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1.
Oncology ; 102(2): 114-121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37699374

RESUMO

INTRODUCTION: Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer. METHODS: This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient's symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5-109) months. RESULTS: Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, p < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110-2,607) preoperatively and 6,095.2 (1,612.3-14,431.8) postoperatively (p = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (p = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis. CONCLUSIONS: Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients' symptoms and nutritional status and may result in improved prognosis.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Proteína C-Reativa , Estado Nutricional , Neoplasias Colorretais/patologia , Ovariectomia/métodos , Prognóstico , Adenocarcinoma/cirurgia , Adenocarcinoma/secundário
2.
Int Immunol ; 35(5): 231-241, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36521002

RESUMO

CD8αα+ intestinal intraepithelial lymphocytes (iIELs) are known for their unique role in keeping the integrity of the intestinal epithelial barrier, but factors affecting the development of these cells have not been thoroughly understood. Here, we found that the transcriptional regulator interferon regulatory factor-2 (IRF-2) plays a cell-intrinsic, indispensable role in establishing iIEL populations. CD8αα+, but not CD8αß+, iIELs bearing TCRαß or TCRγδ were severely reduced in numbers in mice lacking this factor (Irf2-/- mice). Moreover, the majority of residual CD8αα+TCRαß+ iIELs in these mice was immature as judged from their Thy1.2high phenotype and inefficient T-bet expression. Thymic IEL precursors isolated from Irf2-/- mice failed to efficiently generate CD8αα+TCRαß+ and TCRγδ+ IELs upon transfer in vivo and CD8αα+TCRαß+ cells in response to IL-15 in vitro. Double mutant mice lacking both interleukin-15 (IL-15) and IRF-2 showed an even more severe iIEL defect than in mice lacking IL-15 alone. Upon increasing agonistic TCR signal strength through OT-II TCR transgenesis, CD8αα+TCRαß+ iIELs became more abundant but remained immature on the Irf2-/- background. Our current observations, thus, revealed the unique bimodal role that IRF-2 plays in promoting not only generation of IEL progenitors in the thymus but also maturation of iIELs in the periphery in IL-15-dependent and -independent manners.


Assuntos
Mucosa Intestinal , Linfócitos Intraepiteliais , Camundongos , Animais , Antígenos CD8/metabolismo , Mucosa Intestinal/metabolismo , Linfócitos Intraepiteliais/metabolismo , Interleucina-15 , Transdução de Sinais , Fator Regulador 2 de Interferon , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T CD8-Positivos/metabolismo
3.
Chemotherapy ; 68(2): 87-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36327945

RESUMO

INTRODUCTION: Extrapulmonary neuroendocrine carcinoma (EPNEC) is a clinicopathological entity distinct from neuroendocrine carcinoma of the lung. Here, we reviewed the clinical features, treatment modalities, and prognosis of EPNEC patients in a single-institution series. METHODS: We retrospectively reviewed the medical records of EPNEC patients and examined the clinical profiles and treatment outcomes at our hospital between 2013 and 2021. RESULTS: Thirty-one EPNEC patients (21 men and 10 women) with a median age of 65 years were included. The primary sites were as follows: stomach (n = 7); rectum and bladder (n = 3 each); prostate, esophagus, cervix, and pancreas (n = 2 each); maxillary sinus, parotid gland, gallbladder, anal canal, larynx, uterine body, ovary, appendix, anterior mediastinum, and unknown primary lesion (n = 1 each). Thirteen patients had locally advanced stage and 18 cases had distant metastases. Chemotherapy using platinum-combined CPT-11 or VP-16 was mainly performed. Various therapeutic modalities were used, especially in locally advanced cases. Ten patients underwent surgery, including initial surgery in 5 and conversion in 5 after chemotherapy. The response rate to initial chemotherapy was 56.5%, and the median overall survival in all patients was 12.8 (95% CI: 9.6-34.5) months. Survival was significantly longer in patients with locally advanced stage (80.3 months) and receiving surgery (not reached) than in those with metastatic disease (9.9 months) and without surgery (9.6 months). CONCLUSION: EPNEC occurs in various organs and has poor prognosis. Long-term survival may be possible with surgical resection in cases with early-stage disease or tumor shrinkage due to chemotherapy.


Assuntos
Carcinoma Neuroendócrino , Masculino , Humanos , Feminino , Idoso , Estudos Retrospectivos , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/tratamento farmacológico , Resultado do Tratamento , Prognóstico , Platina
4.
Oncology ; 99(10): 632-640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280933

RESUMO

INTRODUCTION: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. METHODS: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. RESULTS: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). CONCLUSIONS: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.


Assuntos
Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nivolumabe , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
5.
Int Immunol ; 31(8): 489-498, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30783658

RESUMO

Innate lymphoid cells (ILCs), composed of heterogeneous populations of lymphoid cells, contribute critically to immune surveillance at mucosal surfaces. ILC subsets develop from common lymphoid progenitors through stepwise lineage specification. However, the composition and temporal regulation of the transcription factor network governing such a process remain incompletely understood. Here, we report that deletion of the transcription factor interferon regulatory factor 2 (IRF-2), known also for its importance in the maturation of conventional NK cells, resulted in an impaired generation of ILC1, ILC2 and ILC3 subsets with lymphoid tissue inducer (LTi)-like cells hardly affected. In IRF-2-deficient mice, PD-1hi ILC precursors (ILCPs) that generate these three ILCs but not LTi-like cells were present at normal frequency, while their sub-population expressing high amounts of PLZF, another marker for ILCPs, was severely reduced. Notably, these IRF-2-deficient ILCPs contained normal quantities of PLZF-encoding Zbtb16 messages, and PLZF expression in developing invariant NKT cells within the thymus was unaffected in these mutant mice. These results point to a unique, cell-type selective role for IRF-2 in ILC development, acting at a discrete step critical for the generation of functionally competent ILCPs.


Assuntos
Imunidade Inata/imunologia , Fator Regulador 2 de Interferon/imunologia , Linfócitos/imunologia , Células Progenitoras Linfoides/imunologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
BMC Surg ; 20(1): 168, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711489

RESUMO

BACKGROUND: Adhesive small bowel obstruction (ASBO) is one of the most common causes of postoperative morbidity. According to Boyle's law, decreased barometric pressure expands the volume of intestinal gas. We aimed to elucidate the relationship between barometric pressure and ASBO. METHODS: We divided 215 admissions of 120 patients with ASBO into three groups: the fasting group, which responded to fasting (n = 51); the decompression group, which was successfully treated with gastrointestinal decompression (n = 104); and the surgery group which required emergency or elective surgery to treat ASBO (n = 60). We compared and examined clinical backgrounds, findings on admission, and barometric pressure during the peri-onset period (29 days: from 14 days before to 14 days after the onset of ASBO). RESULTS: There were significant differences among the three groups regarding gender, history of ASBO, hospital length of stay, and barometric pressure on the onset day of ASBO. Barometric pressure on the onset day was significantly higher in the fasting group than in the decompression group (p = 0.005). During pre-onset day 5 to post-onset day 2, fluctuations in the barometric pressure in the fasting and decompression groups showed reciprocal changes with a symmetrical axis overlapping the median barometric pressure in Matsumoto City; the fluctuations tapered over time after onset. In the fasting group, the barometric pressure on the onset day was significantly higher than that on pre-onset days 14, 11, 7, 4, 3, and 2; post-onset days 3 and 10; and the median pressure in Matsumoto City. Conversely, in the decompression group, the barometric pressure on the onset day was lower than that on pre-onset days 14, 5-2; post-onset days 1, 2, 7, 8, 11, 13, and 14; and the median pressure in Matsumoto City. In the surgery group, the barometric pressure on the onset day was equivalent to those on the other days. CONCLUSIONS: ASBO with response to conservative treatment is vulnerable to barometric pressure. Additionally, ASBO that is successfully treated with fasting and decompression is associated with a different barometric pressure on the onset day and reciprocal fluctuations in the barometric pressure during the peri-onset period.


Assuntos
Pressão Atmosférica , Obstrução Intestinal , Intestino Delgado/fisiopatologia , Aderências Teciduais/complicações , Idoso , Idoso de 80 Anos ou mais , Jejum/fisiologia , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/fisiopatologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/terapia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Intubação Gastrointestinal , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Aderências Teciduais/cirurgia , Resultado do Tratamento
8.
Int J Surg Case Rep ; 106: 108229, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37084554

RESUMO

INTRODUCTION AND IMPORTANCE: Appendiceal goblet cell adenocarcinoma is in 0.3-0.9 % of appendectomy specimens. There is still controversy regarding whether surgery with dissection or additional resection is necessary for goblet cell adenocarcinoma and whether adjuvant chemotherapy is practical. We present three cases of goblet cell adenocarcinomas. CASE PRESENTATION: Case 1: A 30-year-old woman was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells and tumour infiltration into the subserosa. The patient underwent laparoscopic ileocecal resection, and the main lymph nodes at the root of the feeding vessels were removed. Case 2: A 50-year-old man was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells; malignant cells were found at the surgical resection margins. The patient underwent laparoscopic ileocolic resection. Case 3: A 60-year-old man undergoing treatment for malignant melanoma. He was diagnosed with appendicitis associated with an appendiceal tumour, and emergency laparoscopic caecal resection was performed and diagnosed as goblet cell adenocarcinoma. We decided to prioritize treatment for malignant melanoma, and the patient is under follow-up for goblet cell adenocarcinoma and no metastasis was detected. CLINICAL DISCUSSION: We performed additional resection in two case of goblet cell adenocarcinoma. Diagnosing appendiceal goblet cell adenocarcinoma is difficult, and the prognosis of patients with positive lymph nodes is poor. Surgical treatment should be considered for the advanced stages of this disease. CONCLUSION: Goblet cell adenocarcinoma, diagnosed after appendectomy, additional resection including lymph node dissection may provide a long-term prognosis.

9.
Surg Case Rep ; 9(1): 31, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36847887

RESUMO

BACKGROUND: Non-obstructive intestinal ischemia (NOMI) is caused by intestinal vascular spasm and has a poor prognosis if not diagnosed and treated early. Indocyanine green (ICG) fluorescence imaging has been reported to be useful for the intraoperative assessment of the extent of intestinal resection required for NOMI. Few reports have described massive intestinal bleeding after conservative management of NOMI. We report a case of NOMI with massive postoperative bleeding from the site of an ICG contrast defect found before the initial surgery. CASE PRESENTATION: A 47-year-old woman with hemodialysis-dependent chronic kidney disease presented complaining of severe abdominal pain. A computed tomography scan showed portal gas and dilation of the small intestine, leading to a diagnosis of NOMI and subsequent emergency surgery. At the time of initial surgery, the contrast effect of ICG was slightly reduced, showing a granular distribution in the ascending colon to cecum (fine grain pattern) and significantly reduced in parts of the terminal ileum except around blood vessels (perivascular pattern). However, there was no obvious gross necrosis of the serosal surface, and the intestinal tract was not resected. The acute postoperative course was uneventful; however, the patient went into shock on the 24th postoperative day due to massive, small intestinal bleeding, and emergency surgery was performed. The bleeding originated from the section of the ileum that had complete loss of ICG contrast effect before the initial surgery. A right hemicolectomy with the terminal ileum resection was performed, and an ileo-transverse anastomosis was performed. The second post-operative course was uneventful. CONCLUSIONS: We report a case of delayed hemorrhage of the ileum shown to have poor blood flow on ICG imaging at the initial surgery. Intraoperative ICG fluorescence imaging is useful in assessing the degree of intestinal ischemia for NOMI. When patients with NOMI are followed up without surgery, complications such as bleeding should be noted.

10.
Asian J Endosc Surg ; 16(4): 822-826, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37448191

RESUMO

We report our experience in a patient with adenoma located in the horizontal part of the duodenum, which was effectively treated with the transmesenteric laparoscopic endoscopic cooperative surgery (LECS) approach. This approach, which entails incising the mesentery of the colon, simplified laparoscopic access to the horizontal part of the duodenum, which was minimally mobilized. Thus, the bulb and descending part of the duodenum were fixed to the retroperitoneum, facilitating stable handling of the endoscope and enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. This approach enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. The advantages of this method include a secure field of view, lower probability of damage to large vessels, and minimizing the defect to the intestine caused by the incision.

11.
Surg Laparosc Endosc Percutan Tech ; 33(4): 395-401, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37505918

RESUMO

BACKGROUND: Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. MATERIALS AND METHODS: Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. RESULTS: In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10 d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7 d, P = 0.003). CONCLUSIONS: Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.


Assuntos
Transtornos de Deglutição , Neoplasias Esofágicas , Humanos , Pacientes Internados , Pontuação de Propensão , Neoplasias Esofágicas/cirurgia , Transtornos de Deglutição/etiologia , Stents/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
12.
Asian J Endosc Surg ; 16(3): 496-499, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36592948

RESUMO

Gastric glomus tumors are rare submucosal mesenchymal neoplasms that are difficult to diagnose preoperatively. We present a case of a 60-year-old woman who was diagnosed with a gastric glomus tumor using endoscopic ultrasonography-guided fine-needle aspiration biopsy. The tumor was successfully resected with laparoscopic endoscopic cooperative surgery (LECS). LECS could be an effective method for the resection of gastric glomus tumors.


Assuntos
Tumor Glômico , Laparoscopia , Neoplasias Gástricas , Feminino , Humanos , Pessoa de Meia-Idade , Tumor Glômico/diagnóstico , Tumor Glômico/cirurgia , Tumor Glômico/patologia , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastroscopia/métodos , Tomografia Computadorizada por Raios X
13.
Cancer Lett ; 567: 216264, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37336286

RESUMO

The Kirsten rat sarcoma (KRAS) oncogene was "undruggable" until sotorasib, a KRASG12C selective inhibitor, was developed with promising efficacy. However, inhibition of mutant KRAS in colorectal cancer cells (CRC) is ineffective due to feedback activation of MEK/ERK downstream of KRAS. In this study, we screened for combination therapies of simultaneous inhibition to overcome sotorasib resistance using our previously developed Mix Culture Assay. We evaluated whether there was an additive effect of sotorasib administered alone and in combination with two or three drugs: trametinib, a MEK inhibitor, and cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody. The MAPK pathway was reactivated in KRASG12C-mutated cell lines treated with sotorasib alone. Treatment with KRAS and MEK inhibitors suppressed the reactivation of the MAPK pathway, but upregulated EGFR expression. However, the addition of cetuximab to this combination suppressed EGFR reactivation. This three-drug combination therapy resulted in significant growth inhibition in vitro and in vivo. Our data suggest that reactive feedback may play a key role in the resistance signal in CRC. Simultaneously inhibiting KRAS, MEK, and EGFR is a potentially promising strategy for patients with KRASG12C-mutated CRC.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Cetuximab/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno , Mutação
14.
Discov Oncol ; 14(1): 14, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719602

RESUMO

BACKGROUND: Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. METHOD: In this study we report the clinical courses of three cases with HDGC from a single Japanese family. RESULTS: The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. CONCLUSION: It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.

15.
Technol Cancer Res Treat ; 22: 15330338221146024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617975

RESUMO

BACKGROUND: RAS homolog family member A (RhoA), a member of the Rho family of small GTPases, and Vav1, a guanine nucleotide exchange factor for Rho family GTPases, have been reported to activate pathways related to the actin cytoskeleton and regulation of cell shape, attachment, and motility. The interaction between these molecules in lymphoma is involved in malignant signaling, but its function in epithelial malignancy is unknown. Here, we investigated the malignant signal of mutant RhoA in gastric cancer and demonstrated the potential of RhoA G17E/Vav1 as a therapeutic target for diffuse gastric cancer. METHODS: The RhoA mutants R5W, G17E, and Y42C were retrovirally transduced into the gastric cancer cell line MKN74. The stably transduced cells were used for morphology, proliferation, and migration/invasion assays in vitro. MKN74 cells stably transduced with ectopic wild-type RhoA and mutant RhoA (G17E) were used in a peritoneal xenograft assay. RESULTS: The RhoA mutations G17E and Y42C induced morphological changes in MKN74. G17E induced Vav1 expression at the mRNA and protein levels and promoted the migration and invasion of MKN74. An RNA interference assay of Vav1 revealed that RhoA G17E enhanced cancer cell invasion via Vav1. Furthermore, immunoprecipitation revealed that Vav1 and RhoA G17E specifically bind and function together through matrix metalloproteinase -9. In a peritoneal xenograft model of nude mice, RhoA G17E promoted peritoneal dissemination, whereas Vav1 knockdown suppressed it. CONCLUSION: Overall, our findings indicate that RhoA G17E is associated with Vav1 and promoted cancer invasion via matrix metalloproteinase -9 in gastric cancer cells. Thus, RhoA G17E/Vav1 signaling in diffuse gastric cancer may be a useful therapeutic target.


Assuntos
Proteínas Proto-Oncogênicas c-vav , Neoplasias Gástricas , Proteína rhoA de Ligação ao GTP , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Neoplasias Gástricas/patologia
16.
Ann Gastroenterol Surg ; 6(6): 873-879, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36338584

RESUMO

To prevent chylothorax after esophageal cancer surgery, it is important to recognize morphological patterns of the thoracic duct intraoperatively. The present study aimed to evaluate the safety and usefulness of near-infrared (NIR) fluorescence imaging with subcutaneous inguinal injection of indocyanine green (SII-ICG) to detect the thoracic duct during thoracoscopic esophagectomy for esophageal cancer. Patients (n = 16) who underwent thoracoscopic esophagectomy in the prone position with SII-ICG at Shinshu University Hospital between June 2020 and January 2022 were enrolled in the present study and retrospectively reviewed. Immediately prior to thoracoscopic esophagectomy, we injected 0.2-0.5 mg/kg ICG into the subcutaneous tissue in the bilateral inguinal region. The identification rate of the thoracic duct was 93.8% (n = 15), and the success rate of fluorescence using SII-ICG was 87.5% (n = 14). The visible thoracic ducts had four patterns: a typical pattern in 50% (n = 8), duplication pattern in 18.8% (n = 3), branching pattern in 12.5% (n = 2), and plexiform pattern in 12.5% (n = 2). In all cases, ICG fluorescence did not disappear and was visible during the thoracic surgery. No SII-ICG-related complications were observed. Intraoperative NIR fluorescence imaging of the thoracic duct using SII-ICG is a simple and safe method with very high detection sensitivity. This method can be a powerful tool for avoiding thoracic duct injuries during esophageal cancer surgery.

17.
J Laparoendosc Adv Surg Tech A ; 32(10): 1064-1070, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35446138

RESUMO

Background: The effectiveness of laparoscopic surgery for adhesive small bowel obstruction (ASBO) remains unclear. We aimed to compare the outcomes and safety of open and laparoscopic surgeries for ASBO. Methods: In this retrospective study, we analyzed an inpatient database of 42 national university hospitals in Japan. Patients who underwent surgery for the first episode of ASBO between April 2013 and March 2018 were identified. Using the propensity score method, patients who underwent laparoscopic surgery were matched one-to-one with those who underwent open surgery. We investigated postoperative clinical outcomes, including morbidity, mortality, length of hospital stay (LOS), and recurrence. Results: Overall, 306 and 96 patients underwent open and laparoscopic surgery, respectively (96 propensity score-matched pairs). The incidence rates of postoperative morbidity, mortality, and recurrence were comparable between the two groups. Cox regression analysis revealed a hazard ratio (HR) of 1.020 (P = .959) for readmission due to ASBO in the laparoscopic surgery group relative to the open surgery group. Postoperative hospital stay was longer for open surgery than for laparoscopic surgery (13.0 days versus 10.0 days, P < .001). Cox regression analysis revealed that laparoscopic surgery was associated with earlier postoperative discharge compared with open surgery (HR 1.641, P = .002). Conclusions: The postoperative LOS was shorter with laparoscopic surgery than with open surgery for ASBO, but there were no differences between the procedures in other clinical outcomes. Laparoscopic surgery is suitable to treat patients with ASBO.


Assuntos
Obstrução Intestinal , Laparoscopia , Adesivos , Humanos , Pacientes Internados , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Aderências Teciduais/cirurgia , Resultado do Tratamento
18.
Cureus ; 14(4): e24176, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35586353

RESUMO

INTRODUCTION: The influence of air temperature on adhesive small bowel obstruction (ASBO) is unknown. This study aimed to investigate the relationship between air temperature and postoperative ASBO. METHODS: Overall, 312 patients with postoperative ASBO were included. They were categorized into two groups: the surgery group (n = 83) comprising patients who needed surgery, and the non-surgery group (n = 229) comprising patients who responded to conservative treatment. The associations between patients' characteristics and weather variables on days of symptom onset with the need for surgical management were investigated. Weather variables included the daily mean barometric pressure, daily mean air temperature, day-to-day differences, daily variances, and diurnal variation in the air temperature. Day-to-day differences in weather variables were calculated as the daily mean variables on the day of symptom onset minus those on the previous day. The daily variances in weather variables were defined as the absolute value of day-to-day differences. RESULTS: Compared to the non-surgery group, the surgery group had older patients (75 vs. 70 years, p = 0.009), a higher proportion of female patients (44.6% vs. 32.3%, p = 0.046), increased incidence of closed-loop sign (50.6% vs. 0.9%, p < 0.001), a lower proportion of feces sign (18.1% vs. 31.3%, p = 0.024), and a prolonged hospital stay (11 vs. 22 days, p < 0.001). The number distribution of patients in the surgery group in day-to-day differences in air temperature was different from that of the non-surgery group; the former has several peaks whereas the latter has almost one peak. Daily variance in mean air temperature on the day of symptom onset was higher in the surgery group than in the non-surgery group (2.3 vs. 1.3℃, p < 0.001). Multiple logistic regression analysis revealed that increased daily variance in air temperature on the onset day was associated with the need for surgical management (odds ratio 1.254, p = 0.002) and closed-loop obstruction (odds ratio 1.235, p = 0.017). Regarding seasonal variations, the risk of the need for surgery and closed-loop obstruction in each ASBO patient was the highest in spring, followed by that in summer, autumn, and winter. Consistently, the daily variance in mean air temperature in spring was higher than that in summer, autumn, and winter (p < 0.0001, p < 0.0001, and p = 0.0047, respectively). The risk of the need for surgery and closed-loop obstruction in each ASBO patient was the highest in spring, followed by that in summer, autumn, and winter. Consistently, daily variance in mean air temperature was higher in spring than that in summer, autumn, and winter (p < 0.0001, p < 0.0001, and p = 0.0047, respectively). CONCLUSION: Increased daily variance in mean air temperature on the day of onset is associated with the need for surgical management and closed-loop obstruction. Spring is characterized by the highest daily variance in mean air temperature among the four seasons, and is associated with high proportions of the need for surgery and closed-loop obstruction. These results can be clinically useful in terms of hospital resource reallocation and staffing, and can help clarify the pathogenesis of ASBO.

19.
Ann Gastroenterol Surg ; 6(4): 569-576, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35847441

RESUMO

Aim: Whether seasonal and meteorological factors affect the incidence of adhesive small bowel obstruction (ASBO) remains unclear. This study aimed to clarify the impacts of seasonal and meteorological factors on the occurrence of ASBO. Methods: Clinical data of patients with ASBO were acquired from 42 national university hospitals in Japan, using a national inpatient database, between April 2012 and March 2020. Meteorological data were obtained from the Japan Meteorological Agency. The number of monthly admissions of patients with ASBO was compared between each of the 12 months. Daily weather variables were investigated to clarify their association with ASBO patient admissions on a total of 119 802 days (Formula for calculation: study period [2922 days] ×41 cities). Results: Overall, 4985 patients with ASBO were admitted. The number of admissions in June was smaller than that in October, November, and December (39 vs 63.5, P = .002, 39 vs 65, P = .004, and 39 vs 59.5, P = .002, respectively). Logistic regression analysis revealed that January, October, November, and December were associated with increased risk of admission compared to June (odds ratio [OR], 1.264; P = .001; OR, 1.454; P < .001; OR, 1.408; P < .001; OR, 1.330; P < .001), respectively. Regarding the weather variables, higher barometric pressure and lower humidity were associated with increased risk of admission (OR, 1.011; P < .001 and OR, 0.995; P < .001), respectively. Conclusion: The incidence of ASBO is susceptible to barometric pressure and humidity and varies monthly. These results can contribute to the prevention, early detection, and immediate and appropriate management of ASBO.

20.
Surg Res Pract ; 2022: 1737161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386950

RESUMO

Introduction: Acute mesenteric ischemia is a life-threatening complication after cardiovascular surgery with a mortality rate of 52.9-81.3%. However, few studies have evaluated the predictors of clinical outcome after treatment for acute mesenteric ischemia following cardiovascular surgery. Therefore, this study aimed to elucidate prognostic factors in patients who underwent laparotomy for acute mesenteric ischemia after cardiovascular surgery. Methods: We retrospectively analyzed 29 patients (20 men and 9 women; median age, 71.0 years) who underwent laparotomy for acute mesenteric ischemia after cardiovascular surgery between January 2010 and August 2020. These patients were classified into the survivor group (comprising patients who were discharged or referred to another hospital, n = 16) and the nonsurvivor group (comprising those who experienced in-hospital mortality, n = 13). We compared clinical parameters between the groups to identify the predictors of outcomes. Results: More patients in the nonsurvivor group underwent emergency cardiovascular surgery (62.5% vs. 100%, p = 0.017) and received hemodialysis (12.5% vs. 61.5%, p = 0.008) at the onset of acute mesenteric ischemia than those in the survivor group. The prelaparotomy serum creatinine level was higher in the nonsurvivor group than in the survivor group (1.27 vs. 2.33 mg/dL, p = 0.004). Logistic regression analysis revealed an association between preoperative serum creatinine level and in-hospital mortality (odds ratio 5.047, p = 0.046), and Cox regression analysis demonstrated a relationship between serum creatinine level and in-hospital mortality (hazard ratio 1.610, p = 0.009). The area under the curve (receiver operating characteristic analysis) for the serum creatinine level was 0.813. Furthermore, the optimal cutoff value of the serum creatinine level was 1.59 mg/dL with a sensitivity and specificity of 0.846 and 0.687, respectively, in predicting in-hospital mortality. Conclusions: The elevated serum creatinine level was associated with a poor clinical outcome after surgery for acute mesenteric ischemia following cardiovascular surgery.

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