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2.
J Gastroenterol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727823

RESUMO

BACKGROUND: Chronic pancreatitis (CP) is a progressive disease characterized by pancreatic fibrosis for which effective treatment options are lacking. Mesenchymal stem cells (MSCs) have shown potential for fibrosis treatment but face limitations in clinical application. The high-mobility group box 1 (HMGB1) fragment mobilizes MSCs from bone marrow into the blood and has emerged as a promising therapeutic agent for tissue regeneration in various pathological conditions. The aim of this study was to investigate the potential therapeutic effects of systemic administration of the HMGB1 fragment in a mouse model of CP. METHODS: A caerulein-induced CP mouse model was used, and the HMGB1 fragment was administered by tail vein injection. Parameters such as body weight, pancreatic tissue damage, fibrosis, inflammatory cytokine expression, and collagen-related gene expression were evaluated using various assays, including immunohistochemistry, real-time PCR, serum analysis, and single-cell transcriptome analysis. And the migration of MSCs to the pancreas was evaluated using the parabiosis model. RESULTS: Administration of the HMGB1 fragment was associated with significant improvements in pancreatic tissue damage and fibrosis. It suppressed the expression of inflammatory cytokines and activated platelet-derived growth factor receptor-α+ MSCs, leading to their accumulation in the pancreas. The HMGB1 fragment also shifted gene expression patterns associated with pancreatic fibrosis toward those of the normal pancreas. Systemic administration of the HMGB1 fragment demonstrated therapeutic efficacy in attenuating pancreatic tissue damage and fibrosis in a CP mouse model. CONCLUSION: These findings highlight the potential of the HMGB1 fragment as a therapeutic target for the treatment of CP.

3.
Ann Gastroenterol Surg ; 8(3): 498-506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707235

RESUMO

Aim: The number of elderly patients with liver cancer is increasing with the aging society. The Geriatric Prognostic Scoring System is useful in predicting the postoperative prognosis for elderly patients with gastrointestinal cancer. The aim of the present study was to assess the predictive ability of the geriatric prognostic scoring system for postoperative survival in elderly patients with liver cancer. Methods: Eighty-eight patients aged ≥75 years who were treated for primary liver cancer and metastatic liver tumor were retrospectively analyzed. The Geriatric Prognostic Score (GPS) was created by several clinical parameters such as age, sex, type of cancer, stage, performance status, body mass index, and comprehensive geriatric assessment. Each patient was divided into two groups of high-risk to low-risk according to their GPS: ≧30 high-risk group and <30 low-risk. The predictive ability of geriatric prognostic scoring system for postoperative survival was assessed in univariate and multivariate analyses. Results: Of the 88 patients, 75 were diagnosed as hepatocellular carcinoma and 13 as colorectal liver metastasis. After geriatric prognostic scoring system assessments, 26 patients were diagnosed as high-risk and the remaining 62 as low-risk. The 3-year overall survival rates were 78.5% in the low-risk group and 35.1% in the high-risk group (p < 0.001). The univariate and multivariate analyses of overall survival identified high GPS as an independent significant factor (p < 0.001). Conclusions: We could conclude that the geriatric prognostic scoring system is useful in predicting patients' prognosis after hepatectomy and it can provide helpful information to surgeons for determining treatment strategies for elderly patients with liver cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38592474

RESUMO

BACKGROUND: Cell-derived sheets are of global interest for regenerative therapy. Transplanting a sheet for abdominal organs requires a device for laparoscopic delivery to minimize invasiveness. Here, using a porcine model, we aimed to confirm the feasibility of a device developed to deliver sheets to the thoracic cavity in a laparoscopic transplantation procedure. MATERIAL AND METHODS: We used the device to transplant human skeletal myoblast cell sheets onto the liver and measured extra-corporeal, intra-abdominal, and total procedure times for sheet transplantation. Tissues, including the liver and the sheet, were collected two days after transplantation and analyzed histologically. RESULTS: In all experiments (n = 27), all sheets were successfully placed at target locations. The mean (± standard deviation) extra-corporeal, intra-abdominal, and total procedure times were 44 ± 29, 33 ± 12, and 77 ± 36 s, respectively. We found no difference between the two surgeons in procedure times. Histological analyses showed no liver damage with the transplantation and that sheets were transplanted closely onto the liver tissue without gaps. CONCLUSION: We confirmed the feasibility of a simple universal device to transplant cell-derived sheets via laparoscopic surgery. This device could support a minimally invasive procedure for sheet transplantation.

6.
Ann Surg Oncol ; 31(6): 3718-3736, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38502294

RESUMO

BACKGROUND: High skeletal muscle mass might be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC); however, the underlying reason is unclear. We hypothesized that myokines, which are cytokines secreted by the skeletal muscle, function as suppressors of PDAC. We specifically examined irisin, a myokine, which plays a critical role in the modulation of metabolism, to clarify the anticancer mechanisms. METHODS: First, the effect of the conditioned medium (CM) from skeletal muscle cells and from irisin-knockdown skeletal muscle cells on PDAC cell lines was evaluated. We then investigated the effects and anticancer mechanism of irisin in PDAC cells, and evaluated the anticancer effect of recombinant irisin in a PDAC xenograft mouse model. Finally, patients undergoing pancreatic resection for PDAC were divided into two groups based on their serum irisin level, and the long-term outcomes were evaluated. RESULTS: The CM enhanced gemcitabine sensitivity by inducing apoptosis and decreasing cell migration by inhibiting epithelial-mesenchymal transition (EMT) in PDAC cell lines. The CM derived from irisin-knockdown skeletal muscle cells did not affect the PDAC cell lines. The addition of recombinant irisin to PDAC cell lines facilitated sensitivity to gemcitabine by inhibiting the mitogen-activated protein kinase (MAPK) pathway, and decreased migration by inhibiting EMT via the transforming growth factor-ß/SMAD pathway. Xenografts injected with gemcitabine and recombinant irisin grew slower than the xenografts injected with gemcitabine alone. The overall survival was prolonged in the high-irisin group compared with that in the low-irisin group. CONCLUSIONS: Skeletal muscle-derived irisin may affect PDAC by enhancing its sensitivity to gemcitabine and suppressing EMT.


Assuntos
Antimetabólitos Antineoplásicos , Apoptose , Carcinoma Ductal Pancreático , Movimento Celular , Proliferação de Células , Desoxicitidina , Transição Epitelial-Mesenquimal , Fibronectinas , Gencitabina , Músculo Esquelético , Neoplasias Pancreáticas , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Feminino , Humanos , Masculino , Camundongos , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Camundongos Nus , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Idoso
7.
Cancer Sci ; 115(5): 1520-1535, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38475666

RESUMO

Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.


Assuntos
Proliferação de Células , Neoplasias do Colo , Células Endoteliais , Calicreínas , Neoplasias Hepáticas , Animais , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Camundongos , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Humanos , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Calicreínas/metabolismo , Calicreínas/genética , Microambiente Tumoral , Masculino , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Movimento Celular , Feminino , Camundongos Endogâmicos BALB C
8.
Updates Surg ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526700

RESUMO

The clinical impact of replaced right hepatic artery (rRHA) resection during pancreaticoduodenectomy (PD) has not been thoroughly investigated. We therefore assessed the short- and long-term effects of rRHA resection during PD, with special reference to alterations in the volumetric profile of the liver. Patients with rRHA were divided into two groups based on the presence (R group) or absence (nR group) of resection. The nR group included cases of rRHA resection and reconstruction. We compared the postoperative short-term complications and detailed liver volume profile by CT volumetry in the long term between the R and nR groups. Forty-seven patients were eligible for the analyses of short-term outcomes (R: n = 7, nR: n = 40), and no marked difference was observed in the incidence of short-term postoperative complications. The patient cohort for the long-term investigations included 34 cases (R: n = 6, nR: n = 28), excluding patients with early recurrence. There was no significant difference in the preoperative liver volume profiles between the two groups. At 12 postoperative months, although the whole liver (WL) volume did not significantly change in either group, the ratio of the volume of the anterior/posterior sections significantly increased in the R group (R: pre- vs. 12 months, 1.01 vs. 1.28, p < 0.05; nR: pre- vs. 12 months, 1.40 vs. 1.33, p = 0.99). Long-term rRHA resection did not significantly affect the WL volume with alteration of the liver volumetric profile of each section.

10.
Ann Surg Oncol ; 31(5): 2932-2942, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368291

RESUMO

BACKGROUND: Appropriate re-evaluation after neoadjuvant treatment (NAT) is important for optimal treatment selection. Nonetheless, determining the operative eligibility of patients with a modest radiologic response remains controversial. This study aimed to assess the prognostic significance of biologic factors for patients showing a modest radiologic response to NAT and investigate the tumor markers (TMs), CA19-9 alone, DUPAN-II alone, and their combination, to create an index that combines these sialyl-Lewis antigen-related TMs associated with treatment outcomes. METHODS: This study enrolled patients deemed to have a "stable disease" by RECIST classification with slight progression (tumor size increase rate, ≤20%) as their radiologic response after NAT. A sialyl-Lewis-related index (sLe index), calculated by adding one fourth of the serum DUPAN-II value to the CA19-9 value, was created. The prognostic significances of CA19-9, DUPAN-II, and the sLe index were assessed in relation to postoperative outcomes. RESULTS: An sLe index lower than the cutoff value (45.25) was significantly associated with favorable disease-free survival. Moreover, the post-NAT sLe index had a higher area under the curve value for recurrence within 24 months than the post-NAT levels of CA19-9 or DUPAN-II alone. Multivariable analysis showed that a post-NAT sLe index higher than 45.25 was the single independent predictive factor for recurrence within 24 months. CONCLUSIONS: Additional evaluation of biologic factors can potentially enhance patient selection, particularly for patients showing a limited radiologic response to NAT. The authors' index is a simple indicator for the biologic evaluation of multiple combined sialyl-Lewis antigen-related TMs and may offer a better predictive significance.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais , Antígeno CA-19-9 , Antígenos do Grupo Sanguíneo de Lewis , Prognóstico , Fatores Biológicos , Terapia Neoadjuvante , Antígenos de Neoplasias , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/cirurgia , Estudos Retrospectivos
11.
Updates Surg ; 76(2): 479-486, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349569

RESUMO

Postoperative CA19-9 elevation after pancreatic cancer resection suggests recurrence but can also occur in benign conditions. This study aimed to investigate the interpretation of postoperative CA19-9 elevation after pancreatic cancer surgery in terms of cancer recurrence. A cohort of patients undergoing pancreatectomy for pancreatic cancer at our hospital was included. Among them, 52 patients exhibited postoperative CA19-9 elevation without radiological evidence of recurrence. These patients were evaluated with follow-up CA19-9 measurements. The CA19-9 increase rates were calculated based on the first elevation and the follow-up measurement. The association between the CA19-9 increase rate and tumor recurrence was assessed. Patients with a CA19-9 increase rate of ≥ 30% had a significantly higher frequency of recurrence within 3 months compared to those without such an increase (p = 0.0002). Multivariate analysis demonstrated that a CA19-9 increase rate of ≥ 30% was an independent risk factor for recurrence (odds ratio 8.17, p = 0.0309). The CA19-9 value at the first elevation (p = 0.1794) and at the follow-up measurement (p = 0.1121) were not associated with recurrence. After the first postoperative CA19-9 elevation, the CA19-9 increase rate based on follow-up measurements can serve as a predictive factor for tumor recurrence.


Assuntos
Antígeno CA-19-9 , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Prognóstico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Biomarcadores Tumorais
12.
Commun Med (Lond) ; 4(1): 30, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409262

RESUMO

BACKGROUND: Liver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear. METHODS: We longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses. RESULTS: Here, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs. CONCLUSIONS: The third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.


People with a liver transplant don't have as strong an immune response to COVID-19 vaccines as healthy people. This study investigates how these individuals produce protective proteins, called antibodies, and CD4 and CD8 T cell immune responses. CD4 T cells are responsible for commanding the immune response and CD8 T cells for remembering and fighting the virus in future. We found that liver transplant recipients have a weaker ability to produce antibodies after vaccination, which is even more noticeable in those taking drugs to prevent transplant rejection. While a third vaccine dose improves their ability to produce antibodies, and to have a CD4 T cell response, it doesn't boost the CD8 T cell response. In summary, an extra vaccine dose can strengthen the immune response in liver transplant recipients but doesn't improve some aspects of their immune memory.

13.
Hepatol Res ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254248

RESUMO

AIM: Tumor Ki-67 expression reflects prognosis and cancer grade, and biopsy-based preoperative assessment of Ki-67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki-67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki-67 expression in intrahepatic cholangiocarcinoma (ICC). METHOD: We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki-67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n = 18) and low (n = 21) Ki-67 expression. To assess the diagnostic performance of the ADC values for Ki-67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC). RESULTS: The mean and minimum ADC values were significantly lower in the group with high Ki-67 expression. For predicting high Ki-67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki-67 expression level in ICC. CONCLUSION: Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki-67 expression.

14.
Hepatol Res ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279693

RESUMO

AIM: Neoadjuvant transcatheter arterial chemoembolization (TACE) for large tumors is controversial, especially in the minimally invasive surgery era. The aim of this study was to compare features between groups treated with neoadjuvant TACE followed by surgery (TACE + surgery) or upfront surgery for hepatocellular carcinoma >5 cm. METHODS: In this exploratory, multicenter, randomized phase I study, the primary measure was 2-year disease-free survival (DFS). Secondary measures were resection rate, necrosis rate by TACE, 2-year overall survival, and site of recurrence. A total of 30 patients were randomly allocated to each arm. RESULTS: The two arms did not differ in patient characteristics. The median time to surgery from randomization was 48 days for TACE + surgery and 29 for surgery only (p < 0.001). Postoperative morbidities did not differ between arms. The 2-year DFS, overall survival, and resection rates were 56.7%, 80.0%, and 93.3%, respectively, in the TACE + surgery arm, and 56.1%, 89.9%, and 90.0% in the upfront surgery arm. Minimally invasive surgery was carried out in 35.7% in the TACE + surgery arm and in 29.6% in the upfront surgery arm. The median necrosis rate by TACE was 90.0%. In resected specimens, invasion to the hepatic vein was less with TACE + surgery (3.6% vs. 22.2%, p = 0.0380). In cases of 100% necrosis with TACE, 2-year DFS was 100%. Site of recurrence did not differ between groups. CONCLUSION: Neoadjuvant TACE did not improve 2-year DFS, and neoadjuvant TACE allowed delay of surgical treatment without increased morbidity and cancer progress. CLINICAL TRIAL REGISTRATION: UMIN: 000005241.

15.
Surg Laparosc Endosc Percutan Tech ; 34(1): 62-68, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38063517

RESUMO

OBJECTIVE: Percutaneous transhepatic gallbladder aspiration (PTGBA) and/or drainage (PTGBD) are useful approaches in the management of acute cholecystitis in patients who cannot tolerate surgery because of poor general condition or severe inflammation. However, reports regarding its effect on the surgical outcomes of subsequent laparoscopic cholecystectomy (LC) are sparse. The aim of this retrospective study was to investigate the influence of PTGBA on surgical outcomes of subsequent LC by comparing the only-PTGBA group, including patients who did not need the additional-PTGBD, versus the additional-PTGBD group, including those who needed the additional-PTGBD after PTGBA. PATIENTS AND METHODS: We conducted a post hoc analysis of our multi-institutional data. This study included 63 patients who underwent LC after PTGBA, and we compared the surgical outcomes between the only-PTGBA group (n = 56) and the additional-PTGBD group (n = 7). RESULTS: No postoperative complications occurred among the 63 patients, and the postoperative hospital stay was 11 ± 12 days. Fourteen patients (22.2%) had a recurrence of cholecystitis, of whom 7 patients (11.1%) needed the additional-PTGBD after PTGBA. Significantly longer operative time (245 ± 74 vs 159 ± 65 min, P = 0.0017) and postoperative hospital stay (22 ± 27 vs 10 ± 9 d, P = 0.0118) and greater intraoperative blood loss (279 ± 385 vs 70 ± 208 mL, P = 0.0283) were observed among patients in the additional-PTGBD group compared with the only-PTGBA group, whereas the rates of postoperative complications (Clavien-Dindo grade ≥3: 0% each) and conversion to open surgery (28.6% vs 8.9%, P = 0.1705) were comparable. CONCLUSION: PTGBA for acute cholecystitis could result in good surgical outcomes of subsequent LC, especially regarding postoperative complications. However, we should keep in mind that the additional-PTGBD after PTGBA failure, which sometimes happened, would be associated with increased operative difficulty and longer recovery.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Humanos , Vesícula Biliar/cirurgia , Estudos Retrospectivos , Colecistite Aguda/cirurgia , Colecistite Aguda/etiologia , Drenagem/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
16.
Int J Cancer ; 154(5): 912-925, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37699232

RESUMO

Insufficient cancer treatment can induce senescent cancer cell formation and treatment resistance. The characteristics of induced senescent cancer (iSnCa) cells remain unclear. Pancreatic ductal adenocarcinoma (PDAC) has a low and nondurable response rate to current treatments. Our study aimed to analyze the properties of iSnCa cells and the relationship between cellular senescence and prognosis in PDAC. We evaluated the characteristics of gemcitabine-induced senescent cancer cells and the effect of senescence-associated secretory phenotype (SASP) factors released by iSnCa cells on surrounding PDAC cells. The relationship between cellular senescence and the prognosis was investigated in 50 patients with PDAC treated with gemcitabine-based neoadjuvant chemotherapy. Exposure to 5 ng/mL gemcitabine-induced senescence, decreased proliferation and increased senescence-associated ß-galactosidase-cell staining without cell death in PDAC cells; the expression of glutaminase1 (GLS1) and SASP factors also increased and caused epithelial-mesenchymal transition in surrounding PDAC cells. iSnCa cells were selectively removed by the GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) through apoptosis induction. Cellular senescence was induced in PDAC cells via insufficient gemcitabine in subcutaneous tumor model mice. GLS1 expression was an independent prognostic factor in patients with PDAC who received gemcitabine-based neoadjuvant chemotherapy. This is the first study to identify the relationship between senescence and GLS1 in PDAC. Low-dose gemcitabine-induced senescence and increased GLS1 expression were observed in PDAC cells. Cellular senescence may contribute to treatment resistance of PDAC, hence targeting GLS1 in iSnCa cells may improve the therapeutic effect.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Gencitabina , Desoxicitidina , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos
17.
Langenbecks Arch Surg ; 408(1): 353, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37695403

RESUMO

PURPOSE: This study aimed to investigate whether clinical outcomes varied based on the tumor location within the pancreatic body and tail in patients with pancreatic cancer (PC). METHODS: Ninety-five patients who had undergone a distal pancreatectomy for resectable (R) or borderline resectable (BR) PC within the pancreatic body or tail region were retrospectively investigated and divided into four groups (three subgroups of R-PC according to tumor location, and BR-PC): R-PC in the pancreatic body region (group A, n = 24), R-PC on the right side of the pancreatic tail region (group B, n = 17), R-PC on the left side of the pancreatic tail region (group C, n = 29), and BR-PC located in any region within the pancreatic body and tail (group BR, n = 25). RESULTS: Group C patients showed a higher incidence of pretreatment splenic artery and vein involvement than group A and B patients (splenic artery: 8.3/11.8/41.4%, p < 0.010; splenic vein: 25.0/23.5/79.3%, p < 0.010, in groups A/B/C, respectively). The overall survival of group C patients was significantly unfavorable compared to that of group A and B patients (median: 3.9/4.2/2.3 years in groups A/B/C, p = 0.029, respectively). Pretreatment clinical factors were comparable between group C and group BR. Median survival rates were comparable between group C and BR patients (2.3 and 2.0 years, respectively) (p = 0.93). CONCLUSIONS: Differences in anatomical location within the pancreatic body and tail characterize the unfavorable outcomes of PC near the splenic hilum.


Assuntos
Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Baço , Pâncreas/cirurgia
18.
Clin Transplant ; 37(11): e15090, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37534624

RESUMO

INTRODUCTION: Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. METHODS: We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14 days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. RESULTS: The mean/median donor and recipient BSAs were 1.63 m2 /1.65 m2 , and 1.57 m2 /1.55 m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14 days was significantly higher in the high group than in the low group (p < .01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p < .01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. CONCLUSION: D/R size mismatch is associated with graft thrombosis after pancreas transplantation.


Assuntos
Transplante de Rim , Transplante de Pâncreas , Trombose , Humanos , Estudos Retrospectivos , Transplante de Pâncreas/efeitos adversos , Doadores de Tecidos , Sobrevivência de Enxerto , Trombose/etiologia , Pâncreas , Fatores de Risco
19.
Surg Case Rep ; 9(1): 143, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561260

RESUMO

BACKGROUND: After orthotopic liver transplantation (OLT), complications such as hepatic artery stenosis, thrombosis, and bleeding are possible. Hepatic artery pseudoaneurysms (HAP) are prone to rupture, rupture hemorrhage, and increased mortality risk. Endovascular treatment of HAP may result in recurrence, even after successful embolization with thrombin. Formation of a HAP in the common hepatic artery (CHA) is challenging because the CHA is the only artery in the liver graft after OLT. Therefore, CHA embolization in HAP is not an initial option. We report a case of HAP at the CHA after OLT that was treated with endovascular therapy, resulting in the occlusion of the CHA with coil embolization, achieving a radical cure. CASE PRESENTATION: A 59-year-old man with decompensated hepatitis C virus cirrhosis underwent deceased donor whole-liver transplantation after graft failure of a living donor liver transplantation. After the second transplantation, the patient developed infectious narrow-necked HAP at the CHA associated with postoperative pancreatic fistula. Repeated transcatheter arterial embolization with thrombin and n-butyl-2-cyanoacrylate was unsuccessful, as confirmed by postprocedure angiography, which revealed recanalization and regrowth of the HAP. Eight months after the first transcatheter arterial embolization, the patient presented with a chief complaint of abdominal pain due to an enlarged HAP. Angiography of the superior mesenteric artery (SMA) revealed a collateral bypass around the bile duct from the SMA to the liver graft. Coil embolization of the HAP in the CHA completely occluded the HAP without complications. More than 2 years after coil embolization, the liver graft function test results remained within normal limits without HAP recurrence. CONCLUSIONS: HAP at the CHA after liver transplantation can be fatal if ruptured. Because the liver is a highly angiogenic organ, even if initial treatment is not successful, radical treatment to occlude the CHA with HAP is possible if sufficient collateral vessels are developed.

20.
Langenbecks Arch Surg ; 408(1): 340, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37639107

RESUMO

PURPOSE: Pancreaticoduodenectomy (PD) for pancreatic cancer carries a high risk of massive intraoperative blood loss. The artery first approach (AFA) prevents blood loss during PD, but the optimal approach is unclear. The first jejunal vein (FJV) often comprises multiple veins and broadly supports venous drainage of the proximal jejunum. Its ligation carries a risk of proximal jejunum congestion. Here we investigated the anatomical characteristics of PD-associated vessels and AFA approach selection based on FJV anatomy. METHODS: This study included 148 Japanese living donors for liver transplantation. We reviewed their computed tomography images and assessed the anatomical pattern of PD-associated vessels in terms of FJV anatomy. RESULTS: The FJV traveled posterior to the superior mesenteric artery in 128 patients (86.5%, dorsal group) and anterior in 20 (13.5%, ventral group). The predominant draining vein of the inferior pancreaticoduodenal vein was the superior mesenteric vein in the ventral group (87.5%) and the FJV in the dorsal group (97.9%). Compared with the dorsal group, the ventral group had a significantly greater percentage with the superior mesenteric vein ventral to the superior mesenteric artery (30.0% versus 10.9%) and a significantly larger posterior superior pancreaticoduodenal vein diameter (3.2 ± 0.9 versus 2.7 ± 0.6 mm, p = 0.0029). These results were validated in patients with pancreatic head cancer. CONCLUSIONS: The anatomical characteristics of PD-associated vessels differed significantly between groups defined by FJV anatomy. Understanding the venous anatomy, especially the FJV, could support selection of the best approach in AFA for PD.


Assuntos
Veias Mesentéricas , Pancreaticoduodenectomia , Humanos , Artéria Mesentérica Superior/diagnóstico por imagem , Veias Mesentéricas/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas
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