Pancreas-visceral fat CT value ratio and serrated pancreatic contour are strong predictors of postoperative pancreatic fistula after pancreaticojejunostomy.

BACKGROUND: Our aim is to elucidate the true preoperative risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), making it possible to select POPF high-risk patients preoperatively regardless of intraoperative pancreatic consistency judged by the surgeon's hand. METHODS: Among the 298 patients who underwent PD with pancreaticojejunostomy from 2007 to 2016, 262 patients had preoperative CT configurations that could be precisely evaluated. Risk factor analyses were conducted using various perioperative factors, including preoperative CT findings, such as CT values of the pancreas, pancreas-visceral fat CT value ratio and pancreatic outer contour. Pancreatic outer contour was further divided into smooth- (smooth interlobular) and serrated-type contours (feathery, irregular interlobular) by preoperative CT. RESULTS: In terms of the incidence of POPF, among the 262 patients, POPF grade B/C was found in 27 (10.3%): grade B in 23 (8.8%) and grade C in 4 (1.5%). According to multivariate analysis, a high pancreas-visceral fat CT value ratio (p = 0.002), serrated-type contour (p = 0.02) and no history of chemoradiotherapy (p = 0.019) were identified as independent risk factors for POPF grade B/C. Even in patients with soft pancreas, the incidence of POPF grade B/C was 0% (0/57) in patients with a pancreas-visceral fat CT value ratio of less than - 0.4 and smooth-type contour, whereas the incidence was markedly high (45.0%, 9/20) in patients with a pancreas-visceral fat CT value ratio of - 0.4 or greater and serrated-type contour, indicating that patients with soft pancreas should be categorized into POPF high-risk and low-risk groups according to preoperative CT scan results. CONCLUSIONS: The pancreas-visceral fat CT value ratio and serrated-type pancreas are useful markers to preoperatively identify true POPF high-risk groups in patients undergoing PD, regardless of the pancreatic texture judged intraoperatively.

The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

Clinical Significance of Plasma Apolipoprotein-AII Isoforms as a Marker of Pancreatic Exocrine Disorder for Patients with Pancreatic Adenocarcinoma Undergoing Chemoradiotherapy, Paying Attention to Pancreatic Morphological Changes.

BACKGROUND: Circulating apolipoprotein-AII (apoAII-) ATQ/AT is a potential useful biomarker for early stage pancreatic ductal adenocarcinoma (PDAC), but its clinical significance in PDAC patients remains uncertain. The aim of the current study was to assess the usefulness of apoAII-ATQ/AT as a surrogate for the effect of chemoradiotherapy (CRT) and its association with pancreatic exocrine disorder, paying attention to morphological changes of the pancreas. METHODS: In the 264 PDAC patients who were enrolled in our CRT protocol, the following parameters were measured at specified time points before and after CRT: serum levels of albumin, total cholesterol, and amylase as indices of pancreatic exocrine function, serum levels of CA19-9, and the pancreatic morphology including tumor size (TS), main pancreatic duct diameter (MPDD), and pancreatic parenchymal volume excluding tumor volume (PPV) by using computed tomography (CT) images. Plasma apoAII-ATQ/AT levels were simultaneously measured with enzyme-linked immunosorbent assay in 4 healthy volunteers and the 44 PDAC patients before and after CRT. Plasma apoAII-ATQ/AT levels after CRT were analyzed according to small/large-MPDD and small/large-PPV groups based on their median values after CRT. Plasma samples after CRT were measured after incubation with human pancreatic juice (PJ) to examine the relevance between apoAII isoforms and circulating pancreatic enzymes. RESULTS: The serum levels of albumin, amylase, CA19-9, TS, MPDD, and PPV after CRT were significantly lower than those before CRT (median, before vs. after: 3.9 g/dl, 74 U/l, 180.2 U/ml, 58.1 mm, 4.0 mm, and 34.8 ml vs. 3.8, 59, 43.5, 55.6, 3.6, and 25.2). ApoAII-ATQ/AT levels (median, µg/ml) of PDAC patients before CRT were significantly lower than those in healthy volunteers: 32.9 vs. 61.2, and unexpectedly those after CRT significantly decreased: 14.7. The reduction rate of apoAII-ATQ/AT was not correlated with those of CA19-9 and TS, indicating that apoAII-ATQ/AT is not a tumor-specific marker. On the other hand, the patient group with large MPDD and small PV exhibited higher apoAII-ATQ levels than those with small MPDD and large PPV. The incubation of plasma samples after CRT with PJ did not alter apoAII-ATQ/AT and apoAII-AT levels but significantly decreased apoAII-ATQ levels, suggesting that circulating pancreatic enzymes markedly influenced apoAII-ATQ levels. CONCLUSIONS: ApoAII-ATQ/AT levels are not useful for evaluation of clinical effect of CRT for PDAC, but apoAII isoforms are very useful to assess pancreatic exocrine disorder because pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes are considered likely to influence apoAII-ATQ levels.

Prognostic Nutritional Index After Chemoradiotherapy Was the Strongest Prognostic Predictor Among Biological and Conditional Factors in Localized Pancreatic Ductal Adenocarcinoma Patients.

Background: In many malignancies, including pancreatic ductal adenocarcinoma (PDAC), host-related inflammatory/immunonutritional markers, such as the prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and C-reactive protein (CRP)/albumin ratio are reported to be prognostic factors. However, the prognostic influence of these factors before and after chemoradiotherapy (CRT) has not been studied in PDAC patients. Methods: Of 261 consecutive PDAC patients who were scheduled for CRT with gemcitabine or S1 plus gemcitabine between February 2005 and December 2015, participants in this study were 176 who completed CRT and had full data available on inflammatory/immunonutritional markers as well as on anatomical and biological factors for the investigation of prognostic/predictive factors. Results: In multivariate analysis, the significant prognostic factors were RECIST classification, cT category, performance status, post-CRT carcinoembryonic antigen, post-CRT C-reactive protein/albumin ratio, post-CRT mGPS, and post-CRT PNI. Post-CRT PNI (cut-off value, 39) was the strongest host-related prognostic factor according to the p-value. In the patients who underwent resection after CRT, median survival time (MST) was significantly shorter in the 12 patients with low PNI (<39) than in the 97 with high PNI (≥39), at 15.5 months versus 27.2 months, respectively (p = 0.0016). In the patients who did not undergo resection, MST was only 8.9 months in those with low PNI and 12.3 months in those with high PNI (p < 0.0001), and thus was similar to that of the resected patients with low PNI. Conclusions: Post-CRT PNI was the strongest prognostic/predictive indicator among the independent biological and conditional prognostic factors in PDAC patients who underwent CRT.

The clinical impact of portal venous patency ratio on prognosis of patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy with combined resection of portal vein following preoperative chemoradiotherapy.

We analyzed the significance of portal vein (PV) patency ratio (minimum diameter/maximum diameter) during preoperative chemoradiotherapy (CRT) on the outcomes of patients with pancreatic-ductal adenocarcinoma (PDAC). METHODS: The 261 PDAC patients had been prospectively registered to our CRT protocol (Gemcitabine or S1+Gemcitabine) from 2005 to 2015. Among them, the subjects were the 84 PDAC- patients with preoperative PV contact who underwent pancreatectomy with PV resection. RESULTS: The 3- and 5-year disease-specific survival (DSS) rates of all 84 patients were 44% and 39%, respectively. Pathological PV invasion (pPV) was seen in 22, and PV patency ratio after CRT (cut-off:0.62) was most relevant factor to predict pPV (sensitivity:54.8%, specificity:91.9%, accuracy:81.5%). Multivariate analysis revealed that PV patency ratio after CRT and improvement of PV patency ratio were selected as independent prognostic indicators. The 3- and 5-year DSS in 39 patients with PV patency ratio after CRT >0.6 were significantly higher than those in 45 patients <0.6: 65% and 60% vs. 24% and 20% (p = 0.0001). The patients with PV patency ratio >0.6, were significantly associated with the lower incidence of pPV, higher response for CRT, and better R0 resection rate. Even when severe PV strictures were seen before CRT, DSS of the patients whose PV patency ratio had recovered after CRT was excellent compared with those without improvement. CONCLUSIONS: The PV patency ratio and its improvement are new prognostic indicators for PDAC treated with preoperative CRT. Even when PV was severely constricted, patients could obtain favorable outcomes, if its patency had recovered after CRT.

Comparative Study Between Gemcitabine-Based and Gemcitabine Plus S1-Based Preoperative Chemoradiotherapy for Localized Pancreatic Ductal Adenocarcinoma, With Special Attention to Initially Locally Advanced Unresectable Tumor.

OBJECTIVES: To evaluate clinical/histological response and prognosis between preoperative gemcitabine-based chemoradiation therapy (G-CRT) and gemcitabine plus S1-based CRT (GS-CRT) for localized pancreatic ductal adenocarcinoma patients according to the 3 resectability groups. METHODS: Among 199 patients who had 90% or more relative dose intensity of chemotherapy and completion of radiotherapy preoperatively (G-CRT: 98 and GS-CRT: 101), the subjects were 113 patients (G-CRT: 60 and GS-CRT: 53) who underwent curative-intent resection, and we compared clinical and histological effects between the 2 regimens. RESULTS: There is a significant improvement in clinical and histological responses as assessed by reduction rate in tumor size, post-CRT serum level of carbohydrate antigen 19-9, and the ratio of histological high responder according to the Evans grading system in GS-CRT, as compared with G-CRT, which in turn significantly increased R0 resection rate (P = 0.013). These effects of GS-CRT resulted in significant improvement of disease-specific survival (median survival time, 36.0 vs 27.2 months; P = 0.042), especially in patients with unresectable locally advanced disease (36.0 vs 18.1 months, P = 0.014). CONCLUSIONS: For localized pancreatic ductal adenocarcinoma patients, GS-CRT, as compared with G-CRT, provides significant improvement in clinical and histological response as well as long-time survival, especially in patients with unresectable locally advanced disease.

The Critical Role of Biliary Candidiasis in Development of Surgical Site Infections after Pancreatoduodenectomy: Results of Prospective Study Using a Selective Culture Medium for Candida Species.

In accordance with previous reports, the incidence of biliary candidiasis (BC) after pancreaticoduodenectomy (PD) was reported to be 0 to 5%, and the clinical significance of BC still has been elusive. In this study, we prospectively evaluated the precise incidence of BC after PD using the CHROMagar Candida plate in an attempt to elucidate whether BC has a significant impact on the clinical outcomes after PD. Patients and Method. From November 2014 to March 2016, the consecutive 51 patients who underwent PD were enrolled for this study. The bile juice was prospectively collected through the biliary stent tube on postoperative days (POD) 3, 7, and 14 and directly incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. In the presence or absence of BC, we compared the incidence of SSIs. Results. The incidence of postoperative BC was 15% on POD 3, 24% on POD 7, and 39% on POD 14, respectively. Taken together, 22 patients out of 51 (43.1%) developed BC after PD. Moreover, the incidence of SSIs was significantly higher in patients with BC than in those without it (71% versus 7%, p=0.005). BC was selected as the only significant risk factor of SSIs after PD among the various risk factors. Even though a cause of BC is unknown, high level of alkaline phosphatase (cut-off line >300 IU/L) was selected as the only preoperative risk factor of the development of BC. Conclusion. We elucidated new evidence in which BC could be the independent cause of SSIs after PD and should not be recognized as just contamination artifacts. Preoperative assessment for identifying carriers of Candida species might be essential for reducing the incidence of SSIs after PD.

Survival Analysis in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Chemoradiotherapy Followed by Surgery According to the International Consensus on the 2017 Definition of Borderline Resectable Cancer.

Background: The aim of this study was to validate a new definition of borderline resectable pancreatic ductal adenocarcinoma (PDAC) provided by the 2017 international consensus on the basis of three dimensions of anatomical (A), biological (B), and conditional (C) factors, using the data of the patients who had been registered for our institutional protocol of chemoradiotherapy followed by surgery (CRTS) for localized patients with PDAC. Methods: Among 307 consecutive patients pathologically diagnosed with localized PDAC who were enrolled in our CRTS protocol from February 2005 to December 2016, we selected 285 patients who could be re-evaluated after CRT. These 285 patients were classified according to international consensus A definitions as follows: R (resectable; n = 62), BR-PV (borderline resectable, superior mesenteric vein (SMV)/portal vein (PV) involvement alone; n = 27), BR-A (borderline resectable, arterial involvement; n = 50), LA (locally advanced; n = 146). Disease-specific survival (DSS) was analyzed according to A, B (serum CA 19-9 levels and lymph node metastasis diagnosed by computed tomography findings before CRT), and C factors (performance status (PS)) factors. Results: The rates of resection and R0 resection were similar between R (83.9 and 98.0%) and BR-PV (85.2 and 95.5%), but much lower in BR-A (70.0 and 84.8%) and LA (46.6 and 62.5%). DSS evaluated by median survival time (months) showed a similar trend to surgical outcomes: 33.7 in R, 27.3 in BR-PV, 18.9 in BR-A and 19.3 in LA, respectively. DSS in R patients with CA 19-9 levels > 500 U/mL was significantly poorer than in patients with CA 19-9 levels ≤ 500 U/mL, but there were no differences in DSS among BR-PV, BR-A, and LA patients according to CA 19-9 levels. Regarding lymph node metastasis, there was no significant difference in DSS according to each resectability group. DSS in R patients with PS ≥ 2 was significantly worse than in patients with PS 0-1. Conclusions: The international consensus on the definition of BR-PDAC based on three dimensions of A, B, and C is useful and practicable because prognosis of PDAC patients is influenced by anatomical factors as well as biological and conditional factors, which in turn may help to decide treatment strategy.

Clinical Significance of Histological Effect and Intratumor Stromal Expression of Tenascin-C in Resected Specimens After Chemoradiotherapy for Initially Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC. METHODS: Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction >50%) and low (≤50%) responders according to the Evans grading system. Tenascin-C expression was immunohistologically evaluated in all patients except one with complete response. RESULTS: The 12 high responders achieved a significantly higher R0 rate than did the 34 low responders (83.3 vs 47.1%), but disease-specific survival (DSS) time was not significantly different (median survival time, 29.8 vs 21.0 months). Tenascin-C expression was inversely correlated with histologic effect of CRT. The 22 patients with negative TN-C had significantly longer DSS time than did the 23 with positive TN-C (29.3 vs 17.1 months). In multivariate analysis, only TN-C expression was a significant prognostic factor for DSS. CONCLUSIONS: Intratumor stromal expression of TN-C is a strong prognostic indicator in UR-LA PDAC patients with resection after CRT.

Incidence and Risk Factors of Postoperative Delirium following Pancreatic Surgery: Does the Administration of TJ-54 Reduce the Incidence of Delirium.

PURPOSES: To clarify the incidence and risk factors of postoperative delirium in patients following pancreatic surgery, and the impact of yokukansan (TJ-54) administered to reduce delirium. METHODS: Fifty-nine consecutive patients who underwent pancreatic surgery (2012.4-2013.5) were divided into 2 groups: TJ-54 group: patients who received TJ-54 (n = 21) due to insomnia and the No-TJ-54 group: patients who did not receive TJ-54 (n = 38), and the medical records including the delirium rating scale - Japanese version (DRS-J) were retrospectively reviewed. RESULTS: Postoperative delirium occurred in 2 patients (9.5%) in the TJ-54 group and in 4 (10.5%) patients in the No-TJ-54 group (p = 0.90). The DRS-J on 5 days after surgery was lower in the TJ-54 group than in the No-TJ-54 group (rough p = 0.006), however, without any statistically significant differences with the Bonferroni correction. As for the hospital cost, there was no difference between the TJ-54 and the No-TJ-54 groups (p = 0.78). History of delirium was identified as an independent risk factor of postoperative delirium. CONCLUSION: The patients with preoperative insomnia, who were treated with TJ-54, did not have a higher incidence of postoperative delirium, compared to those without preoperative insomnia. The patients who had a history of delirium have an increased risk of postoperative delirium and should be cared for and treated prophylactically to prevent it.

Long-term outcomes after pancreaticoduodenectomy using pair-watch suturing technique: Different roles of pancreatic duct dilatation and remnant pancreatic volume for the development of pancreatic endocrine and exocrine dysfunction.

BACKGROUND: We evaluated long-term outcomes including endo- and exocrine functions after pancreaticoduodenectomy (PD) with standardized pancreaticojejunostomy, paying attention to postoperative pancreatic duct dilatation (PDD) and remnant pancreatic volume (RPV), and examined whether postoperative pancreatic fistula (POPF) influenced the configuration of remnant pancreas. METHODS: We analyzed the records of 187 patients with PD who could have RPV measured by CT volumetry at 1 month after operation and had been followed for more than 6 months. We assessed the risk factors of diabetes mellitus (DM) and PDD, and evaluated association between RPV and pancreatic endo- and exocrine functions assessed by several markers such as albumin, cholesterol, amylase and HbA1c. RESULTS: Regarding RPV, pancreatic exocrine functions were significantly impaired in the small-volume group (SVG: less than 10 ml) than in the large-volume group (LVG: 10 ml or more). The incidence of new-onset or exacerbation of DM did not differ between SVG and LVG. PDD and the primary disease (pancreatic ductal adenocarcinoma compared to bile duct cancer) were selected as the independent risk factors of new-onset or exacerbation of DM by multivariate analysis. Unexpectedly, there was no significant association between POPF and PDD. CONCLUSIONS: Early occurrence of POPF after PD did not influence the development of PDD in late period, and long-term follow-up should be made by paying attention to PDD and RPV, because PDD was recognized as the most important risk factor of new-onset or exacerbation of DM and the patients with small RPV suffered from prolonged exocrine dysfunction rather than endocrine dysfunction.

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study.

OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute pancreatitis (SAP) according to the segment presenting with low enhanced pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography. METHODS: This was a post hoc analysis of a multicenter, retrospective study conducted at 44 institutions in Japan. Patients diagnosed as having SAP according to the Japanese Severity Score between January 2009 and December 2013 were included. We compared the effect of LEPP in each segment on mortality. RESULTS: A total of 1097 patients were assessed. The numbers of patients with LEPP in the pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was significantly related to mortality (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67 [P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70; 95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early contrast-enhanced computed tomography was independently associated with increased mortality in SAP. These patients require close observation to ensure timely and adequate intervention.

Superiority of stapled side-to-side gastrojejunostomy over conventional hand-sewn end-to-side gastrojejunostomy for reducing the risk of primary delayed gastric emptying after subtotal stomach-preserving pancreaticoduodenectomy.

BACKGROUND AND PURPOSE: Delayed gastric emptying (DGE) is the most common complication following pancreaticoduodenectomy (PD). The clinical efficacy of stapled side-to-side anastomosis using a laparoscopic stapling device during alimentary reconstruction in PD is not well understood and its superiority over conventional hand-sewn end-to-side anastomosis remains controversial. The objective of this study was to evaluate the effectiveness of the stapled side-to-side anastomosis in preventing the development of DGE after PD. METHODS: The subjects of this retrospective study were 137 patients who underwent pancreaticoduodenectomy, as subtotal stomach-preserving pancreaticoduodenectomy (SSPPD; n = 130), or conventional whipple procedure (n = 7) with Child reconstruction, between January 2010 and May 2014. The patients were divided into two groups according to whether they had had a stapled side-to-side anastomosis (SA group; n = 57) or a conventional hand-sewn end-to-side anastomosis (HA group; n = 80). RESULTS: SA reduced the operative time (SA vs. HA: 508 vs. 557 min, p = 0.028) and the incidence of delayed gastric emptying (SA vs. HA: 21.1 vs. 46.3%, p = 0.003) and was associated with shorter hospitalization (SA vs. HA: 33 vs. 39.5 days, p = 0.007). In this cohort, SA was the only significant factor contributing to a reduction in the incidence of DGE (p = 0.002). CONCLUSIONS: Stapled side-to-side gastrojejunostomy reduced the operative time and the incidence of DGE following PD with Child reconstruction, thereby also reducing the length of hospitalization.

Role of spleen in hepatic ischemia reperfusion injury: Splenic congestion during ischemia accelerates leukocyte infiltration within the liver after reperfusion.

AIM: The precise mechanism by which prophylactic splenectomy reduces hepatic ischemia-reperfusion injury (IRI) are still unclear. In this study, we focused on the histological changes of spleen during hepatic IRI, and tested how splenectomy provided cytoprotective effects against hepatic IRI. METHODS: Rats underwent 70% warm hepatic IRI with or without splenectomy prior to IRI. To determine whether splenic congestion by itself induces liver damage in the absence of hepatic IRI, we also undertook a splenic vein clamp model. RESULTS: Liver injury and macrophage and neutrophil infiltration into the liver after reperfusion were significantly depressed in the animals with prophylactic splenectomy, compared to those without splenectomy. Histology of the spleens showed noted congestion during hepatic ischemia (hepatic hilar clamp), which promptly disappeared after declamping. At 6 and 24 h after reperfusion, the spleens showed remarkable recongestion and parenchymal damage, and the splenic venous level of interleukin-2, which is secreted by T cells and enhances macrophage recruitment, and its mRNA levels within the spleen were significantly elevated. In the splenic vein clamp model, the splenic vein clamp by itself produced a certain liver injury and macrophage infiltration within liver even without hepatic IRI. CONCLUSION: Spleen plays an important role as an accelerator in hepatic IRI, because splenic congestion and parenchymal damage during ischemia-reperfusion promote splenic IL-2 excretion and macrophage infiltration within the liver, which in turn exacerbate hepatic injury.

Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of Early Judgment of Resectability and Safe Vascular Reconstruction.

In the most common surgical procedure for perihilar cholangiocarcinoma, the margin status of the proximal bile duct is determined at the final step. Our procedure, the transhepatic hilar approach, confirms a cancer-negative margin status of the proximal bile duct first. We first performed a partial hepatic parenchymal transection to expose the hilar plate, and then transected the proximal bile duct to confirm margin status. Then, divisions of the hepatic artery and portal vein of the future resected liver are performed, followed by the residual hepatic parenchymal transection. The transhepatic hilar approach offers a wide surgical field for safe resection and reconstruction of the portal vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011 to 2015. A combined vascular resection and reconstruction was carried out in 14 patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the overall 3-year survival rate was 52.9% (median survival time 52.4 months). The transhepatic hilar approach is useful and practicable regardless of local tumor extension, enabling us to determine tumor resectability and perform safe resection and reconstruction of the portal vein early in the operation.

A Novel Predictor of Posttransplant Portal Hypertension in Adult-To-Adult Living Donor Liver Transplantation: Increased Estimated Spleen/Graft Volume Ratio.

BACKGROUND: In adult living donor liver transplantation (ALDLT), graft-to-recipient weight ratio of less than 0.8 is incomplete for predicting portal hypertension (>20 mm Hg) after reperfusion. We aimed to identify preoperative factors contributing to portal venous pressure (PVP) after reperfusion and to predict portal hypertension, focusing on spleen volume-to-graft volume ratio (SVGVR). METHODS: In 73 recipients with ALDLT between 2002 and 2013, first we analyzed survival according to PVP of 20 mm Hg as the threshold, evaluating the efficacy of splenectomy. Second, we evaluated various preoperative factors contributing to portal hypertension after reperfusion. RESULTS: All of the recipients with PVP greater than 20 mm Hg (n = 19) underwent PVP modulation by splenectomy, and their overall survival was favorable compared with 54 recipients who did not need splenectomy (PVP ≤ 20 mm Hg). Graft-to-recipient weight ratio had no correlation with PVP.Multivariate analysis revealed that estimated graft and spleen volume were significant factors contributing to PVP after reperfusion (P < 0.0001 and P < 0.0001, respectively). Furthermore, estimated SVGVR showed a significant negative correlation to PVP after reperfusion (R = 0.652), and the best cutoff value for portal hypertension was 0.95. CONCLUSIONS: In ALDLT, preoperative assessment of SVGVR is a good predictor of portal hypertension after reperfusion can be used to indicate the need for splenectomy before reperfusion.

Factor Analysis Influencing Postoperative Hospital Stay and Medical Costs for Patients with Definite, Suspected, or Unmatched Diagnosis of Acute Cholecystitis according to the Tokyo Guidelines 2013.

Purpose. To identify significant independent preoperative factors influencing postoperative hospital stay (PHS) and medical costs (MC) in 171 patients who underwent cholecystectomy for benign gallbladder diseases and had definite, suspected, or unmatched acute cholecystitis (AC) diagnosis according to the Tokyo Guidelines 2013 (TG13). Methods. The 171 patients were classified according to the combination of diagnostic criteria including local signs of inflammation (A), systemic signs of inflammation (B), and imaging findings (C): A+ B+ C (definite diagnosis, n = 84), A+ B (suspected diagnosis, n = 25), (A or B) + C (n = 10), A (n = 41), and B (n = 11). Results. The A+ B + C and (A or B) + C groups had equivalent PHS and MC, suggesting that imaging findings were essential for AC diagnosis. PHS and MC were significantly increased in the order of severity grades based on TG13. Performance status (PS), white blood cell count, and severity grade were identified as preoperative factors influencing PHS by multivariate analysis, and significant independent preoperative factors influencing MC were age, PS, preoperative biliary drainage, hospital stay before surgery, albumin, and severity grade. Conclusion. PS and severity grade significantly influenced prolonged PHS and increased MC.

Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury.

UNLABELLED: Activated protein C (APC) has cytoprotective effects on liver ischemia-reperfusion injury (IRI). However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI. METHODS: Mice fed either normal diets (ND mice) or high fat diets (HF mice), were treated with APC or saline (control) and were performed 60 min partial IRI. Moreover, primary steatotic hepatocytes were either untreated or treated with APC and then incubated with H2O2. RESULTS: APC significantly reduced serum transaminase levels and the inflammatory cells infiltration compared with control at 4 h in ND mice and at 24 h in HF mice. APC inhibited sinusoidal endothelial injury in ND mice, but not in HF mice. In contrast, APC activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HF mice, but not in ND mice. In the in vitro study, APC significantly increased AMPK phosphorylation, ATP concentration, and survival rates of hepatocytes compared with control. CONCLUSION: During IRI in normal liver, APC attenuated initial damage by inhibiting inflammatory cell infiltration and sinusoidal endothelial injury, but not in steatotic liver. However, in steatotic liver, APC might attenuate late damage via activation of AMPK.