There is an urgent need to establish biomarkers for the treatment of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the usefulness of the combined assessment of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and duke pancreatic monoclonal antigen type 2 (DUPAN-2) in PDAC.We retrospectively investigated the impact of three tumor markers on overall survival (OS) and recurrence-free survival (RFS). Patients were classified into two groups: upfront surgery (US) and neoadjuvant chemoradiation (NACRT) groups.In total, 310 patients were evaluated. In the US group, patients who had all three elevated markers showed a significantly worse prognosis than the others (median: 16.4 months, P = .005). In the NACRT group, patients who had elevated CA 19-9 and CEA levels after NACRT had significantly worse prognosis than the others (median: 26.2 months, P < .001). The elevated DUPAN-2 levels before NACRT were associated with significantly worse prognosis than normal levels (median: 44.0 vs 59.2 months, P = .030). Patients who had elevated DUPAN-2 levels before NACRT with elevated CA 19-9 and CEA levels after NACRT showed extremely poor RFS (median: 5.9 months). Multivariate analysis revealed that a modified triple-positive tumor marker indicating elevated DUPAN-2 levels before NACRT and elevated CA19-9 and CEA levels after NACRT was an independent prognostic factor of OS (hazard ratio: 2.49, P = .007) and RFS (hazard ration: 2.47, P = .007).The combined evaluation of three tumor markers may provide useful information for the treatment of patients with PDAC.
Abstract 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.
Background/Aims: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. Methods: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. Results: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. Conclusion: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.
Abstract Background Gastric artery aneurysms are rarely caused by segmental arterial mediolysis (SAM), a condition that often involves multiple vessels. The clinical course of SAM after vessel rupture may vary depending on the involved vessels. For example, the “double-rupture phenomenon” observed following the rupture of the splenic artery aneurysm manifests as a biphasic and relatively slow clinical course. Even in cases of rupture of gastric artery aneurysm, the double-rupture phenomenon has only been reported in two cases so far. However, the rupture was not caused by SAM in either case. Herein, we present the apparent first case of a right gastric artery (RGA) aneurysm rupture caused by SAM that presented with a biphasic clinical course, possibly due to the double-rupture phenomenon. Case presentation A 54-year-old woman was transferred to the emergency department with severe abdominal pain and a cold sweat for a duration of 3 h. She had developed mild abdominal pain and nausea 3 days earlier. Her vital signs were stable. Physical examination revealed tenderness in the epigastric area. Abdominal contrast-enhanced computed tomography revealed an RGA aneurysm with contrast media extravasation. A diagnosis of hemoperitoneum following a ruptured RGA aneurysm was made, and the patient underwent angiography. However, this modality did not reveal any extravasation from the RGA due to an interruption in the peripheral branch of the artery. Nevertheless, to prevent major bleeding, we performed coil embolization at the point of interruption in the RGA, which we suspected to be a ruptured aneurysm. A distal gastrectomy with Roux-en-Y reconstruction for aneurysm resection was performed the following day. There were no postoperative complications, and the patient was discharged 17 days after surgery. Histologically, the RGA demonstrated multiple vacuoles in the medial muscle layer, which were characteristic of SAM. Conclusions An RGA aneurysm rupture should be considered a differential diagnosis in patients presenting with hemoperitoneum with a slow or biphasic clinical course.
Abstract Background The impact of the surgical margin (SM) on long-term survival remains controversial. This study retrospectively investigated the impact of the SM on prognosis and recurrence of intrahepatic cholangiocarcinoma (ICC) and evaluated the optimal margin width. Methods We reviewed the medical records of 58 ICC patients who underwent macroscopically curative surgery. Results The patients were classified into five categories according to the SM; R1, 0 to < 1 mm, 1 to < 5 mm, 5 to < 10 mm, and ≥ 10 mm. The prognosis tended to be different for SM < 1 mm or SM ≥ 1 mm, therefore, the cut-off value was set at 1 mm. Thirty-three (56.9%) patients had an SM ≥ 1 mm, and 25 (43.1%) had an SM < 1 mm. The multivariate analysis identified SM < 1 mm ( p = 0.027) and microvascular invasion ( p = 0.026) as independent prognostic factors of overall survival. After the propensity score-matching based on tumor-related factors, the overall survival and relapse-free survival rates of the SM < 1 mm group were significantly lower than those of the SM ≥ 1 mm group ( p = 0.013 and p = 0.025, respectively). Peritoneal dissemination was significantly increased in the SM < 1 mm group than in the SM ≥ 1 mm group ( p = 0.007). The post-recurrence survival rate of the SM < 1 mm group was significantly lower than that of the SM ≥ 1 mm group ( p = 0.012). Conclusions This study suggests that an SM of at least 1 mm should be achieved during ICC resection. An SM < 1 mm may indicate a higher risk of peritoneal dissemination.
Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long-term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19-9 (CA19-9) levels at diagnosis and preoperative chemotherapy with normalization of CA19-9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long-term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5-year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long-term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.
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