Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 307
Filtrar
1.
Mol Cancer Res ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579815

RESUMO

Accumulating scientific evidences strongly support the importance of cancer-derived extracellular vesicles (EVs) in organization of tumor microenvironment and metastatic niches, which are also considered as ideal tools for cancer liquid biopsy. To uncover the full scope of proteomic information packaged within EVs secreted directly from human colorectal cancer (CRC), we cultured surgically-resected viable tissues and obtained tissue-exudative extracellular vesicles (Te-EVs). Our quantitative profiling of 6,307 Te-EV proteins and 8,565 tissue proteins from primary CRC and adjacent normal mucosa (n = 17) allowed identification of a specific cargo in CRC-derived Te-EVs, high affinity cationic amino acid transporter 1 (CAT1, p = 5.0 × 10-3, fold change = 6.2), in addition to discovery of a new class of EV markers, VPS family proteins. The EV sandwich ELISA confirmed escalation of the EV-CAT1 level in plasma from CRC patients compared to healthy donors (n = 119, p = 3.8 × 10-7). Further metabolomic analysis revealed that CAT1-overexpressed EVs drastically enhanced vascular endothelial cell growth and tubule formation via upregulation of arginine transport and downstream nitric oxide metabolic pathway. These findings demonstrate the potency of CAT1 as an EV-based biomarker for CRC and its functional significance on tumor angiogenesis. Implications: This study provides a proteome-wide compositional dataset for viable CRC tissue-derived EVs and especially emphasizes importance of EV-CAT1 as a key regulator of angiogenesis.

2.
Nat Commun ; 12(1): 560, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495473

RESUMO

The squamous-columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal-distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells within the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.


Assuntos
Células Epiteliais/metabolismo , Fator de Transcrição GATA4/genética , Regulação da Expressão Gênica , Junções Intercelulares/genética , Sistema de Sinalização das MAP Quinases/genética , Fatores de Transcrição SOXB1/genética , Animais , Células Cultivadas , Feminino , Fator de Transcrição GATA4/metabolismo , Mucosa Gástrica/metabolismo , Queratina-7/genética , Queratina-7/metabolismo , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Camundongos Transgênicos , Fatores de Transcrição SOXB1/metabolismo
3.
J Anus Rectum Colon ; 4(4): 174-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134598

RESUMO

Objective: Additional surgery is considered for patients at high risk for lymph node metastasis (LNM) after local resection for early rectal cancer. Several factors are considered as indications for additional surgery, although there are currently no definitive criteria. This study aimed to clarify the need for additional surgery based on the number of risk factors for LNM and to evaluate the significance of submucosal invasion on recurrence. Methods: Patients with early rectal cancer harboring risk factors for LNM who underwent local resection between March 2005 and December 2016 were retrospectively analyzed. Associations among the number of risk factors, prognosis, and additional treatment after local resection were investigated. Results: A total of 29 eligible patients were classified into the surgery (n = 10), chemoradiotherapy (n = 7), and no-additional-treatment (NAT, n = 12) groups. Among the 29 patients, 15 patients (52%) with only one risk factor did not relapse. The NAT group harbored fewer risk factors for LNM, and 8 of the 12 patients (67%) had only deep submucosal invasion. Local recurrence occurred in one patient in the chemoradiotherapy group. The estimated 5-year overall survival rates were 88.9%, 75.0%, and 81.5% in the surgery, chemoradiotherapy, and NAT groups, respectively. There were no disease-specific deaths in the overall cohort. Conclusions: In the present study, no recurrence occurred in patients who did not receive additional surgery with deep submucosal invasion as the only risk factor. A multicenter investigation is necessary to confirm the safety of nonsurgical options.

4.
Ann Gastroenterol Surg ; 4(5): 549-561, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33005850

RESUMO

Background: Emergency gastrointestinal surgery, although rare, is known for its high mortality and morbidity. However, the risks of emergency surgery for gastrointestinal cancer have not been investigated in depth. This study aimed to investigate the impact of emergency surgery on mortality and morbidity in patients with gastrointestinal cancers and to identify associated risk factors. Methods: We extracted data from the National Clinical Database, a nationwide surgery registration system in Japan, for patients with gastrointestinal cancer who underwent esophageal resection, total gastrectomy, distal gastrectomy, right hemicolectomy, or low anterior resection between 2012 and 2017. The impacts of emergency surgery on 30-day mortality and incidence of overall postoperative complications were compared with those of non-emergency surgery. Risk factors for mortality and overall postoperative complications were then sought in patients who underwent emergency surgery. Results: Thirty-day mortality and incidence of overall postoperative complications were significantly higher in emergency surgeries for gastric, colon, and rectal cancers than in non-emergency surgeries (odds ratios 4.86-6.98 and 1.68-2.18, respectively; all P < .001). Various risk factors were identified in the group that underwent emergency surgery, including preoperative sepsis and lower body mass index. Some of the risk factors were common to all types of surgery and others were specific to a certain type of surgery. Conclusion: The actual risk of emergency surgery and the risk factors for overall postoperative complications in emergency cases are shown to serve as a reference for postoperative management. Emergency surgery had an additional burden on patients depending on the type of surgery.

5.
Surg Case Rep ; 6(1): 257, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006721

RESUMO

BACKGROUND: Indocyanine green (ICG) is useful for evaluating the intestinal perfusion of anastomosis. Especially for patients with prior surgeries, ICG imaging enables surgeons in visualizing the anatomical field. Here, we reported the positive and negative staining techniques of ICG fluorescence with vessel clamp for determining the optimal resection area of vessels and mesentery. CASE PRESENTATION: An 80-year-old man, who had an ileal conduit constructed after a prior total cystectomy, was diagnosed with ascending colon cancer. Although the tumor-feeding vessel was primarily the ileocecal artery, there was no detailed information about the blood running through the ileal conduit. At first, the ascending colon and the marginal vessels were transected at distal side of the tumor. Next, both, the ileocecal artery and the marginal artery of oral side of the ileal anastomotic site were clamped. Finally, we injected ICG intravenously to assess the blood flow. As a result, the blood flow between the ileal anastomotic site and transected ascending colon was not identified (negative staining). Therefore, we cut the root of the ileocecal artery, and dissected the peripheral mesocolon including the ileal anastomotic site. After the ileo-ascending colon anastomosis, we injected ICG intravenously again. The blood flow to the ileal conduit was preserved (positive staining). CONCLUSION: ICG fluorescence imaging with vessel clamp can clearly visualize the demarcation line between ischemic and non-ischemic intestinal tract. In colorectal surgeries, this technique is useful to assess the anastomotic perfusion and determine optimal dissection area of vessels and mesentery in secondary intestinal surgery.

6.
Surg Today ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043400

RESUMO

PURPOSE: Video review is a reliable method for surgical education in laparoscopic gastrectomy (LG), but more objective methods are still needed. The purpose of this study was to determine whether the energy device records reflected surgical competency, and thereby may improve surgical education. METHODS: A total of 16 patients who underwent LG for gastric cancer using the Thunderbeat® device were preliminarily retrospectively analyzed. This device has the function of 'intelligent tissue monitoring' (ITM), a safety assist system stopping energy output, and can record ITM detections and firing time during surgery. The number of ITM detections and firings, and the total firing time during gastrocolic ligament dissection and infrapyloric dissection were compared between trainees (n = 9 by 5 surgeons) and experts (n = 7 by 5 surgeons). The non-edited videos (n = 16) were scored, and the correlations between the scores and the records were then analyzed. RESULTS: Significantly more ITM detections, firings, and a longer total firing time were observed in trainees than in experts. The number of ITM detections and firing had negative correlations with the scores of the operation speed, the use of the non-dominant hand, and the use of an energy device. CONCLUSIONS: Our preliminary study suggested that the above described energy device records reflected surgical competency, and thereby may improve surgical education.

7.
J Surg Oncol ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32959406

RESUMO

BACKGROUND AND OBJECTIVES: This prospective study aimed to identify long-term changes in sexual function of men with rectal cancer from point of diagnosis to 24 months postoperatively. METHODS: Male patients undergoing laparoscopic rectal cancer surgery were prospectively enrolled. International Index of Erectile Function (IIEF) Questionnaire scores were collected at diagnosis; first follow-up; and 6, 12, and 24 months postoperatively. Missing values were managed via multiple imputations using the propensity score method. Paired t tests were applied to examine changes in IIEF scores over time. RESULTS: This study analyzed 115 patients. For erectile function, there were no significant changes in scores from the point of diagnosis to first treatment (9.4 vs. 9.8 as mean scores; p = .227). Scores deteriorated postoperatively and recovered until 12 months post-surgery, but did not improve significantly from 12 months to 24 months post-surgery (8.7 vs. 8.2 as mean scores; p = .440). This pattern of change was observed in all other domains: orgasmic function, sexual desire, orgasmic satisfaction, and overall satisfaction. CONCLUSIONS: Sexual function was not influenced by a rectal cancer diagnosis. Sexual function deteriorated following surgery and recovered until 12 months post-surgery; however, it did not significantly improve from 12 months to 24 months postoperatively.

8.
Int Cancer Conf J ; 9(4): 170-174, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32904044

RESUMO

Laparoscopic approaches have become a standard strategy for colon cancer patients who undergo surgical treatment. Complete mesocolic excision (CME) with central vascular ligation (CVL) is the fundamental principle of radical resection of colon cancers. Splenic flexure colon cancer (SFCC) is rare, accounting for less than 4% of all colorectal cancer cases. Moreover, a laparoscopic approach for SFCC following the CME/CVL concept can be challenging because the blood supply of the splenic flexure is derived from either the middle colic artery (MCA) branching from the superior mesenteric artery, the left colic artery (LCA) branching from the inferior mesenteric artery. In addition, approximately one third of SFCC patients have an accessory MCA that can originate from the celiac trunk. Herein, we describe the technical procedure of a laparoscopic left hemicolectomy for SFCC using indocyanine green (ICG) for necessary and sufficient lymphadenectomy followed by intracorporeal anastomosis. Two injections of ICG (0.5 mg/0.2 ml × 2) into the subserosa of the proximal and distal sides of the tumor preceded the surgical procedure after pneumoperitoneum. Near infrared images obtained throughout the laparoscopic procedure helped visualize lymphatic drainage vessels and inform decision making for determining vessels requiring ligation according to the CVL concept: MCA, LCA or accessory MCA. Complete intracorporeal anastomosis following necessary and sufficient lymphadenectomy with ICG can minimize the dissecting area of the laparoscopic left hemicolectomy for SFCC patients. Intravenous ICG injection (2.5 mg) after anastomosis helps confirm blood perfusion at the anastomosis site. Four patients with SFCC underwent a laparoscopic colectomy under ICG navigation in 2019 at our institute. The median operative time was 237 min, the median estimated blood loss was 0 ml, and the median number of dissected lymph nodes was 13. No patients experienced postoperative complications. In conclusion, laparoscopic left hemicolectomy with ICG navigation and intracorporeal anastomosis for SFCC patients may be a feasible option for the radical resection of colon cancer.

9.
Ann Surg Oncol ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32892268

RESUMO

BACKGROUND: Whether robot-assisted minimally invasive surgery (RAMIE) is more beneficial than conventional minimally invasive surgery (MIE) remains unclear. METHODS: In total, 165 consecutive patients with esophageal carcinoma who underwent esophagectomy between January 2015 and April 2020 were retrospectively assessed. A 1:1 propensity score matching analysis was performed to compare the short-term outcomes between RAMIE and conventional MIE. RESULTS: After matching, 45 patients were included in the RAMIE and conventional MIE groups. RAMIE had a significantly longer total operative time (708 vs. 612 min, P < 0.001) and thoracic operative time (348 vs. 285 min, P < 0.001) than conventional MIE. However, there were no significant differences in terms of oncological outcomes, such as R0 resection rate and number of resected lymph nodes. The overall postoperative morbidity (Clavien-Dindo [C-D] grade II or higher) rate of RAMIE and conventional MIE were 51% and 73% (P = 0.03), respectively, and the severe postoperative morbidity (C-D grade III or higher) rates were 11% and 29% (P = 0.04), respectively. The incidence rate of recurrent laryngeal nerve palsy was halved in RAMIE (7%) compared with conventional MIE (20%) (P = 0.06). Finally, the pulmonary complication rate (18%) was significantly lower in patients who underwent RAMIE than in those who underwent conventional MIE (44%) (P = 0.006). CONCLUSIONS: RAMIE was safe and feasible, even during the early period of its application at a specialized center. Moreover, it may be a promising alternative to conventional MIE, with better short-term outcomes, including significantly lower incidence of pulmonary complications.

11.
Esophagus ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32613326

RESUMO

The azygos arch is usually divided during esophagectomy. To achieve thorough lymphadenectomy up to upper mediastinum, many surgeons prefer to retract the distal stump of the azygos arch by pulling out the thread which ligates the stump to the skin through the dorsal side of the intercostal space. However, the access to the dorsal chest wall near vertebrae for percutaneous puncture is difficult during robot-assisted minimally invasive esophagectomy in the prone position. This paper reports a new simple method of azygos arch division and retraction using a polymer locking ligation system Hem-o-lok (Teleflex, Morrisville, NC, USA) and a barbed suture device. This technique can be easily performed completely as a robotic procedure without extra puncture, and it is also applicable for conventional thoracoscopic procedures with the potential benefits of less trauma and bleeding.

12.
Cancers (Basel) ; 12(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708005

RESUMO

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients.

13.
Int Cancer Conf J ; 9(3): 102-106, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32582511

RESUMO

Although the application of laparoscopic rectal surgery has been widely accepted by accumulated evidence, it remains technically difficult in some cases of obesity, narrow male pelvis, bulky tumors, or involvement of adjacent organs. After robotic rectal surgery has been covered by the health insurance system in Japan since April 2018, we have employed robotic rectal surgery for an increasing number of cases by taking advantages of its 3D vision and wrist function. When a colorectal cancer involves the urinary bladder, the surgical treatment of choice is an anterior resection with en bloc (partial or total) bladder resection, depending on the site and extent of bladder involvement. In the attached video, robotic surgery was conducted with the aid of intraoperative cystoscopy, which resulted in curative resection with negative margin. Given that the robotic system provides excellent stability and dexterity for bladder reconstruction, the robotic approach can be technically suitable for locally advanced T4 colorectal cancer with urinary involvement.

14.
Surg Today ; 50(11): 1507-1514, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32524272

RESUMO

PURPOSE: To clarify the usefulness of chemoradiotherapy (CRT) for low rectal cancer, we investigated the current status of CRT in Japan and its short- and long-term outcomes versus surgery alone for low rectal cancer in a large multicenter cohort study. METHODS: Between January 2010 and December 2011, data from 1608 patients with clinical Stage II-III rectal adenocarcinoma were collected from 69 specialized centers. Of these 1608 patients, 923 were diagnosed with clinical stage III low rectal cancer, 838 were enrolled in this study, divided into the surgery-alone group (n = 649) and preoperative CRT group (n = 189), and analyzed. RESULTS: The following parameters were significantly lower in the CRT versus surgery-alone group: blood loss (210 vs. 431.5 mL), postoperative complications (27.5% vs 39.0%), and the incidence of anastomotic leakage (3.7% vs. 8.8%). The 3-year overall survival, relapse-free and local recurrence-free survival rates did not between the two groups to a statistically significant extent (91.2% vs. 87.4%, 68.8% vs. 66.4%, and 88.2% vs. 88.4%, respectively). CONCLUSIONS: The present study revealed the current status of CRT for low rectal cancer in Japan. The results showed that CRT could be safely performed for advanced low rectal cancer in comparison to surgery alone.


Assuntos
Adenocarcinoma/cirurgia , Quimiorradioterapia Adjuvante , Cuidados Pré-Operatórios , Neoplasias Retais/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/epidemiologia , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/patologia , Fatores de Tempo , Resultado do Tratamento
15.
Dig Endosc ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32416608

RESUMO

Spontaneous regression (SR) has been reported in various malignant tumors. However, SR in colorectal cancer (CRC) is particularly rare and the mechanism remains unclear. We here report three cases of CRCs displaying SR, which were experienced at two institutions. Intriguingly, all of these cases displayed the common endoscopic characteristics; superficial elevated lesion accompanied by a central depression (0-IIa + IIc, in the Paris classification), with a nonpolypoid growth, located in the ascending colon. Furthermore, immunohistology of biopsy specimens revealed the lack of DNA mismatch repair proteins within the CRC lesions, suggesting that these were mismatch repair-deficient (dMMR) CRCs. One of the major features of dMMR cancers is an increase in the number of tumor-infiltrating lymphocytes. Thus, the dMMR phenotype might be associated with SR of CRCs through the activation of anti-tumor host immune responses.

16.
Nutrition ; 77: 110807, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402940

RESUMO

OBJECTIVE: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). METHODS: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. RESULTS: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. CONCLUSIONS: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events.

17.
J Hepatobiliary Pancreat Sci ; 27(8): 496-509, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32362018

RESUMO

BACKGROUND/PURPOSE: To investigate the long-term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. METHODS: Recurrence and survival data with long-term follow-up were analyzed in the cohort of a multi-institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). RESULTS: A total of 22/12 patients with K-RAS wild-type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left-sided primary tumors than in right-sided tumors (75.0% vs 30.0%, P = .022). The median follow-up was 72.6 months. The 5-year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5-year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow-up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5-year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1-4). CONCLUSIONS: Conversion hepatectomy achieved a similar long-term survival to the results of previous studies in initially resectable patients, although many of them experienced several post-hepatectomy recurrences. Left-sided primary was found to be the predictor for conversion hepatectomy.

18.
Cancer Lett ; 487: 53-62, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473241

RESUMO

Tumor-stromal interaction is implicated in tumor progression. Although CCR1 expression in myeloid cells could be associated with pro-tumor activity, it remains elusive whether disruption of CCR1-mediated myeloid cell accumulation can suppress tumor progression. Here, we investigated the role of CCR1 depletion in myeloid cells in two syngeneic colorectal cancer mouse models: MC38, a transplanted tumor model and CMT93, a liver metastasis model. Both cells induced tumor accumulation of CCR1+ myeloid cells that express MMP2, MMP9, iNOS, and VEGF. Lack of the Ccr1 gene in host mice dramatically reduced MC38 tumor growth as well as CMT93 liver metastasis. To delineate the contribution of CCR1+ myeloid cells, we performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type or Ccr1-/- mice. Mice reconstituted with Ccr1-/- BM exhibited marked suppression of MC38 tumor growth and CMT93 liver metastasis, compared with control mice. Consistent with these results, administration of a neutralizing anti-CCR1 monoclonal antibody, KM5908, significantly suppressed MC38 tumor growth and CMT93 liver metastases. Our findings highlight the importance of the application of CCR1 blockade as a therapeutic strategy.

19.
Updates Surg ; 72(3): 573-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32415666

RESUMO

Many systematic reviews have been published to evaluate the clinical benefits of robotic surgery for gastric cancer. However, these reviews have investigated various outcomes and differ considerably in quality. In this overview, we summarize the findings and quality of these reviews. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials to identify systematic reviews and meta-analyses that compared robotic surgery with laparoscopic surgery for gastric cancer. We summarized the results of the meta-analyses and evaluated the quality of the reviews using the AMSTAR-2 tool. The literature search identified 14 eligible reviews. The reviews showed that estimated blood loss was significantly less and time to resumption of oral intake was significantly shorter in patients who underwent robotic surgery than in those who underwent laparoscopic surgery. However, no significant differences in other outcomes were found between the two types of surgery. The quality of the included reviews was judged to be critically low. In conclusion, the available evidence, albeit of critically low quality, suggests that robotic surgery decreases estimated blood loss and shortens the time to resumption of oral intake in patients with gastric cancer. There is currently no high-quality evidence that robotic surgery has clinical benefits for gastric cancer patients.


Assuntos
Laparoscopia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Qualidade da Assistência à Saúde , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Ingestão de Alimentos , Humanos , Duração da Cirurgia , Resultado do Tratamento
20.
Int J Clin Oncol ; 25(8): 1441-1449, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32448950

RESUMO

BACKGROUND: There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess the efficacy and safety of chemotherapy for patients with unresectable or metastatic SBA. METHODS: In accordance with the PRISMA statements, literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The included studies were prospective randomized, nonrandomized, or observational studies. Risk of bias was assessed the ROBINS-I tool. RESULTS: Seven prospective single-arm Phase II studies were included in this review. Six of them were assessed as having a moderate risk of bias and one as having a serious risk of bias. A meta-analysis was not performed, because the studies were single-arm. Systemic chemotherapy based on fluoropyrimidine regimens achieved favorable outcomes with acceptable adverse effects as a first therapy; however, the regimens differed in each study. The object response rate was 18-50%, and the disease control rate was 29-87%. With 5-fluorouracil, adriamycin, and mitomycin-C regimen, one treatment-related death occurred. A second line of therapy including chemotherapy with nab-paclitaxel also showed favorable efficacy. The object response rate was 20%, and the disease control rate was 50%. CONCLUSIONS: Systemic chemotherapy based on fluoropyrimidine regimens was mainly used for unresectable or metastatic SBA. While it may achieve favorable outcomes with acceptable adverse effects, further evidence is needed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Intestino Delgado/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Albuminas/administração & dosagem , Doxorrubicina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Intestino Delgado/efeitos dos fármacos , Paclitaxel/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA