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1.
Cancer Immunol Immunother ; 73(7): 126, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733406

RESUMO

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/µL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Fatores de Risco , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Incidência
2.
Oncol Lett ; 27(6): 286, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38736740

RESUMO

Tailgut cyst is a rare congenital cyst occurring in the retrorectal space and development of neoplastic lesions in tailgut cyst has been reported. Due to the rarity of the tumor, the histogenesis of neoplastic lesions in tailgut cyst has remained elusive. In the present study, the clinicopathological features of tailgut cyst were analyzed with a particular focus on the development of neoplastic lesions. The clinicopathological features of four patients with tailgut cyst (one female and three males) were retrospectively reviewed. No symptoms were present in two patients. Perineal discomfort, and constipation and urinary retention, were described in the other two patients, respectively. Magnetic resonance imaging showed that the cystic lesions were hypointense on T1- and hyperintense on T2-weigted images in all patients. Histopathological analysis revealed that all lesions were multilocular, and cystic walls were covered by squamous and ciliated epithelia without nuclear atypia. The development of neoplastic lesions was noted in two patients. Dysplastic change composed of piling-up proliferation of glandular cells with mild to moderate nuclear atypia was present in one patient, and invasive adenocarcinoma with a dysplasia component was observed in another patient. Dysplasia of the glandular cells, as seen in two patients in the present series, may be a precursor lesion of invasive adenocarcinoma; therefore, adenocarcinoma arsing in tailgut cyst may show a dysplasia-carcinoma sequence. While the reported incidence of neoplastic lesions in tailgut cysts is ~9% or less, their frequency remains to be accurately determined. Therefore, complete surgical resection is important for the management of patients with tailgut cyst. Additional clinicopathological and molecular studies with large cohorts may be required to clarify the histogenesis of neoplastic lesion in tailgut cyst.

3.
Cureus ; 16(4): e57929, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725791

RESUMO

Appendiceal metastases of breast cancer (BC) are very rare, and there are few reports of resection. Asymptomatic appendiceal enlargement is often suspected to be a primary appendiceal tumor, making it difficult to suspect metastatic tumors, especially metastases from BC. On the other hand, advances in drug therapy, including hormonal therapy for BC, have prolonged survival, and there is a possibility of encountering metastatic cases that have rarely been seen before. We herein present a case in which an enlarged appendix, identified during hormonal therapy for advanced BC, was laparoscopically removed and diagnosed as BC metastasis. A 53-year-old woman had been diagnosed with invasive ductal carcinoma (IDC) based on a breast biopsy, and the appendiceal specimen was diagnosed as invasive lobular carcinoma (ILC). We herein report this unique case and provide a detailed review of 13 previous reports.

4.
Mol Biol Rep ; 51(1): 643, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727775

RESUMO

BACKGROUND: Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms. METHODS AND RESULTS: Male Sprague-Dawley rats received either baicalein (5 mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15 min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30 min after hepatic ischemia and hepatectomy. In interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1ß-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt. CONCLUSIONS: Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.


Assuntos
Apoptose , Modelos Animais de Doenças , Flavanonas , Hepatectomia , Hepatócitos , Interleucina-1beta , Fígado , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Hepatectomia/métodos , Masculino , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Apoptose/efeitos dos fármacos , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Pancreatology ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548551

RESUMO

PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

7.
Front Oncol ; 14: 1365305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515576

RESUMO

Background: Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and irradiation of light at an excitation wavelength that damages tumor cells without causing significant damage to normal tissue. We developed indocyanine green (ICG)-modified liposomes in which paclitaxel (PTX) was encapsulated (ICG-Lipo-PTX). ICG-Lipo-PTX accumulates specifically in tumors due to the characteristics of the liposomes. The thermal and photodynamic effects of ICG and the local release of PTX by irradiation are expected to induce not only antitumor effects but also cancer immunity. In this study, we investigated the antitumor effects of ICG-Lipo-PTX in breast cancer. Methods: The antitumor effects of ICG-Lipo-PTX were examined in xenograft model mice subcutaneously implanted with KPL-1 human breast cancer cells. ICG-Lipo-PTX, ICG-Lipo, or saline was administered intraperitoneally, and the fluorescence intensity was measured with a fluorescence imaging system (IVIS). Intratumor temperature, tumor volume, and necrotic area of tumor tissue were also compared. Next, we investigated the induction of cancer immunity in an allogeneic transplantation model in which BALB-MC mouse breast cancer cells were transplanted subcutaneously in the bilateral inguinal region. ICG-Lipo-PTX was administered intraperitoneally, and PDT was performed on only one side. The fluorescence intensity measured by IVIS and the bilateral tumor volumes were compared. Cytokine secretory capacity was also evaluated by ELISPOT assay using splenocytes. Results: In the xenograft model, the fluorescence intensity and temperature during PDT were significantly higher with ICG-Lipo-PTX and ICG-Lipo in tumor areas than in nontumor areas. The fluorescence intensity in the tumor area was reduced to the same level as that in the nonirradiated area after two times of irradiation. Tumor growth was significantly reduced and the percentage of necrotic area in the tumor was higher after PDT in the ICG-Lipo-PTX group than in the other groups. In the allograft model, tumor growth on day 14 in the ICG-Lipo-PTX group was significantly suppressed not only on the PDT side but also on the non-PDT side. In addition, the secretion of interferon-γ and interleukin-2 was enhanced, whereas that of interleukin-10 was suppressed, in the ICG-Lipo-PTX group. Conclusion: The PDT therapy with ICG-Lipo-PTX may be an effective treatment for breast cancer.

8.
Oncol Lett ; 27(3): 124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38348389

RESUMO

Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and highly lethal subtype of HCC. The present study aimed to explore the unique markers of SHCC using whole gene expression analysis. Subsequently, gene expression analysis was performed using five sarcomatoid and seven carcinomatoid components of seven tissues from patients with SHCC. The results demonstrated a significant downregulation of polybromo 1 (PBRM1) gene expression in the sarcomatoid components. Immunohistochemical staining also indicated a decreased expression of PBRM1 in the sarcomatoid components. Moreover, gene ontology enrichment analysis revealed that most of the 336 differentially expressed genes between the sarcomatoid and carcinomatoid components were involved in functions associated with DNA replication and histone methylation, which was consistent with the loss of function of PBRM1 which encodes Switch/sucrose-non-fermentable chromatin remodeling complex protein. Therefore, the results of the present study suggested that PBRM1 may be a candidate biomarker for the evaluation of SHCC.

9.
Colorectal Dis ; 26(4): 760-765, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321510

RESUMO

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.


Assuntos
Implantes Absorvíveis , Laparoscopia , Recidiva Local de Neoplasia , Ácido Poliglicólico , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/radioterapia , Laparoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Resultado do Tratamento , Duração da Cirurgia
10.
Int J Mol Sci ; 25(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38203749

RESUMO

Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1ß-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.


Assuntos
Hepatectomia , Isotiocianatos , Traumatismo por Reperfusão , Sulfóxidos , Animais , Ratos , NF-kappa B , Fator de Necrose Tumoral alfa , Isquemia Quente , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Mediadores da Inflamação , Interleucina-1beta/genética , Isquemia
11.
Nutrients ; 16(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38257149

RESUMO

A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration.


Assuntos
Traumatismo por Reperfusão , Cogumelos Shiitake , Animais , Ratos , Hepatectomia/efeitos adversos , Fígado , Isquemia , Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Mediadores da Inflamação , RNA Mensageiro
12.
BMC Surg ; 23(1): 314, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845691

RESUMO

PURPOSE: This study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images at intervals every 6 months. METHODS: We retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images. RESULTS: 470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3-55.6]. In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0-58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14-13.05], p = 0.0003). CONCLUSION: IH occurred in 10% and 7.9% at 1 year and 6 months after LC. By examining CT images taken for the postoperative surveillance of colorectal cancer, we were able to investigate the occurrence of IH in detail.


Assuntos
Neoplasias Colorretais , Hérnia Incisional , Laparoscopia , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Colectomia/efeitos adversos , Colectomia/métodos , Incidência , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Fatores de Risco
13.
J Gastrointest Surg ; 27(12): 2780-2786, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37884751

RESUMO

INTRODUCTION: It is unclear whether the histological glandular differentiation (HGD) score that evaluates the tumor grade of two dominant components is prognostic for survival in patients with intrahepatic cholangiocarcinoma (ICC). METHOD: We retrospectively analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at 5 university hospitals in the Kansai region of Japan. RESULTS: Survival was statistically significantly stratified by trinal HGD grade (p < 0.05). Median disease-free survival (DFS) of patients with high HGD grade was significantly shorter compared with moderate HGD grade (13.0 vs 31.2 months, respectively; p = 0.004). By Cox proportional hazards regression analysis, HGD grade had the fifth-highest hazard ratio (HR = 1.77, p = 0.002) for DFS after vascular and/or biliary invasion, extrahepatic invasion, lymph node metastasis and multiple tumors. Multivariate logistic regression analysis revealed four predictors of early recurrence after hepatectomy (lymph node metastasis: odds ratio [OR] = 3.74, p = 0.001; tumor size > 50 mm: OR = 2.80, p = 0.002; HGD grade, high: OR = 2.11, p = 0.012; and vascular or biliary tract invasion: OR = 2.11, p = 0.048). CONCLUSION: Trinal HGD grade had a significant prognostic impact on the survival of patients with ICC after radical hepatectomy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Estudos Retrospectivos , Ductos Biliares Intra-Hepáticos/cirurgia , Metástase Linfática/patologia , Neoplasias dos Ductos Biliares/patologia , Prognóstico , Hepatectomia
14.
Cancers (Basel) ; 15(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37296868

RESUMO

BACKGROUND/PURPOSE: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. METHODS: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. RESULTS: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58-0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48-0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. CONCLUSION: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy.

15.
Jpn J Clin Oncol ; 53(8): 704-713, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37248668

RESUMO

OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.


Assuntos
Proteína C-Reativa , Neoplasias Pancreáticas , Humanos , Proteína C-Reativa/metabolismo , Quimioterapia de Indução , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
16.
Shock ; 60(1): 84-91, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37141168

RESUMO

ABSTRACT: Sepsis after a major hepatectomy is a critical problem. In septic shock, the inflammatory mediator, nitric oxide (NO), is overproduced in hepatocytes and macrophages. The natural antisense (AS) transcripts, non-coding RNAs, are transcribed from a gene that encodes inducible nitric oxide synthase (iNOS). iNOS AS transcripts interact with and stabilize iNOS mRNAs. A single-stranded "sense oligonucleotide" (designated as SO1) corresponding to the iNOS mRNA sequence inhibits mRNA-AS transcript interactions and reduces iNOS mRNA levels in rat hepatocytes. In contrast, recombinant human soluble thrombomodulin (rTM) treats disseminated intravascular coagulopathy by suppressing coagulation, inflammation, and apoptosis. In this study, the combination therapy of SO1 and a low dose of rTM was evaluated for hepatoprotection in a rat septic shock model after partial hepatectomy. Rats underwent 70% hepatectomy, followed by intravenous (i.v.) injection of lipopolysaccharide (LPS) after 48 h. SO1 was injected (i.v.) simultaneously with LPS, whereas rTM was injected (i.v.) 1 h before LPS injection. Similarly to our previous report, SO1 increased survival after LPS injection. When rTM, which has different mechanisms of action, was combined with SO1, it did not interfere with the effect of SO1 and showed a significant increase in survival compared with LPS alone treatment. In serum, the combined treatment decreased NO levels. In the liver, the combined treatment inhibited iNOS mRNA and protein expression. A decreased iNOS AS transcript expression by the combined treatment was also observed. The combined treatment decreased mRNA expression of the inflammatory and pro-apoptotic genes while increasing that of the anti-apoptotic gene. Furthermore, the combined treatment reduced the number of myeloperoxidase-positive cells. These results suggested that the combination of SO1 and rTM has therapeutic potential for sepsis.


Assuntos
Sepse , Choque Séptico , Humanos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Hepatectomia , RNA Mensageiro/metabolismo , Oligonucleotídeos , Lipopolissacarídeos/farmacologia , Trombomodulina/genética , Trombomodulina/uso terapêutico , Trombomodulina/metabolismo , Sepse/tratamento farmacológico , Óxido Nítrico/metabolismo
17.
Pancreatology ; 23(4): 367-376, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37088586

RESUMO

BACKGROUND: /Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications. METHODS: Twenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences. RESULTS: Of the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and ß-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01). CONCLUSIONS: The diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.


Assuntos
Carcinoma Ductal Pancreático , Microbioma Gastrointestinal , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Desoxicitidina/uso terapêutico , RNA Ribossômico 16S , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Pancreáticas
18.
Asian Pac J Cancer Prev ; 24(3): 1089-1094, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974565

RESUMO

OBJECTIVE: Liver resection in the super elderly patients remains challenging because of comorbidities and operative tolerability. METHODS: In this study, we compared postoperative complications and survival in patients aged ≥85 yr included five patients aged ≥90 yr with those aged 70-79 and 80-84 yr at a single institution. RESULTS: Three hundred sixty-seven patients aged ≥70 yr underwent liver resection and were divided into three groups based on age at operation between 2010 and 2022; (a) 70-79 yr (median of 74 yr, n=245), (b) 80-84 yr (median of 82 yr, n=81), and (c) ≥85 yr (median of 87 yr, n=41). In the ≥85 yr group (90-yr-old group), twenty-five patients (four) had hypertension, fourteen (one) had diabetes mellitus, seven (one) had cardiovascular disease, and five patients (one) had dementia. The rate of comorbidities did not differ significantly among three groups. The rate of postoperative complications (Clavien-Dindo grade 3a≤) was 25% in the 70- to 79-yr-old group, 27% in the 80- to 84-yr-old group, and 17% in the ≥85-yr-old group (20% in the ≥90-yr-old group) (N.S.). The 1- and 5-yr patient survival rates in the ≥85-yr-old group were 90.1% and 48.5% respectively, compared with 86.7% and 60.9% in the 70- to 79-yr-old group and 83.8% and 66.3% in the 80- to 84-yr-old group, respectively (N.S.). CONCLUSION: Despite the management of comorbidities, liver resection for well-selected super elderly patients, such as those aged ≥85 yr included ≥90yr, has acceptable outcomes. The age of patient is not an absolute contraindication to liver resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Hepatectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
19.
Surg Today ; 53(9): 1100-1104, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36790475

RESUMO

Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.


Assuntos
Estudantes de Medicina , Humanos , Inquéritos e Questionários , Universidades , Japão
20.
Surg Case Rep ; 9(1): 17, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36732357

RESUMO

BACKGROUND: Malignant tumors with rhabdoid features are rare, highly aggressive, and some of them are characterized by SMARCB1 (INI1) loss. Although cases of rhabdoid carcinoma are extremely rare, its occurrence in the colon has been reported previously. CASE PRESENTATION: A 71-year-old Japanese female patient presented with loss of appetite, fatigue, and weight loss. Computed tomography demonstrated a tumor in the right colon that infiltrated the surrounding kidneys and swelling of the left supraclavicular and periaortic lymph nodes. Laparotomy revealed that the tumor was unresectable because it had directly invaded the head of the pancreas and duodenum. Therefore, ileocecal vascularized bulky lymph nodes were sampled, and gastrojejunostomy with Braun's anastomosis and ileotransversostomy were performed as palliative procedures. Histopathological examination of the lymph nodes revealed that the neoplastic cells had rich eosinophilic cytoplasm and eccentrically located large nuclei characteristic of rhabdoid carcinoma. In addition, these neoplastic cells lacked SMARCB1 expression; therefore, the patient was diagnosed with SMARCB1-negative rhabdoid carcinoma. The postoperative course was uneventful. Molecular analysis confirmed that the neoplastic cells had high microsatellite instability (MSI); therefore, two cycles of pembrolizumab were administered. However, no clinical benefit was noted, and the patient died 3 months postoperatively. CONCLUSION: This is the first report of a case of SMARCB1-negative rhabdoid colon carcinoma with high MSI treated with pembrolizumab. Rhabdoid carcinoma is highly aggressive; therefore, additional studies are required to determine the therapeutic strategy for SMARCB1-negative rhabdoid colorectal carcinoma.

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