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1.
Am J Case Rep ; 25: e944720, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39143729

RESUMO

BACKGROUND Reversed intestinal malrotation is an extremely rare disease, with an incidence of 1 in 250 000. In Japan, application of robotic-assisted colorectal cancer surgery is expected to increase. There are no reports of robot-assisted surgery for cecal cancer with reversed intestinal malrotation. CASE REPORT An 84-year-old Japanese man with epigastric pain and abdominal distention was referred to our hospital's Department of Gastroenterology for thorough examination. Colonoscopy revealed a semicircumferential type 2 tumor in the cecum and ascending colon. Gastrografin contrast study showed that the large intestine was entirely on the patient's right side and the small intestine was shifted to the left side. Contrast-enhanced computed tomography revealed enlarged lymph nodes near the tumor, and masses were observed at the liver, which were believed to be metastases. Following examination, reversed intestinal malrotation and concurrent cecal cancer was diagnosed. The patient was referred to our department for surgery and underwent robot-assisted ileocecal resection with D3 lymphadenectomy. The postoperative course was favorable, and patient was discharged on the sixth postoperative day, without complications. According to the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma 9th edition, the pathological diagnosis was pT4b (ileum), pN1b, cM1a (H1 [grade A]), and pStage IVa cancer. After considering tumor stage and patient's overall condition in consultation with his family, we decided against palliative systemic therapy. The patient was provided with best supportive care. CONCLUSIONS Robot-assisted surgery might be useful in manipulation of the dissection of adhesions, owing to its capacity for high-resolution 3-dimensional imaging and forceps manipulation, using articulated functions.


Assuntos
Neoplasias do Ceco , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Neoplasias do Ceco/cirurgia , Neoplasias do Ceco/complicações , Idoso de 80 Anos ou mais , Volvo Intestinal/cirurgia , Anormalidades do Sistema Digestório/cirurgia , Anormalidades do Sistema Digestório/complicações , Adenocarcinoma/cirurgia , Adenocarcinoma/complicações
2.
World J Surg Oncol ; 22(1): 209, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097743

RESUMO

INTRODUCTION: Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs. METHODS: Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I). RESULTS: Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts. CONCLUSION: Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Retais , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Hepatectomia/mortalidade , Hepatectomia/métodos , Taxa de Sobrevida , Prognóstico , Idoso , Seguimentos , Japão/epidemiologia , Adulto , China/epidemiologia , Estudos Retrospectivos
3.
Ann Surg ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016004

RESUMO

OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=-0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

4.
Cancer Gene Ther ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039195

RESUMO

Toca 511, a tumor-selective retroviral replicating vector encoding the yeast cytosine deaminase (yCD) gene, exerts direct antitumor effects through intratumoral prodrug 5-fluorocytosine (5-FC) conversion to active drug 5-fluorouracil by yCD, and has demonstrated therapeutic efficacy in preclinical and clinical trials of various cancers. Toca 511/5-FC treatment may also induce antitumor immunity. Here, we first examined antitumor immune responses activated by Toca 511/5-FC treatment in an immunocompetent murine pancreatic cancer model. We then evaluated the therapeutic effects achieved in combination with anti-programmed cell death protein 1 antibody. In the bilateral subcutaneous tumor model, as compared with the control group, enhanced CD8+ T-cell-mediated cytotoxicity and increased T-cell infiltration in Toca 511-untransduced contralateral tumors were observed. Furthermore, the expression levels of T-cell co-inhibitory receptors on CD8+ T-cells increased during treatment. In the bilateral subcutaneous tumor model, combination therapy showed significantly stronger tumor growth inhibition than that achieved with either monotherapy. In an orthotopic tumor and peritoneal dissemination model, the combination therapy resulted in complete regression in both transduced orthotopic tumors and untransduced peritoneal dissemination. Thus, Toca 511/5-FC treatment induced a systemic antitumor immune response, and the combination therapy could be a promising clinical strategy for treating metastatic pancreatic cancer.

5.
Endocr J ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069495

RESUMO

As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49-66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.

6.
Ann Gastroenterol Surg ; 8(4): 660-667, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957557

RESUMO

Purpose: Operations for malignant diseases of the bile duct, pancreas, and esophagus are the most invasive gastroenterological surgeries. The frequency of complications after these surgeries is high, which affects the postoperative course and mortality. In patients who undergo these types of surgeries, continuous monitoring of the perioperative central venous oxygen saturation (ScvO2) is possible via a central venous catheter. We aimed to investigate the relationship between continuously monitored perioperative ScvO2 values and postoperative complications. Methods: The medical records of 115 patients who underwent highly invasive gastroenterological surgeries and ScvO2 monitoring from April 2012 to March 2014 were analyzed. Sixty patients met the inclusion criteria, and their ScvO2 levels were continuously monitored perioperatively. The relationship between ScvO2 levels and major postoperative complications, defined as Clavien-Dindo grade ≥ III, was examined using uni- and multivariate analysis. Results: Thirty patients developed major postoperative complications. The adequate cut-off value derived from receiver operating curves of the postoperative average ScvO2 levels for predicting major complications was 75%. Multivariate analysis revealed that low average postoperative ScvO2 levels (p = 0.016) and blood loss ≥ 1000 mL (p = 0.039) were significant predictors of major postoperative complications. Conclusions: Low perioperative ScvO2 values were associated with an increased risk of major postoperative complications. Continuous ScvO2 monitoring will help prevent postoperative complications.

7.
Gan To Kagaku Ryoho ; 51(6): 651-653, 2024 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-39009524

RESUMO

The patient, an 83-year-old woman, was diagnosed with ER- and PgR-positive left breast cancer(T2N0M0, Stage ⅡA) at the age of 68. At the time, she underwent preoperative chemotherapy followed by Bp+Ax and postoperative radiotherapy to the conserved breast. She also received endocrine therapy as adjuvant therapy. At the age of 73, she underwent radiotherapy for multiple bone metastases and left axillary lymphadenectomy due to left axillary lymph node recurrence. After surgery, she received 4 regimens of endocrine therapy over a period of 5 years and 1 month for bone metastases. At the age of 79, S-1 was administered for pulmonary metastasis which continued for the next 2 years and 8 months. At the age of 81, palbociclib+letrozole were administered for 1 year and 8 months owing to the progression of bone metastases. At the age of 83, she developed liver metastases and was administered ethinyl estradiol, starting at 1.5 mg/day and continued at a reduced dose of 0.5 mg/day for 9 months. The reduction in tumor markers after treatment initiation was rapid, and there were no serious adverse events. Ethinyl estradiol was useful for maintaining QOL in this elderly patient with recurrent breast cancer.


Assuntos
Neoplasias da Mama , Etinilestradiol , Recidiva , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Etinilestradiol/administração & dosagem , Etinilestradiol/uso terapêutico , Idoso de 80 Anos ou mais , Receptores de Estrogênio/análise , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores de Progesterona/metabolismo
8.
Surg Today ; 54(8): 817-828, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38829562

RESUMO

Telesurgery is expected to improve medical access in areas with limited resources, facilitate the rapid dissemination of new surgical procedures, and advance surgical education. While previously hindered by communication delays and costs, recent advancements in information technology and the emergence of new surgical robots have created an environment conducive to societal implementation. In Japan, the legal framework established in 2019 allows for remote surgical support under the supervision of an actual surgeon. The Japan Surgical Society led a collaborative effort, involving various stakeholders, to conduct social verification experiments using telesurgery, resulting in the development of a Japanese version of the "Telesurgery Guidelines" in June 2022. These guidelines outline requirements for medical teams, communication environments, robotic systems, and security measures for communication lines, as well as responsibility allocation, cost burden, and the handling of adverse events during telesurgery. In addition, they address telementoring and full telesurgery. The guidelines are expected to be revised as needed, based on the utilization of telesurgery, advancements in surgical robots, and improvements in information technology.


Assuntos
Sociedades Médicas , Telemedicina , Japão , Humanos , Procedimentos Cirúrgicos Robóticos/normas , Equipe de Assistência ao Paciente , Tecnologia da Informação , Guias de Prática Clínica como Assunto , Cirurgia Geral/educação
9.
JAMA Netw Open ; 7(6): e2417625, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38888920

RESUMO

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Idoso , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Estudos de Coortes , Oxaliplatina/uso terapêutico , Pancreatectomia
10.
Chin Clin Oncol ; 13(3): 43, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38859608

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become key agents in the treatment of non-small cell lung cancer worldwide. However, immune-related adverse events (irAEs) must be addressed to maximize the efficacy of ICIs. Mycobacterium tuberculosis (Mtb) infection is considered as a type of irAE associated with ICIs, but the underlying mechanism is not completely understood. Here, we present a case of pulmonary tuberculosis (TB) that developed during administration of nivolumab and ipilimumab for pulmonary adenocarcinoma that recurred just 2 months after completion of anti-TB treatment. CASE DESCRIPTION: A 67-year-old man with lung adenocarcinoma was referred to our hospital for chemotherapy. He was a former smoker and had been diagnosed with stage IVA (cT4N1M1a) lung adenocarcinoma. Interferon-gamma release assay (IGRA) yielded positive results at the start of treatment. One month after initiating treatment with nivolumab and ipilimumab, he presented with productive cough and Mtb complex was cultured from sputum samples. Two months after completing anti-TB treatment, recurrence of TB was observed. The series of strains were found to be identical. CONCLUSIONS: This represents the first report of pulmonary TB that developed during nivolumab and ipilimumab treatment, and recurred 2 months after completing anti-TB treatment. Physicians should be mindful of the potential for TB recurrence following the use of ICIs, particularly in patients showing positive results from IGRA.


Assuntos
Adenocarcinoma de Pulmão , Ipilimumab , Nivolumabe , Tuberculose Pulmonar , Humanos , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Masculino , Idoso , Tuberculose Pulmonar/tratamento farmacológico , Adenocarcinoma de Pulmão/tratamento farmacológico , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Antituberculosos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico
11.
J Hepatobiliary Pancreat Sci ; 31(8): 549-558, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38845092

RESUMO

BACKGROUND: Endoscopic retrograde cholangiography (ERC)-related procedures, usually performed before biliary tract cancer (BTC) surgery, are associated with increased risk for various complications, which can cause sarcopenia. No study has previously elucidated the relationship between preoperative ERC-related procedures and sarcopenia/skeletal muscle mass loss. METHODS: Patients with BTC who underwent radical surgical resection following ERC-related procedures were included. Skeletal muscle mass was evaluated using the psoas muscle mass index (PMI), which was determined using computed tomography images, and the change in PMI before the initial pre-ERC and surgery (ΔPMI) was calculated. Risk factors for advanced skeletal muscle mass loss, defined as a large ΔPMI, were evaluated. RESULTS: The study cohort included 90 patients with a median age of 72 (interquartile range, 65-75) years. The median PMI pre-ERC and surgery was 4.40 and 4.15 cm2/m2, respectively (p < .01). The median ΔPMI was -6.2% (interquartile range, -10.9% to 0.5%). By multivariate analysis, post-ERC pancreatitis and cholangitis before surgery were independent predictive factors for large PMI loss (odds ratio, 4.57 and 3.18, respectively; p = .03 and p = .02, respectively). CONCLUSIONS: Skeletal muscle mass decreases preoperatively in most patients with BTC undergoing ERC. Post-ERC pancreatitis and cholangitis before surgery were independent risk factors for large skeletal muscle mass loss.


Assuntos
Neoplasias do Sistema Biliar , Sarcopenia , Humanos , Masculino , Feminino , Idoso , Neoplasias do Sistema Biliar/cirurgia , Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/complicações , Neoplasias do Sistema Biliar/patologia , Sarcopenia/diagnóstico por imagem , Sarcopenia/complicações , Fatores de Risco , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Colangiopancreatografia Retrógrada Endoscópica , Músculos Psoas/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Pessoa de Meia-Idade , Período Pré-Operatório , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Medição de Risco
12.
J Neuroeng Rehabil ; 21(1): 76, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745235

RESUMO

BACKGROUND: Gait disorder remains a major challenge for individuals with stroke, affecting their quality of life and increasing the risk of secondary complications. Robot-assisted gait training (RAGT) has emerged as a promising approach for improving gait independence in individuals with stroke. This study aimed to evaluate the effect of RAGT in individuals with subacute hemiparetic stroke using a one-leg assisted gait robot called Welwalk WW-1000. METHODS: An assessor-blinded, multicenter randomized controlled trial was conducted in the convalescent rehabilitation wards of eight hospitals in Japan. Participants with first-ever hemiparetic stroke who could not walk at pre-intervention assessment were randomized to either the Welwalk group, which underwent RAGT with conventional physical therapy, or the control group, which underwent conventional physical therapy alone. Both groups received 80 min of physical therapy per day, 7 days per week, while the Welwalk group received 40 min of RAGT per day, 6 days per week, as part of their physical therapy. The primary outcome was gait independence, as assessed using the Functional Independence Measure Walk Score. RESULTS: A total of 91 participants were enrolled, 85 of whom completed the intervention. As a result, 91 participants, as a full analysis set, and 85, as a per-protocol set, were analyzed. The primary outcome, the cumulative incidence of gait-independent events, was not significantly different between the groups. Subgroup analysis revealed that the interaction between the intervention group and stroke type did not yield significant differences in either the full analysis or per-protocol set. However, although not statistically significant, a discernible trend toward improvement with Welwalk was observed in cases of cerebral infarction for the full analysis and per-protocol sets (HR 4.167 [95%CI 0.914-18.995], p = 0.065, HR 4.443 [95%CI 0.973-20.279], p = 0.054, respectively). CONCLUSIONS: The combination of RAGT using Welwalk and conventional physical therapy was not significantly more effective than conventional physical therapy alone in promoting gait independence in individuals with subacute hemiparetic stroke, although a trend toward earlier gait independence was observed in individuals with cerebral infarction. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ; jRCT 042180078) on March 3, 2019.


Assuntos
Transtornos Neurológicos da Marcha , Paresia , Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Feminino , Idoso , Robótica/métodos , Robótica/instrumentação , Pessoa de Meia-Idade , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/etiologia , Paresia/reabilitação , Paresia/etiologia , Acidente Vascular Cerebral/complicações , Marcha/fisiologia , Terapia por Exercício/métodos , Terapia por Exercício/instrumentação , Método Simples-Cego , Modalidades de Fisioterapia/instrumentação , Resultado do Tratamento
13.
Sci Rep ; 14(1): 12224, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806529

RESUMO

Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Interleucina-6 , Pancreatite , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Fator de Transcrição STAT3 , gama-Glutamiltransferase , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Pancreatite/genética , Pancreatite/etiologia , Humanos , Interleucina-6/metabolismo , Interleucina-6/genética , Animais , gama-Glutamiltransferase/metabolismo , gama-Glutamiltransferase/genética , Camundongos , Masculino , Feminino , Pessoa de Meia-Idade , Alelos , Receptor gp130 de Citocina/genética , Receptor gp130 de Citocina/metabolismo , Predisposição Genética para Doença , NF-kappa B/metabolismo , Transdução de Sinais
14.
Updates Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758469

RESUMO

Advanced gastric cancer that has not invaded the greater curvature is a good indication for total gastrectomy (TG) with spleen-preserving suprapancreatic and splenic hilar lymph node dissection (LND). However, the suprapancreatic and splenic hilar LND increases the area of dissection of the pancreas, and prolonged pressure drainage of the pancreas is required to maintain a clear operative view. This can lead to an increased risk of postoperative pancreatic complications. To report the efficacy of our novel preemptive retropancreatic approach (PRA) for the suprapancreatic and splenic hilar LND in robotic TG (RTG). We report our experience with nine patients with gastric cancer who underwent spleen-preserving splenic hilar LND using PRA during RTG at Hokkaido University from October 2018 to November 2021. The PRA involves initial dissection of the left side of the retropancreatic space, followed by the release of the adherence between the retroperitoneum surface and the pancreas (fusion fascia), which provides a good operative field and prevents contact with the pancreas during the suprapancreatic and splenic hilar LND in RTG. The median operating time was 488 min (254-564 min). The median intraoperative bleeding was 55 mL (0-115 mL). One patient had postoperative complications (above grade II of the Clavien-Dindo classification), but there were no postoperative pancreatic complications. The spleen-preserving suprapancreatic and splenic hilar LND using PRA could help to reduce the postoperative pancreatic complications associated with RTG.Trial registration number and date of registration The Hokkaido University Hospital institutional review board approved the data collection and analysis. The trial registration number and date of registration are No. 021-0022 and July 26, retrospectively registered.

15.
Clin Gastroenterol Hepatol ; 22(7): 1416-1426.e5, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38615727

RESUMO

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Japão/epidemiologia , Adulto , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/diagnóstico , Idoso de 80 Anos ou mais , Metástase Linfática , Gradação de Tumores , Carga Tumoral
16.
Gan To Kagaku Ryoho ; 51(4): 417-420, 2024 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-38644309

RESUMO

The use of nivolumab as first-line therapy for unresectable advanced gastric cancer has now become a standard practice, and its efficacy has been established. This is the first report of a patient with advanced gastric cancer who underwent conversion surgery after first-line nivolumab combination chemotherapy. The patient was a 58-year-old woman. Her medical history included hypertension and dyslipidemia. She had advanced gastric cancer with extensive lymph node metastasis in the left supraclavicular fossa and around the abdominal aorta. After confirming the HER2-negative status and the PD-L1 CPS score to be ≥5, nivolumab was administered in combination with chemotherapy. After the treatment, she underwent a total gastrectomy with D2 dissection, combined splenectomy and pancreatic tail resection for adhesions, and para-aortic lymph node sampling as a conversion surgery. There was no obvious cancerous remnant in the resected specimen, and the pathological response was Grade 3. The patient was alive and recurrence-free at 4 months postoperatively.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Gastrectomia , Nivolumabe , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Pessoa de Meia-Idade , Feminino , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento
17.
Trauma Case Rep ; 51: 101010, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38600911

RESUMO

Impalement injuries are rare and complex problems, often involving multiple organ injuries. An 18-year-old male was admitted to our emergency department after a car accident. Positioned in the right-side recumbent position, he had a 4.5 cm diameter pipe penetrating from his left abdomen to his back. Given the pipe's length exceeding the CT gantry's capacity, further imaging tests were not feasible. Consequently, the patient proceeded directly to the operating room without preoperative imaging. Before laparotomy, a left thoracotomy was conducted for aortic cross-clamping, anticipating uncontrollable bleeding during pipe removal. The subsequent laparotomy, with the patient in the right-side recumbent position, revealed the pipe impaling through the mesentery of the descending colon without evident major vessel injury. The pipe was cautiously extracted. The patient was subsequently discharged on day 26. The absence of imaging feasibility emphasized that current hemodynamic stability does not rule out the potential for significant vessel injury. Therefore, the sequential approach of left thoracotomy for aortic cross-clamping followed by laparotomy emerges as a potentially beneficial strategy in cases of transabdominal impalement. The impalement injury requires our preparedness and flexibility, which should be tailored to the individual case.

18.
BMC Surg ; 24(1): 116, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643112

RESUMO

BACKGROUND: Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. METHODS: We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. RESULTS: In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). CONCLUSIONS: The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Estado Nutricional , Prognóstico , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Músculos Psoas , Estudos Retrospectivos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia
19.
Intern Med ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631853

RESUMO

We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

20.
Anticancer Res ; 44(5): 1877-1883, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677758

RESUMO

BACKGROUND/AIM: Human gastric cancer stem-like cells (CSCs)/cancer-initiating cells can be identified as aldehyde dehydrogenase-high (ALDHhigh) cells. Cancer immunotherapy employing immune checkpoint blockade has been approved for advanced gastric cancer cases. However, the effectiveness of cancer immunotherapy against gastric CSCs/CICs remains unclear. This study aimed to investigate the susceptibility of gastric CSCs/CICs to immunotherapy. MATERIALS AND METHODS: Gastric CSCs/CICs were isolated as ALDHhigh cells using the human gastric cancer cell line, MKN-45. ALDHhigh clone cells and ALDHlow clone cells were isolated using the ALDEFLUOR assay. ALDH1A1 expression was assessed via qRT-PCR. Sphere-forming ability was evaluated to confirm the presence of CSCs/CICs. A model neoantigen, AP2S1, was over-expressed in ALDHhigh clone cells and ALDHlow clone cells, and susceptibility to AP2S1-specific TCR-T cells was assessed using IFNγ ELISPOT assay. RESULTS: Three ALDHhigh clone cells were isolated from MKN-45 cells. ALDHhigh clone cells exhibited a stable phenotype in in vitro culture for more than 2 months. The High-36 clone cells demonstrated the highest sphere-forming ability, whereas the Low-8 cells showed the lowest sphere-forming ability. High-36 cells exhibited lower expression of HLA-A24 compared to Low-8 cells. TCR-T cells specific for AP2S1 showed lower reactivity to High-36 cells compared to Low-8 cells. CONCLUSION: High-36 cells and Low-8 cells represent novel gastric CSCs/CICs and non-CSCs/CICs, respectively. ALDHhigh CSCs/CICs evade T cells due to lower expression of HLA class 1.


Assuntos
Família Aldeído Desidrogenase 1 , Células-Tronco Neoplásicas , Neoplasias Gástricas , Linfócitos T Citotóxicos , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Família Aldeído Desidrogenase 1/metabolismo , Família Aldeído Desidrogenase 1/genética , Linhagem Celular Tumoral , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Retinal Desidrogenase/metabolismo , Evasão Tumoral/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia
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