Role of Serum Carcinoma Embryonic Antigen (CEA) Level in Localized Pancreatic Adenocarcinoma: CEA Level Before Operation is a Significant Prognostic Indicator in Patients With Locally Advanced Pancreatic Cancer Treated With Neoadjuvant Therapy Followed by Surgical Resection: A Retrospective Analysis.

OBJECTIVE: The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. SUMMARY OF BACKGROUND DATA: Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. MATERIALS AND METHOD: From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. RESULTS: In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CONCLUSIONS: CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

Association between gastric Candida colonization and surgical site infections after high-level hepatobiliary pancreatic surgeries: the results of prospective observational study.

AIM: High-level hepatobiliary pancreatic (HBP) surgeries are highly associated with surgical site infections (SSIs), in which microorganisms have a significant role. In the present study, we investigated whether gastric Candida colonization had a significant role in SSIs after high-level HBP surgeries. METHODS: Between May 2016 and February 2017, the 66 patients who underwent high-level HBP surgeries were enrolled in the present study. The gastric juice was prospectively collected through nasogastric tube after general anesthesia induction and was incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. First of all, we compared the incidence of SSIs according to the presence or absence of Candida species in gastric juice. Secondly, we evaluated the variables contributing to the development of SSIs by multivariate analysis. The protocol was approved by the medical ethics committee of Mie University Hospital (No.2987). RESULTS: Gastric Candida colonization was identified in 21 patients (group GC) and was not identified in the other 45 patients (group NGC). There were no differences in preoperative variables including compromised status, such as age, nutritional markers, complications of diabetes mellitus, and types of primary disease between the two groups. SSIs occurred in 57.1% (12/21) of group GC and in 17.8% (8/45) of group NGC, showing a significant difference (p = 0.001). Multivariate analysis revealed gastric Candida colonization as a significant risk factor of SSIs (OR 6.17, p = 0.002). CONCLUSION: Gastric Candida colonization, which is not a result of immunocompromised status, is highly associated with SSIs after high-level HBP surgeries. TRIAL REGISTRATION: Japan Primary Registries Network; UMIN-CTR ID: UMIN000040486 (retrospectively registered on 22nd May, 2020).

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status.

BACKGROUND: The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. METHODS: Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. RESULTS: Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. CONCLUSION: Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection.

BACKGROUND: Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. METHODS: Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). RESULTS: In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). CONCLUSION: This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

Prolonged operating time is a significant perioperative risk factor for arterial pseudoaneurysm formation and patient death following hemorrhage after pancreaticoduodenectomy.

BACKGROUND: Arterial pseudoaneurysm is a rare but potentially fatal complication after pancreaticoduodenectomy (PD). This study aimed to evaluate the incidence and predictors associated with pseudoaneurysm formation and patient death caused by its rupture. PATIENTS AND METHOD: We retrospectively reviewed the data of 453 patients who underwent PD from April 2007 to February 2019. Uni- and multivariate analysis and receiver operating characteristic (ROC) curve analysis were performed to identify risk factors and optimal cutoff values. RESULTS: Among the 453 patients, 22 (4.9%) developed pseudoaneurysm after PD. Median duration from surgery to detection of pseudoaneurysm was 17.0 (1-51) days. The locations of pseudoaneurysms were hepatic artery in 8, splenic artery in 3, gastroduodenal artery in 4, gastric artery in 2 and others in 5 patients, and 72.7% (16/22) of patients presented with hemorrhage. All pseudoaneurysms were treated using angioembolization. Lower age (<65.5 years, p = 0.004), prolonged operation time (Cutoff ˃610 min, p = 0.026) and postoperative pancreatic fistula (POPF) (p = 0.013) were the independent risk factors for development of pseudoaneurysm. 6 (27.3%) patients died due to rupture of pseudoaneurysm and prolonged operation time (Cutoff ˃657 min, p = 0.043) was a significant risk factor for death related to pseudoaneurysm. CONCLUSION: Prolonged operating time was identified as a risk factor for both pseudoaneurysm formation and patient death following pseudoaneurysm bleeding. Interventional radiology treatment offered a central role in the treatment of pseudoaneurysms after PD. Therefore, it is important to have a high index of suspicion in high risk patients of the possibility of pseudoaneurysm formation and bleeding.

Influence of muscle mass on the estimation of glomerular filtration rate in Japanese terminal cancer patients.

BACKGROUND: Estimated glomerular filtration rate (eGFR) based on serum cystatin C (Scys) is useful for patients with decreased muscle mass, but has been also reported to be affected by cancer. The usefulness of Scys in eGFR in terminal cancer patients with decreased muscle mass is unknown. Therefore, we analyzed appropriate eGFR formulae for terminal cancer patients. METHODS: Study design was a retrospective observational study. Based on creatinine height index (CHI), 184 terminal cancer patients were stratified into CHI ≥ 90% (normal muscle mass, 59 patients); CHI 60-89% (mildly to moderately decreased muscle mass, 64 patients); and CHI < 60% (severely decreased muscle mass, 61 patients) groups. Twenty-four-hour creatinine clearance was measured and converted to the glomerular filtration rate (GFR) as a renal function measure. To estimate GFR, various eGFR formulae for Japanese were used: eGFRScys, eGFRScr5 and eGFRScr3, eGFRaverage and eGFRScys-Scr, and eGFRCG, based on Scys, serum creatinine (Scr), Scys and Scr combined, and Cockcroft-Gault formula (CG), respectively. Errors between measured and estimated values of renal function were verified using mean prediction errors (ME). When a 95% confidence interval (CI) of ME included 0, the accuracy of the eGFR formula was graded as good. RESULTS: eGFRScys ME was 0.2 (95% CI lower limit - 3.7, upper limit 4.0) mL/min/1.73 m2 in CHI 60-89% group and 9.2 (6.1, 12.9) mL/min/1.73 m2 in CHI < 60% group. eGFRScys was most accurate among the eGFR formulae. CONCLUSIONS: eGFR based on Scys was demonstrated as useful in terminal cancer patients with decreased muscle mass.

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 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.

A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus.

BACKGROUND: Much evidence has demonstrated the influence of Hepatitis B virus (HBV) mutations on the clinical course of HBV infection. As large (L) protein plays a crucial role for viral entry, we hypothesized that mutations in the pre-S1 promoter region might affect the expression of L protein and subsequently change the biological characters of virus. METHODS: Patients infected with genotype C HBV were enrolled for analysis. HBV DNA sequences were inserted into a TA cloning vector and analyzed. To evaluate the effects of mutations in the pre-S1 promoter region, promoter activity and the expression of mRNA and L protein were analyzed using HepG2 cells. RESULTS: In total, 35 patients were enrolled and 13 patients (37.1%) had a single base substitution in the pre-S1 promoter region; the most frequent substitution was a G-to-A substitution at the 2765th base (G2765A) in the Sp1 region. The HBV viral load showed a negative correlation with the substitution ratio of the Sp1 region or G2765A (r = - 0.493 and - 0.473, respectively). Among those with a viral load ≤5.0 log IU/ml, patients with the G2765A substitution showed a significantly lower HBV viral load than those with the wild-type sequence. HepG2 cells transfected with the G2765A substitution vector showed reduced luciferase activity of the pre-S1 promoter, as well as reduced expression of pre-S1 mRNA and L protein. Furthermore, the G2765A substitution greatly reduced the L protein expression level of vector-produced virus particles. CONCLUSION: G2765A substitution in the pre-S1 promoter reduced the expression of L protein and resulted in a low viral load and less severe disease in chronic HBV infections.

Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury.

BACKGROUND: Functional and structural damages in sinusoidal endothelial cells (SECs) have a crucial role during hepatic ischemia-reperfusion injury (IRI). In regulating endothelial function, sphingosine-1-phosphate receptor 1 (S1PR1), which is a G protein-coupled receptor, has an important role. The present study aimed to clarify whether SEW2871, a selective S1PR1 agonist, can attenuate hepatic damage caused by hepatic IRI, focusing on SEC functions. METHODS: In vivo, using a 60-min partial-warm IRI model, mice were treated with SEW2871 or without it (with vehicle). In vitro, isolated SECs pretreated with SEW2871 or without it (with vehicle) were incubated with hydrogen peroxide. RESULTS: Compared with the IRI + vehicle group, SEW2871 administration significantly improved serum transaminase levels and liver damage, attenuated infiltration of Ly-6G and mouse macrophage antigen-1-positive cells, suppressed the expression of vascular cell adhesion molecule-1 and proinflammatory cytokines in the liver, and enhanced the expressions of endothelial nitric oxide synthase (eNOS) and vascular endothelial (VE) cadherin in the liver (eNOS/ß-actin [median]: 0.24 versus 0.53, P = 0.008; VE-cadherin/ß-actin [median]: 0.21 versus 0.94, P = 0.008). In vitro, compared with the vehicle group, pretreatment of SECs with SEW2871 significantly increased the expressions of eNOS and VE-cadherin (eNOS/ß-actin [median]: 0.22 versus 0.29, P = 0.008; VE-cadherin/ß-actin [median]: 0.38 versus 0.67, P = 0.008). As results of investigation of prosurvival signals, SEW2871 significantly increased Akt phosphorylation in SECs and decreased lactate dehydrogenase levels in supernatants of SECs. CONCLUSIONS: These results indicate that S1PR1 agonist induces attenuation of hepatic IRI, which might be provided by preventing SEC damage. S1PR1 may be a therapeutic target for the prevention of early sinusoidal injury after hepatic IRI.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

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.

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.

Significance of Simultaneous Splenic Artery Resection in Left-Sided Portal Hypertension After Pancreaticoduodenectomy with Combined Portal Vein Resection.

BACKGROUND: In pancreaticoduodenectomy (PD) with resection of portal vein (PV)/superior mesenteric vein (SMV) confluence, the splenic vein (SV) division may cause left-sided portal hypertension (LPH). METHODS: The 88 pancreatic ductal adenocarcinoma patients who underwent PD with PV/SMV resection after chemoradiotherapy were classified into three groups: both SV and splenic artery (SA) were preserved in Group A (n = 16), SV was divided and SA was preserved in Group B (n = 58), and both SV and SA were divided in Group C (n = 14). We evaluated the influence of resection of SV and/or SA on LPH after PD with resection of PV/SMV confluence. RESULTS: The incidence of postoperative varices in Groups A, B and C was 6.3, 67.2 and 38.5%, respectively (p < 0.001), and variceal bleeding occurred only in Group B (n = 4: 6.8%). In multivariate analysis, Group B was the only significant risk factor for the development of postoperative varices (Groups B vs. A: odds ratio = 39.6, p = 0.001, Groups C vs. A: odds ratio = 8.75, p = 0.066). The platelet count ratio at 6 months after operation comparing to preoperative value was 0.93, 0.73 and 1.09 in Groups A, B and C, respectively (Groups B vs. C: p < 0.05), and spleen volume ratio at 6 months was 1.00, 1.37 and 0.96 in Groups A, B and C, respectively (Groups B vs. A and C: p < 0.01 and p < 0.05). CONCLUSION: In PD with resection of PV-SMV confluence, the SV division causes LPH, but the concomitant division of SV and SA may attenuate it.

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.

Benefit of technetium-99m galactosyl human serum albumin scintigraphy instead of indocyanine green test in patients scheduled for hepatectomy.

AIM: The aim of this study was to evaluate the benefit of technetium-99m galactosyl human serum albumin ((99m) Tc-GSA) scintigraphy instead of the indocyanine green retention rate at 15 min (ICGR15) in the patients scheduled for hepatectomy, paying special attention to the factors causing the discrepancy between the ICGR15 and the hepatic uptake ratio of (99m) Tc-GSA scintigraphy at 15 min (LHL15). METHODS: The medical records on the 197 patients who underwent hepatectomy between 2006 and 2010 were retrospectively reviewed. We defined ICG-good as less than 15% at ICGR15 and ICG-poor as 15% or more, and LHL-good as 0.9 or more at LHL15 and LHL-poor as less than 0.9. RESULTS: The patients were divided into the four groups ICG-good/LHL-good, ICG-good/LHL-poor, ICG-poor/LHL-good and ICG-poor/LHL-poor, showing the discrepancy between the two tests in 47 (23.8%) patients. In the ICG-good group, the incidence of liver cirrhosis (LC) was significant higher in the ICG-good/LHL-poor group than in the ICG-good/LHL-good group at 54.5% versus 14.9% (P = 0.014). In the ICG-poor group, the incidence of LC was significant lower in the ICG-poor/LHL-good group than in the ICG-poor/LHL-poor group at 44.4% versus 77.8% (P = 0.004). In multivariate analysis of the factors causing discrepancy, the factor contributing to LHL-poor was hepatitis C infection and those contributing to LHL-good were albumin and hyaluronic acid. CONCLUSION: (99m) Tc-GSA scintigraphy is very helpful to assess the hepatic functional reserve in the ICG-good patients who have hepatitis C infection and in the ICG-poor patients who have relatively good levels of albumin and hyaluronic acid.

Splenectomy increases the number of circulating hematopoietic stem/progenitor cells in patients with hepatitis C virus-associated liver cirrhosis.

AIM: The spleen is not believed to contribute to hematopoiesis in healthy adults. However, several reports have demonstrated that the spleen in adults contains a large number of hematopoietic stem/progenitor cells (HSC). Although splenectomy increases platelet and leukocyte counts, the effects of splenectomy on circulating HSC have not been elucidated. In this study, we evaluated the association between the number of circulating HSC and splenectomy in patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC). METHODS: In 48 patients with various stages of HCV-associated chronic liver disease and seven patients with LC who underwent splenectomy, and 10 healthy volunteers, we determined the numbers of circulating CD34+ cells and colony-forming unit culture by flow cytometry and methylcellulose culture, respectively. Plasma stromal cell-derived factor-1α (SDF-1α) concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: The numbers of circulating CD34+ cells and colony-forming unit culture decreased but the plasma SDF-1α concentration increased with the progression of liver disease. There was an inverse correlation between the number of circulating HSC and the plasma SDF-1α concentration. The numbers of circulating HSC and platelets were determined before and after splenectomy in seven patients with LC. In these patients, the numbers of circulating HSC and platelets increased significantly after splenectomy and the enhancing effect persisted for a long time. CONCLUSION: Our data suggest that the spleen plays an important role in modulating HSC dynamics in patients with HCV-associated chronic liver disease. Our results also imply that splenectomy may improve liver function in patients with LC.

[Studies on the distribution of doripenem in pancreatic tissues, especially on the importance of the ratio in pancreatic tissue concentration of doripenem/serum concentration of doripenem].

Doripenem (DRPM) which is injectable carbapenem antimicrobial agent is a compound with high antimicrobial activity against severe acute pancreatitis in carbapenem agents. It does not have a report of the distribution in human pancreatic tissue until now. This time, we performed examination about the distribution in pancreatic tissue of DRPM. Blood and pancreatic tissues were collected from six patients who were administered DRPM intravenously at a dose of 0.5 g after 1 hour from the start of injection. The concentration of DRPM in the serum and pancreatic tissues were measured. The concentrations of DRPM in the pancreatic tissues and serum were 0.58-5.39 microg/g and 0.02-0.24 microg/mL, respectively. DRPM distributed in pancreatic tissues sufficiently, and we could expect that DRPM was useful agent of pancreas infection in acute pancreatitis.

Changes in oral health status in terminal cancer patients during the last weeks of life.

BACKGROUND: Many studies have shown deterioration of the oral health environment in palliative care patients; however, most of these studies are cross-sectional. In this longitudinal observational study, we aimed to determine the oral symptoms and how they change in palliative care patients. METHODS: The participants were 82 patients (37 men, 45 women) admitted to two palliative care units in Japan between January 2018 and December 2021. The oral condition was evaluated once a week from the time of admission using the Oral Health Assessment Tool (OHAT) and performance status (PS). Friedman tests were performed on the OHAT and PS scores at 1, 2, and 3 weeks before the week of death. In addition, the Bonferroni method was used to determine how many weeks before death the changes occurred. RESULTS: PS continuously deteriorated from three weeks before death. The total OHAT score 2 weeks before death (3.44±2.10) was significantly different compared to that in the week of death (4.37±2.45). In terms of oral conditions, the properties of the saliva changed, and dry mouth became obvious. CONCLUSIONS: The results of this study revealed that the oral environment of palliative care patients became significantly dry 2 weeks before death, suggesting that it may be useful for predicting the stage of death.