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1.
Langenbecks Arch Surg ; 409(1): 171, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829557

RESUMO

PURPOSE: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery. METHODS: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position. RESULTS: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046). CONCLUSION: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Artéria Esplênica , Humanos , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Feminino , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Artéria Esplênica/cirurgia , Neoplasias Pancreáticas/cirurgia , Excisão de Linfonodo/métodos , Adulto , Resultado do Tratamento , Ligadura , Dissecação/métodos , Laparoscopia/métodos
2.
Langenbecks Arch Surg ; 409(1): 56, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38332380

RESUMO

BACKGROUND: Portal vein embolization (PVE) is often performed prior to right hemihepatectomy (RH) to increase the future liver remnants. However, intraoperative removal of portal vein thrombus (PVT) is occasionally required. An algorithm for treating the right branch of the PV using laparoscopic RH (LRH) after PVE is lacking and requires further investigation. METHODS: In our department, after the confirmation of a lack of extension of PVT to the main portal trunk or left branch on preoperative examination (ultrasound and contrast-enhanced computed tomography), a final evaluation was performed using intraoperative ultrasonography (IOUS). Here we present the cases of eight patients who underwent LRH after PVE and examine the safety of our treatment strategies. RESULTS: IOUS revealed PVT extension into the main portal trunk in two cases. For the other six patients without PVT extension, we continued the laparoscopic procedure. In contrast, in the two cases with PVT extension, we converted to laparotomy after hepatic transection and removed the PVT. The median operation time for hepatectomy was 562 min (421-659 min), the median blood loss was 293 mL (85-1010 mL), no liver-related postoperative complications were observed, and the median length of stay was 10 days (6-34 days). CONCLUSIONS: PVT evaluation and removal are important in cases of LRH after PVE. Our strategy is safe and IOUS is particularly useful for laparoscopically evaluating PVT extension.


Assuntos
Embolização Terapêutica , Laparoscopia , Neoplasias Hepáticas , Trombose , Humanos , Hepatectomia/métodos , Veia Porta/cirurgia , Neoplasias Hepáticas/cirurgia , Embolização Terapêutica/métodos , Trombose/cirurgia
3.
Ann Surg Oncol ; 31(5): 3069-3070, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38291303

RESUMO

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.


Assuntos
Neoplasias Colorretais , Embolização Terapêutica , Laparoscopia , Neoplasias Hepáticas , Humanos , Hepatectomia , Veia Porta/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/cirurgia , Ligadura , Tireotropina , Resultado do Tratamento
6.
Ann Surg Oncol ; 31(2): 1347-1357, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37952022

RESUMO

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia , Veia Porta/cirurgia , Resultado do Tratamento
9.
HPB (Oxford) ; 26(2): 282-290, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985325

RESUMO

INTRODUCTION: This study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy. MATERIALS AND METHODS: Since 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data. RESULTS: Of 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified. CONCLUSION: In patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Terapia Neoadjuvante/efeitos adversos , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia
10.
Ann Surg Oncol ; 31(1): 514-524, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37803089

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained. METHODS: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated. RESULTS: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01). CONCLUSIONS: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.


Assuntos
Carcinoma Ductal Pancreático , Diabetes Mellitus , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/patologia , Diabetes Mellitus/cirurgia , Pancreatectomia , Biologia , Taxa de Sobrevida , Prognóstico
11.
Surg Endosc ; 37(11): 8871-8878, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37749200

RESUMO

BACKGROUND: In pancreaticoduodenectomy (PD), the approach to superior mesenteric artery (SMA) is a critical process that supports adequate surgical margins and radicality for pancreatic tumors. In most of the reports on laparoscopic PD, the right-sided approach in which the jejunum is pulled out to the right side for peri-SMA dissection is used, since the left side of the SMA is difficult to dissect, and the only way to do this is to dissect the vein first. METHODS: We devised a method to simplify and safely perform peri-SMA dissection by reversing the process, starting from the left side of the SMA. The first step involves the mobilization of the pancreatic head, which allows for rotation around the SMA. The second step involves the dissection of the left side of the SMA and transection of the jejunum. The key point is to change the incision line between the anterior and posterior mesojejunum. The third process includes the inferior pancreatoduodenal artery (IPDA) and first jejunal artery (J1A) dissection, which can be easily performed from the left side because the SMA rotates by simply continuing the dissection along the previously exposed SMA, and the IPDA/J1A are safely dissected at the root because they are drawn to the left side. The remaining processes are performed on the right side. RESULTS: This method was performed in 16 cases, and in most cases IPDA/J1A were divided from the left side. CONCLUSION: The technique for SMA dissection from the left posterior side was described with illustrations and video. Our method allows safe oncologic dissection around SMA avoiding anatomical misorientation during laparoscopic PD.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/métodos , Artéria Mesentérica Superior/cirurgia , Pancreatectomia/métodos , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Laparoscopia/métodos
12.
Ann Surg Oncol ; 30(11): 6680-6681, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37535269

RESUMO

BACKGROUND: The optimal procedure during distal pancreatectomy (DP) for patients who have undergone distal gastrectomy (DG) remains unclear. Several papers on remnant gastric ischemia have reported that the preserved splenic vessels are essential for the proximal remnant stomach.1-4 We evaluated the outcomes of DP for post-DG patients in our hospital and introduced robotic splenic vessels preserving DP (R-SPDP). METHODS: Postoperative short-term outcomes of DP for post-DG patients during 2014 and 2021 were evaluated. Next, R-SPDP was performed for a post-DG patient with the intention of preserving the remnant stomach safely. The double bipolar method was used to dissect the adhesions around the splenic vessels.5,6 The splenic artery was clamped at the root side to prevent bleeding.7 All short gastric arteries and veins, which were the main feeders of the remnant stomach, were preserved and resection was completed. After resection, the indocyanine green (ICG) fluorescence angiography confirmed blood flow in the short gastric arteries and veins and good return blood flow to the splenic vein.8 RESULTS: Of four patients (50.0%, of 8 DP patients) in whom the remnant stomach was preserved, one conventional DP case had poor ICG perfusion and presented with remnant stomach ischemia postoperatively. The R-SPDP case with good ICG perfusion had a total operation time of 371 minutes and intraoperative blood loss of 10 mL. The oral diet was started on postoperative Day 3, and the postoperative course was uneventful. CONCLUSIONS: R-SPDP can be a good option for post-DG patients to preserve the remnant stomach safely.


Assuntos
Coto Gástrico , Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/métodos , Coto Gástrico/cirurgia , Gastrectomia/métodos , Isquemia , Neoplasias Pancreáticas/cirurgia
13.
Jpn J Clin Oncol ; 53(12): 1144-1152, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37609670

RESUMO

OBJECTIVE: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases. METHODS: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model. RESULTS: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months. CONCLUSIONS: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival.


Assuntos
Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pulmonares/patologia , Prognóstico , Modelos de Riscos Proporcionais , Pulmão/patologia , Estudos Retrospectivos
15.
Biosci Trends ; 17(4): 310-317, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37648468

RESUMO

Although the importance of adjuvant chemotherapy (AC) has been recognized in pancreatic cancer (PC) patients, there are few studies to address the underlying mechanisms of failure to complete AC. This study aims to investigate the relationship between nutritional state represented by sarcopenia and failure to complete AC in patients after curative-intent surgery for PC. This study included 110 patients who underwent pancreaticoduodenectomy for potentially resectable pancreatic cancers with intention of adjuvant S-1. Sarcopenia was defined using the psoas muscle mass index with cutoff values of 6.36 cm2/m2 for men and 3.92 cm2/m2 for women, which were calculated with a 3-D volumetric software. The relation between sarcopenia and successful AC and long-term survival were investigated. Twenty-nine (26%) patients were diagnosed as having sarcopenia (Sarcopenia group). Sarcopenia group comprised significantly older patients than Non-sarcopenia group (72 vs. 67 years old, p = 0.0087). AC was successfully completed in 14 patients (48%) in Sarcopenia group compared to 72 patients (89%) in Non-sarcopenia group (p < 0.0001). Multivariate analysis identified age ≥ 70 years and sarcopenia as significant risk factors for failure of AC. Among patients ≥ 70 years old, rate of successful AC was significantly higher in sarcopenia groups than non-sarcopenia group (17% vs. 78%, p < 0.001). In conclusions, age and sarcopenia were critical risk factors for the failure of 6 months of adjuvant chemotherapy. Among elderly patients, sarcopenia can predict the poor success rate of AC.


Assuntos
Neoplasias Pancreáticas , Idoso , Masculino , Humanos , Feminino , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Anastomose Cirúrgica , Quimioterapia Adjuvante , Análise Multivariada , Neoplasias Pancreáticas
18.
Pancreatology ; 23(6): 682-688, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37507301

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.


Assuntos
Carcinoma Ductal Pancreático , Gastroenterologia , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Japão , Pâncreas/cirurgia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Conferências de Consenso como Assunto
19.
Br J Surg ; 110(10): 1387-1394, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37469172

RESUMO

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.


Assuntos
Artéria Celíaca , Neoplasias Pancreáticas , Humanos , Idoso , Artéria Celíaca/patologia , Artéria Celíaca/cirurgia , Pancreatectomia/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
20.
J Pathol Clin Res ; 9(5): 339-353, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37291757

RESUMO

Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (ptrend < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (ptrend = 0.003) and to develop liver metastasis (ptrend = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.


Assuntos
Carcinoma , Neoplasias Pancreáticas , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Mutação , Proteína Smad4/genética , Proteína Smad4/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Pancreáticas
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