In pancreatic cancer, postoperative complications (POCs) are associated with disease outcomes. The geriatric nutritional risk index (GNRI) is known to predict POCs after pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in patients with hepatobiliary pancreatic tumors, including pancreatic cancer. Through POC occurrence risk, we aimed to determine whether GNRI could predict prognosis in patients who underwent PD or DP for resectable pancreatic cancer. This retrospective study examined 139 patients who underwent radical pancreatectomy for resectable pancreatic cancer at Ehime University. All patients were subjected to nutritional screening using GNRI and were followed up for POC diagnosis and patient outcomes such as overall survival (OS). Patients were divided based on the GNRI value of 99 (Low group: N = 74, GNRI < 99; High group: N = 65, GNRI ≥ 99), which was determined by receiver operating characteristic curve analysis. Multivariate analysis showed that GNRI < 99 was statistically correlated with POCs after curative pancreatic resection (p = 0.02). Univariate and multivariate analyses confirmed that GNRI < 99 was significantly associated with long OS (p = 0.04). GNRI could be a potential prognostic marker for resectable pancreatic cancer after curative pancreatic resection despite being a simple and noninvasive approach.

Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells.

Surgical site infections (SSIs) are a well‑known potential complication of surgery. They are assocaited with preoperative malnutrition and lead to increased medical costs and longer hospital stays. Therefore, surgeons should appropriately identify patients who are at a high risk. The geriatric nutritional risk index (GNRI) is a tool, increasingly utilized to assess the degree of malnutrition, particularly in elderly patients. Therefore, the present study attempted to validate whether GNRI could predict the risk of SSI in patients following pancreaticoduodenectomy (PD). A cohort study was retrospectively conducted on 106 patients in the Department of Digestive Surgery, Kawaguchi Municipal Medical Center, Japan from January 2007 to December 2017. All patients were subjected to nutritional screening using GNRI and followed up for the occurrence of postoperative complications, including SSI post PD. Additionally, risk factors for developing SSI, and the patient's height, body mass index and preoperative laboratory values were documented. Patients were divided into SSI (n=15) and non‑SSI (n=91) groups with a determined incidence of 14.2% (15/106) for SSI. The results revealed that the SSI group had GNRI values that were significantly reduced compared with the non‑SSI group (P<0.001). Receiver operating characteristic curve analysis was performed to determine the cut‑off value of GNRI that conferred an increased risk of SSI; it was determined as 94 (sensitivity 80.0%, specificity 83.5%). Univariate analysis confirmed that a GNRI <94 was significantly associated with SSI (P<0.001), whereas multivariate logistic regression analysis revealed that a GNRI <94 was independently associated with SSI following PD (relative risk=1.73, 95% confidence interval=1.23‑2.43; P<0.001). Therefore, a GNRI <94 is a potential predictive marker for SSI risk following PD.

Postoperative pancreatic fistula (POPF) are major postoperative complications (POCs) following distal pancreatectomy (DP). Notably, POPF may worsen the prognosis of patients with pancreatic cancer. Previously reported risks for POCs include body mass index, pancreatic texture, and albumin levels. Moreover, the C-reactive protein-to-albumin ratio (CAR) is a valuable parameter for prognostication. On the other hand, POCs sometimes lead to a worse prognosis in several cancer types. Thus, we assumed that CAR could be a risk factor for POPFs. This study investigated whether CAR can predict POPF risk in patients with pancreatic cancer following DP. This retrospective study included 72 patients who underwent DP for pancreatic cancer at Ehime University between January 2009 and August 2022. All patients underwent preoperative CAR screening. Risk factors for POPF were analyzed. POPF were observed in 17 of 72 (23.6%) patients. POPF were significantly associated with a higher CAR (p = 0.001). The receiver operating characteristic curve analysis determined the cutoff value for CAR to be 0.05 (sensitivity: 76.5%, specificity: 88.9%, likelihood ratio: 6.88), indicating an increased POPF risk. Univariate and multivariate analysis revealed that CAR ≥ 0.05 was a statistically independent factor for POPF (p < 0.001, p = 0.013). Therefore, CAR has the potential to predict POPF following DP.

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Background: Surgical site infections (SSIs), which are associated with preoperative malnutrition, are a well-known potential complication of surgery that leads to increased medical costs and longer hospitalizations. Thus, surgeons need to accurately identify patients at high-risk for SSIs. Considering that the Geriatric Nutritional Risk Index (GNRI) was designed to assess the degree of malnutrition specifically among elderly patients, previous evidence (Kawaguchi study) proved that GNRI predicted the risk of SSIs in patients following pancreatoduodenectomy (PD). In this study, we aimed to validate whether that the same index could predict the risk of SSI among patients who underwent PD in our patient cohort (Ageo study). Methods: The current validation cohort study was retrospectively conducted on 93 patients at the Department of Surgery, Ageo Central General Hospital, Japan, from January 2015 to October 2019. All patients were subjected to nutritional screening using the GNRI and were followed up for the occurrence of postoperative complications. Additionally, risk factors for developing SSI, as well as patient’s height, body mass index, and preoperative laboratory values, were recorded. Results: Patients were divided into the SSI (N=30) and non-SSI (N=63) groups with a determined SSI incidence rate of 32.3% (30/93). The SSI group had significantly lower GNRI than the non-SSI group (P<0.001). Receiver operating characteristic curve analysis determined a cutoff GNRI value of 94 (sensitivity, 83.3%; specificity, 83.6%), similar to that in the previous study. Univariate and multivariate analyses confirmed that a GNRI of <94 was significantly associated with SSI (P<0.001). Conclusions: The present Ageo study confirmed the consistency of results in Kawaguchi study. Thus, lower GNRI can be a universal marker for SSI risk following PD.