Anatomical Quantitative Volumetric Evaluation of Liver Segments in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy: Key Parameters Influencing Untreated Liver Hypertrophy.

Background: Factors affecting morphological changes in the liver following selective internal radiation therapy (SIRT) are unclear, and the available literature focuses on non-anatomical volumetric assessment techniques in a lobar treatment setting. This study aimed to investigate quantitative changes in the liver post-SIRT using an anatomical volumetric approach in hepatocellular carcinoma (HCC) patients with different levels of treatment selectivity and evaluate the parameters affecting those changes. This retrospective, single-institution, IRB-approved study included 88 HCC patients. Whole liver, liver segments, tumor burden, and spleen volumes were quantified on MRI at baseline and 3/6/12 months post-SIRT using a segmentation-based 3D software relying on liver vascular anatomy. Treatment characteristics, longitudinal clinical/laboratory, and imaging data were analyzed. The Student's t-test and Wilcoxon test evaluated volumetric parameters evolution. Spearman correlation was used to assess the association between variables. Uni/multivariate analyses investigated factors influencing untreated liver volume (uLV) increase. Results: Most patients were cirrhotic (92%) men (86%) with Child-Pugh A (84%). Absolute and relative uLV kept increasing at 3/6/12 months post-SIRT vs. baseline (all, p ≤ 0.005) and was maximal during the first 6 months. Absolute uLV increase was greater in Child-Pugh A5/A6 vs. ≥B7 at 3 months (A5, p = 0.004; A6, p = 0.007) and 6 months (A5, p = 0.072; A6, p = 0.031) vs. baseline. When the Child-Pugh class worsened at 3 or 6 months post-SIRT, uLV did not change significantly, whereas it increased at 3/6/12 months vs. baseline (all p ≤ 0.015) when liver function remained stable. The Child-Pugh score was inversely correlated with absolute and relative uLV increase at 3 months (rho = -0.21, p = 0.047; rho = -0.229, p = 0.048). In multivariate analysis, uLV increase was influenced at 3 months by younger age (p = 0.013), administered 90Y activity (p = 0.003), and baseline spleen volume (p = 0.023). At 6 months, uLV increase was impacted by younger age (p = 0.006), whereas treatment with glass microspheres (vs. resin) demonstrated a clear trend towards better hypertrophy (f = 3.833, p = 0.058). The amount (percentage) of treated liver strongly impacted the relative uLV increase at 3/6/12 months (all f ≥ 8.407, p ≤ 0.01). Conclusion: Liver function (preserved baseline and stable post-SIRT) favored uLV hypertrophy. Younger patients, smaller baseline spleen volume, higher administered 90Y activity, and a larger amount of treated liver were associated with a higher degree of untreated liver hypertrophy. These factors should be considered in surgical candidates undergoing neoadjuvant SIRT.

Blockade of isoprenoids biosynthesis by simvastatin induces autophagy-mediated cell death via downstream c-Jun N-terminal kinase activation and cell cycle dysregulation in canine T-cell lymphoma cells.

Statins are inhibitors of the mevalonic acid pathway that mediates cellular metabolism by producing cholesterol and isoprenoids and are widely used in treating hypercholesterolaemia in humans. Lipophilic statins, including simvastatin, induce death in various tumour cells. However, the cytotoxic mechanisms of statins in tumour cells remain largely unexplored. This study aimed to elucidate the cytotoxic mechanisms of simvastatin in canine lymphoma cells. Simvastatin induced cell death via c-Jun N-terminal kinase (JNK) activation and autophagy in canine T-cell lymphoma cell lines Ema and UL-1, but not in B-cell lines. Cell death was mediated by induction of caspase-dependent apoptosis in UL-1 cells, but not in Ema cells. Blockade of autophagy by lysosomal inhibitors attenuated simvastatin-induced JNK activation and cell death. Isoprenoids, including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, attenuated simvastatin-induced autophagy, JNK activation, and cell death. In UL-1 cells, simvastatin treatment resulted in the cell cycle arrest at the G2/M phase, which was altered to G0/1 phase cell cycle arrest by treatment with lysosomal inhibitors. These findings demonstrate that depletion of isoprenoids by simvastatin induces autophagy-mediated cell death via downstream JNK activation and cell cycle dysregulation in canine T-cell lymphoma cells.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Technical Strategy for Pancreatic Body Cancers: A Raison d'etre of Distal Pancreatectomy with Portal Resection.

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.

Neoadjuvant chemotherapy for borderline resectable colorectal cancer liver metastases: a single-institution retrospective study.

INTRODUCTION: This study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy. MATERIALS AND METHODS: Since 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data. RESULTS: Of 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified. CONCLUSION: In patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.

New approach of circumferential lymph node dissection around the superior mesenteric artery for pancreatic cancer during pancreaticoduodenectomy (with video).

PURPOSE: Various approaches have been reported for the resection of the nervous and lymphatic tissues around the superior mesenteric artery (SMA) during pancreaticoduodenectomy (PD) for pancreatic cancer. We developed a new procedure for circumferential lymph node dissection around the SMA to minimize local recurrence. METHODS: We included 24 patients who underwent PD with circumferential lymph node dissection around the SMA (circumferential dissection) and 94 patients who underwent classical mesopancreatic dissection (classical dissection) between 2019 and 2021. The technical details of this new method are described in the figures and videos, and the clinical characteristics and outcomes of this technique were compared with those of classical dissection. RESULTS: The median follow-up durations in the circumferential and classical dissection groups were 39 and 36 months, respectively. The patients' characteristics, including tumor resectability, preoperative and adjuvant chemotherapy rates, postoperative complication rates, and tumor stage, were similar between the two groups. No differences were observed in recurrence-free survival and overall survival between the two groups; however, the classical dissection group tended to have more local recurrences than the circumferential dissection group (8.3% vs. 33.3%, P = 0.168). Although no case of nodular-type recurrence after circumferential dissection was observed, 61.1% of local recurrences after classical dissection were of the nodular-type, and 36.4% were located on the left side of the SMA. CONCLUSIONS: Performing circumferential lymph node dissection around the SMA during PD can be conducted safely with minimal risks of local recurrence and may enhance the completeness of local resection.

Phenotypic and molecular characterization of novel pulmonary adenocarcinoma cell lines established from a dog.

Canine pulmonary adenocarcinoma (PAC) resembles human lung tumors in never-smokers, but it is rarer than human pulmonary adenocarcinoma. Therefore, research on canine PAC is challenging. In the present study, we successfully established various novel canine PAC cell lines from a single lesion in a dog, including two parent cell lines and fourteen cloned cell lines, and characterized their cellular properties in vitro. Several of these cell lines showed epithelial-mesenchymal transition (EMT)-like and/or cancer stem cell (CSCs)-like phenotypes. We additionally assessed the sensitivity of the cells to vinorelbine in vitro. Three clonal lines, two of which showed EMT- and CSC-like phenotypes, were resistant to vinorelbine. Furthermore, we evaluated the expression and activation status of EGFR, HER2, and Ras signaling factors. The findings indicated that the cell lines we established preserved the expression and activation of these factors to varying extents. These novel canine PAC cell lines can be utilized in future research for understanding the pathogenesis and development of treatments for canine PAC.

Robotic Splenic Vessels Preserving Distal Pancreatectomy in a Post-Distal Gastrectomy Patient.

BACKGROUND: The optimal procedure during distal pancreatectomy (DP) for patients who have undergone distal gastrectomy (DG) remains unclear. Several papers on remnant gastric ischemia have reported that the preserved splenic vessels are essential for the proximal remnant stomach.1-4 We evaluated the outcomes of DP for post-DG patients in our hospital and introduced robotic splenic vessels preserving DP (R-SPDP). METHODS: Postoperative short-term outcomes of DP for post-DG patients during 2014 and 2021 were evaluated. Next, R-SPDP was performed for a post-DG patient with the intention of preserving the remnant stomach safely. The double bipolar method was used to dissect the adhesions around the splenic vessels.5,6 The splenic artery was clamped at the root side to prevent bleeding.7 All short gastric arteries and veins, which were the main feeders of the remnant stomach, were preserved and resection was completed. After resection, the indocyanine green (ICG) fluorescence angiography confirmed blood flow in the short gastric arteries and veins and good return blood flow to the splenic vein.8 RESULTS: Of four patients (50.0%, of 8 DP patients) in whom the remnant stomach was preserved, one conventional DP case had poor ICG perfusion and presented with remnant stomach ischemia postoperatively. The R-SPDP case with good ICG perfusion had a total operation time of 371 minutes and intraoperative blood loss of 10 mL. The oral diet was started on postoperative Day 3, and the postoperative course was uneventful. CONCLUSIONS: R-SPDP can be a good option for post-DG patients to preserve the remnant stomach safely.

Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment.

BACKGROUND: Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. METHODS: This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5 cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. RESULTS: During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25 ng/mL and/or CA19-9 ≥ 50 U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50 U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50 U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). CONCLUSIONS: High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.

Feasibility of laparoscopic radical antegrade modular pancreatosplenectomy (RAMPS) as a standard treatment for distal resectable pancreatic cancer.

INTRODUCTION: Laparoscopic (Lap-) radical antegrade modular pancreatosplenectomy (RAMPS) is an attractive radical procedure that aims to achieve negative posterior retroperitoneal margin in pancreatic ductal adenocarcinoma (PDAC) resections. However, only few institutions are adapting Lap-RAMPS due to the technical difficulties and the lack of supporting evidence for the clinical applications. METHODS: A retrospective cohort study was performed on consecutive patients who underwent RAMPS for distal resectable PDACs. We analyzed the short- and long-term outcomes including local control and the induction of adjuvant chemotherapy compared between Lap- and Open-RAMPS. RESULTS: Of the 118 RAMPS patients, 43 patients underwent Lap-RAMPS and 75 patients underwent Open-RAMPS. The blood loss was lower (125 vs. 390 mL, p < 0.001), and postoperative hospital stay was shorter (17 vs. 21 days, p = 0.018) in the Lap-RAMPS group. There was no difference in the postoperative complications and no mortality in both groups. R0 resection rate was 100.0% in the Lap-RAMPS and 90.7% in the Open-RAMPS (p = 0.039). Among the patients eligible for adjuvant chemotherapy, the Lap-RAMPS group showed a favorable induction rate (100.0 vs. 89.6%, p = 0.037). Both groups showed a favorable 3-year local recurrence rate (8.7 vs. 10.0%, p = 0.976) and 3-year overall survival (69.8 vs. 71.1%, p = 0.996). CONCLUSIONS: The safety and efficacy of Lap-RAMPS were comparable to those of Open-RAMPS in terms of achieving local control and adjuvant chemotherapy induction. A higher early induction of adjuvant chemotherapy is an advantage of minimally invasive surgery.

Diagnosis and management of postpancreatectomy hemorrhage: A single-center experience of consecutive 1,096 pancreatoduodenectomies.

BACKGROUND/OBJECTIVES: This study aimed to assess the outcomes and characteristics of post-pancreatectomy hemorrhage (PPH) in over 1000 patients who underwent pancreatoduodenectomy (PD) at a high-volume hepatopancreaticobiliary center. METHODS: This retrospective study analyzed consecutive patients who underwent PD from 2010 through 2021. PPH was diagnosed and managed using our algorithm based on timing of onset and location of hemorrhage. RESULTS: Of 1096 patients who underwent PD, 33 patients (3.0%) had PPH; incidence of in-hospital and 90-day mortality relevant to PPH were one patient (3.0%) and zero patients, respectively. Early (≤24 h after surgery) and late (>24 h) PPH affected 9 patients and 24 patients, respectively; 16 patients experienced late-extraluminal PPH. The incidence of postoperative pancreatic fistula (p < 0.001), abdominal infection (p < 0.001), highest values of drain fluid amylase (DFA) within 3 days, and highest value of C-reactive protein (CRP) within 3 days after surgery (DFA: p < 0.001) (CRP: p = 0.010) were significantly higher in the late-extraluminal-PPH group. The highest values of DFA≥10000U/l (p = 0.022), CRP≥15 mg/dl (p < 0.001), and incidence of abdominal infection (p = 0.004) were identified as independent risk factors for PPH in the multivariate analysis. Although the hospital stay was significantly longer in the late-extraluminal-PPH group (p < 0.001), discharge to patient's home (p = 0.751) and readmission rate within 30-day (p = 0.765) and 90-day (p = 0.062) did not differ between groups. CONCLUSIONS: Standardized management of PPH according to the onset and source of hemorrhage minimizes the incidence of serious deterioration and mortality. High-risk patients with PPH can be predicted based on the DFA values, CRP levels, and incidence of abdominal infections.

Evaluation of local recurrence after pancreaticoduodenectomy for borderline resectable pancreatic head cancer with neoadjuvant chemotherapy: Can the resection level change after chemotherapy?

BACKGROUND: Neoadjuvant treatment has significant survival benefits for patients with pancreatic cancer. However, local recurrence remains a serious issue, even after neoadjuvant treatment. This study investigated local recurrence after pancreaticoduodenectomy and determined the optimal resection level after neoadjuvant treatment. METHODS: This retrospective study analyzed consecutive patients who underwent pancreaticoduodenectomy for borderline resectable pancreatic cancer after 4 cycles of neoadjuvant treatment-gemcitabine plus nab-paclitaxel between April 2015 and March 2020. Patients with borderline resectable-artery pancreatic cancer were classified according to the dissection level around the artery: level 3 group, hemi-, or whole circumferential arterial nerve plexus was dissected; and level 2 group, the nerve plexus was preserved. RESULTS: Fifty-six patients with borderline resectable-artery pancreatic cancer underwent pancreaticoduodenectomy after neoadjuvant treatment (level 3 group, n = 40; level 2 group, n = 16). The resection level in the level 2 group was changed based on post-neoadjuvant treatment computed tomography images or intraoperative frozen section diagnosis. The overall and local recurrence rates were significantly higher in the level 2 group than in the level 3 group (overall recurrence, 93.8% vs 70.0%; P = .037) (local recurrence, 50.0% vs 5.0%; P < .001). Ten patients experienced local recurrence, of which 8 belonged to the level 2 group. Among them, 4 patients were confirmed as cancer-negative by surgical margin analysis or intraoperative frozen section diagnosis but experienced recurrence around the arteries. CONCLUSION: For treating borderline resectable-artery pancreatic cancer, changing the resection level based on post-neoadjuvant treatment computed tomography images increased the risk of local recurrence. All patients with borderline resectable-artery should undergo level 3 dissection, regardless of the response to neoadjuvant treatment.

Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations 2022.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. METHODS: A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. RESULTS: A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. CONCLUSIONS: These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.

Optimizing the selection of technically unresectable colorectal liver metastases.

BACKGROUND: The prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases. METHODS: In this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014-2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume. RESULTS: Of the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P < .001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0-2], B [3-4], and C [5-6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P < .001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P < .001). CONCLUSION: Patients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.

Serum DUPAN-2 could be an Alternative Biological Marker for CA19-9 Nonsecretors with Pancreatic Cancer.

OBJECTIVE: This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors. BACKGROUND: Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors. METHODS: We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL). RESULTS: Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection. CONCLUSION: DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group.

Expression profile of immunoregulatory factors in canine tumors.

Cancers utilize a variety of molecules to escape host immune responses. Better understanding the immune environment surrounding cancer may facilitate application of innovative cancer immunotherapies, such as immune checkpoint inhibitors, to dogs as well as humans. In this study, we screened the expression of 20 immune regulatory molecules in diverse canine tumors (n = 59). Quantitative RT-PCR (qPCR) analysis revealed that some immune regulatory molecules, such as LGALS9 (coding Galectin-9) and CD48, were expressed in most canine tumors, but other molecules, such as CD274 (coding PD-L1), IL4I1, PVR, TNFSF18, ICOSLG, and TNFSF4, were rarely expressed. NECTIN2 was highly expressed in epithelial tumors but was low in non-epithelial tumors. In contrast, VSIR and CD200 expressions were low in epithelial tumors but high in non-epithelial tumors. Interestingly, several tumors expressed distinctive immunoregulatory factors. Hepatocellular carcinomas expressed FGL1, mast cell tumors expressed PDCD1LG2 (coding PD-L2), transitional cell carcinomas expressed VTCN1 (coding B7x), and lymphomas and squamous cell carcinomas expressed CD70. Consistent with qPCR results, immunofluorescence staining confirmed that hepatocellular carcinomas expressed FGL-1 protein. Thus, this study reveals the expression profile of immunoregulatory molecules in canine tumors and opens the door to better understanding the relationship between canine tumors and host immunity.

Association between CT-Based Preoperative Sarcopenia and Outcomes in Patients That Underwent Liver Resections.

This retrospective observational study aimed to evaluate whether preoperative sarcopenia, assessed by CT imaging, was associated with postoperative clinical outcomes and overall survival in patients that underwent liver resections. Patients operated on between January 2014 and February 2020 were included. The skeletal muscle index (SMI) was measured at the level of the third lumbar vertebra on preoperative CT scans. Preoperative sarcopenia was defined based on pre-established SMI cut-off values. The outcomes were postoperative morbidity, length of hospital stay (LOS), and overall survival. Among 355 patients, 212 (59.7%) had preoperative sarcopenia. Patients with sarcopenia were significantly older (63.5 years) and had significantly lower BMIs (23.9 kg/m2) than patients without sarcopenia (59.3 years, p < 0.01, and 27.7 kg/m2, p < 0.01, respectively). There was no difference in LOS (8 vs. 8 days, p = 0.75), and the major complication rates were comparable between the two groups (11.2% vs. 11.3%, p = 1.00). The median overall survival times were comparable between patients with sarcopenia and those without sarcopenia (15 vs. 16 months, p = 0.87). Based on CT assessment alone, preoperative sarcopenia appeared to have no impact on postoperative clinical outcomes or overall survival in patients that underwent liver resections. Future efforts should also consider muscle strength and physical performance, in addition to imaging, for preoperative risk stratification.