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1.
BMC Surg ; 19(1): 179, 2019 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-31775813

RESUMEN

BACKGROUND: This study aimed to externally validate and upgrade the recent difficulty scoring system (DSS) proposed by Halls et al. to predict intraoperative complications (IOC) during laparoscopic liver resection (LLR). METHODS: The DSS was validated in a cohort of 128 consecutive patients undergoing pure LLRs between 2008 and 2019 at a single tertiary referral center. The validated DSS includes four difficulty levels based on five risk factors (neoadjuvant chemotherapy, previous open liver resection, lesion type, lesion size and classification of resection). As established by the validated DSS, IOC was defined as excessive blood loss (> 775 mL), conversion to an open approach and unintentional damage to surrounding structures. Additionally, intra- and postoperative outcomes were compared according to the difficulty levels with usual statistic methods. The same five risk factors were used for validation done by linear and advanced nonlinear (artificial neural network) models. The study was supported by mathematical computations to obtain a mean risk curve predicting the probability of IOC for every difficulty score. RESULTS: The difficulty level of LLR was rated as low, moderate, high and extremely high in 36 (28.1%), 63 (49.2%), 27 (21.1%) and 2 (1.6%) patients, respectively. IOC was present in 23 (17.9%) patients. Blood loss of >775 mL occurred in 8 (6.2%) patients. Conversion to open approach was required in 18 (14.0%) patients. No patients suffered from unintentional damage to surrounding structures. Rates of IOC (0, 9.5, 55.5 and 100%) increased gradually with statistically significant value among difficulty levels (P < 0.001). The relations between the difficulty level, need for transfusion, operative time, hepatic pedicle clamping, and major postoperative morbidity were statistically significant (P < 0.05). Linear and nonlinear validation models showed a strong correlation (correlation coefficients 0.914 and 0.948, respectively) with the validated DSS. The Weibull cumulative distribution function was used for predicting the mean risk probability curve of IOC. CONCLUSION: This external validation proved this DSS based on patient's, tumor and surgical factors enables us to estimate the risk of intra- and postoperative complications. A surgeon should be aware of an increased risk of complications before starting with more complex procedures.


Asunto(s)
Hepatectomía/métodos , Complicaciones Intraoperatorias/epidemiología , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
2.
Radiol Oncol ; 53(4): 465-472, 2019 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-31652124

RESUMEN

Background In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence. Patients and methods Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8-10 weeks after completition of CRT. Results From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR. ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.


Asunto(s)
Quimioradioterapia , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Neoplasias del Recto/terapia , Adulto , Capecitabina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Factores de Riesgo , Eslovenia , Tasa de Supervivencia , Resultado del Tratamiento
3.
Radiol Oncol ; 53(3): 331-336, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31553701

RESUMEN

Background Diverting stoma is often performed in rectal cancer surgery for reducing the consequences of possible anastomotic failure. Closing of stoma follows in most cases after a few months. The aim of our study was to evaluate morbidity and mortality after diverting stoma closure and to identify risk factors for complications of this procedure. Patients and methods At our department, we have performed a retrospective cohort analysis of data for 260 patients with diverting stoma closure from 2003 to 2015. Age, stoma type, patient's preoperative ASA score, surgical technique and time to stoma closure were investigated as factors which could influence the complication rate. Results 218 patients were eligible for investigation. Postoperative complications developed in 54 patients (24.8%). Most common complications were postoperative ileus (10%) and wound infection (5%). Four patients died (1.8%). There was no effect on complication rate regarding type of stoma, closing technique, patient's ASA status and patient age. The only factor influencing the complication rate was the time to stoma closure. We found that patients which had the stoma closed prior to 8 months after primary surgery had lower overall complication rate (p<0. 05). Conclusions To reduce overall complication rate, our data suggest a shorter period than 8 months after primary surgery before closure of diverting stoma. As diverting stoma closure is not a simple operation, all strategies should be taken to reduce significant morbidity and mortality rate.


Asunto(s)
Técnicas de Cierre de Herida Abdominal/efectos adversos , Técnicas de Cierre de Herida Abdominal/mortalidad , Colostomía , Ileostomía , Complicaciones Posoperatorias/mortalidad , Neoplasias del Recto/cirugía , Técnicas de Cierre de Herida Abdominal/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Colostomía/métodos , Colostomía/estadística & datos numéricos , Femenino , Humanos , Ileostomía/métodos , Ileostomía/estadística & datos numéricos , Ileus/epidemiología , Ileus/etiología , Masculino , Persona de Mediana Edad , Morbilidad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Factores de Tiempo
4.
Biomed Res Int ; 2019: 7585486, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31915703

RESUMEN

The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms "probiotic" AND "wound infection." During a comprehensive review and critique of the selected research, fourteen in vitro studies, 8 animal studies, and 19 clinical studies were found. Two of these in vitro studies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the species Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus. All in vitro studies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.


Asunto(s)
Antibacterianos/uso terapéutico , Lacticaseibacillus casei/fisiología , Lactobacillus acidophilus/fisiología , Lactobacillus plantarum/fisiología , Probióticos/uso terapéutico , Infección de Heridas/prevención & control , Animales , Quimioterapia Adyuvante , Cicatriz/prevención & control , Humanos , Ratones , Conejos , Ratas , Cicatrización de Heridas
5.
Radiol Oncol ; 52(1): 65-74, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29520207

RESUMEN

BACKGROUND: Adenocarcinomas at the cardia are biologically aggressive tumors with poor long-term survival following curative resection. For resectable adenocarcinoma of the cardia, mostly esophagus extended total gastrectomy or esophagus extended proximal gastric resection is performed; however, the surgical approach, transhiatal or transthoracic, is still under discussion. Postoperative morbidity, mortality and long-term survival were analyzed to evaluate the potential differences in clinically relevant outcomes. PATIENTS AND METHODS: Of altogether 844 gastrectomies performed between January 2000 and December 2016, 166 were done for the adenocarcinoma of the gastric cardia, which we analyzed with using the Cox proportional hazards model. RESULTS: 136 were esophagus extended total gastrectomy and 125 esophagus extended proximal gastric resection. A D2 lymphadenectomy was performed in 88.2%, splenectomy in 47.2%, and multivisceral resections in 12.4% of patients. R0 resection rate was 95.7%. The mean proximal resection margin on the esophagus was 42.45 mm. It was less than 21 mm in 9 patients. Overall morbidity regarding Clavien-Dindo classification (> 1) was altogether 28.6%. 15.5% were noted as surgical and 21.1% as medical complications. The 30-day mortality was 2.2%. The 5-year survival for R0 resections was 33.4%. Multivisceral resection, depth of tumor infiltration, nodal stage, and curability of the resection were identified as independent prognostic factors. CONCLUSIONS: Transhiatal approach for resection of adenocarcinoma of the cardia is a safe procedure for patients with Siewert II and III regarding the postoperative morbidity and mortality; moreover, long-term survival is comparable to transthoracic approach. The complications associated with thoracoabdominal approach can therefore be avoided with no impact on the rate of local recurrence.

6.
Radiol Oncol ; 52(1): 42-53, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29520205

RESUMEN

BACKGROUND: The aim of the study was to compare the outcome of pure laparoscopic and open simultaneous resection of both the primary colorectal cancer and synchronous colorectal liver metastases (SCLM). PATIENTS AND METHODS: From 2000 to 2016 all patients treated by simultaneous resection were assessed for entry in this single center, clinically nonrandomized trial. A propensity score matching was used to compare the laparoscopic group (LAP) to open surgery group (OPEN). Primary endpoints were perioperative and oncologic outcomes. Secondary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 82 patients identified who underwent simultaneous liver resection for SCLM, 10 patients underwent LAP. All these consecutive patients from LAP were matched to 10 comparable OPEN. LAP reduced the length of hospital stay (P = 0.044) and solid food oral intake was faster (P = 0.006) in this group. No patient undergoing the laparoscopic procedure experienced conversion to the open technique. No difference was observed in operative time, blood loss, transfusion rate, narcotics requirement, clinical risk score, resection margin, R0 resections rate, morbidity, mortality and incisional hernias rate. The two groups did not differ significantly in terms of the 3-year OS rate (90 vs. 75%; P = 0.842) and DFS rate (60 vs. 57%; P = 0.724). CONCLUSIONS: LAP reduced the length of hospital stay and offers faster solid food oral intake. Comparable oncologic and survival outcomes can be achieved. LAP is beneficial for well selected patients in high volume centers with appropriate expertise.

7.
Adv Skin Wound Care ; 30(6): 256-261, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28520603

RESUMEN

OBJECTIVE: Negative-pressure wound therapy (NPWT) is the most modern and sophisticated method of temporary abdominal closure. The aim of the study was to determine the significant predictors for mortality in patients with NPWT. SETTING: University Clinical Centre Maribor, Slovenia MATERIALS AND METHODS:: The authors performed a retrospective cohort study of all patients treated with NPWT between January 1, 2011, and December 31, 2014. RESULTS: In the univariate analysis, the type of wound closure, more than 7 NPWT changes, the total days with NPWT, and time to wound closure were significantly associated with death of the patient. In the multivariate analysis, only the number of more than 7 NPWT changes was found as a significant predictor for death (P = .038). CONCLUSIONS: Negative-pressure wound therapy is a method of choice for the treatment of open abdomen if there is a clear indication. However, clinicians should try all measures to remove the NPWT system and close the abdomen as soon as possible because prolonged use is associated with significantly higher mortality.


Asunto(s)
Traumatismos Abdominales/cirugía , Laparotomía/efectos adversos , Terapia de Presión Negativa para Heridas , Seguridad del Paciente/estadística & datos numéricos , Cicatrización de Heridas/fisiología , Técnicas de Cierre de Herida Abdominal , Análisis de Varianza , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Laparotomía/métodos , Masculino , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Tasa de Supervivencia , Resultado del Tratamiento
8.
Int J Radiat Oncol Biol Phys ; 96(5): 1003-1010, 2016 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-27727065

RESUMEN

BACKGROUND AND PURPOSE: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. METHODS AND MATERIALS: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m2/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). RESULTS: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. CONCLUSIONS: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.


Asunto(s)
Adenocarcinoma/terapia , Antimetabolitos Antineoplásicos/administración & dosificación , Capecitabina/administración & dosificación , Quimioradioterapia/efectos adversos , Fraccionamiento de la Dosis de Radiación , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Recto/terapia , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal , Antimetabolitos Antineoplásicos/efectos adversos , Capecitabina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano/métodos , Periodo Preoperatorio , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Factores de Tiempo
9.
Coll Antropol ; 40(1): 35-40, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27301235

RESUMEN

The aim of our study was to demonstrate higher concentrations of lactic acid bacteria (LAB) on the colonic mucosa in operated colorectal cancer patients treated with oral intake of synbiotics or prebiotics preoperatively. We also tried to prove that the systemic inflammatory response after surgery is not so severe in patients who took synbiotics or prebiotics, furthermore these patients have less postoperative complications and a favorable postoperative course. 73 patients with preceding colorectal operations were recruited. They were randomized into three groups. One group received preoperatively prebiotics, the second synbiotics in and third was preoperatively cleansed. We have defined the number of four different probiotic bacteria on colonic mucosa with polymerase chain reaction (PCR). Serum levels of interleukin-6, CRP, fibrinogen, white cell count and differential blood count were measured pre- and postoperatively to determine systemic inflammatory response. We succeed in confirming that in the synbiotic group there were considerably more LAB presented on the mucosa. They did pass the upper gastrointestinal tract and were isolated in colonic mucosa. On the other hand, we did not find any statistical differences in systemic inflammatory response measured by upper factors and no differences in postoperative course and complications rate between all three groups.


Asunto(s)
Colectomía , Neoplasias Colorrectales/cirugía , ADN Bacteriano/análisis , Complicaciones Posoperatorias/prevención & control , Prebióticos , Cuidados Preoperatorios/métodos , Simbióticos , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/inmunología , Método Doble Ciego , Femenino , Fibrinógeno/inmunología , Humanos , Interleucina-6/inmunología , Lactobacillus/genética , Lactobacillus plantarum/genética , Leuconostoc/genética , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pediococcus/genética , Complicaciones Posoperatorias/inmunología , Probióticos , Síndrome de Respuesta Inflamatoria Sistémica/inmunología
11.
Coll Antropol ; 36(2): 419-23, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22856225

RESUMEN

In last two decades there was a huge step forward concerning rectal cancer treatment. The aim of our study was comparison of two time intervals regarding the methods of treatment and results of radical rectal cancer surgery. 407 patients operated on for rectal cancer were included in study. Those were patients with elective radical resection of solitary rectal tumor who survived first month after the operation. Patients were divided in two groups regarding the time of operation. In group one were patients operated on between 1996 and 2000 and in group two patients operated on between 2001 and 2005. We compared our results in both intervals with special interest about type of operation considering localization of the tumor, local recurrence and cancer related survival. Significant differences were found between two groups. There were more sphincter saving operations in second group, less local recurrences and better survival than in first group. This study observed significant improvements at recurrence rates and total survival for patients operated on rectal cancer.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Recurrencia Local de Neoplasia/mortalidad , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Análisis de Supervivencia
12.
Wien Klin Wochenschr ; 122 Suppl 2: 26-30, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20517667

RESUMEN

BACKGROUND: Preoperative bowel cleaning for elective colorectal surgery is a routine procedure. Synbiotics (probiotics plus prebiotics) are known for their beneficial effects on gut immune function and maintenance of the gut barrier. The main purpose of this study was to replace preoperative mechanical bowel cleaning with synbiotics and to assess the systemic inflammatory response and clinical outcome in patients undergoing colorectal surgery. PATIENTS AND METHODS: A prospective double-blind randomized placebo-controlled trial was conducted in 68 patients. The first group of 20 patients received synbiotics, the second group of 28 patients prebiotics and heat-deactivated probiotics, and the third (control) group of 20 patients mechanical bowel cleaning prior to the operation. RESULTS: Significantly higher values of interleukin 6 (IL-6) were detected 72 h after the operation in the synbiotic group (P = 0.025), as well as an increase of fibrinogen at 24 h postoperatively (P = 0.030). No statistical differences were found in leukocytes count, C-reactive protein or the lymphocyte/granulocyte ratio. There were no differences in postoperative complications between the groups. Mean hospital stay was 9.2 days in the prebiotic group, 9.5 days in the control group, and 10.95 days in the synbiotic group. CONCLUSIONS: Preoperative administration of prebiotics in elective colorectal surgery appears to have the same protective effect in preventing a postoperative inflammatory response as mechanical bowel cleaning. Further prospective studies are needed to verify the effects of synbiotics.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Colorrectales/cirugía , Prebióticos , Cuidados Preoperatorios/métodos , Probióticos/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antraquinonas/administración & dosificación , Proteína C-Reactiva/metabolismo , Catárticos/administración & dosificación , Método Doble Ciego , Electrólitos , Femenino , Fibrinógeno/metabolismo , Humanos , Mediadores de Inflamación/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polietilenglicoles , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Irrigación Terapéutica
13.
World J Gastroenterol ; 12(28): 4565-8, 2006 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-16874874

RESUMEN

AIM: To evaluate the prognostic value of some pathological variables in rectal cancer survival. METHODS: 247 patients who underwent curative resection of rectal cancer were included in the study. The influence on survival of five pathological variables (histopathological tumor type, histopathological tumor grade differentiation, blood vessel invasion, perineural invasion and lymphatic invasion) was assessed using statistical analyses. RESULTS: Overall 5-year survival was 71.2%. Univariate analysis of all tested variables showed an effect on survival but only the effect of lymphatic invasion was statistically significant. At stages three and four it had a negative effect on survival (P = 0.0212). Lymphatic invasion also significantly affected cancer related survival in multivariate analysis at stages three and four. At lower stages (stage 0, stage 1 and stage 2) multivariate analysis showed a negative effect of perineural invasion on cancer related survival. CONCLUSION: Patients with lymphatic and perineural invasion have a higher risk for rectal cancer related death after curative resection. Examination of these variables should be an important step in detecting patients with a poorer prognosis.


Asunto(s)
Invasividad Neoplásica/patología , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Neoplasias del Recto/tratamiento farmacológico , Estudios Retrospectivos , Análisis de Supervivencia
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