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1.
Oncol Rep ; 45(4): 1-8, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33649846

RESUMO

Fluorouracil (5FU) is converted to its active metabolite fluoro­deoxyuridine monophosphate (FdUMP) through the orotate phosphoribosyl transferase (OPRT)­ribonucleotide reductase (RR) pathway and thymidine phosphatase (TP)­thymidine kinase (TK) pathway and inhibits thymidylate synthase (TS), leading to inhibition of thymidine monophosphate (dTMP) synthesis through a de novo pathway. We investigated the mechanism of 5FU resistance and strategies to overcome it by focusing on 5FU metabolism. Colon cancer cell lines SW48 and LS174T and 5FU­resistant cell lines SW48/5FUR and LS174T/5FUR were used. FdUMP amount was measured by western blotting. The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU. Drug cytotoxicity was observed by crystal violet staining assay. FdUMP was synthesized through the OPRT­RR pathway in SW48 cells but was scarcely synthesized through either the OPRT­RR or TP­TK pathway in SW48/5FUR cells. FdUMP amount in SW48/5FUR cells was reduced by 87% vs. SW48 cells. Expression levels of OPRT and TP were lower in SW48/5FUR when compared with these levels in the SW48 cells, indicating decreased synthesis of FdUMP­led 5FU resistance. These results indicated that fluoro­deoxyuridine (FdU) rather than 5FU promotes FdUMP synthesis and overcomes 5FU resistance. Contrastingly, FdUMP was synthesized through the OPRT­RR and TP­TK pathways in LS174T cells but mainly through the TP­TK pathway in LS174T/5FUR cells. FdUMP amount was similar in LS174T/5FUR vs. the LS174T cells. OPRT and RR expression was lower and TK expression was higher in LS174T/5FUR vs. the LS174T cells, indicating that dTMP synthesis increased through the salvage pathway, thus leading to 5FU resistance. LS174T/5FUR cells also showed cross­resistance to FdU and TS inhibitor, suggesting that nucleoside analogs such as trifluoro­thymidine should be used to overcome 5FU resistance in these cells. 5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU­resistant cells.

2.
Cell Rep ; 34(8): 108772, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33626352

RESUMO

Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With KrasG12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

3.
J Mol Histol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389427

RESUMO

LDLR-related protein 1B (LRP1B) is believed to internalize ligands through receptor-mediated endocytosis. Previous epigenetic and genetic studies have indicated that impaired LRP1B mRNA expression might be related to gastric carcinogenesis. However, expression and prognostic significance of LRP1B protein remain to be elucidated. This study aimed to unravel the clinicopathological characteristics of LRP1B protein expression in gastric cancer. Immunohistochemical staining with antibodies specific to LRP1B peptide, which has an EXXXLL motif-containing region in the C-terminal flexible loop for intracellular sorting, was performed with 100 gastric cancer tissue specimens. Out of 100 tissue specimens, 45 exhibited cytoplasmic localization of LRP1B immunoreactivity. This cytoplasmic localization of LRP1B was significantly higher (P = 0.044) in intestinal-type gastric cancer (25 of 44) than in diffuse-type gastric cancer (20 of 56). Notably, cytoplasmic LRP1B immunoreactivity was significantly associated with low clinicopathological stage and favorable prognosis of patients with diffuse-type gastric cancer (P = 0.014), but nor with intestinal-type gastric cancer (P = 0.994). Multivalent analysis revealed that cytoplasmic LRP1B immunoreactivity had an independent favorable prognostic value in diffuse-type gastric cancer (P = 0.046; hazard ratio 3.058, 95% confidence interval 1.022-9.149). In contrast, no significant relation of cytoplasmic LRP1B immunoreactivity to patients' prognosis was found in intestinal-type gastric cancer. Double immunocytochemical staining demonstrated that cytoplasmic LRP1B was co-localized with RAB11FIP1, which constituted the endocytic recycling compartments in diffuse-type gastric cancer cells. The findings of this study indicated that impaired endocytosis of the cytoplasmic domain of LRP1B, resulting in insufficient ligand internalization, is related to poor prognosis of patients with diffuse-type gastric cancer.

5.
Anticancer Res ; 41(1): 533-541, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419853

RESUMO

BACKGROUND/AIM: We compared the efficacy and safety of second-line FOLFIRI with bevacizumab (Bmab) or aflibercept (AFL) in patients with unresectable metastatic colorectal cancer (mCRC) to clarify selection criteria for anti-angiogenic agents. PATIENTS AND METHODS: The subjects were patients with mCRC who received second-line FOLFIRI in combination with Bmab or AFL. The primary endpoint was median overall survival (OS). Secondary endpoints were median time to treatment failure (TTF), overall response rate (ORR) and incidence of adverse events. RESULTS: Data from 26 patients in the Bmab group and 19 in the AFL group were analyzed. Median OS was slightly longer in the AFL group compared to the Bmab group, whereas median TTF was similar. ORR tended to be higher in the AFL group. The incidence of ≥grade 2 diarrhea and proteinuria was significantly higher in the AFL group than the Bmab group. CONCLUSION: In patients given combination treatment with FOLFIRI for second-line treatment of mCRC, AFL can increase response rates compared to Bmab, which may contribute to longer survival.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Retratamento , Resultado do Tratamento
6.
In Vivo ; 35(1): 203-213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402467

RESUMO

BACKGROUND/AIM: At present, there are no biomarkers to predict the effects of molecular targeted drugs in patients with CRC with liver metastasis. Thus, we performed this study to explore potential biomarkers for these patients. MATERIALS AND METHODS: We obtained cancer tissue specimens from liver metastasis-bearing CRC patients who received the following preoperative neoadjuvant chemotherapies with molecular targeted drugs: i) no therapy (n=3), ii) 5-FU+oxaliplatin+anti-EGFR (n=3), iii) and 5-FU+oxaliplatin+anti-VEGF (n=3). RESULTS: We investigated the RNA expression of 84 genes related to cancer drug resistance using an RT-PCR array. The MYC gene was the only gene that was significantly up-regulated in CRC tissue specimens from anti-EGFR group in comparison to the anti-VEGF group. CONCLUSION: MYC up-regulation in the primary CRC tissues may be a potentially useful biomarker for selecting anti-EGFR combination therapy in neoadjuvant chemotherapy for CRC with liver metastasis.

7.
World J Surg Oncol ; 18(1): 314, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256771

RESUMO

BACKGROUND: The rate of pulmonary metastasectomy from colorectal cancer (CRC) has increased with recent advances in chemotherapy, diagnostic techniques, and surgical procedures. The purpose of this study was to investigate the prognostic factors for response to pulmonary metastasectomy and the efficacy of repeat pulmonary metastasectomy. METHODS: This study was a retrospective, single-institution study of 126 CRC patients who underwent pulmonary metastasectomy between 2000 and 2019 at the Gifu University Hospital. RESULTS: The 3- and 5-year survival rates were 84.9% and 60.8%, respectively. Among the 126 patients, 26 (20.6%) underwent a second pulmonary metastasectomy for pulmonary recurrence after initial pulmonary metastasectomy. Univariate analysis of survival identified seven significant factors: (1) gender (p = 0.04), (2) past history of extra-thoracic metastasis (p = 0.04), (3) maximum tumor size (p = 0.002), (4) mediastinal lymph node metastasis (p = 0.02), (5) preoperative carcinoembryonic antigen (CEA) level (p = 0.01), (6) preoperative carbohydrate antigen 19-9 (CA19-9) level (p = 0.03), and (7) repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001). On multivariate analysis, only mediastinal lymph node metastasis (p = 0.02, risk ratio 8.206, 95% confidence interval (CI) 1.566-34.962) and repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001, risk ratio 0.054, 95% CI 0.010-0.202) were significant. Furthermore, in the evaluation of surgical outcomes, the safety of second pulmonary metastasectomy was almost the same as that of initial pulmonary metastasectomy. CONCLUSIONS: Repeat pulmonary metastasectomy is likely to be safe and effective for recurrent cases that meet the surgical criteria. However, mediastinal lymph node metastasis was a significant independent prognostic factor for worse overall survival.

8.
Anticancer Res ; 40(12): 7067-7075, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288604

RESUMO

BACKGROUND/AIM: Nivolumab is effective against advanced gastric cancer (AGC) refractory to or in patients intolerant of standard chemotherapy. This study was designed to clarify the impact of cancer cachexia in patients with AGC who received nivolumab. PATIENTS AND METHODS: We recruited AGC patients who were treated with nivolumab from October 2017 to December 2019. Clinical outcomes were compared between patients with and without cancer cachexia at the start of nivolumab. Cancer cachexia was defined as weight loss >5%; weight loss >2% and body mass index (BMI) <20; or sarcopenia and BMI <20. Primary endpoints were median overall survival (OS) and median time to treatment failure (TTF), while secondary endpoints were overall response rate (ORR) and incidence of adverse events. RESULTS: The study enrolled 44 patients. Median OS and TTF were significantly shorter in patients with cancer cachexia than in those without cancer cachexia (OS: 6.6 vs. 2.3 months; HR=2.65; 95%CI=1.28-5.49; p=0.008, TTF: 2.6 vs. 1.9 months; HR=2.17; 95%CI=1.09-4.32, p=0.027). On Cox proportional hazards analysis, cancer cachexia was significantly associated with shorter OS. The incidence of adverse events did not differ between the two groups. Nivolumab was associated with better OS and TTF outcomes in AGC patients without cachexia than in those with cachexia, albeit there was no difference in the incidence of adverse events. CONCLUSION: Cancer cachexia may be associated with worse clinical outcomes in patients with AGC treated with nivolumab.

9.
BMC Surg ; 20(1): 307, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261613

RESUMO

BACKGROUND: Hemobilia occurs mainly due to iatrogenic factors such as impairment of the right hepatic or cystic artery, and/or common bile duct in hepatobiliary-pancreatic surgery. However, little or no cases with hemobilia from the intra-pancreatic remnant bile duct after bile duct resection (BDR) has been reported. Here, we report a case of massive hemobilia due to the perforation of psuedoaneurysm of the gastroduodenal artery (GDA) to the intra-pancreatic remnant bile duct after hepatectomy with BDR. CASE PRESENTATION: A 68-year-old male underwent extended right hepatectomy with BDR for gallbladder carcinoma. He presented with upper gastrointestinal bleeding 2 months after the initial surgery. Upper endoscopy identified a blood clot from the ampulla of Vater and simultaneous endoscopic balloon tamponade contributed to temporary hemostasis. Abdominal CT and angiography revealed a perforation of the psuedoaneurysm of the GDA to the intra-pancreatic remnant bile duct resulting in massive hemobilia. Subsequent selective embolization of the pseudoaneurysm with micro-coils could achieve complete hemostasis. He survived without any recurrence of cancer and bleeding. CONCLUSION: Hemobilia could occur in a patient with BDR due to perforation of the pseudoaneurysm derived from the GDA to the intra-pancreatic remnant bile duct. Endoscopic balloon tamponade was useful for a temporal hemostasis and a subsequent radiologic interventional approach.

10.
Int J Surg Case Rep ; 78: 192-196, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33360334

RESUMO

INTRODUCTION AND IMPORTANCE: Recent advances in chemotherapy and chemoradiotherapy allow performance of conversion surgery by improving tumor shrinkage in select patients with initially unresectable locally advanced pancreatic cancer (LAPC), thereby providing curative potential. The number of conversion surgeries requiring arterial reconstruction for select patients with initially unresectable LAPC following favorable responses is expected to increase, so providing effective options for safe arterial reconstruction is critical. CASE PRESENTATION: Herein we report a case of successful conversion surgery for initially unresectable LAPC with splenic artery transposition for hepatic arterial reconstruction after gemcitabine/nab-paclitaxel (GnP). A 71-year-old woman was referred to our hospital for evaluation of a pancreatic head mass after developing diabetes. She was diagnosed with unresectable LAPC, which was in wide contact with the common hepatic artery (CHA), proper hepatic artery (PHA), and splenic artery (SA). She received GnP, and after 6 cycles, durations of disease control and normalization of serum carbohydrate antigen 19-9 (CA19-9) exceeded 7 months. She underwent radical subtotal stomach-preserving pancreaticoduodenectomy with CHA-PHA and portal vein (PV) resection (SA-right hepatic artery anastomosis/PV-superior mesenteric vein direct end-to-end anastomosis). Histopathological examination revealed R0 resection with a histological response of Evans grade IIB. No signs of tumor recurrence have been observed for 14 months postoperatively. CLINICAL DISCUSSION: No consensus has been reached regarding the optimal treatment regimen, duration, or criteria for conversion surgery in patients with LAPC, especially in cases requiring arterial resection. SA transposition for hepatic arterial reconstruction is generally very consistent, easily accessible, and offers adequate length and diameter for successful arterial anastomosis. CONCLUSION: Even for a SA initially in contact with the tumor, SA transposition for hepatic artery reconstruction is a safe and effective option when tumor contact disappears due to chemotherapy.

11.
World J Surg Oncol ; 18(1): 291, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160387

RESUMO

BACKGROUND: Postoperative anastomotic stenosis is a common complication in colorectal cancer patients (3-30%). Complete anastomotic stenosis is rare; however, when it occurs, almost all cases require surgical treatment. We herein report a case in which endoscopic dilation was effective for treating complete anastomotic stenosis after high anterior resection in a rectal cancer patient. CASE PRESENTATION: The patient was a 67-year-old man who underwent laparoscopic high anterior resection for rectal cancer (RS, T4a, N0, M0, Stage IIB (TNM Classification of Malignant Tumors)) in May 2018. The postoperative course was good and the patient was discharged on the 12th postoperative day. Subsequently adjuvant chemotherapy was initiated with oral uracil and tegafur plus leucovorin (UFT/LV); however, he complained of frequent defecation and melena after completion of the first course of chemotherapy. Thus, colonoscopy was performed, which revealed anastomotic stenosis. Endoscopic dilation was initially attempted, but failed. Thus, low anterior resection was performed with diverting colostomy. Four additional courses of chemotherapy were administered for 1 month after surgery. At 6 months after the second surgery, colonoscopy was performed, and complete anastomotic stenosis was pointed out again. The patient was successfully treated by endoscopic dilation using the rendezvous method. After this treatment, the lumen of the anastomotic site was observed to have narrowed again and endoscopic dilatation to treat anastomotic stenosis was repeated. In addition, he received local injection of steroids in anastomotic stenosis site. The lumen of anastomotic stenosis remained after the local injection of steroids and closure of colostomy was performed 9 months after the second operation. CONCLUSIONS: Endoscopic dilation using the rendezvous method was effective for treating anastomotic stenosis after colorectal surgery.

12.
Int J Surg ; 84: 147-153, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212225

RESUMO

BACKGROUND: Although perioperative outcomes following donor hepatectomy (DH) have been reported, little is known about the long-term outcomes in living donors of liver transplantation. The aim of this study was to investigate the short-term and long-term outcomes following DH. METHODS: A total of 408 living donors who underwent DH between 1996 and 2019 were analyzed in this retrospective study, focusing on short-term outcomes with respect to the operation period (era) and the graft type, as well as long-term outcomes. RESULTS: The overall incidence of postoperative complications was 40.4%. These included minor (30.4%), major (10.0%), and biliary (14.0%) complications. Short-term outcomes after DH slightly improved over time, and outcomes did not differ significantly between the graft types. With regards to long-term outcomes, the incidence of surgery-related complications such as keloids, incisional hernias, and mechanical bowel obstructions was 6.6% over a median follow-up of 7.2 years. In addition, some donors developed comorbidities such as lifestyle diseases and cancers during the follow-up period. CONCLUSIONS: Our study confirmed an improvement of perioperative outcomes in living donors. There was no significant association between the graft type and postoperative outcomes. Donors could develop various morbidities during long-term follow-up. Therefore, a careful perioperative management and long-term follow-up should be provided to living donors.

13.
Clin J Gastroenterol ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245556

RESUMO

We report a case of a submucosal abscess of the esophagus that required differentiation from a mediastinal abscess. A 48-year-old man presented with a chief complaint of fever and sore throat. He did not remember swallowing a foreign body, and his oral cavity showed no signs of inflammation. Contrast-enhanced computed tomography showed a low density area with enhancement in the mediastinum, especially around the esophageal wall. We planned to perform surgical drainage with the intention of performing intraoperative endoscopy from the beginning. We performed surgical drainage through a left cervical oblique incision; however, there was no exudate obtained from the mediastinal space. Despite the reported absence of accidental ingestion of a foreign substance, intraoperative endoscopy was performed that revealed a laceration in the esophageal mucosa 24 cm from the incisors. We diagnosed it as a submucosal abscess of the esophagus and prescribed parenteral antibiotics. Submucosal abscess of the esophagus can occur even in the absence of awareness of a foreign body ingestion or oral infection. In case that the abscess was not localized clearly within the outer membrane of the esophagus, the coincidental mediastinal drainage via a cervical incision and intraoperative endoscopy seemed to be useful.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33253659

RESUMO

BACKGROUND: Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Early studies suggest that extensive intraoperative peritoneal lavage (EIPL) might reduce the risk of peritoneal recurrence and improve survival. We aimed to evaluate the survival benefit of EIPL in patients with gastric cancer undergoing curative gastrectomy. METHODS: In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres from South Korea, China, Japan, Malaysia, Hong Kong, and Singapore. Patients were randomly assigned to receive surgery and EIPL (EIPL group) or surgery alone (standard surgery group) via a web-based programme in random permuted blocks in varying block sizes of four and six, assuming equal allocation between treatment groups. Randomisation was stratified according to study site and the sequence was generated using a computer program and concealed until the interventions were assigned. After surgery in the EIPL group, peritoneal lavage was done with 1 L of warm (42°C) normal 0·9% saline followed by complete aspiration; this procedure was repeated ten times. The primary endpoint was overall survival. All analyses were done assuming intention to treat. This trial is registered with ClinicalTrials.gov, NCT02140034. FINDINGS: Between Sept 16, 2012, and Aug 3, 2018, 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402). Two patients in the EIPL group and one in the standard surgery group withdrew from the trial immediately after randomisation and were excluded from the intention-to-treat analysis. At the third interim analysis on Aug 28, 2019, the predictive probability of overall survival being significantly higher in the EIPL group was less than 0·5%; therefore, the trial was terminated on the basis of futility. With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62). 3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group. 60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. The most common adverse events included anastomotic leak (ten [3%] of 346 patients in the EIPL group vs six [2%] of 362 patients in the standard surgery group), bleeding (six [2%] vs six [2%]), intra-abdominal abscess (four [1%] vs five [1%]), superficial wound infection (seven [2%] vs one [<1%]), and abnormal liver function (six [2%] vs one [<1%]). Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death. INTERPRETATION: EIPL and surgery did not have a survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for gastric cancer. FUNDING: National Medical Research Council, Singapore.

15.
World J Surg Oncol ; 18(1): 265, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050929

RESUMO

PURPOSE: Malignant large-bowel obstruction (MLBO) is a highly urgent condition in colorectal cancer with high complication rates. Self-expandable metal stent (SEMS) placement in MLBO is a new decompression treatment in Japan. Preoperative stent placement (bridge to surgery: BTS) avoids emergency surgery, but oncological influences of stent placement and post-BTS surgical approach remain unclear. We examined short- and long-term results of surgery for MLBO after SEMS placement in our hospital. METHODS: We retrospectively reviewed 75 patients with MLBO who underwent resection after SEMS placement at our hospital from June 2013 to December 2018. Postoperative morbidity and mortality were evaluated by comparison with the surgical approach. RESULTS: Tumor location was significantly higher in the left-side colon and rectum (n = 59, 78.7%) than right-side colon (n = 16, 21.3%). Technical and clinical success rates for SEMS placement were 97.3% and 96.0%, respectively. Laparoscopic surgery was performed in 54 patients (69.0%), and one-stage anastomosis was performed in 73 (97.3%). Postoperative complications were similar in the open surgery (open) group (n = 5, 23.8%) and laparoscopic surgery (lap) group (n = 7, 13.0%), with no severe complications requiring reoperation. Three-year overall survival (OS) and relapse-free survival (RFS) rates were not significantly different in the lap vs open group (67.5% vs 66.4%; 82.2% vs 62.5%). CONCLUSION: Preoperative stent treatment avoids stoma construction but allows anastomosis. One-time surgery was performed safely contributing to minimally invasive treatment and acceptable short- and long-term results.

16.
Int J Surg Case Rep ; 76: 251-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053483

RESUMO

INTRODUCTION: The liver hanging maneuver is an essential technique for controlling bleeding in hepatectomy, however it is often difficult in laparoscopic major hepatectomy. The present study describes a novel modified hanging maneuver in laparoscopic left hemihepatectomy. PRESENTATION OF CASE: A 29-year-old female underwent laparoscopic left hemihepatectomy for mucinous cystic neoplasm. After mobilizing the left lobe, the liver parenchyma was dissected along the demarcation line. For the hanging technique, the upper edge of the hanging tape was placed on the lateral side of the left hepatic vein, and fixed with the Falciform ligament. The lower edge of the tape was extracted outside the abdomen. Accordingly the hanging tape can be controlled extraperitoneally during the liver parenchyma dissection. DISCUSSION: This technique includes several advantages including no need of assistance using forceps, easy control of the hanging tape extraperitoneally, outflow control, better exposure of surgical field, and helpful guide of the liver dissection line toward the root of the left hepatic vein. CONCLUSION: Our novel modified hanging maneuver is easy and reproducible to use in laparoscopic left hemihepatectomy. Moreover, this technique can be applied to other laparoscopic hepatectomy.

17.
Gastric Cancer ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037492

RESUMO

BACKGROUND: Despite interest in surgeon and hospital volume effects on total gastrectomy (TG), clinical significance has not been confirmed in a large-scale population. This study aimed at clarifying the association of surgeon and hospital volume on postoperative mortality after TG for gastric cancer among Japanese patients in National Clinical Database (NCD). METHODS: Between 2011 and 2015, we retrospectively extracted data on TG for gastric cancer from the NCD. The primary outcome was operative mortality. We divided surgeon volume as the number of TGs performed by a patient's surgeon in the previous year: S1 (0-2 cases), S2 (3-9), S3 (10-25), S4 (26-79) and hospital volume by the number of TGs performed in the previous year: H1 (0-11 cases), H2 (12-26), H3 (27-146). We calculated the 95% confidence interval (CI) for the mortality rate based on odds ratios (OR) estimated from a hierarchical logistic regression model. RESULTS: We analyzed 71,307 patients at 2051 institutions. Low-volume surgeons and hospitals had significantly older and poorer-risk patients with various comorbidities. The operative mortality rate decreased with surgeon volume, 2.5% in S1 and 0.6% in S4. The operative mortality was 3.1% in H1, 1.7% in H2, and 1.2% in H3. After risk adjustment for surgeon, hospital volume and patient characteristics, hospital volume was significantly associated with operative morality (H3: OR = 0.53, 95% CI 0.43-0.63). CONCLUSIONS: We demonstrate hospital volume has an impact on postoperative mortality after TG in a nationwide population study. These findings suggest centralization may improve outcomes after TG.

18.
Sci Rep ; 10(1): 16554, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024179

RESUMO

Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. In the current study, we defined "M1" macrophage and "M1"/"M2" ratio by transcriptomic signatures using xCell. We investigated the association between high level of "M1" macrophage or "M1"/"M2" ratio and the tumor immune microenvironment by analyzing the transcriptome of publicly available cohorts, TCGA and METABRIC. We found that "M1" high tumors were not associated with prolonged survival compared with "M1" low tumors, or with the response to neoadjuvant chemotherapy. "M1" high tumors were associated with clinically aggressive features and "M1" high tumors enriched the cell proliferation and cell cycle related gene sets in GSEA. At the same time, "M1" high tumors were associated with high immune activity and favorable tumor immune microenvironment, as well as high expression of immune check point molecules. Strikingly, all these results were mirrored in "M1"/"M2" ratio high tumors. In conclusion, transcriptomically defined "M1" or "M1"/"M2" high tumors were associated with aggressive cancer biology and favorable tumor immune microenvironment but not with survival benefit, which resembled only part of their conventional clinical characteristics.

19.
J Geophys Res Biogeosci ; 125(3)2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33101822

RESUMO

The western subarctic Pacific (WSP) is known as one of the most productive regions among the world's oceans in spring. However, its oceanic waters are also known as a High Nutrient, Low Chlorophyll (HNLC) region during summer due to low iron (Fe) availability in seawater. Indeed, recent studies have demonstrated that the distribution of Fe in the WSP is complex and heterogeneous. This study thus investigated the effects of Fe availability on the community composition and photophysiology of surface phytoplankton from coastal to offshore waters in the WSP in the summer of 2014. Although relatively high concentrations (>2 mg m-3) of chlorophyll (chl) a were found in the Sea of Okhotsk and some coastal waters, low chl a concentrations (<1 mg m-3) were commonly observed in offshore waters. Based on dissolved Fe and macronutrient concentrations, we deduced that low Fe availability limited phytoplankton growth in offshore waters, whereas low silicate and/or nitrate levels limited growth in the shelf areas. Scanning electron microscopy also revealed that the centric diatom Chaetoceros exclusively dominated the diatom assemblages in the shelf and coexisted with pennate diatoms in offshore waters, respectively. Primary productivity in surface waters was negatively correlated with the bottom of the euphotic layer or the light saturation index of the photosynthesis-irradiance curve, which indicates that the phytoplankton assemblages were well acclimated to in situ light conditions regardless of the water masses.

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