogram and calculator can help surgeons anticipate, select, and manage critical complications.

Which one is better? Laparoscopic versus robotic reconstruction in the remnant soft pancreas with a small pancreatic duct following pancreaticoduodenectomy: a multicenter study with propensity score matching analysis.

BACKGROUND: Evidence of the advantages of robotic pancreaticoduodenectomy (RPD) over laparoscopic pancreaticoduodenectomy (LPD) is limited. Thus, this study aimed to compare the surgical outcomes of laparoscopic reconstruction L-recon) versus robotic reconstruction (R-recon) in patients with soft pancreas and small pancreatic duct. METHOD: Among 429 patients treated with minimally invasive pancreaticoduodenectomy (MIPD) between October 2012 and June 2020 by three surgeons at three institutions, 201 patients with a soft pancreas and a small pancreatic duct (< 3 mm) were included in this study. RESULTS: Sixty pairs of patients who underwent L-recon and R-recon were selected after propensity score matching. The perioperative outcomes were comparable between the reconstruction approaches, with comparable clinically relevant postoperative pancreatic fistula (CR-POPF) rates (15.0% [L-recon] vs. 13.3% [R-recon]). The sub-analysis according to the type of MIPD procedure also showed comparable outcomes, but only a significant difference in postoperative hospital stay was identified. During the learning curve analysis using the cumulative summation by operation time (CUSUMOT), two surgeons who performed both L-recon and R-recon procedures reached their first peak in the CUSUMOT graph earlier for the R-recon group than for the L-recon group (i.e., 20th L-recon case and third R-recon case of surgeon A and 43rd L-recon case and seventh R-recon case of surgeon B). Surgeon C, who only performed R-recon, demonstrated the first peak in the 22nd case. The multivariate regression analysis for risk factors of CR-POPF showed that the MIPD procedure type, as well as other factors, did not have any significant effect. CONCLUSION: Postoperative pancreatic fistula rates and the overall perioperative outcomes of L-recon and R-recon were comparable in patients with soft-textured pancreas and small pancreatic duct treated by experienced surgeons.

Validation of original, alternative, and updated alternative fistula risk scores after open and minimally invasive pancreatoduodenectomy in an Asian patient cohort.

BACKGROUND: This study aimed to validate and compare the performance of the original fistula risk scores (o-FRS), alternative (a-FRS), and updated alternative FRS (ua-FRS) after open pancreatoduodenectomy (OPD) and laparoscopic pancreatoduodenectomy (LPD) in an Asian patient cohort. METHODS: Data of 597 consecutive patients who underwent PD (305 OPD, 274 LPD) were collected from two tertiary centers. Model performance was assessed using the area under the receiver operating curve (AUC). RESULTS: The overall AUC values of o-FRS, a-FRS, and ua-FRS were 0.67, 0.69, and 0.68, respectively, which were lower than those of the Western validation. Three FRS systems had similar AUC values in the overall and OPD groups, whereas ua-FRS had a higher AUC than o-FRS in the LPD group. The accuracy of ua-FRS (47.2%) was higher than that of o-FRS (39.0%) and a-FRS (19.5%) overall, but low specificity and low positive predictive value were observed regardless of the operative type across the three FRS systems. In the multivariate analysis, pathology, estimated blood loss, and body mass index were not independent risk factors for CR-POPF in the OPD and LPD groups. CONCLUSIONS: Current FRS systems have some limitations, including a relatively lower performance in an Asian cohort, low positive predictive values, and inclusion of insignificant risk factors.

Anticancer effect of locally applicable aptamer-conjugated gemcitabine-loaded atelocollagen patch in pancreatic cancer patient-derived xenograft models.

We investigated the anticancer effect of the aptamer-conjugated gemcitabine-loaded atelocollagen patch in a pancreatic cancer patient-derived xenograft (PDX) model to propose a future potential adjuvant surgical strategy during curative pancreatic resection for pancreatic cancer. A pancreatic cancer PDX model was established. Animals were grouped randomly into a no-treatment control group; treatment group treated with intraperitoneal gemcitabine injection (IP-GEM) or aptamer-conjugated gemcitabine (APT:GEM); and transplant with three kinds of patches: atelocollagen-aptamer-gemcitabine (patch I), atelocollagen-inactive aptamer-gemcitabine (patch II), and atelocollagen-gemcitabine (patch III). Tumor volumes and response were evaluated based on histological analysis by H&E staining and Immunohistochemistry (IHC) was performed. Anticancer therapy-related toxicity was evaluated by hematologic findings. The patch I group showed the most significant reduction of tumor growth rate, compared with the no-treatment group (p < 0.05). However, other treatment groups were not found to show significant reduction in tumor growth rate (0.05 < p < 0.1). There was no microscopic evidence suggesting potential toxicity, such as inflammation, nor necrotic changes in liver, lung, kidney, and spleen tissue. In addition, no leukopenia, anemia, or neutropenia was observed in the patch I group. This implantable aptamer-drug conjugate system is thought to be a new surgical strategy to augment the oncologic significance of margin-negative resection in treating pancreatic cancer in near future.

Molecular Characterization of Biliary Tract Cancer Predicts Chemotherapy and Programmed Death 1/Programmed Death-Ligand 1 Blockade Responses.

BACKGROUND AND AIMS: Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS: We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS: This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.

Surgical Outcomes and Comparative Analysis of Transduodenal Ampullectomy and Pancreaticoduodenectomy: A Single-Center Study.

BACKGROUND: Transduodenal ampullectomy (TDA) is performed for adenoma or early cancer of the ampulla of Vater (AoV). This study aimed to analyze the short- and long-term outcomes of TDA (TDA group) when compared with conventional pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PD group). METHODS: Patients who underwent TDA between January 2006 and December 2019, and PD cases performed for AoV malignancy with carcinoma in-situ (Tis) (high-grade dysplasia, HGD) and T1 and T2 stage from January 2010 to December 2019 were reviewed. RESULTS: Forty-six patients underwent TDA; 21 had a benign tumor, and 25 cases with malignant tumors were compared with PD cases (n = 133). Operation time (p < 0.001), estimated blood loss (p < 0.001), length of hospital stays (p = 0.003), and overall complication rate (p < 0.001) were lower in the TDA group than in the PD group. Lymph node metastasis rates were 14.6% in pT1 and 28.9% in pT2 patients. The 5-year disease-free survival and 5-year overall survival rates for HGD/Tis and T1 tumor between the two groups were similar (TDA group vs PD group, 72.2% vs 77.7%, p = 0.550; 85.6% vs 79.2%, p = 0.816, respectively). CONCLUSION: TDA accompanied with lymph node dissection is advisable in HGD/Tis and T1 AoV cancers in view of superior perioperative outcomes and similar long-term survival rates compared with PD.

Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy.

BACKGROUND: The Systemic Inflammation Response Index (SIRI) has been used to predict the prognosis of various cancers. This study examined SIRI as a prognostic factor in the neoadjuvant setting and determined whether it changing after chemotherapy is related to patient prognosis. METHODS: Patients who underwent pancreatic surgery following neoadjuvant chemotherapy for pancreatic cancer were retrospectively analyzed. To establish the cut-off values, SIRIpre-neoadjuvant, SIRIpost-neoadjuvant, and SIRIquotient (SIRIpost-neoadjuvant/SIRIpre-neoadjuvant) were calculated and significant SIRI values were statistically determined to examine their effects on survival rate. RESULTS: The study included 160 patients. Values of SIRIpost-neoadjuvant ≥ 0.8710 and SIRIquotient <0.9516 affected prognosis (hazard ratio [HR], 1.948; 95% confidence interval [CI], 1.210-3.135; ∗∗P = 0.006; HR, 1.548; 95% CI, 1.041-2.302; ∗∗P = 0.031). Disease-free survival differed significantly at values of SIRIpost-neoadjuvant < 0.8710 and SIRIpost-neoadjuvant ≥ 0.8710 (P = 0.0303). Overall survival differed significantly between SIRIquotient <0.9516 and SIRIquotient ≥0.9516 (P = 0.0368). CONCLUSIONS: SIRI can predict the survival of patients with pancreatic ductal adenocarcinoma after resection and neoadjuvant chemotherapy. Preoperative SIRI value was correlated with disease-free survival, while changes in SIRI values were correlated with overall survival.

Total laparoscopic versus robotic-assisted laparoscopic pancreaticoduodenectomy: which one is better?

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a challenging procedure. Laparoscopic pancreaticoduodenectomy (LPD) is feasible and safe. Since the development of robotic platforms, the number of reports on robot-assisted pancreatic surgery has increased. We compared the technical feasibility and safety between LPD and robot-assisted LPD (RALPD). METHODS: From September 2012 to August 2020, 257 patients who underwent MIPD for periampullary tumors were enrolled. Of these, 207 underwent LPD and 50 underwent RALPD. We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographics and surgical outcomes. RESULTS: After PSM analysis, no difference was noted in demographics. Operation times and estimated blood loss were similar, as was the incidence of complications (p > 0.05). In subgroup analysis in patients with soft pancreas with pancreatic duct ≤ 2 mm, no significant between-group difference was noted regarding short-term surgical outcomes, including clinically relevant POPF (CR-POPF) (p > 0.05). In multivariable analysis, the only soft pancreatic texture was a predictive factor (HR 3.887, 95% confidence interval 1.121-13.480, p = 0.032). CONCLUSION: RALPD and LPD are safe and effective for MIPD and can compensate each other to achieve the goal of minimally invasive surgery.

Minimally invasive (laparoscopic and robot-assisted) versus open approach for central pancreatectomies: a single-center experience.

BACKGROUND: There continues to be an interest in minimally invasive approaches to pancreatic surgery. At our institution, there has been a progressive change from an open to minimally invasive surgery (MIS) (laparoscopic, robotic, or laparoscopic-robotic) approach for central pancreatectomies (CP). The aim of this study was to evaluate surgical outcomes with open CP (O-CP) versus minimally invasive CP (MI-CP). METHODS: A retrospective medical review of patients who underwent CP between 1993 and 2018 at Yonsei University Health System, Seoul, Korea was performed. Short-term perioperative outcomes were compared between O-CP and MI-CP. RESULTS: Thirty-one CPs (11 open, 20 MIS) were identified during the study period. No difference was observed in admission days between O-CP and MI-CP (21.2 vs. 16.7 days, p = 0.340), although operating time was significantly increased in the MI-CP group (296.8 vs. 374.8 min, p = 0.036). Blood loss was significantly less in MI-CP vs. O-CP (807.1 vs. 214.0 mls, p = 0.001), with no difference in post-operative new-onset diabetes (9% vs. 5%). The overall post-operative pancreatic fistula rate was 25.8%, and no significant difference between O-CP and MI-CP or complication rates (45% vs. 40%) was observed. CONCLUSION: Despite increased operative time, MI-CP is feasible and comparable to conventional O-CP with regard to surgical outcomes in well-selected patients.

Wrapping the pancreas with a polyglycolic acid sheet before stapling reduces the risk of fluid collection on the pancreatic stump after distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) and postoperative fluid collection (POFC) are common complications after distal pancreatectomy (DP). The previous method of reducing the risk of POPF was the application of a polyglycolic acid (PGA) sheet to the pancreatic stump after cutting the pancreas with a stapler (After-stapling); the new method involves wrapping the pancreatic resection line with a PGA sheet before stapling (Before-stapling). The study aimed to compare the incidence of POPF and POFC between two methods. METHODS: Data of patients who underwent open or laparoscopic DPs by a single surgeon from October 2010 to February 2020 in a tertiary referral hospital were retrospectively analyzed. POPF was defined according to the updated International Study Group of Pancreatic Fistula criteria. POFC was measured by postoperative computed tomography (CT). RESULTS: Altogether, 182 patients were enrolled (After-stapling group, n = 138; Before-stapling group, n = 44). Clinicopathologic and intraoperative findings between the two groups were similar. Clinically relevant POPF rates were similar between both groups (4.3% vs. 4.5%, p = 0.989). POFC was significantly lesser in the Before-stapling group on postoperative day 7 (p < 0.001). CONCLUSIONS: Wrapping the pancreas with PGA sheet before stapling was a simple and effective way to reduce POFC.

EGFR-targeted fluorescent imaging using the da Vinci® Firefly™ camera for gallbladder cancer.

BACKGROUND: Fluorescent imaging may aid with the precise diagnosis and treatment of patients with gallbladder cancer. In this study, we sought to demonstrate whether the da Vinci® surgical system and Firefly™ camera could detect EGFR-targeted fluorescent images in orthotopic mouse models of gallbladder cancer. METHODS: An orthotopic mouse model of gallbladder cancer was created by injecting NOZ gallbladder cancer cells mixed with Matrigel into the gallbladder. In vivo imaging of subcutaneous and orthotopic gallbladder tumors was performed after the injection of DyLight 650- or 800-conjugated EGFR antibody. RESULTS: Western blotting, flow cytometry, and confocal microscopy showed the presence of EGFR in NOZ cells, but not in HEK293 cells. Subcutaneous NOZ cell tumors fluoresced after injection with fluorescent EGFR antibody, but subcutaneous HEK293 tumors did not. Fluorescent EGFR antibody made orthotopic NOZ tumors fluoresce, with an intensity stronger than that in the surrounding normal tissues. Histochemical examination confirmed the location of the tumors inside the gallbladder and adjacent liver parenchyma. Fluorescent signal was also detected in orthotopic gallbladder tumors with Firefly™ camera. CONCLUSION: Our study showed that fluorescent EGFR antibodies and the Firefly camera in the da Vinci system can detect fluorescing gallbladder tumors, which demonstrates their potential use for molecular imaging-based prevision surgery in the near future.

Comparison of oncologic outcomes between open and laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma using data from the KOTUS-BP national database: overcoming selection bias and the necessity of definite indications.

BACKGROUND: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role.

Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive. We first evaluated the diagnostic accuracy of ComB-CAN using plasma samples from healthy donors (HDs), patients with chronic pancreatitis (CP), and patients with different PC stages (I/II vs III/IV). An analysis of the area under the curve (AUC) by PanelComposer using logistic regression revealed that ComB-CAN has a superior diagnostic ability for early-stage PC (97.1.% [95% confidence interval (CI): (97.1-97.2)]) compared with CFB (94.3% [95% CI: 94.2-94.4]) or CA19-9 alone (34.3% [95% CI: 34.1-34.4]). In the comparisons of all stages of patients with PC vs CP and HDs, the AUC values of ComB-CAN, CFB, and CA19-9 were 0.983 (95% CI: 0.983-0.983), 0.950 (95% CI: 0.950-0.951), and 0.873 (95% CI: 0.873-0.874), respectively. We then investigated the molecular mechanism underlying the detection of early-stage PC by using stable cell lines of CFB knockdown and CFB overexpression. A global transcriptomic analysis coupled to cell invasion assays of both CFB-modulated cell lines suggested that CFB plays a tumor-promoting role in PC, which likely initiates the PI3K-AKT cancer signaling pathway. Thus our study establishes ComB-CAN as a reliable early diagnostic marker for PC that can be clinically applied for early PC screening in the general public.

Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

BACKGROUND: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. METHODS: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. RESULTS: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. CONCLUSION: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.

Biologic behavior of resected BRCA-mutated pancreatic cancer: Comparison with sporadic pancreatic cancer and other BRCA-related cancers.

BACKGROUND: Since margin-negative resection is essential for the cure of pancreatic cancer (PC), early detection of PC is important. Although PC is the third most common cancer associated with BRCA1/2 mutations, clinical research regarding BRCA mutations in resected PC are rare. In this study, we investigated the oncologic characteristics of resected PC with BRCA mutation to suggest management strategies. METHODS: We retrospectively reviewed data from 493 patients who were confirmed to be pathogenic BRCA1/2 mutation carriers between January 2007 and December 2019. We investigated the oncologic characteristics of PC patients by comparing them with resected sporadic PC and other BRCA-related cancer groups (breast cancer, ovarian cancer, and others). RESULTS: Ten BRCA mutation carriers (2.0%) experienced PC, and PC onset was significantly later than that of BRCA-related breast cancer (age: breast vs. pancreas, 45.0 vs. 53.5 years, p = 0.050). Six patients underwent pancreatectomy and their long-term survival outcomes did not differ from those of sporadic PC patients (disease free survival: BRCA1/2 vs. sporadic, 10.0 months vs. 9.0 months, p = 0.504; overall survival: BRCA1/2 vs. sporadic, 29.0 months vs. 35.0 months, p = 0.520). CONCLUSION: BRCA-mutated PC occurs later than BRCA-mutated breast cancer. Active genetic testing to identify BRCA1/2 mutation carriers at the onset of breast cancer and continuous long-term surveillance of these patients can provide opportunities to detect BRCA-mutated PC at a resectable stage.