Implementable assay for monitoring minimum residual disease after radical treatment for colorectal cancer.

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the "amplicon of methylated sites using a specific enzyme" assay as "AMUSE." We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

International Multicenter Study of Ultra-Low GRWR Grafts in Adult Living Donor Liver Transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

TEMPORARY REMOVAL: A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

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Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein.

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.

The Gastrohepatic Ligament Approach Using Multiple Traction Tapes in Laparoscopic Spleen-Preserving Distal Pancreatectomy with Preservation of Splenic Vessels (with Video).

BACKGROUND: The gastrohepatic ligament approach is a form of robot-assisted spleen-preserving distal pancreatectomy (SPDP).1,2 This approach does not require omentum transection, peri-splenic dissection, or stomach traction. METHODS: Considering the advantages of preserving collateral pathways around the spleen, the authors performed the gastrohepatic ligament approach in laparoscopic SPDP while preserving splenic vessels (LSPDP), with specific modifications for laparoscopic surgery. The following surgical technique was performed. First, the gastrohepatic ligament was divided extensively, and all subsequent procedures were performed through the gastrohepatic ligament route. The superior and inferior borders of the pancreas then were dissected to encircle the common hepatic and splenic arteries with vessel loops and to expose the superior mesenteric vein (SMV) and portal vein. After taping of the pancreas on the SMV, the pancreas was divided using a linear stapler. Next, the pancreas was dissected from proximal to distal with preservation of the splenic vessels. Re-taping and traction of the splenic vessels and pancreas could facilitate the dissection of the pancreas body, especially at the splenic hilum. The appropriate counter traction using traction tapes allowed efficient laparoscopic procedures. The LSPDP was performed for three patients, including one obese patient (body mass index, 36 kg/m2) and two patients with an anomalous left hepatic artery branching from the left gastric artery. RESULTS: The mean operation time was 186 min, and the intraoperative blood loss was 37 mL. CONCLUSION: The gastrohepatic ligament approach could be an option for performing LSPDP with the counter traction technique for low-grade malignant tumors.

Prognostic significance of occult vertebral fracture in patients undergoing pancreatic resection for pancreatic cancer.

OBJECTIVE: The prognostic impact of occult vertebral fracture (OVF) in patients with malignancies is a new cutting edge in cancer research. This study was performed to analyze the prognostic impact of OVF after surgery for pancreatic cancer. METHODS: This study involved 200 patients who underwent surgical treatment of pancreatic ductal adenocarcinoma. OVF was diagnosed by quantitative measurement using preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumbar vertebra. RESULTS: OVF was diagnosed in 65 (32.5 %) patients. The multivariate analyses showed that male sex (p = 0.01), osteopenia (p < 0.01), OVF (p < 0.01), a carbohydrate antigen 19-9 level of ≥400 U/mL (p < 0.01), advanced stage of cancer (p < 0.01), and non-adjuvant chemotherapy (p = 0.02) were independent risk factors for overall survival. An age of ≥74 years (p < 0.01) and obstructive jaundice (p = 0.03) were independent risk factors for OVF. Furthermore, the combination of OVF and osteopenia further worsened disease-free survival and overall survival compared with osteopenia or OVF alone (p < 0.01; respectively). CONCLUSION: Evaluation of preoperative OVF might be a useful prognostic indicator for patients with pancreatic ductal adenocarcinoma.

An international survey of venous thromboembolic events and current practices of peri-operative VTE prophylaxis after living donor hepatectomy.

BACKGROUND: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy . The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. METHODS: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri-operative thromboembolic prophylaxis and an audit of -perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016-2020). RESULTS: Fifty-one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016-2020. All centers included pre-operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual-mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post-operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. CONCLUSION: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence-based guidelines regarding risk assessment, and peri-operative prophylaxis are needed.

Protein kinase C delta enhances the diagnostic performance of hepatocellular carcinoma.

BACKGROUND: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need. OBJECTIVE: This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs. METHODS: PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC. RESULTS: In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels. CONCLUSIONS: PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.

The clinical implications of occult inguinal hernia identified during laparoscopic peritoneal dialysis catheter insertion.

BACKGROUND: Occult inguinal hernias predispose patients undergoing peritoneal dialysis (PD) to symptomatic inguinal hernia formation causing complications. We conducted a retrospective study to assess the usefulness of routine laparoscopic examination for occult inguinal hernia during PD catheter insertion and the risk profile of occult inguinal hernia according to hernia classification in patients with PD. METHODS: This study included 79 patients who underwent initial laparoscopic PD catheter insertion between 2021 and 2022. An occult hernia was defined as an internal hernial sac of all sizes that was not detectable on physical examination. The European Hernia Society groin hernia classification was used to describe the hernia type. We investigated the association between event-free survival and occult inguinal hernias in patients undergoing PD. RESULTS: Occult inguinal hernias were diagnosed in 24 (32%) patients. Among these patients, 5 (21%) patients underwent metachronous repair. In patients with L2 occult hernias, the cumulative incidence rates of right and left symptomatic hernias within one year were 100% and 50%, respectively. Multivariate analysis revealed that L2 occult hernias were associated with metachronous hernia repair. CONCLUSION: The L2 occult inguinal hernia during PD was associated with metachronous repair, suggesting the importance of routine examination of inguinal hernias during laparoscopic PD catheter insertion.

Prognostic impact of osteosarcopenia in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma.

BACKGROUND: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. RESULTS: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). CONCLUSION: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC.

Predictors for early recurrence beyond up-to-7 or distant metastasis after hepatocellular carcinoma resection: proposal for borderline resectable HCC.

BACKGROUND: The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5 years and early recurrence (within 1 year) is now recognized as having a poor prognosis and has limited treatment options. METHODS: We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1 year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes. RESULTS: Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1 year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis. CONCLUSIONS: In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

Long-term outcomes of choledochoduodenostomy for choledocholithiasis: increased incidence of postoperative cholangitis after total or distal gastrectomy.

PURPOSE: Choledochoduodenostomy (CDD) is performed to treat choledocholithiasis (CDL) cases where endoscopic stone removal is difficult. Recognizing CDD characteristics is important for CDL treatment planning. METHODS: A total of 116 patients, including 33 patients ≥ 80 years old (29 with previous total gastrectomy, 19 with previous distal gastrectomy, 20 with built-up stones, 19 with periampullary diverticulum, 10 with confluence stones, 8 with repetitive recurrent stones, 4 with hard stones, 3 with endoscopic retrograde cholangiography [ERC] not available due to lack of cooperation, 2 with a history of pancreatitis post-ERC, and 2 in whom ERC could not be performed due to a disturbed anatomy) underwent CDD for CDL. Postoperative complications and long-term outcomes were evaluated. RESULTS: The in-hospital mortality rate was 0%. The morbidity (grade ≥ IIIA according to the Clavien-Dindo classification) rates in the elderly (≥ 80 years old) and non-elderly (51-79 years old) patients were 3.0% (1/33) and 2.4% (2/83), respectively (p = 0.85). Long-term complications included cholangitis in eight (7%) patients, of which three cases were repetitive and seven had an operative history of total or distal gastrectomy. The incidence of postoperative cholangitis after total or distal gastrectomy was 15% (7/48), which was significantly higher than that involving other causes (1.5%, 1/68; p < 0.01). Two patients with cholangitis after total gastrectomy experienced early recurrence of lithiasis at 2 and 9 months after surgery. CONCLUSIONS: CDD is safe, even in elderly patients. However, a history of total gastrectomy or distal gastrectomy may increase the incidence of postoperative cholangitis.

Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer.

PURPOSE: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. METHODS: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). RESULTS: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. CONCLUSION: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer.

The postoperative platelet-to-lymphocyte ratio predicts the outcome of patients undergoing pancreaticoduodenectomy for pancreatic head cancer.

PURPOSE: The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated. METHODS: We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed. RESULTS: A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028). CONCLUSIONS: The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection.

Osteosarcopenia is a significant predictor of recurrence and the prognosis after resection for extrahepatic bile duct cancer.

PURPOSE: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC). METHODS: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. RESULTS: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively). CONCLUSIONS: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC.

Histological and radiological analysis of simultaneous dual hepatic vein embolization for right-sided major hepatectomy.

PURPOSE: Simultaneous dual hepatic vein embolization (DHVE) has been proposed for safe right-sided hepatectomy, with good results for liver hypertrophy and function. However, the histological and radiological findings of DHVE have not been thoroughly investigated. METHODS: This study included 14 patients who underwent DHVE before right-sided major hepatectomy. DHVE was performed if the future liver remnant was < 35% or borderline, but with concomitant vascular resection. The liver function was assessed using the signal intensity on Gd-EOB-DTPA-MRI. A histological evaluation of the area of DHVE and portal vein embolization (PVE) were performed. RESULTS: The median pre- and post-functional liver remnants were 363 ml and 498 ml, respectively (p < 0.001). The median growth rate was 48.6%, and there was no post-hepatectomy liver failure in the patients who underwent DHVE. The signal intensity ratio in the area of DHVE was lower than that in the areas of PVE and the remnant liver (p < 0.01). The degree of congestion and necrosis was greater in the area of DHVE than in the area of PVE alone (p < 0.01 and p = 0.04, respectively). CONCLUSIONS: We observed good liver hypertrophy after DHVE and histological and radiological changes in the area of DHVE. Our findings provide a compelling rationale for further investigation of the mechanism of liver hypertrophy in DHVE.

Abdominal aortic calcification volume as a preoperative prognostic predictor for pancreatic cancer.

PURPOSE: Atherosclerosis and cancer may progress through common pathological factors. This study was performed to investigate the association between the abdominal aortic calcification (AAC) volume and outcomes following surgical treatment for pancreatic cancer. METHODS: The subjects of this retrospective study were 194 patients who underwent pancreatic cancer surgery between 2007 and 2020. The AAC volume was assessed through routine preoperative computed tomography. Univariate and multivariate analyses were performed to evaluate the impact of the AAC volume on oncological outcomes. RESULTS: A higher AAC volume (≥ 312 mm3) was identified in 66 (34%) patients, who were significantly older and had a higher prevalence of diabetes and sarcopenia. Univariate analysis revealed several risk factors for overall survival (OS), including male sex, an AAC volume ≥ 312 mm3, elevated carbohydrate antigen 19-9, prolonged operation time, increased intraoperative bleeding, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy. Multivariate analysis identified an AAC volume ≥ 312 mm3, prolonged operation time, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy as independent OS risk factors. The OS rate was significantly lower in the high AAC group than in the low AAC group. CONCLUSION: The AAC volume may serve as a preoperative prognostic indicator for patients with pancreatic cancer.

Sphingosine-1-phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy.

BACKGROUND AND AIMS: Chronic liver congestion reflecting right-sided heart failure (RHF), Budd-Chiari syndrome, or Fontan-associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood. APPROACH AND RESULTS: Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut-derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine-1-phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver. CONCLUSIONS: In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.

Right-Lateral Pringle Maneuver Using Endovascular Clip for Open and Laparoscopic Hepatectomy After Esophagectomy (with Video).

BACKGROUND: Laparoscopic hepatectomy after esophageal cancer surgery is a technically challenging procedure as it is difficult to control hepatic inflow due to adhesion 1. Ann Hepatobiliary Pancreat Surg. 22:344-349; 2. Dis Esophagus. 28:483-487; 3. Surg Endosc. 35:5375-5380; 4. Surg Laparosc Endosc Percutan Tech. 23:e103-105. Thus, we introduce our technique for hepatic inflow control using an endovascular clip. METHODS: After the confirmation of space between the right and dorsal side of the hepatoduodenal ligament and the inferior vena cava, an endovascular clip was introduced laterally from the right side of the hepatoduodenal ligament to control hepatic inflow. The control of hepatic inflow was confirmed using intraoperative Doppler ultrasound and then a hepatic parenchymal transection was performed. The video demonstrates our technique using an endovascular clip for hepatic inflow control to perform safe open or laparoscopic hepatectomy after esophageal cancer surgery. Patient 1 was an 82-year-old woman with a history of laparoscopic assisted esophagectomy for esophageal neuroendocrine cancer. She underwent open anatomical resection of segment 3 for a 38-mm liver tumor. Patient 2 was a 71-year-old man with a history of laparoscopic esophagectomy for esophageal cancer. He underwent laparoscopic partial resection of segment 6 for a 24-mm liver tumor. RESULTS: The operation times were 105 and 123 min, and the estimated blood loss was 30 g and 10 g, respectively. The patients' postoperative courses were uneventful and the patients were discharged on postoperative days 9 and 8, respectively. CONCLUSION: Right-lateral Pringle maneuver using an endovascular clip may be a safe and feasible technique in both open and laparoscopic hepatectomy after esophagectomy.