Building and decoding ubiquitin chains for mitophagy.

Mitochondria produce energy in the form of ATP via oxidative phosphorylation. As defects in oxidative phosphorylation can generate harmful reactive oxygen species, it is important that damaged mitochondria are efficiently removed via a selective form of autophagy known as mitophagy. Owing to a combination of cell biological, structural and proteomic approaches, we are beginning to understand the mechanisms by which ubiquitin-dependent signals mark damaged mitochondria for mitophagy. This Review discusses the biochemical steps and regulatory mechanisms that promote the conjugation of ubiquitin to damaged mitochondria via the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase parkin and how ubiquitin chains promote autophagosomal capture. Recently discovered roles for parkin and PINK1 in the suppression of mitochondrial antigen presentation provide alternative models for how this pathway promotes the survival of neurons. A deeper understanding of these processes has major implications for neurodegenerative diseases, including Parkinson disease, where defects in mitophagy and other forms of selective autophagy are prominent.

Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and Model Systems Revealed by Digital Snapshot Proteomics.

Flux through kinase and ubiquitin-driven signaling systems depends on the modification kinetics, stoichiometry, primary site specificity, and target abundance within the pathway, yet we rarely understand these parameters and their spatial organization within cells. Here we develop temporal digital snapshots of ubiquitin signaling on the mitochondrial outer membrane in embryonic stem cell-derived neurons, and we model HeLa cell systems upon activation of the PINK1 kinase and PARKIN ubiquitin ligase by proteomic counting of ubiquitylation and phosphorylation events. We define the kinetics and site specificity of PARKIN-dependent target ubiquitylation, and we demonstrate the power of this approach to quantify pathway modulators and to mechanistically define the role of PARKIN UBL phosphorylation in pathway activation in induced neurons. Finally, through modulation of pS65-Ub on mitochondria, we demonstrate that Ub hyper-phosphorylation is inhibitory to mitophagy receptor recruitment, indicating that pS65-Ub stoichiometry in vivo is optimized to coordinate PARKIN recruitment via pS65-Ub and mitophagy receptors via unphosphorylated chains.

Predicting lymph node metastasis using preoperative parameters in patients with T1 ampulla of vater cancer.

BACKGROUND: Lymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer. METHODS: We included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed. RESULTS: Among 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 - 9 (CA 19 - 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728. CONCLUSION: Our newly developed prediction model using age, CA 19 - 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.

Computed tomography scan accuracy for the prediction of lobe and division of liver tumors by four board-certified radiologists.

OBJECTIVE: (1) Evaluate the accuracy of computed tomography (CT) scans for localization of liver masses. (2) Assess the agreement between radiologists on localization. (3) Determine if location influences the accuracy of localization and histopathologic diagnosis. (4) Determine what lobar vasculature radiologists found most useful for localization. STUDY DESIGN: Retrospective. ANIMALS: A total of 67 client-owned dogs with a total of 75 hepatic masses. METHODS: Records were reviewed for relevant data. Localization for each hepatic mass was performed by four radiologists (JH, EH, ML, JF) independently. RESULTS: Overall accuracy of mass localization was 217/292 (74.3%) by lobe and 264/300 (88%) by division. Accuracy for the quadrate lobe (11/27, 40.7%) was lower (p < .05) than for the caudate process of the caudate lobe (19/24, 79.2%), left medial lobe (47/64, 73.4%) and left lateral lobe (95/101, 89.6%). Accuracy for the right lateral lobe (17/35, 48.6%) was lower (p < .05) lower than for the left lateral lobe (95/101, 89.6%). Accuracy of localization was 173/192 (90.1%) for masses located in the left division, 37/48 (77.1%) in the central division, and 53/60 (88.3%) for the right division. The agreement (kappa) between radiologists was good (0.61-0.8) to excellent (0.81-1) for division and moderate (0.41-0.6) to good for lobe localization. CONCLUSION: CT localization was more accurate for division than lobe localization of canine hepatic masses. Similarly, radiologists had a better agreement for division than lobe localization. CLINICAL SIGNIFICANCE: This study supports CT as a useful modality for liver mass localization based on division. CT localization to specific lobes should be interpreted with some caution.

Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

Quantitative intravital imaging in zebrafish reveals in vivo dynamics of physiological-stress-induced mitophagy.

Mitophagy, the selective recycling of mitochondria through autophagy, is a crucial metabolic process induced by cellular stress, and defects are linked to aging, sarcopenia and neurodegenerative diseases. To therapeutically target mitophagy, the fundamental in vivo dynamics and molecular mechanisms must be fully understood. Here, we generated mitophagy biosensor zebrafish lines expressing mitochondrially targeted, pH-sensitive fluorescent probes, mito-Keima and mito-EGFP-mCherry, and used quantitative intravital imaging to illuminate mitophagy during physiological stresses, namely, embryonic development, fasting and hypoxia. In fasted muscle, volumetric mitolysosome size analyses documented organelle stress response dynamics, and time-lapse imaging revealed that mitochondrial filaments undergo piecemeal fragmentation and recycling rather than the wholesale turnover observed in cultured cells. Hypoxia-inducible factor (Hif) pathway activation through physiological hypoxia or chemical or genetic modulation also provoked mitophagy. Intriguingly, mutation of a single mitophagy receptor (bnip3) prevented this effect, whereas disruption of other putative hypoxia-associated mitophagy genes [bnip3la (nix), fundc1, pink1 or prkn (Parkin)] had no effect. This in vivo imaging study establishes fundamental dynamics of fasting-induced mitophagy and identifies bnip3 as the master regulator of Hif-induced mitophagy in vertebrate muscle.

Highly Efficient and Stable Inverted Perovskite Solar Cell Using Pure δ-FAPbI3 Single Crystals.

Pure δ-formamidinium lead triiodide (δ-FAPbI3 ) single crystal for highly efficient perovskite solar cell (PCS) with long-term stability is prepared by a new method consisting of liquid phase reaction of FAI and PbI2 in N,N-dimethyl formamide and antisolvent crystallization using acetonitrile. In this method, the incorporation of any impurity into the crystal is excluded by the molecular recognition of the crystal growth site. This pure crystal is used to fabricate α-FAPbI3 inverted PSCs which showed excellent power conversion efficiency (PCE) due to much-reduced trap-states. The champion device exhibited a high PCE of 23.48% under the 1-Sun condition. Surface-treated devices with 3-(aminomethyl)pyridine showed a significantly improved PCE of 25.07%. In addition, the unencapsulated device maintained 97.22% of its initial efficiency under continuous 1-Sun illumination for 1,000 h at 85 °C in an N2 atmosphere ensuring long-term thermal and photo stabilities of PSCs, whereas the control device kept only 89.93%.

Use of individualized 3D-printed models of pancreatic cancer to improve surgeons' anatomic understanding and surgical planning.

OBJECTIVES: Three-dimensional (3D) printing has been increasingly used to create accurate patient-specific 3D-printed models from medical imaging data. We aimed to evaluate the utility of 3D-printed models in the localization and understanding of pancreatic cancer for surgeons before pancreatic surgery. METHODS: Between March and September 2021, we prospectively enrolled 10 patients with suspected pancreatic cancer who were scheduled for surgery. We created an individualized 3D-printed model from preoperative CT images. Six surgeons (three staff and three residents) evaluated the CT images before and after the presentation of the 3D-printed model using a 7-item questionnaire (understanding of anatomy and pancreatic cancer [Q1-4], preoperative planning [Q5], and education for trainees or patients [Q6-7]) on a 5-point scale. Survey scores on Q1-5 before and after the presentation of the 3D-printed model were compared. Q6-7 assessed the 3D-printed model's effects on education compared to CT. Subgroup analysis was performed between staff and residents. RESULTS: After the 3D-printed model presentation, survey scores improved in all five questions (before 3.90 vs. after 4.56, p < 0.001), with a mean improvement of 0.57‒0.93. Staff and resident scores improved after a 3D-printed model presentation (p < 0.05), except for Q4 in the resident group. The mean difference was higher among the staff than among the residents (staff: 0.50‒0.97 vs. residents: 0.27‒0.90). The scores of the 3D-printed model for education were high (trainees: 4.47 vs. patients: 4.60) compared to CT. CONCLUSION: The 3D-printed model of pancreatic cancer improved surgeons' understanding of individual patients' pancreatic cancer and surgical planning. CLINICAL RELEVANCE STATEMENT: The 3D-printed model of pancreatic cancer can be created using a preoperative CT image, which not only assists surgeons in surgical planning but also serves as a valuable educational resource for patients and students. KEY POINTS: • A personalized 3D-printed pancreatic cancer model provides more intuitive information than CT, allowing surgeons to better visualize the tumor's location and relationship to neighboring organs. • In particular, the survey score was higher among staff who performed the surgery than among residents. • Individual patient pancreatic cancer models have the potential to be used for personalized patient education as well as resident education.

The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy.

Damaged mitochondria are detrimental to cellular homeostasis. One mechanism for removal of damaged mitochondria involves the PINK1-PARKIN pathway, which poly-ubiquitylates damaged mitochondria to promote mitophagy. We report that assembly of ubiquitin chains on mitochondria triggers autophagy adaptor recruitment concomitantly with activation of the TBK1 kinase, which physically associates with OPTN, NDP52, and SQSTM1. TBK1 activation in HeLa cells requires OPTN and NDP52 and OPTN ubiquitin chain binding. In addition to the known role of S177 phosphorylation in OPTN on ATG8 recruitment, TBK1-dependent phosphorylation on S473 and S513 promotes ubiquitin chain binding in vitro as well as TBK1 activation, OPTN mitochondrial retention, and efficient mitophagy in vivo. These data reveal a self-reinforcing positive feedback mechanism that coordinates TBK1-dependent autophagy adaptor phosphorylation with the assembly of ubiquitin chains on mitochondria to facilitate efficient mitophagy, and mechanistically links genes mutated in Parkinson's disease and amyotrophic lateral sclerosis in a common selective autophagy pathway.

Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1.

A novel probiotics-derived protein, P8, suppresses the growth of colorectal cancer (CRC). P8 can penetrate the cell membrane via endocytosis and cause cell cycle arrest in DLD-1 cells through down-regulation of CDK1/Cyclin B1. However, neither the protein involved in the endocytosis of P8 nor the cell cycle arrest targets of P8 are known. We identified two P8-interacting target proteins [importin subunit alpha-4 (KPNA3) and glycogen synthase kinase-3 beta (GSK3ß)] using P8 as a bait in pull-down assays of DLD-1 cell lysates. Endocytosed P8 in the cytosol was found to bind specifically to GSK3ß, preventing its inactivation by protein kinases AKT/CK1ε/PKA. The subsequent activation of GSK3ß led to strong phosphorylation (S33,37/T41) of ß-catenin, resulting in its subsequent degradation. P8 in the cytosol was also found to be translocated into the nucleus by KPNA3 and importin. In the nucleus, after its release, P8 binds directly to the intron regions of the GSK3ß gene, leading to dysregulation of GSK3ß transcription. GSK3ß is a key protein kinase in Wnt signaling, which controls cell proliferation during CRC development. P8 can result in a cell cycle arrest morphology in CRC cells, even when they are in the Wnt ON signaling state.

Thoracic CT incidental pulmonary bullae in dogs: Characterization, interobserver variability, and general anesthesia risks.

Ruptures of pulmonary blebs and bullae are the most common cause of spontaneous pneumothorax in dogs. Incidental bullae/blebs have been documented in otherwise healthy people, however information for veterinary patients is currently lacking. Objectives of this retrospective, observer agreement, analytical study were to characterize incidental bullae in thoracic CT studies of dogs, assess interobserver variability for characterizing the bullae, and assess anesthesia risks. Inclusion criteria were dogs presenting for non-pneumothorax related reasons that had a thoracic CT at a single specialty and emergency hospital from 2012 to 2021 and had a bulla listed in the CT report. Medical records for dogs meeting inclusion criteria were reviewed to collect data on signalment, weight, total number of general anesthesia procedures 2 years prior and 2 years following the CT scan, and adverse anesthesia events. In addition, the CT images were reviewed by three American College of Veterinary Radiology-certified veterinary radiologists to collect data on the location, size, number of bullae and thickness of the bulla wall. A total of 1119 dogs met initial inclusion criteria and 74 dogs were included in analyses. There was no sex predilection for incidental pulmonary bullae. Bullae were more commonly found in older (median age 11.3 years), large breed dogs (median weight 20.7 kg). A solitary bulla of less than 1 cm was the most common finding with no apparent predilection for a particular lung lobe. There was strong correlation among the three radiologists for bulla location, size, and number, but weak correlations for bulla wall thickness. No adverse anesthesia events were found following CT anesthesia or following repetitive anesthesia procedures.

Propensity score matching analysis of perioperative outcomes including quality of life after multi-port vs. single port laparoscopic cholecystectomy: a nationwide prospective multicenter study in Korea.

INTRODUCTION: The usefulness of single-port laparoscopic cholecystectomy (SPLC) as compared to multi-port laparoscopic cholecystectomy (MPLC) remains controversial. Between SPLC and MPLC, we compared outcomes, especially subjective aspects, such as quality of life (QoL). MATERIAL AND METHODS: This multi-center study, involving 20 institutions from 2016 to 2017, enrolled 2507 patients who underwent laparoscopic cholecystectomy. Various perioperative outcomes, pain assessed by the numeric rating scale (NRS) score, and QoL evaluated by the gastrointestinal QoL index (GIQLI) questionnaire, were compared between the two procedures. We generated balanced groups after propensity score matching (PSM) using preoperative factors that influence the decision to perform MPLC or SPLC. RESULTS: MPLC and SPLC were performed in 2176 and 331 patients, respectively. Nine hundred and twelve and 329 patients, respectively, were selected from the two groups by PSM. Operation time was longer and surgical difficulty was lower in SPLC. There were no significant differences in most outcomes, including biliary complications. Significant superiority of SPLC over MPLC was shorter hospitalization, lower NRS score, and favorable GIQLI. CONCLUSIONS: From nationwide prospective data, SPLC showed outcomes comparable to MPLC. In SPLC, morbidity was not high and postoperative QoL was favorable. In the future, more implementations and studies are needed to ensure the safety and feasibility of SPLC.

Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis.

Phosphorylation is often used to promote protein ubiquitylation, yet we rarely understand quantitatively how ligase activation and ubiquitin (UB) chain assembly are integrated with phosphoregulation. Here we employ quantitative proteomics and live-cell imaging to dissect individual steps in the PINK1 kinase-PARKIN UB ligase mitochondrial control pathway disrupted in Parkinson's disease. PINK1 plays a dual role by phosphorylating PARKIN on its UB-like domain and poly-UB chains on mitochondria. PARKIN activation by PINK1 produces canonical and noncanonical UB chains on mitochondria, and PARKIN-dependent chain assembly is required for accumulation of poly-phospho-UB (poly-p-UB) on mitochondria. In vitro, PINK1 directly activates PARKIN's ability to assemble canonical and noncanonical UB chains and promotes association of PARKIN with both p-UB and poly-p-UB. Our data reveal a feedforward mechanism that explains how PINK1 phosphorylation of both PARKIN and poly-UB chains synthesized by PARKIN drives a program of PARKIN recruitment and mitochondrial ubiquitylation in response to mitochondrial damage.

Abdominopelvic MR to CT registration using a synthetic CT intermediate.

Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.

Surgical outcomes and prognostic factors of distal common bile duct adenocarcinoma: chronological analysis in a single high-volume institutional experience.

BACKGROUND: Distal common bile duct (dCBD) cancer is typical indication for pancreaticoduodenectomy (PD). We aimed to retrospectively evaluate surgical outcomes and investigate prognostic factors of dCBD adenocarcinoma for which PD was performed at a single institution. METHODS: We searched consecutive cases of dCBD adenocarcinoma undergone PD at Samsung Medical Center from 1995 to 2018. Cases with distant metastasis or palliative intent were excluded. The year in which the survival rate was dramatically improved was identified and entire years were divided into two periods for comparison. To balance between the two periods, we conducted propensity score matching (PSM) analysis using age, sex, body mass index (BMI), and American Society of Anesthesiologist score. RESULTS: Total of 804 cases were enrolled in this study. The entire period was divided into early period of 18 years and recent period of 6 years. The early and late period included 466 and 338 patients, respectively. As a result of PSM, balanced 316 patients were selected from each of the two periods. Significant improvements in surgical outcomes were identified, including shorter operation time, fewer blood loss, shorter hospitalization, and favorable overall survival. As results of multivariable analysis of independent risk factors for overall survival, older age and advanced N stage were identified, as expected. It was distinct that aggressive surgery and advanced tumor state in the early period and a lower BMI in the late period negatively affected the survival, respectively. CONCLUSIONS: Surgical outcomes of dCBD cancer underwent PD was improved. There were few modifiable factors to improve survival and continuous further study is needed to detect dCBD cancer in the early stages.

miR-22-3p and miR-30e-5p Are Associated with Prognosis in Cervical Squamous Cell Carcinoma.

Alteration in expression of miRNAs can cause various malignant changes and the metastatic process. Our aim was to identify the miRNAs involved in cervical squamous cell carcinoma (SqCC) and metastasis, and to test their utility as indicators of metastasis and survival. Using microarray technology, we performed miRNA expression profiling on primary cervical SqCC tissue (n = 6) compared with normal control (NC) tissue and compared SqCC that had (SqC-M; n = 3) and had not (SqC-NM; n = 3) metastasized. Four miRNAs were selected for validation by qRT-PCR on 29 SqC-NM and 27 SqC-M samples, and nine metastatic lesions (ML-SqC), from a total of 56 patients. Correlation of miRNA expression and clinicopathological parameters was analyzed to evaluate the clinical impact of candidate miRNAs. We found 40 miRNAs differentially altered in cervical SqCC tissue: 21 miRNAs were upregulated and 19 were downregulated (≥2-fold, p < 0.05). Eight were differentially altered in SqC-M compared with SqC-NM samples: four were upregulated (miR-494, miR-92a-3p, miR-205-5p, and miR-221-3p), and four were downregulated (miR-574-3p, miR-4769-3p, miR-1281, and miR-1825) (≥1.5-fold, p < 0.05). MiR-22-3p might be a metastamiR, which was gradually further downregulated in SqC-NM > SqC-M > ML-SqC. Downregulation of miR-30e-5p significantly correlated with high stage, lymph node metastasis, and low survival rate, suggesting an independent poor prognostic factor.

Anti-Cancer Activity of Buthus occitanus Venom on Hepatocellular Carcinoma in 3D Cell Culture.

Hepatocellular carcinoma (HCC) is the most dominant primary liver cancer, which can be caused by chronic hepatitis virus infections and other environmental factors. Resection, liver transplantation, and local ablation are only a few of the highly effective and curative procedures presently accessible. However, other complementary treatments can reduce cancer treatment side effects. In this present work, we evaluated the activity of Moroccan scorpion venom Buthus occitanus and its fractions obtained by chromatography gel filtration against HCC cells using a 3D cell culture model. The venom was fractionated by gel filtration chromatography, each fraction and the crude venom was tested on normal hepatocytes (Fa2N-4 cells). Additionally, the fractions and the crude venom were tested on MCTSs (multicellular tumor spheroids), and this latter was generated by cultivate Huh7.5 cancer cell line with WI38 cells, LX2 cells, and human endothelial cells (HUVEC). Our results indicate that Buthus occitanus venom toxin has no cytotoxic effects on normal hepatocytes. Moreover, it is reported that F3 fraction could significantly inhibit the MCTS cells. Other Protein Separation Techniques (High-performance liquid chromatography) are needed in order to identify the most active molecule.

Gastrointestinal Intramural Pancreatic Pseudocysts in a Dog: A Case Report and Human Literature Review.

A 9.5 yr old Yorkshire terrier presented with chronic intermittent vomiting and lethargy of 1.5 yr duration that progressed to generalized weakness. Insulin:glucose ratio was consistent with an insulinoma. Triple-phase computed tomography revealed a mid-body pancreatic nodule. The mid-body pancreatic nodule was enucleated; histopathology was consistent with an insulinoma. Two weeks after the operation, the dog presented for anorexia and diarrhea. Abdominal ultrasound revealed a thick-walled cystic lesion along the dorsal stomach wall. An intramural gastric pseudocyst was diagnosed via exploratory laparotomy and intraoperative gastroscopy. Comparison of amylase and lipase levels of the cystic fluid with that of concurrent blood serum samples confirmed the lesion was of pancreatic pseudocyst origin. The gastric pseudocyst was omentalized. Two weeks after the operation, the dog re-presented for anorexia, regurgitation, and diarrhea. An intramural duodenal pseudocyst was identified and treated with a duodenal resection and anastomosis. The dog has remained asymptomatic and recurrence free based on serial abdominal ultrasounds 22 mo following insulinoma removal. To our knowledge, this phenomenon of pancreatic pseudocysts forming in organs other than the pancreas has not been reported in dogs. This case report and comprehensive human literature review purpose is to raise awareness of this disease process in dogs.

Optimal timing of portal vein embolization (PVE) after preoperative biliary drainage for hilar cholangiocarcinoma.

BACKGROUND: Preoperative biliary drainage (PBD) followed by portal vein embolization (PVE) has increased the chance of resection for hilar cholangiocarcinoma (CCC). We aim to identify the optimal timing of PVE after PBD in patients undergoing hepatectomy for hilar CCC. METHODS: We retrospectively reviewed 64 patients who underwent hepatectomy after PBD and PVE for hilar CCC. The patients were classified into 3 groups: Group 1 (PBD-PVE interval ≤7 days), Group2 (8-14 days) and Group 3 (>14 days). The primary end points were 90 days mortality and grade B/C posthepatectomy liver failure (PHLF). RESULTS: There was no significant difference in primary end points between three groups. A marginally significant difference was found in the incidence of Clavien-Dindo grade ≥3 complications and wound infection (57.1% vs 38.1% vs 72.4%, p = 0.053 and 21.4% vs 38.1% vs 55.2%, p = 0.099). In multivariable analysis, Bismuth type IIIb or IV was independent risk factors for grade B/C PHLF (HR: 4.782, 95% CI 1.365-16.759, p = 0.014). CONCLUSIONS: Considering that the PBD-PVE interval did not affect PHLF, and the surgical complications increased as the interval increases, PVE as early as possible after PBD would be beneficial.

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.