Critical Role of Preoperative Hyperglycemia in Association with GFAT-1 Expression in Resected Pancreatic Cancer.

BACKGROUND: Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data. METHODS: The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity. RESULTS: Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time [MST]: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression. CONCLUSIONS: The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.

Feasibility and efficacy of cell-free and concentrate ascites reinfusion therapy (CART) for advanced pancreatic cancer patients with massive malignant ascites.

BACKGROUND: The management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites. METHODS: This study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group. RESULTS: Among the 47 procedures, adverse events (AEs) were observed in 9 procedures (19 %). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p = 0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group. CONCLUSION: CART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients.

Clinical impact of carbonic anhydrase 9 expression on neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma.

BACKGROUND: PDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines. RESULTS: CA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation. CONCLUSIONS: CA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT.

Persistent acute kidney injury: Postoperative impact and predictors in patients undergoing liver resection.

AIM: Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long-term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC). METHODS: We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine ≥ 0.3 mg/dL or ≥50% from baseline 1 month after surgery. RESULTS: The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90-day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p < 0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p = 0.005). The long-term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p < 0.001 for both). Chronic kidney disease, albumin-bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p = 0.001, p = 0.039, and p = 0.015, respectively). CONCLUSIONS: Persistent AKI adversely affects postoperative outcomes and long-term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients.

Preoperative predictors of very early recurrence in patients with hepatocellular carcinoma beyond the Milan criteria.

PURPOSE: Hepatocellular carcinoma (HCC) patients beyond the Milan criteria (MC) who undergo liver resection have high recurrence rates and poor prognosis, and sometimes experience very early recurrence (VER) within six months after surgery. This study aimed to identify predictive factors, including the newly proposed C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, for VER after surgery for HCC beyond MC. METHODS: We included patients who underwent initial liver resection for HCC beyond MC between 2000 and 2021. We defined VER as recurrence within six months after surgery and compared the clinicopathological factors and long-term prognosis between the VER and non-VER groups. Multivariate analysis identified risk factors for VER and evaluated the potential for prognostic stratification using these factors. RESULTS: The overall survival (OS) and post-recurrence survival were significantly worse in the VER group compared to patients with recurrence in 7-12 months, over 12 months, and without recurrence (median survival time (MST) 1.16 vs. 5.14, 7.26, and undefined; and MST 0.81 vs. 4.34, and 5.48, respectively, P < 0.01). Alpha-fetoprotein (AFP) ≥ 200, non-simple nodule (SN) type on preoperative imaging, and CALLY index < 2.8 were independent prognostic factors (P < 0.01 for all). An increased risk factor count was correlated with poorer VER and OS rates, allowing for effective stratification. CONCLUSION: VER after hepatic resection for HCC beyond MC was associated with a significantly poorer prognosis. AFP, non-SN type on imaging, and CALLY index are valuable preoperative indicators. Patients with multiple risk factors have a worse prognosis and may be candidates for multimodal treatment.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Although the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. METHODS: This study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. RESULTS: This study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). CONCLUSIONS: A combination of a high-level carbohydrate antigen 19-9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.

Significance of multiple tumor markers measurements in conversion surgery for unresectable locally advanced pancreatic cancer.

BACKGROUND: This study aimed to evaluate the significance of multiple tumor markers (TMs) measurements in determining the indications for conversion surgery (CS) in the management of unresectable locally advanced pancreatic cancer (UR-LAPC). METHODS: A total of 103 patients with UR-LAPC, treated between 2008 and June 2021, were enrolled in this study. Three TMs, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and Duke pancreatic monoclonal antigen type 2 (DUPAN-2), were measured. RESULTS: Twenty-five patients (24%) underwent CS. The median preoperative treatment period was 9.5 months. The median survival time (MST) from the initial treatment for patients with CS was significantly longer than that for patients without surgery (34.6 vs. 18.9 months, P < 0.001). The number of elevated TMs before CS was one in five patients and two in five patients, while 15 patients had normal levels of all three TMs. Notably, the MST from the initial treatment for patients with all three preoperative normal TMs levels was favorable for 70.5 months. In contrast, patients with one or two preoperatively elevated TMs levels had a significantly worse prognosis (25.4 and 21.0 months, respectively, P < 0.001). Furthermore, the relapse-free survival of patients with three preoperative normal TMs levels was significantly longer than those with one or two elevated TMs levels (21.9 vs. 11.3 or 3.0 months, respectively, P < 0.001). Non-normal values of all TMs before CS were identified as independent poor prognostic factors. CONCLUSIONS: Simultaneous measurement and assessment of the three TMs levels may help determine the surgical indications for UR-LAPC after systemic anticancer treatment.

Impact of the Prolonged Intermittent Pringle Maneuver on Post-Hepatectomy Liver Failure: Comparison of Open and Laparoscopic Approaches.

BACKGROUND: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy. METHODS: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors. RESULTS: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min. CONCLUSIONS: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.

Detailed analysis of recurrent sites after wedge resection for primary hepatocellular carcinoma considering the potential usefulness of anatomic resection: a retrospective cohort study.

PURPOSE: We investigated the detailed recurrent sites after wedge liver resection for primary hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 278 patients with primary HCC who underwent curative liver resection between 2000 and 2016. Recurrent sites were divided into four groups: around the initial HCC (segmental recurrence), within the same section as the primary HCC (sectional recurrence), within the same lobe as the primary HCC (lobar recurrence), and contralateral or extrahepatic recurrence (extra recurrence). RESULTS: Recurrence was observed in 101 of 147 patients who underwent wedge resection. At first recurrence, segmental recurrence was observed in 18 patients (17.8%), while 28 patients (27.7%) were with sectional recurrence and 48 patients (47.5%) were with lobar recurrence. However, the cumulative recurrent sites of each patient showed extra recurrence in 53 patients (52.5%) at initial recurrence, 79 patients (78.2%) until the second recurrence, 89 patients (88.1%) until the third recurrence, 94 patients (93.0%) until the fourth, and 96 patients (95.0%) until the fifth recurrence. CONCLUSION: Some intrahepatic recurrence after wedge resection might have been avoided if anatomic resection had been performed instead. However, the number of contralateral or extrahepatic recurrences increased with the number of recurrences.

Clinical impact of sarcopenia in early-stage intrahepatic recurrent hepatocellular carcinoma: an association with impaired host immunity.

PURPOSE: This study investigated the role of sarcopenia in the long-term outcomes of patients with early-stage intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS: The study included 136 patients with intrahepatic recurrent Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC following liver resection diagnosed between 2006 and 2020 and underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE). Sarcopenia was defined based on the skeletal muscle index using computed tomography at the time of recurrence, and its association with long-term outcomes was evaluated. Tumor-infiltrating lymphocytes (CD4 + , CD8 + , and CD45RO + T cells) were assayed using immunohistochemistry on specimens obtained from repeat hepatectomies, and their association with sarcopenia was evaluated. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) rates after initial recurrence of patients with sarcopenia were significantly lower than those without sarcopenia (p < 0.001 and p < 0.001, respectively). Multivariate analysis identified sarcopenia as an independent prognostic factor for RFS (p < 0.001). In patients without sarcopenia, surgery resulted in better RFS than RFA or TACE. Contrastingly, in patients with sarcopenia, the RFS was extremely poor regardless of the treatment type: surgery, RFA, or TACE (median RFS, 11.7, 12.7, and 10.1 months). Significantly low levels of tumor-infiltrating CD4 + , CD8 + , and CD45RO + lymphocytes were observed in patients with sarcopenia (p = 0.001, p = 0.001, and p = 0.001, respectively). CONCLUSIONS: This study suggests that patients with sarcopenia have poor RFS regardless of the treatment type for early-stage intrahepatic recurrent HCC. Impaired host immunity might be one of the underlying mechanisms.

Pre- and postoperative C-reactive protein as a risk factor of organ/space surgical site infection after hepatectomy.

BACKGROUND: Organ/space surgical site infection (SSI) is one of the most common complications of liver resection, with significant impact on morbidity and mortality, so patients at high risk should be identified early. This study aimed to determine whether pre- and postoperative C-reactive protein (CRP) levels could predict organ/space SSIs. METHODS: The hospital records of consecutive patients who underwent hepatectomy without biliary reconstruction at our institutions between 2008 and 2015 were reviewed retrospectively. Preoperative, intraoperative, and postoperative variables were compared between patients with or without organ/space SSIs. Its risk factors were also determined. RESULTS: Among 443 identified patients, 55 cases (12.5%) developed organ/space SSIs; they more frequently experienced other complications and bile leakage (47.3% vs. 16.6%, p = 0.001; 40.0% vs. 8.5%, p < 0.001, respectively). Postoperative CRP elevation from postoperative day (POD) 3 to 5 was significantly more frequent in the SSI group (21.8% vs. 4.9%, p < 0.001). Multivariate analysis identified preoperative CRP ≥ 0.2 mg/dL (odds ratio (OR), 2.01, p = 0.044], preoperative cholangitis (OR, 15.7; p = 0.020), red cell concentrate (RCC) transfusion (OR, 2.61, p = 0.018), bile leakage (OR, 9.51; p < 0.001), and CRP level elevation from POD 3 to 5 (OR, 3.81, p = 0.008) as independent risk factors for organ/space SSIs. CONCLUSIONS: Preoperative CRP elevation and postoperative CRP trajectory are risk factors for organ/space SSIs after liver resection. A prolonged CRP level elevation at POD 5 indicates its occurrence. If there were no risk factors and no CRP elevation at POD 5, its presence could be excluded.

The Prognostic Significance of the Geriatric Nutritional Risk Index in Colorectal Cancer Patients.

This study retrospectively investigated the prognostic impact of the geriatric nutritional risk index (GNRI) in colorectal cancer (CRC). This study reviewed the medical records of 329 CRC patients who underwent curative surgery. The GNRI was calculated from the serum albumin level and the body weight. The cutoff value for the GNRI was set at 98. One hundred ninety (57.8%) patients had a GNRI of ≥98, and 139 (42.9%) had a GNRI of <98. The patients with a lower GNRI had a significantly lower overall survival (OS) rate than those with a higher GNRI (p < 0.001). The multivariate analysis demonstrated that the GNRI was an independent predictor of the OS (p = 0.042). Non-cancer death was more frequent in the patients with a lower GNRI than in those with a higher GNRI (p = 0.003). The mean age was significantly higher in the patients with a lower GNRI (p < 0.001). The GNRI was significantly associated with tumor location (p = 0.048), tumor depth (p < 0.001) and carcinoembryonic antigen (CEA) level (p = 0.032). The GNRI is a simple and useful prognostic factor in CRC. The present study suggests that a low GNRI be associated with a higher risk of non-cancer death.

Impact of laparoscopic liver resection on liver regeneration.

BACKGROUND: Liver regeneration after liver resection plays an important role in preventing posthepatectomy liver failure. In this study, we aimed to evaluate and compare the impact of laparoscopic liver resection (LLR) and open liver resection (OLR) on liver regeneration. METHODS: Patients who underwent curative anatomical liver resection for hepatocellular carcinoma, cholangiocellular carcinoma, and colorectal liver metastases at our institution between January 2010 and December 2018 were included in this study. The patients were divided into the OLR and LLR groups. Preoperative liver volume (PLV), future remnant liver volume, resected liver volume (RLV), liver volume at 1 month after the surgery, and liver volume at 6 months after the surgery were calculated. The liver regeneration rate was defined as the increase in the rate of RLV, and the liver recovery rate was defined as the rate of return to the PLV. RESULTS: The study included 72 patients. Among them, 43 were included in the OLR group and 29 were included in the LLR group. No differences were observed in the baseline characteristics and surgical procedures between the two groups. Moreover, no significant difference was observed in the liver regeneration rate at 1 month after the surgery (OLR vs. LLR: 68.9% vs. 69.0%, p = 0.875) and at 6 months after the surgery (91.8% vs. 93.2%, p = 0.995). Furthermore, the liver recovery rates were not significantly different between the two groups at 1 month after the surgery (90.3% vs. 90.6%, p = 0.893) and at 6 months after the surgery (96.9% vs. 98.8%, p = 0.986). CONCLUSION: Liver regeneration after liver resection is not affected by the type of surgical procedure and both laparoscopic and open procedures yield similar regeneration and recovery rates.

Clinically Relevant Late-Onset Biliary Complications After Pancreatoduodenectomy.

BACKGROUND: Late-onset biliary complications (LBC) after pancreatoduodenectomy (PD) can be serious. This study aimed to clarify the frequency and risk factors of severe LBC after PD. METHODS: We defined LBC as biliary complications occurring 3 months after PD and severe LBC as cases that required intensive care. A total of 318 patients who underwent PD between 2010 and 2018 with at least 1 year of postoperative follow-up were evaluated. RESULTS: Hospitalization for severe LBC was required in 59 patients (19%), of whom 20 had liver abscesses (6.3%); 18, acute cholangitis (5.7%); 12, biliary stones (3.8%); and 21, biliary strictures (6.6%). Interventional radiological or endoscopic treatment was required in 32 patients (10%), of whom 9 had a benign primary disease with biliary stones and/or strictures. Thirteen of the remaining 23 patients with a malignant primary disease had liver abscesses and cholangitis. Significant independent risk factors for severe LBC in patients with malignant primary disease were recurrence around the hepaticojejunostomy (odds ratio 6.5, P = 0.013) and chemotherapy (odds ratio 13.5, P < 0.001). CONCLUSIONS: Severe LBC after PD may occur regardless of whether the primary disease is benign or malignant. The course of severe LBC differs according to the primary disease, and therefore, appropriate follow-up and optimal treatment should be recommended according to the condition of the patient and the disease state.

Integrative analysis identifies activated anti-tumor immune microenvironment in lung metastasis of pancreatic cancer.

BACKGROUND: Although the prognosis of patients experiencing recurrences after surgery for pancreatic cancer is extremely poor, patients who develop recurrence in the lung have a better prognosis compared to other types of recurrence. We performed a histo-immunological analysis of the metastatic specimens to identify specific features of this patient subgroup. METHODS: We performed immunohistochemistry for CD4+, CD8+, CD45RO+, Foxp3, and PD-L1 in the lung (n = 22), peritoneal (n = 18), and liver (n = 6) metastases of pancreatic cancer. As microenvironmental and immunonutritional investigations, the tumor-stroma ratio and prognostic nutritional index (PNI) were utilized in the integrative analysis of immunological features. RESULTS: We identified significantly increased tumor-infiltrating CD4+, CD8+, and CD45RO+ cells in lung metastasis, compared with peritoneal and liver metastases (lung vs. peritoneum/liver, CD4: P < 0.001/P = 0.015, CD8: P < 0.001/P = 0.038, CD45RO: P = 0.022/P = 0.012). The CD8/Foxp3 ratio was higher in the lung than in the liver (P = 0.024). PD-L1 expression was significantly higher in lung metastasis than in peritoneal metastasis (P = 0.010). Furthermore, we found that lung metastasis had fewer cancer stroma than peritoneal metastasis (P < 0.001). A higher PNI was observed in patients with lung metastasis, and PNI was positively correlated with tumor-infiltrating lymphocytes in metastatic sites. CONCLUSION: We identified that lung metastasis revealed an immunologically "hot" tumor with increased TILs and PD-L1 expression. This specific feature suggests that patients with lung metastasis can be candidates for immunotherapy, such as immune checkpoint inhibitors; therefore, our study provides a framework for developing individualized treatment strategies for this patient subgroup.

Spinel-Type MgMn2O4 Nanoplates with Vanadate Coating for a Positive Electrode of Magnesium Rechargeable Batteries.

Spinel-type MgMn2O4 nanoplates ∼10 nm thick were prepared as a positive electrode for magnesium rechargeable batteries by the transformation of metal hydroxide nanoplates. Homogeneous coating with a vanadate layer thinner than 3 nm was achieved on the spinel oxide nanoplates via coverage of the precursor and subsequent mild calcination. We found that the spinel oxide nanoplates with the homogeneous coating exhibit improved electrochemical properties, such as discharge potential, capacity, and cyclability, due to the enhanced insertion and extraction of magnesium ions and suppressed decomposition of electrolytes. The nanometric platy morphology of the spinel oxide and the vanadate coating act synergistically for the improvement of the electrochemical performance.

Highly accurate and explainable detection of specimen mix-up using a machine learning model.

Background Delta check is widely used for detecting specimen mix-ups. Owing to the inadequate specificity and sparseness of the absolute incidence of mix-ups, the positive predictive value (PPV) of delta check is considerably low as it is labor consuming to identify true mix-up errors among a large number of false alerts. To overcome this problem, we developed a new accurate detection model through machine learning. Methods Inspired by delta check, we decided to conduct comparisons with the past examinations and broaden the time range. Fifteen common items were selected from complete blood cell counts and biochemical tests. We considered examinations in which ≥11 among the 15 items were measured simultaneously in our hospital; we created individual partial time-series data of the consecutive examinations with a sliding window size of 4. The last examinations of the partial time-series data were shuffled to generate artificial mix-up cases. After splitting the dataset into development and validation sets, we allowed a gradient-boosting-decision-tree (GBDT) model to learn using the development set to detect whether the last examination results of the partial time-series data were artificial mixed-up results. The model's performance was evaluated on the validation set. Results The area under the receiver operating characteristic curve (ROC AUC) of our model was 0.9983 (bootstrap confidence interval [bsCI]: 0.9983-0.9985). Conclusions The GBDT model was more effective in detecting specimen mix-up. The improved accuracy will enable more facilities to perform more efficient and centralized mix-up detection, leading to improved patient safety.

Postoperative Serum C-Reactive Protein Level Predicts Long-Term Outcomes in Colorectal Cancer Patients.

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative systemic inflammation in patients with colorectal cancer(CRC). METHODS: This study reviewed the medical records of 382 patients with CRC who underwent curative surgery. We evaluated the postoperative serum C-reactive protein(CRP)level on postoperative day 1 (CRP1)and its peak value(CRPmax)as prognostic factors. RESULTS: CRP1(p=0.001)and CRPmax(p=0.023)were significantly associated with the overall survival(OS)rate. In the multivariate analysis, a high-CRP1, age of≥75 years, and high serum carcinoembryonic antigen level were identified as independent predictors for the poor OS. Death from relapse of CRC was more frequent in the high-CRP1 group than in the low-CRP1 group(18.0% vs 5.6%, p=0.001). CONCLUSIONS: The serum CRP level during the early postoperative period predicts the long-term outcomes in CRC.

The distance and chance of lifetime geographical movement of physicians in Japan: an analysis using the age-period-cohort model.

BACKGROUND: The uneven geographical distribution of physicians in Japan is a result of those physicians electing to work in certain locations. In order to understand this phenomenon, it is necessary to analyze the geographic movement of physicians across the Japanese landscape. METHODS: We obtained individual data on physicians from 1978 to 2012 detailing their attributes, work institutions, and locations. The data are from Japanese governmental sources (the Survey of Physicians, Dentists, and Pharmacists). The total sample size was 122 150 physicians, with 77.5% being male and 22.5% female. After obtaining the data, we calculated the geographical distance of each physician's movement by using geographic information systems software (GIS; ArcGIS, ESRI, Inc., CA, USA). Geographical distance was then converted into time distance. We compared the resulting median values through nonparametric testing and then conducted a multivariate analysis. Our next step involved the use of an age-period-cohort (APC) model to measure the degree of impact three points of data, experience (experience years), the historical and environmental context of the data (survey year), and physician cohort (registration year) had on the movement of each physician. RESULTS: The ratio of female physicians who selected an urban area as their first working location was higher than that of male physicians. However, the selection of an urban area was becoming more popular as a first working location for both males and females as the year of data increased. The overall distance of geographical movement for female physicians was less than it was for male physicians. Physicians moved the greatest distance between their second and fourth years following license acquisition, at which point the time distance became shorter. The median time distance was 46 min in 2000 and 22 min in 2008. The physicians in our study did not move far from their first working location, and the overall distance of movement lessened in the more recent years of study. The median distance of movement after 20 years was 25.9 km for male physicians, and 19.1 km for female physicians. The results of the APC model indicated that the effects of experience years (age) gradually declined, that the survey year (period) effects increased, and that the registration year (cohort) effects increased initially before leveling off. CONCLUSIONS: The trends following the introduction of the new mandatory training system in 2004 may imply that the concentration of physicians in Japan's urban areas is expected to increase. After 2000, the effect of that period on physicians explains their geographical movements more so than the factor of their age.

Mapping Injection Order Messages to Health Level 7 Fast Healthcare Interoperability Resources to Collate Infusion Pump Data.

BACKGROUND: When administering an infusion to a patient, it is necessary to verify that the infusion pump settings are in accordance with the injection orders provided by the physician. However, the infusion rate entered into the infusion pump by the health care provider cannot be automatically reconciled with the injection order information entered into the electronic medical records (EMRs). This is because of the difficulty in linking the infusion rate entered into the infusion pump by the health care provider with the injection order information entered into the EMRs. OBJECTIVES: This study investigated a data linkage method for reconciling infusion pump settings with injection orders in the EMRs. METHODS: We devised and implemented a mechanism to convert injection order information into the Health Level 7 Fast Healthcare Interoperability Resources (FHIR), a new health information exchange standard, and match it with an infusion pump management system in a standard and simple manner using a REpresentational State Transfer (REST) application programming interface (API). The injection order information was extracted from Standardized Structured Medical Record Information Exchange version 2 International Organization for Standardization/technical specification 24289:2021 and was converted to the FHIR format using a commercially supplied FHIR conversion module and our own mapping definition. Data were also sent to the infusion pump management system using the REST Web API. RESULTS: Information necessary for injection implementation in hospital wards can be transferred to FHIR and linked. The infusion pump management system application screen allowed the confirmation that the two pieces of information matched, and it displayed an error message if they did not. CONCLUSION: Using FHIR, the data linkage between EMRs and infusion pump management systems can be smoothly implemented. We plan to develop a new mechanism that contributes to medical safety through the actual implementation and verification of this matching system.