The cachexia index is a prognostic factor for patients with recurrent pancreatic cancer.

PURPOSE: Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer. METHODS: This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival. RESULTS: The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6 months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011). CONCLUSIONS: The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Evaluation of perioperative D-dimer concentration for predicting postoperative deep vein thrombosis following hepatobiliary-pancreatic surgery.

PURPOSE: This study was performed to investigate the predictive value of the perioperative D-dimer concentration for the development of postoperative deep vein thrombosis (DVT) after hepatobiliary-pancreatic (HBP) surgery. METHODS: The subjects of this retrospective study were 178 patients who underwent HBP surgery in our hospital between January, 2017 and December, 2021. The D-dimer concentration was measured preoperatively and on postoperative days (POD) 1, 3, and 5. Postoperative DVT was diagnosed based on compression ultrasonography in both lower limbs on POD 6 or 7. RESULTS: Postoperative DVT developed in 21 (11.8%) of the 178 patients. The D-dimer concentration was significantly higher in the patients with than in those without postoperative DVT before surgery and on PODs 1, 3, and 5. The highest area under the curve of the D-dimer concentration for predicting DVT was 0.762 on POD 3. Multivariate analysis revealed that the D-dimer concentration on POD 3 was an independent predictive risk factor for postoperative DVT, along with the preoperative estimated glomerular filtration rate. Preoperative albumin and D-dimer concentrations were also identified as independent predictive factors of an increase in D-dimer concentration on POD 3. CONCLUSIONS: The D-dimer concentration on POD 3 is a useful predictor of DVT after HBP surgery.

A low cumulative perioperative prognostic nutritional index predicts poor long-term outcomes in patients with gastric cancer: A single-center retrospective study in Japan.

PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.

Modified geriatric nutritional risk index in patients with pancreatic cancer: a propensity score-matched analysis.

BACKGROUND: The modified nutritional geriatric risk index (mGNRI) was developed as a novel index and provides a more appropriate prognostic index than the original GNRI, which was reported to be a useful index for predicting prognoses for various malignancies. This study investigated the prognostic significance of the mGNRI compared with that of the GNRI in patients with pancreatic cancer and the association with psoas muscle volume (PMV) for survival outcomes. METHODS: This retrospective study included 137 patients who had undergone pancreatectomy for pancreatic cancer. The enrolled patients were grouped as high mGNRI (≥ 85.3) or low mGNRI (< 85.3), and high GNRI (≥ 92) or low GNRI (< 92) for prognostic analysis based on cutoff values. A propensity-matched analysis was performed in this study. RESULTS: The 5-year overall survival of patients in the high mGNRI group or high GNRI group was significantly longer than those in the low mGNRI group or low GNRI group. Statistically significant differences for the 5-year OS were observed in the three groups with respect to the combination of mGNRI and PMV. Patients with low mGNRI/low PMV had a worse 5-year OS rate compared with patients with high GNRI/high PMV or those with high GNRI or high PMV, but not both. The concordance index of the mGNRI to predict the 5-year overall survival was greater than that of the GNRI or the combination of the GNRI and PMV, but lower than that of the combination of the mGNRI and PMV. Multivariate analysis revealed that the mGNRI was an independent prognostic factor for patients with pancreatic cancer (P = 0.005). CONCLUSIONS: The mGNRI might be a more useful prognostic factor than the GNRI for patients with pancreatic cancer, and might predict prognostic outcomes more accurately when combined with PMV.

Circular stapling anastomosis with indocyanine green fluorescence imaging for cervical esophagogastric anastomosis after thoracoscopic esophagectomy: a propensity score-matched analysis.

BACKGROUND: Thoracoscopic esophagectomy has been extensively used worldwide as a curative surgery for patients with esophageal cancer; however, complications such as anastomotic leakage and stenosis remain a major concern. Therefore, the objective of this study was to evaluate the efficacy of circular stapling anastomosis with indocyanine green (ICG) fluorescence imaging, which was standardized for cervical esophagogastric anastomosis after thoracoscopic esophagectomy. METHODS: Altogether, 121 patients with esophageal cancer who underwent thoracoscopic esophagectomy with radical lymph node dissection and cervical esophagogastric anastomosis from November 2009 to December 2020 at Tottori University Hospital were enrolled in this study. Patients who underwent surgery before the anastomotic method was standardized were included in the classical group (n = 82) and patients who underwent surgery after the anastomotic method was standardized were included in the ICG circular group (n = 39). The short-term postoperative outcomes, including anastomotic complications, were compared between the two groups using propensity-matched analysis and the risk factors for anastomotic leakage were evaluated using logistic regression analyses. RESULTS: Of the 121 patients, 33 were included in each group after propensity score matching. The clinicopathological characteristics of patients did not differ between the two groups after propensity score matching. In terms of perioperative outcomes, a significantly higher proportion of patients who underwent surgery using the laparoscopic approach (P < 0.001) and narrow gastric tube (P = 0.003), as well as those who had a lower volume of blood loss (P = 0.009) in the ICG circular group were observed after matching. Moreover, the ICG circular group had a significantly lower incidence of anastomotic leakage (39% vs. 9%, P = 0.004) and anastomotic stenosis (46% vs. 21%, P = 0.037) and a shorter postoperative hospital stay (30 vs. 20 days, P < 0.001) than the classical group. According to the multivariate analysis, the anastomotic method was an independent risk factor for anastomotic leakage after thoracoscopic esophagectomy (P = 0.013). CONCLUSIONS: Circular stapling anastomosis with ICG fluorescence imaging is effective in reducing complications such as anastomotic leakage and stenosis.

Antitumor Effect of 5-Aminolevulinic Acid Through Ferroptosis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Due to its tumor-specific metabolic pathway characteristics, 5-aminolevulinic acid (5-ALA) is a natural amino acid widely used in cancer treatment. The current study, demonstrated that 5-ALA induced ferroptosis via glutathione peroxidase 4 (GPX4) and heme oxygenase 1 (HMOX1) and had an antitumor effect in esophageal squamous cell carcinoma (ESCC). METHODS: Expression of GPX4 and HMOX1 in pathologic specimens of 97 ESCC patients was examined, and prognostic analyses were performed. Real-time polymerase chain reaction (RT-PCR), RNA microarray, and Western blotting analyses were used to evaluate the role of 5-ALA in ferroptosis in vitro. In addition, this study used ferrostatin-1, a ferroptosis inhibitor, and a lipid peroxidation reagent against cell lines treated with 5-ALA. Finally, the role of 5-ALA was confirmed by its effect on an ESCC subcutaneous xenograft mouse model. RESULTS: The study showed that upregulation of GPX4 and downregulation of HMOX1 were poor prognostic factors in ESCC. In an RNA microarray analysis of KYSE30, ferroptosis was one of the most frequently induced pathways, with GPX4 suppressed and HMOX1 overexpressed by 5-ALA treatment. These findings were verified by RT-PCR and Western blotting. Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. In vivo, 5-ALA suppressed GPX4 and overexpressed HMOX1 in tumor tissues and led to a reduction in tumor size. CONCLUSIONS: Modulation of GPX4 and HMOX1 by 5-ALA induced ferroptosis in ESCC. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.

The prognostic significance of combined geriatric nutritional risk index and psoas muscle volume in older patients with pancreatic cancer.

BACKGROUND: The geriatric nutritional risk index (GNRI), originally developed as a nutritional assessment tool to evaluate mortality and morbidity in older hospitalized patients (i.e., those aged ≥65 years), is regarded as a prognostic factor in several cancers. Body composition is also an important consideration when predicting the prognosis of patients with cancer. This study aimed to investigate the relationship between the GNRI and psoas muscle volume (PMV) for survival outcomes in patients with pancreatic cancer. METHODS: This retrospective study evaluated the prognostic significance of the GNRI and PMV in 105 consecutive patients aged ≥65 years who underwent pancreatectomy for histologically confirmed pancreatic cancer. The patients were divided into high (GNRI > 98) and low GNRI groups (GNRI ≤98), and into high (PMV > 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) and low PMV (PMV ≤ 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) groups. RESULTS: Both the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly greater among patients in the high GNRI group than among patients in the low GNRI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high PMV group than among patients in the low PMV group. Patients were stratified into three groups: those with both high GNRI and high PMV; those with either high GNRI or high PMV (but not both); and those with both low GNRI and low PMV. Patients with both low GNRI and low PMV had a worse 5-year OS rate, compared with patients in other groups (P <  0.001). The C-index of the combination of the GNRI and PMV for predicting 5-year OS was greater than the C-indices of either the GNRI or PMV alone. Multivariate analysis revealed that the combination of the GNRI and PMV was an independent prognostic factor in patients aged ≥65 years with pancreatic cancer (P = 0.003). CONCLUSIONS: The combination of the GNRI and PMV might be useful to predict prognosis in patients aged ≥65 years with pancreatic cancer.

Impact of skeletal muscle mass in patients with unresectable gastric cancer who received palliative first-line chemotherapy based on 5-fluorouracil.

BACKGROUND: The mortality rate of patients with unresectable gastric cancer (UGC) has decreased with the development of chemotherapies and surgical techniques. However, the survival rate remains low. We retrospectively examined the prognostic significance of the pretreatment skeletal muscle mass index (SMI) and nutritional and inflammatory factors in patients with UGC. METHODS: This study included 83 patients diagnosed with UGC at Tottori University Hospital who received palliative chemotherapy based on 5-fluorouracil. Pretreatment computed tomography (CT) measured overall skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra (L3). We focused on the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and platelet-to-lymphocyte ratio (PLR) as nutritional and inflammatory factors. RESULTS: Receiver operating characteristic curve analysis was performed for median survival time (MST) after palliative chemotherapy. SMIs for males and females (43.9 cm2/m2 and 34.7 cm2/m2, respectively) were the cutoff values, and patients were divided into high (SMIHigh; n = 41) and low SMI groups (SMILow; n = 42). Body mass index (BMI) was significantly higher in patients in the SMIHigh group than in the SMILow group (p < 0.001). The number of patients who received third-line chemotherapy was significantly higher in the SMIHigh group than in the SMILow group (p = 0.037). The MST was significantly higher in the SMIHigh group than in the SMILow group (17.3 vs. 13.8 months; p = 0.008). The incidence of grade 3 or 4 side effects was significantly higher in patients with SMILow UGC (p = 0.028). NLR was significantly higher in patients with SMILow than it was in those with SMIHigh. (p = 0.047). In the univariate analysis, performance status, SMI, histological type, lines of chemotherapy, and NLR were prognostic indicators. The multivariate analysis identified SMI (p = 0.037), NLR (p = 0.002), and lines of chemotherapy (p < 0.001) as independent prognostic factors. CONCLUSIONS: The SMILow group had significantly more grade 3 or 4 side effects, were related to high NLR, and had a significantly worse prognosis than the SMIHigh group. TRIAL REGISTRATION: Retrospectively registerd.

Impact of skeletal muscle mass in patients with recurrent gastric cancer.

BACKGROUND: We retrospectively examined the relationship among skeletal muscle mass index (SMI), prognosis, and chemotherapy side effects in patients with recurrent gastric cancer (RGC). METHODS: Sixty-seven patients who developed recurrence after undergoing curative gastrectomy for gastric cancer at Tottori University Hospital and received palliative chemotherapy were included in this study. Pretreatment computed tomography was performed to measure the skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra. We focused on haematologic toxicity (neutropenia, thrombocytopenia, and anaemia), febrile neutropenia, and gastrointestinal toxicity (diarrhoea, vomiting, and stomatitis) as the side effects of chemotherapy. RESULTS: Median SMIs for males and females (43.9 and 34.7 cm2/m2, respectively) were used as cutoff values. The patients were classified into high (SMIHigh; n = 34) and low SMI groups (SMILow; n = 33). The SMILow group included more patients treated with monotherapy (P = 0.016) compared with the SMIHigh group, had a significantly lower number of chemotherapy lines (P = 0.049), and had a significantly higher incidence of grade 3 or 4 side effects (P = 0.010). The median survival rate was significantly higher in the SMIHigh group (17.8 vs 15.8 months; P = 0.034). In the univariate analysis, body mass index, SMI, histological type, and prognostic nutritional index were identified as prognostic indicators. The multivariate analysis identified SMI (P = 0.037) and histological type (P = 0.028) as independent prognostic factors. CONCLUSION: The incidence of grade 3 or 4 side effects was significantly higher in patients with SMILow RGC. SMI was a useful prognostic marker of RGC.

Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer.

BACKGROUND: Decreased mean platelet volume (MPV) predicts poor prognosis in some cancers. However, its significance as a prognostic indicator in pancreatic cancer (PC) remains unclear. METHODS: A total of 91 PC patients who underwent pancreatectomy were included in this study. MPV and serum carbohydrate antigen 19-9 (CA19-9) were measured within 1 week before surgery. RESULTS: We divided patients into MPVhigh (≥ 8.65; n = 40), MPVlow (< 8.65; n = 51), CA19-9high (≥ 66.3; n = 47), and CA19-9low (< 66.3; n = 44) groups based on the optimal cut-off values determined from receiver operating characteristic curve analysis. The 5-year overall survival (OS) rates were significantly lower in the MPVlow than in the MPVhigh group (16.9% and 56.3%, respectively; P = 0.0038), and the 5-year disease-specific survival (DSS) rates in the MPVlow group and MPVhigh group were 20.5% and 62.2%, respectively (P = 0.0031). Multivariate analysis identified MPV as an independent prognostic indicator for both OS and DSS. The patients were then divided into groups A (MPVhigh and CA19-9low), B (MPVhigh and CA19-9high), C (MPVlow and CA19-9low), and D (MPVlow and CA19-9high), with 5-year OS rates of 73.2%, 40.4%, 25.8%, and 10.3%, respectively (P = 0.0002), and 5-year DSS rates of 80.8%, 44.9%, 27.3%, and 16.4%, respectively (P = 0.0003). CONCLUSIONS: Classification based on MPV and CA19-9 might be useful for predicting long-term outcomes in patients with PC.

[A Case of Cervical Esophageal Cancer with Lymph Node Recurrence Three Times after Definitive Chemoradiotherapy].

A 56-years old man was diagnosed with cervical esophageal cancer with lymph node metastasis. After definitive chemoradiotherapy as the first-line therapy, complete response(CR)was obtained. One year and 3 months after the therapy, lymph node dissection and postoperative chemotherapy was performed for the lymph node metastases of the left neck and axillary lymph node. After 3 years and 10 months from the first-line therapy, follow-up CT revealed left axillary lymph node swelling and diagnosed with lymph node recurrence. Chemoradiotherapy was performed for the recurrence of the lymph node and CR was achieved for the lymph node. However, left axillary lymph node swelling were detected again 6 years after the first-line therapy. After 6 months of chemotherapy with S-1, CR was achieved for the lymph node again. He is now alive without recurrence for 10 years after the first-line therapy.

Disinfection with single or double usage of new antiseptic olanexidine gluconate in general surgery: a randomized study.

PURPOSE: Olanexidine gluconate is a newly developed solution for skin disinfection that was recently approved in Japan. We aimed to compare single and double application of the solution in preventing surgical site infection (SSI) in patients undergoing general surgery. METHODS: This randomized study was conducted at the Tottori University Hospital. Patients scheduled to undergo gastrointestinal or hernia surgery were randomly assigned to one of two groups using either one or two Olanedine applicators for skin disinfection. The primary endpoint was the difference in SSI incidence between the two groups. The secondary endpoint was all adverse events related to olanexidine gluconate. RESULTS: A total of 393 patients qualified for the study protocol: 193 received a single application, and 200 received a double application of Olanedine. SSI occurred in 10 patients (2.5%) overall; nine were superficial incisional SSIs, and one patient had a deep incisional SSI. Of the 10 patients who developed SSI, six (3.1%) were in the group receiving a single application, and four (2.0%) were in the group receiving a double application; there was no statistically significant difference between the two groups (P = 0.537). Allergic reactions or skin disorders related to olanexidine gluconate were not observed. CONCLUSION: There was no difference in the SSI incidence between the use of one or two Olanedine applicators for skin preparation in elective general surgery. Therefore, a single application of Olanedine is sufficient and is recommended for general surgery as a standard disinfection precaution. TRIAL REGISTRATION NUMBER: UMIN000027319; 5/12/2017.

Sarcopenia as a prognostic factor in patients with recurrent pancreatic cancer: a retrospective study.

BACKGROUND: Sarcopenia is a prognostic factor in various cancers. However, the impact of sarcopenia in patients with recurrent pancreatic cancer remains unclear. This study evaluated the prognostic significance of sarcopenia in patients with recurrent pancreatic cancer. METHODS: Seventy-four patients who developed postoperative recurrence of pancreatic cancer after undergoing pancreatectomies were enrolled. Sarcopenia in these patients was defined according to the psoas muscle index (PMI) measured via computed tomography at the third vertebra. RESULTS: The mean PMIs at the time of recurrence were 4.47 ± 1.27 cm2/m2 for men and 3.26 ± 0.70 cm2/m2 for women. Of the 74 patients, 65 (87.8%) were diagnosed with sarcopenia with low PMI. The 2-year post-recurrence survival curve in the sarcopenia group was significantly worse than that in the non-sarcopenia group (P = 0.034). Multivariate analysis revealed that sarcopenia at the time of recurrence was an independent prognostic factor (P = 0.043) along with a high neutrophil-to-lymphocyte ratio (P = 0.004), early recurrence (P = 0.001), and chemotherapy after recurrence (P = 0.005) in patients with recurrent pancreatic cancer. Furthermore, the area under the curve (AUC) of the combination of sarcopenia and time to recurrence for predicting 2-year survival was 0.763, which was much higher than that of sarcopenia alone (AUC = 0.622). CONCLUSIONS: Sarcopenia is a useful prognostic factor in patients with recurrent pancreatic cancer. The combination of sarcopenia and time of recurrence may more accurately predict post-recurrence survival than can sarcopenia alone.

Clinical significance of preoperative CA19-9 and lymph node metastasis in intrahepatic cholangiocarcinoma.

PURPOSE: This study aimed to identify prognostic factors for patients with ICC after a curative resection and clarify the appropriate indications for surgical resection and postoperative adjuvant chemotherapy. METHODS: This retrospective study included 81 patients who underwent curative resection for ICC between April 1995 and December 2014. Kaplan-Meier and Cox regression models were used to analyze the effects of clinicopathological features on overall and recurrence-free survival. RESULTS: The cumulative 5-year overall survival of 81 patients was 57.2%, and the 5-year recurrence-free survival was 24.0%. The multivariate analysis identified the lymph node status and preoperative CA19-9 levels as independent prognostic factors for overall survival. The 5-year overall survival rates were 79.9% and 38.7% in patients with normal and elevated CA19-9, respectively (p < 0.0001). The 5-year overall survival rates of patients with and without nodal metastasis were 33.7% and 60.9%, respectively (p = 0.0007). After adjusting for prognostic factors identified in a Cox regression analysis, we found that nodal-positive disease was significantly associated with benefit from adjuvant chemotherapy (HR 0.32, p = 0.03). CONCLUSIONS: Surgical resection with curative intent combined with regional lymph node dissection should be indicated for ICC patients with normal CA19-9 levels. Postoperative adjuvant chemotherapy should be administered to high-risk patients with a positive nodal status.

Combined prognostic nutritional index ratio and serum amylase level during the early postoperative period predicts pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to investigate the usefulness of the range of change in prognostic nutritional index (PNI) during the early postoperative period as a predictor of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. METHODS: Data were retrospectively analyzed for 192 patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were used to evaluate perioperative variables. PNIP3-Pre ratio represented the range of change in PNI from before surgery to postoperative day (POD) 3, PNIP1-Pre ratio represented the range of change in PNI from before surgery to POD 1, and PNIP3-P1 ratio represented the range of change in PNI from POD 1 to POD 3. RESULTS: The area under the curve (AUC) for PNIP3-P1 for prediction of POPF following pancreaticoduodenectomy was 0.683 (P <  0.001), which was highest among PNI ratios and higher than PNI on POD 3. The AUC for serum amylase level on POD 1 was 0.704 (P <  0.001), which was superior to the corresponding AUC on POD 3. The AUC for the combination of PNIP3-P1 ratio and serum amylase level on POD 1 for prediction of POPF was higher than the AUC of either indicator alone (0.743, P <  0.001). The combination of PNIP3-P1 ratio and serum amylase level on POD 1 was an independent predictor of POPF following pancreaticoduodenectomy (P = 0.018). CONCLUSIONS: The combination of the range of change in PNI from POD 1 to POD 3 and serum amylase levels on POD 1 may be useful for prediction of POPF following pancreaticoduodenectomy.

The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy.

PURPOSE: Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management. METHODS: Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HUmin, HUmax, and HUmean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HUSD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria. RESULTS: The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HUSD (odds ratio 3.092; 95% CI 1.018-9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001-1.00022) as significant risk factors for PF. CONCLUSIONS: The HUSD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C.

BACKGROUND: Pancreatic cancer (PC) is the most lethal malignancy among solid tumors, and the most common risk factor for its development is cigarette smoking. Atypical protein kinase C (aPKC) isozymes function in cell polarity, proliferation, and survival, and have also been implicated in carcinogenesis. However, the involvement of aPKC in PC progression and the effect of nicotine, a major component of cigarette smoke, on the biological activities of aPKC remain to be fully elucidated. METHODS: We investigated the effects of nicotine on the proliferation, migration and invasion of the human PC cell lines Panc1 and BxPC3. We analyzed aPKC localization and activity by immunohistochemistry and in vitro kinase assays, respectively, to assess their involvement in the regulation of PC progression. Moreover, we examined the effect of nicotine on implanted peritoneal tumors of PC cells in mice. RESULTS: Nicotine enhanced cell proliferation, migration and invasion in Panc1 and BxPC3 cells. In nicotine-treated PC cells, the aPKC was significantly activated. We also found that nicotine induced phosphatidylinositol 3-kinase (PI3K) signal activation, and a specific inhibitor of the nicotine acetylcholine receptor (nAChR) as well as knockdown of nAChR prevented nicotine-mediated Akt phosphorylation and aPKC activation. In a peritoneal dissemination model of PC, nicotine-treated mice had larger tumors and increased numbers of nodules. Immunohistochemistry showed enhanced expression levels of aPKC and phosphorylated Akt in nodules from nicotine-treated mice. CONCLUSIONS AND GENERAL SIGNIFICANCE: Nicotine induces aberrant activation of aPKC via nAChR/PI3K signaling in PC cells, resulting in enhancement of cellular proliferation, migration and invasion.

Prognostic indicators based on inflammatory and nutritional factors after pancreaticoduodenectomy for pancreatic cancer.

PURPOSE: We evaluated prognostic indicators based on inflammatory and nutritional factors, namely, the modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR), to determine their efficiency and significance after pancreaticoduodenectomy for pancreatic cancer. METHODS: The subjects of this study were 46 patients who underwent pancreaticoduodenectomy for pancreatic cancer between October 2007 and December 2014. Patients were divided into preoperative mGPS (0/1 and 2), PNI (<40 and ≥40), NLR (<2.5 and ≥2.5), and PLR (<200 and ≥200) groups, to evaluate various perioperative outcomes. RESULTS: Hemoglobin concentrations were significantly lower (P = 0.019), whereas intra-abdominal bleeding was significantly higher (P = 0.040) in the PNI (<40) group than in the PNI (≥40) group. The incidence of postoperative pneumonia was significantly higher in the mGPS (2) group (P = 0.009), and surgical complications greater than grade 3 (Clavien-Dindo classification) were significantly increased in the NLR (≥2.5) group (P = 0.041). Overall survival rates in the PNI (<40) (P = 0.019), NLR (≥2.5) (P = 0.001), and PLR (≥200) (P < 0.001) groups were significantly lower than those in the other groups. The PLR was the only independent prognostic indicator (P = 0.002) according to multivariate analysis. CONCLUSIONS: The mGPS, PNI, and NLR were effective predictive indicators of postoperative complications. The PLR was the most useful prognostic indicator for pancreatic cancer patients after pancreaticoduodenectomy.

The estrogen receptor ß-PI3K/Akt pathway mediates the cytoprotective effects of tocotrienol in a cellular Parkinson's disease model.

Tocotrienols (T3s) are members of the vitamin E family, have antioxidant properties, and are promising candidates for neuroprotection in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). However, whether their antioxidant capacities are required for their cytoprotective activity remains unclear. In this regard, the antioxidant-independent cytoprotective activity of T3s has received considerable attention. Here, we investigated the signaling pathways that are induced during T3-dependent cytoprotection of human neuroblastoma SH-SY5Y cells, as these cells are used to model certain elements of PD. T3s were cytoprotective against 1-methyl-4-phenylpyridinium ion (MPP(+)) and other PD-related toxicities. γT3 and δT3 treatments led to marked activation of the PI3K/Akt signaling pathway. Furthermore, we identified estrogen receptor (ER) ß as an upstream mediator of PI3K/Akt signaling following γT3/δT3 stimulation. Highly purified γT3/δT3 bound to ERß directly in vitro, and knockdown of ERß in SH-SY5Y cells abrogated both γT3/δT3-dependent cytoprotection and Akt phosphorylation. Since membrane-bound ERß was important for the signal-related cytoprotective effects of γT3/δT3, we investigated receptor-mediated caveola formation as a candidate for the early events of signal transduction. Knockdown of caveolin-1 and/or caveolin-2 prevented the cytoprotective effects of γT3/δT3, but did not affect Akt phosphorylation. This finding suggests that T3s and, in particular, γT3/δT3, exhibit not only antioxidant effects but also a receptor signal-mediated protective action following ERß/PI3K/Akt signaling. Furthermore, receptor-mediated caveola formation is an important event during the early steps following T3 treatment.