Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

BACKGRUOUND: The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development. METHODS: We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining. RESULTS: Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group. CONCLUSION: Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.

Fate of small remnant pancreatic tail in splenic hilum after laparoscopic spleen preserving distal pancreatectomy: a retrospective study.

Purpose: When performing laparoscopic spleen-preserving distal pancreatectomy (LSPDP), sometimes, anatomically challenging patients are encountered, where the pancreatic tail is deep in the splenic hilum. The purpose of this study was to discuss the experience with the surgical technique of leaving the deep pancreatic tail of the splenic hilum in these patients. Methods: Eleven patients who underwent LSPDP with remnant pancreatic tails between November 2019 and August 2021 at Samsung Medical Center in Seoul, Korea were included in the study. Their short-term postoperative outcomes were analyzed retrospectively. Results: The mean operative time was 168.6 ± 26.0 minutes, the estimated blood loss was 172.7 ± 95.8 mL, and the postoperative length of stay was 6.1 ± 1.0 days. All 11 lesions were in the body or tail of the pancreas and included 2 intraductal papillary mucinous neoplasms, 6 neuroendocrine tumors, 2 cystic neoplasms, and 1 patient with chronic pancreatitis. In 10 of the 11 patients, only the pancreatic tail was left inside the distal portion of the splenic hilum of the branching splenic vessel, and there was a collection of intraabdominal fluid, which was naturally resolved. One patient with a remnant pancreatic tail above the hilar vessels was readmitted due to a postoperative pancreatic fistula with fever and underwent internal drainage. Conclusion: In spleen preservation, leaving a small pancreatic tail inside the splenic hilum is feasible and more beneficial to the patient than performing splenectomy in anatomically challenging patients.

Laparoscopic liver resection as a treatment option for intrahepatic cholangiocarcinoma.

Laparoscopic liver resection (LLR) remains controversial in the treatment of intrahepatic cholangiocarcinoma (ICC). The aim of the present study is to investigate the outcomes of LLR for ICC compared to open liver resection (OLR). We retrospectively reviewed patients who underwent surgery for ICC between January 2013 and February 2020. OLR and LLR were compared after propensity score matching (PSM). Overall survival (OS) and recurrence-free survival (RFS) were compared between the matched groups. During the study period, 219 patients met the inclusion criteria (OLR = 170 patients, 77.6%; LLR = 49 patients, 22.4%). Two groups of 43 patients each were analyzed after PSM. The 5-year RFS and OS were 44.6% and 47.9% in the OLR group and 50.9% and 39.8% in the LLR group, respectively. Hospital stay and intensive care unit care were significantly shorter and lower in the LLR group than in the OLR group, respectively. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the OLR group and the LLR group. Multiple tumors and lymph node metastases were predisposing factors for tumor recurrence and death in multivariate analysis. The present study suggests that LLR should be considered in selective ICC because of short hospitalization and similar oncologic outcome and overall survival.

Twenty-one years of experience with resected solid pseudopapillary neoplasm: a retrospective single-institutional cohort study.

BACKGROUND: Although the incidence of solid pseudopapillary neoplasm (SPN) is <2% of the incidence of pancreatic tumor, the prevalence seems to be increasing. SPNs are mostly benign. However, they also show malignant features. This study aimed to identify the clinical outcomes of patients who underwent surgery for SPN at a single center. METHODS: Data on 217 patients with SPN who underwent surgery in Samsung Medical Center between 2000 and 2020 were retrospectively analyzed. RESULTS: Herein, the mean age of the 217 patients was 40.0 ± 12.6 years, with a female predominance (80.6%). Most patients had no comorbidity. The mean tumor size was 4.4 ± 3.1 cm. The tumor was located at the pancreatic head in 36 patients (16.6%), the body of the pancreas in 69 patients (31.8%), and the pancreatic tail in 96 patients (44.2%). Of note, 35 patients (16.1%) underwent pancreaticoduodenectomies, 148 patients (68.2%) had distal pancreatectomies, and the other patients had subtotal /total pancreatectomy (9.7%) or enucleation/mass excision (6.0%). No patient had lymph node (LN) metastasis. Moreover, 6 patients (2.8%) had a recurrence in the liver or regional LNs. The 5-year recurrence-free survival rate was 96.8%. The only factor affecting recurrence was tumor size (P = .007). CONCLUSION: Because SPN predominates in relatively young women, patients often hesitate to undergo surgery. Nevertheless, as size is the prognostic factor, early resection is recommended for a better prognosis in the case of surgically feasible, young age, and healthy patients.

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

Background: To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX. Method: Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3). Results: With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS. Conclusions: Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.

Pancreatic Metastasectomy for Secondary Malignancy of the Pancreas: A Single-institution Experience.

BACKGROUND/AIM: Metastasis to the pancreas is rare, and the benefit of resection for secondary pancreatic cancer is poorly defined. Furthermore, there are no guidelines for pancreatic metastasectomy in such patients. The purpose of this study was to discuss our experience with the operative management of secondary pancreatic cancer. PATIENTS AND METHODS: This retrospective study included 76 patients who underwent pancreatic metastasectomy for secondary pancreatic cancer between January 2000 and December 2020 at Samsung Medical Center, Seoul, Republic of Korea. RESULTS: Among the study subjects, 44 underwent distal pancreatectomy, 21 pancreaticoduodenectomy, 5 total pancreatectomy, and 6 enucleation or wedge resection for metastasis. The overall survival (OS) and recurrence-free survival (RFS) were higher in the patients with RCC than in patients with other malignancies (p=0.004 and p=0.051, respectively). Statistically significant differences were not observed in OS and RFS between patients with right RCC (rRCC) or left RCC (lRCC; p=0.523 and p=0.586, respectively). CONCLUSION: Pancreatic metastasectomy may offer promising outcomes regarding curative intent in instances of secondary pancreatic metastasis, particularly in the context of RCC. However, regarding the side of primary RCC, no statistically significant differences were found in OS and RFS between rRCC and lRCC.

Survival Comparison of Different Operation Types for Middle Bile Duct Cancer: Bile Duct Resection versus Pancreaticoduodenectomy Considering Complications and Adjuvant Treatment Effects.

BACKGROUND: Margin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy (PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer. MATERIALS AND METHODS: From 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin. RESULTS: The 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (p = 0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (p < 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (p = 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (p = 0.003). CONCLUSION: The survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes.

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-ß-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.

Usability of the novel ankle training equipment with spring resistance-based plantar press exercises in the standing position: A focus on chronic stroke patients with hemiplegic gait.

BACKGROUND: To improve gait disability in patients with chronic stroke, ankle muscle strengthening and calf muscle stretching exercises are required. However, currently available ankle training equipment limit ankle exercises based on the position. Recently developed ankle training equipment enables spring resistance-based plantar press exercises to be performed in the standing position with weight support. OBJECTIVE: To conduct a usability test of the ankle training equipment in the standing position by stroke patients with hemiplegic gait and verify its effects on ankle movements. METHODS: The ankle training equipment was applied to five patients with chronic stroke and hemiplegic gait. In the standing position, the patients performed forefoot and rearfoot press exercises in the affected side with a day's interval at 20 repetitions maximum (RM). During the exercises, surface electromyography (sEMG) was used to measure the maximum voluntary isometric contraction (%MVIC) of the leg muscles. The System Usability Scale (SUS) was used to assess the ankle training equipment. Wilcoxon signed-rank test was used to evaluate the differences in muscle activity between the two exercises. RESULTS: Forefoot and rearfoot press exercises increased the %MVIC in the biceps femoris. Additionally, the tibialis anterior and medial gastrocnemius activity was significantly different between the two exercises. The SUS was 78.75% (SD 12.7). CONCLUSION: The usability test of the passive-control foot press trainer (PFPT) that with improvements in the structure and functions for convenience, it could be commercialized. PFPT could be an alternative to the ankle rehabilitation robot that necessitates a sitting position.

Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss.

BACKGROUND: Multinucleation is a hallmark of osteoclast formation and has a unique ability to resorb bone matrix. During osteoclast differentiation, the cytoskeleton reorganization results in the generation of actin belts and eventual bone resorption. Tetraspanins are involved in adhesion, migration and fusion in various cells. However, its function in osteoclast is still unclear. In this study, we identified Tm4sf19, a member of the tetraspanin family, as a regulator of osteoclast function. MATERIALS AND METHODS: We investigate the effect of Tm4sf19 deficiency on osteoclast differentiation using bone marrow-derived macrophages obtained from wild type (WT), Tm4sf19 knockout (KO) and Tm4sf19 LELΔ mice lacking the large extracellular loop (LEL). We analyzed bone mass of young and aged WT, KO and LELΔ mice by µCT analysis. The effects of Tm4sf19 LEL-Fc fusion protein were accessed in osteoclast differentiation and osteoporosis animal model. RESULTS: We found that deficiency of Tm4sf19 inhibited osteoclast function and LEL of Tm4sf19 was responsible for its function in osteoclasts in vitro. KO and LELΔ mice exhibited higher trabecular bone mass compared to WT mice. We found that Tm4sf19 interacts with integrin αvß3 through LEL, and that this binding is important for cytoskeletal rearrangements in osteoclast by regulating signaling downstream of integrin αvß3. Treatment with LEL-Fc fusion protein inhibited osteoclast function in vitro and administration of LEL-Fc prevented bone loss in an osteoporosis mouse model in vivo. CONCLUSION: We suggest that Tm4sf19 regulates osteoclast function and that LEL-Fc may be a promising drug to target bone destructive diseases caused by osteoclast hyper-differentiation.

Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer.

Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR.

The role of subspecialized radiologist reviews in preoperative conference for hepato-pancreato-biliary disease.

PURPOSE: To identify the role of subspecialized radiologists in preoperative conferences of radiologists and surgeons in the management of hepato-pancreato-biliary (HPB) diseases. METHODS: We retrospectively evaluated the prospective data of 247 patients (mean age, 63.8 years; 173 men) who were referred for preoperative conferences (n = 258; 11 were discussed twice) for HPB disease between September 2021 and April 2022. Before each preoperative conference, subspecialized radiologists reviewed all available imaging studies and treatment plan information. After each conference, any change to the treatment plan was documented (major, minor, or none). Additional information provided by the radiologists was collected (significant, supplementary, or none). Uni- and multivariable analyses were performed to determine factors that resulted in a major change to the treatment plan. RESULTS: Of the 258 reviewed cases, a major change was made to the treatment plan in 26 cases (10.1 %) and a minor change in 41 (15.9 %). Significant information was provided in 27 cases (10.5 %) and supplementary information in 72 (27.9 %). In the multivariable analysis, additional information about local tumor extent (odds ratio [OR], 6.3; 95 % confidence interval [CI], 2.1-19.5; p = 0.001) and distant metastasis detection (OR, 33.2; 95 % CI, 5.1-216.6; p < 0.001) was significantly associated with a major change. CONCLUSION: The involvement of subspecialized radiologists in preoperative conferences resulted in major treatment plan changes in 10.1 % of the cases, primarily associated with the added information about local tumor extent and distant metastasis.

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.

Feasibility of new patient dose management tool in digital radiography: Using clinical exposure index data of mobile chest radiography in a large university hospital.

The clinical anteroposterior (AP) chest images taken with a mobile radiography system were analyzed in this study to utilize the clinical exposure index (EI) as a patient dose-monitoring tool. The digital imaging and communications in medicine header of 6048 data points exposed under the 90 kVp and 2.5 mAs were extracted using Python for identifying the distribution of clinical EI. Even under the same exposure conditions, the clinical EI distribution was 137.82-4924.38. To determine the cause, the effect of a patient's body shape on EI was confirmed using actual clinical chest AP image data binarized into 0 and 255-pixel values using Python. As a result, the relationship between the direct X-ray area of the chest AP image, the higher the clinical EI, the larger the rate of the direct X-ray area. A conversion equation was also derived to infer entrance surface dose through clinical EI based on the patient thickness. This confirmed the possibility of directly monitoring patient dose through EI without a dosimeter in real-time. Therefore, to use the clinical EI of the mobile radiography system as a patient dose-monitoring tool, the derivation method of clinical EI considers several factors, such as the relationship between patient factors.

Prognosis of pancreaticoduodenectomy in octogenarians for pancreatic ductal adenocarcinoma with propensity score matched analysis.

BACKGROUND: This retrospective study investigates factors affecting surgical and oncological outcome after performing pancreaticoduodenectomy in octogenarian patients diagnosed with pancreatic ductal adenocarcinoma. METHODS: From January 2009 to December 2018, patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were included. Data were analysed by comparing clinicopathological characteristics, complications, survival, recurrence, adjuvant treatment between octogenarians and the younger group. Propensity score matched analysis was performed due to the small size of the octogenarian group. RESULTS: A total of 666 patients were included in this study and 24 (3.6%) were included in the octogenarian group. Short term complication rates (P = 0.119) and hospital stay (P = 0.839) did not differ between two groups. Overall survival between the two groups showed significant difference (<80 median 25 months versus ≥80 median 13 months, P = 0.045). However, after propensity score matched analysis, the two groups did not differ in overall survival (<80 median 18 months versus ≥80 median survival 16 months, P = 0.565) or disease-free survival (P = 0.471). Among the octogenarians, six patients survived longer than 24 months even without satisfying all favourable prognostic factors. CONCLUSION: Considering the general condition of octogenarians diagnosed with pancreatic ductal adenocarcinoma, select patients should be treated more aggressively for the best chance of receiving curative treatment.

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%.

Survival Benefit after Shifting from Upfront Surgery to Neoadjuvant Treatment in Borderline Resectable Pancreatic Cancer.

According to the 2016 National Comprehensive Cancer Network (NCCN) guidelines, patients with borderline resectable pancreatic cancer (BRPC) should receive chemotherapy as the first-line treatment. This study examined the real-world survival benefits of modifying BRPC treatment guidelines. Patients treated for BRPC at a single institution from 2013 to 2015 (pre-guideline group) and 2017 to 2019 (post-guideline group) were retrospectively reviewed. According to the treatment method used, patients were classified into upfront surgery (US), surgery after neoadjuvant treatment (NAT), and chemotherapy only (CO) groups. Overall survival (OS) was compared according to period and treatment type. Factors associated with OS were analyzed using a Cox regression model. Among the 165 patients, 63 were in the pre-guideline group and 102 patients were in the post-guideline group. The median OS was significantly improved in the post-guideline group compared to the pre-guideline group (29 vs. 13 months, p < 0.001). According to the treatment method, the median OS of the NAT group was significantly longer than that of the US and CO groups (40 vs. 16 vs. 15 months, respectively, p < 0.001). In multivariate analysis, tumor size, differentiation, NAT, and perineural invasion were significant prognostic factors. NAT is an important treatment option for BRPC and increased patient survival in the real world.

15-Year Experience of Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer-A Korean Nationwide Investigation.

BACKGROUND: As systemic treatment for pancreatic cancer advances, distal pancreatectomy with celiac axis resection (DP-CAR) has been considered a curative-intent surgical option for advanced pancreatic cancer. This study aimed to review the surgical and oncologic outcomes of patients undergoing DP-CAR based on Korean nationwide data. METHODS: We collected the data of patients who underwent DP-CAR for pancreatic cancer between 2007 and 2021 at seven major hospitals in Korea. The clinicopathological characteristics, postoperative complications, and data on the survival of the patients were retrospectively reviewed. Logistic regression analysis was performed to identify risk factors for postoperative complications and survival. RESULTS: A total of 75 patients, consisting mainly of borderline resectable (n = 32) or locally advanced (n = 30) pancreatic cancer, were included in the analysis. Forty-two (56.0%) patients underwent neoadjuvant treatment (NAT). Twenty (26.7%) patients experienced Clavien-Dindo grade ≥ 3 complications, including four patients with ischemic gastropathy, two with hepatic ischemia, and two procedure-related mortalities. Neoadjuvant chemotherapy increased the risk of postoperative complications (p = 0.028). The median recurrence-free and overall survival were 7 and 19 months, with a 5-year survival rate of 13% and 24%, respectively. In the NAT group, a decrease in CA 19-9 and the post-NAT maximum standardized uptake value (SUVmax) in positron emission tomography were associated with survival after surgical resection. CONCLUSIONS: Despite the possibility of major complications, DP-CAR could be a feasible option for achieving curative resection with fair survival outcomes in patients with borderline resectable or locally advanced pancreatic cancer. Further studies investigating the safety of the procedure and identifying proper surgical candidates with potential survival gains are necessary.

The significance of evaluating sphenoid sinus fluid by postmortem computed tomography in cases of drowning.

PURPOSE: In cases of drowning, the presence of sphenoid sinus fluid is a non-specific autopsy finding. However, studies have reported that fluid accumulation in the paranasal sinuses is more commonly observed in drowning victims. Furthermore, some laboratory tests, such as diatom and electrolyte analysis, can serve as supplementary diagnostic tools for diagnosing drowning. Therefore, accurate sphenoid sinus fluid sampling is an important aspect of an autopsy in suspected drowning cases. The aim of this study was to identify the significance of evaluating sphenoid sinus fluid by PMCT images in cases of drowning. METHODS: We retrospectively reviewed 54 drowning victims who underwent PMCT and forensic autopsy. Fluid volume in the sphenoid sinus was measured using a graduated syringe during autopsy and a three-dimensional (3D) workstation based on PMCT images was used for the purpose of comparison. The Mann-Whitney U test and Spearman's rank correlation coefficient was used to evaluate statistically significant differences and correlations. Additionally, a Bland-Altman plot was employed to assess the agreement between PMCT and autopsy. RESULTS: The median volume was 1.65 (range 0.00-12.4) ml and 1.55 (range 0.00-7.00) ml in the PMCT and autopsy, respectively, showing a statistically insignificant difference (p = 0.294) and a significant correlation (Rs = 0.896). In 35 cases, the PMCT overestimated the fluid volume more than the autopsy, whereas in 14 cases, the PMCT underestimated the fluid volume. No fluid was identified in seven cases during the autopsy, whereas in five patients, no fluid was found in both PMCT and autopsy. By analyzing the Bland-Altman plot, a bias of 0.73 ± 1.4 ml and limits of agreement ranging from -2.04 to 3.51 ml were observed for sphenoid sinus fluid volume measurements. CONCLUSIONS: Based on the limitations of traditional fluid volume measurement in the sphenoid sinus during autopsy, we propose the utilization of PMCT volumetric analysis prior to autopsy as a means to enhance the detection of sphenoid sinus fluid in cases of drowning.

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.