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1.
Int J Colorectal Dis ; 38(1): 55, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36847868

RESUMEN

PURPOSE: The optimal surgical approach for removal of colorectal endometrial deposits is unclear. Shaving and discoid excision of colorectal deposits allow organ preservation but risk recurrence with associated functional issues and re-operation. Formal resection risks potential higher complications but may be associated with lower recurrence rates. This meta-analysis compares peri-operative and long-term outcomes between conservative surgery (shaving and disc excision) versus formal colorectal resection. METHODS: The study was registered with PROSPERO. A systematic search was performed on PubMed and EMBASE databases. All comparative studies examining surgical outcomes in patients that underwent conservative surgery versus colorectal resection for rectal endometrial deposits were included. The two main groups (conservative versus resection) were compared in three main blocks of variables including group comparability, operative outcomes and long-term outcomes. RESULTS: Seventeen studies including 2861 patients were analysed with patients subdivided by procedure: colorectal resection (n = 1389), shaving (n = 703) and discoid excision (n = 742). When formal colorectal resection was compared to conservative surgery there was lower risk of recurrence (p = 0.002), comparable functional outcomes (minor LARS, p = 0.30, major LARS, p = 0.54), similar rates of postoperative leaks (p = 0.22), pelvic abscesses (p = 0.18) and rectovaginal fistula (p = 0.92). On subgroup analysis, shaving had the highest recurrence rate (p = 0.0007), however a lower rate of stoma formation (p < 0.00001) and rectal stenosis (p = 0.01). Discoid excision and formal resection were comparable. CONCLUSION: Colorectal resection has a significantly lower recurrence rate compared to shaving. There is no difference in complications or functional outcomes between discoid excision and formal resection and both have similar recurrence rates.


Asunto(s)
Absceso Abdominal , Neoplasias Colorrectales , Endometriosis , Femenino , Humanos , Endometriosis/cirugía , Reoperación , Fístula Rectovaginal
2.
Int J Colorectal Dis ; 38(1): 90, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37017766

RESUMEN

PURPOSE: Combined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes according to surgical approach. METHODS: The study was registered with PROSPERO. A systematic search was performed for all comparative studies describing outcomes in patients that underwent laparoscopic versus open simultaneous resection of colorectal primary tumours and liver metastases. Data was extracted and analysed using a random effects model via Rev Man 5.3 RESULTS: Twenty studies were included with a total of 2168 patients. A laparoscopic approach was performed in 620 patients and an open approach in 872. There was no difference in the groups for BMI (mean difference: 0.04, 95% CI: 0.63-0.70, p = 0.91), number of difficult liver segments (mean difference: 0.64, 95% CI:0.33-1.23, p = 0.18) or major liver resections (mean difference: 0.96, 95% CI: 0.69-1.35, p = 0.83). There were fewer liver lesions per operation in the laparoscopic group (mean difference 0.46, 95% CI: 0.13-0.79, p = 0.007). Laparoscopic surgery was associated with shorter length of stay (p < 0.00001) and less overall postoperative complications (p = 0.0002). There were similar R0 resection rates (p = 0.15) but less disease recurrence in the laparoscopic group (mean difference: 0.57, 95% CI:0.44-0.75, p < 0.0001). CONCLUSION: Synchronous laparoscopic resection of primary colorectal cancers and liver metastases is a feasible approach in selected patients and does not demonstrate inferior peri-operative or oncological outcomes.


Asunto(s)
Neoplasias Colorrectales , Laparoscopía , Neoplasias Hepáticas , Humanos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/cirugía , Neoplasias Colorrectales/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/secundario , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Tiempo de Internación
3.
Colorectal Dis ; 25(2): 234-242, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36227063

RESUMEN

AIM: The aim of this work is to describe a protocol and assess the feasibility of harvesting and analysing the mesocolic apical fragment (MAF) for the presence of central lymph node (LN) metastasis and extra lymphatic free tumour cells in a random subgroup extracted from a cohort of complete mesocolic excision colectomies with central vascular ligation. METHOD: Forty-seven patients diagnosed with colorectal cancer were included. A 2/2 cm pyramid of tissue was cut around the central tie and sent for pathological examination. The MAF was sectioned into 16 slices. High-definition images were taken from the slices which were merged into a panoramic three-dimensional image of the MAF. The distribution of LNs in the MAF was quantified. Immunohistochemistry staining for cytokeratin 14 was used to identify isolated tumour cells and micrometastases in the extranodal tissue. RESULTS: No tumoural cells migrating through the apical zone, outside of the LNs, were identified. Margins of resection, mesocolic tissue and LNs were all negative in the subgroup of ultrastaged MAFs. The number of examined central LNs varied between 0 and 24, with positive MAF LNs being identified only in pN2 stages. The rate of positive apical LNs in our cohort was 4.2% (n = 2). CONCLUSIONS: The MAF can be easily extracted from standard specimens, allowing for accurate analysis of lymphatic and extra-nodal tumour cells on the central resection margins, in central LNs and in the apical mesocolic tissue. Future research on larger cohorts is required to establish if analysing the MAF has an impact on patient staging, prognosis and management.


Asunto(s)
Neoplasias del Colon , Laparoscopía , Mesocolon , Humanos , Escisión del Ganglio Linfático/métodos , Neoplasias del Colon/cirugía , Colectomía/métodos , Mesocolon/cirugía , Pronóstico , Laparoscopía/métodos , Metástasis Linfática/patología , Ganglios Linfáticos/patología
4.
Medicina (Kaunas) ; 59(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37893461

RESUMEN

Background and Objectives: The objective of this study was to investigate quantitative changes in cell-free DNA (cfDNA) found in the bloodstream of patients with locally advanced rectal cancer who received neoadjuvant long-course chemoradiation, assuming a change in DNA fragments release during therapeutic stress. Materials and Methods: This was a prospective observational study that involved 49 patients who had three distinct pathologies requiring neoadjuvant chemoradiation: 18 patients with breast cancer, 18 patients with cervical cancer, and 13 patients with rectal cancer. Both breast cancer and cervical cancer patients were used as a control groups. Breast cancer patients were used as a control group as irradiation targeted healthy tissue after the tumor resection (R0), while cervical cancer patients were used as a control group to evaluate the effect of chemoradiation regarding cfDNA in a different setting (squamous cell carcinomas) and a different tumor burden. Rectal cancer patients were the study group, and were prospectively evaluated for a correlation between fragmentation of cfDNA and late response to chemoradiation. Blood samples were collected before the initiation of treatment and after the fifth radiation dose delivery. cfDNA was quantified in peripheral blood and compared with the patients' clinicopathological characteristics and tumor volume. Conclusion: Thirteen patients with locally advanced rectal cancer (T3/T4/N+/M0) were included in the study, and all of them had their samples analyzed. Eight were male (61.54%) and five were female (38.46%), with an average age of 70.85 years. Most of the patients had cT3 (53.85%) or cT4 (46.15%) tumors, and 92.31% had positive lymph nodes (N2-3). Of the thirteen patients, only six underwent surgery, and one of them achieved a pathological complete response (pCR). The mean size of the tumor was 122.60 mm3 [35.33-662.60 mm3]. No significant correlation was found between cfDNA, tumor volume, and tumor regression grade. cfDNA does not seem to predict response to neoadjuvant chemoradiotherapy and it is not correlated to tumor volume or tumor regression grade.


Asunto(s)
Neoplasias de la Mama , Ácidos Nucleicos Libres de Células , Neoplasias del Recto , Neoplasias del Cuello Uterino , Humanos , Masculino , Femenino , Anciano , Proyectos Piloto , Neoplasias del Cuello Uterino/patología , Neoplasias del Recto/genética , Neoplasias del Recto/terapia , Quimioradioterapia , Terapia Neoadyuvante , Neoplasias de la Mama/patología , Ácidos Nucleicos Libres de Células/uso terapéutico , Estadificación de Neoplasias , Resultado del Tratamiento , Estudios Retrospectivos
5.
Chirurgia (Bucur) ; 118(5): 464-469, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37965831

RESUMEN

AIM: In gastric cancer (GC), D2 lymph node dissection is, alongside negative-margins gastrectomy, of paramount importance. There is a debate between Western and Eastern scientific communities concerning the risk-benefit balance with respect to splenectomy, as Western countries are inclined to perform spleen-preserving gastrectomy due to an increased risk for postoperative complications. In Eastern countries (such as Japan) this is not the case. Our study aimed to determine whether or not spleen-sacrificing total gastrectomy for GC was associated with a higher rate of early postoperative morbidity or mortality. METHOD: We performed a retrospective case-control study in which we included patients who underwent total gastrectomy with D2 lymphadenectomy for GC (stages I-III) with curative intent, in a single high-volume tertiary oncologic centre. We divided the cases into two groups: spleenpreserving (SP) and spleen-sacrificing (SS) and evaluated the early complications rate following surgery. Afterwards, we performed propensity score matching (PSM) and analysis of the two groups. Results: We included 74 patients, 29 in the SS group and 45 in the SP group. Fifteen cases (20.2%) developed early postoperative complications and the complication rate was 53% (n=8) in the SS group and 46% (n=7) in the SP group. The overall 30-day mortality rate was 2.7%. Conclusions: Splenectomy is not associated with increased early morbidity following total gastrectomy with D2 lymphadenectomy if performed by an experienced surgeon.


Asunto(s)
Esplenectomía , Neoplasias Gástricas , Humanos , Esplenectomía/efectos adversos , Estudios de Casos y Controles , Estudios Retrospectivos , Puntaje de Propensión , Resultado del Tratamiento , Gastrectomía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias Gástricas/patología , Morbilidad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
6.
Chirurgia (Bucur) ; 118(4): 399-409, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37698002

RESUMEN

Background: Neutrophil to lymphocyte ratio (NLR) is promoted as a marker reflecting the antitumoral inflammatory response. Herein, we aim to assess whether NLR at the time of diagnosis can predict response to neoadjuvant therapy and long-term survival in a matched cohort of rectal cancer patients. Methods: This is a case control study on rectal cancer patients who underwent standard oncological treatment and had NLR sampled at each stage. ROC curve was used to establish the cut off value of NLR at diagnosis. Two groups (high and low NLR) were compared. Kaplan Meier overall and disease-free survival (DFS) analysis was done comparatively between two groups of patients: low and high NLR. Pearson and Log Rank tests were used to establish statistical significance. Propensity score matching (PSM) was performed, and all variables were compared again on the matched subgroups. Results: One hundred patients were included and 54 were compared again after PSM. NLR at diagnosis did not correlate with tumor regression grade (p=0.77). High NLR at diagnosis (NLR 2.58) was not found to be significantly associated with worse overall survival (p=0.096) or DFS (p=0.128). Similar results were achieved after PSM, except when stage III subgroups were compared, where higher NLR was associated with worse DFS (p=0.04), while results for OS were borderline (p=0.05). Conclusions: Overall, a pretherapeutic high NLR ( 2.58) was not found to predict survival or response do neoadjuvant therapy in patients with rectal cancer. However, a higher NLR may be associated with worse outcomes in advanced colorectal cancer.


Asunto(s)
Neutrófilos , Neoplasias del Recto , Humanos , Pronóstico , Estudios de Casos y Controles , Puntaje de Propensión , Resultado del Tratamiento , Neoplasias del Recto/terapia , Linfocitos
7.
Ann Surg Oncol ; 29(6): 3785-3797, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35103890

RESUMEN

BACKGROUND: Seroma after mastectomy and/or axillary lymph node dissection (ALND) is among the most common issue surgeons have to face in the early postoperative management of breast cancer. Using quilting sutures (QS) to aid in tissue approximation and decrease dead space is proposed as a simple technique to reduce seroma rate. We aimed to perform a systematic review, and analyse, in a meta-analytical model, the role of QS in improving wound outcomes and decrease volume, duration of drainage, and length of stay in hospital. METHODS: The study was registered with PROSPERO. A systematic search of the PubMed, EMBASE, and SCOPUS databases was performed for all comparative studies examining surgical outcomes in patients who underwent QS versus conventional closure (CC) after mastectomy ± ALND. RESULTS: Twenty-one studies with a total of 3473 patients (1736 in the study group and 1737 in the control group) were included based on the selection criteria. The study group showed significantly lower rates of seroma (p < 0.00001), total volume of drainage (p < 0.0001), days to drain removal (p < 0.00001), and length of stay (p < 0.00001) compared with the control group, while wound complication rates (surgical site infection, flap necrosis, hematoma, skin dimpling) were comparable between the two groups. CONCLUSIONS: QS are a reliable intraoperative technique that decrease seroma formation, volume of postoperative drainage, duration of drainage and length of hospital stay, and should be considered in mastectomies with or without ALND.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Drenaje/efectos adversos , Femenino , Humanos , Mastectomía/efectos adversos , Mastectomía/métodos , Complicaciones Posoperatorias/cirugía , Seroma/etiología , Seroma/prevención & control , Seroma/cirugía , Colgajos Quirúrgicos , Técnicas de Sutura/efectos adversos , Suturas/efectos adversos , Resultado del Tratamiento
8.
Chirurgia (Bucur) ; 114(2): 162-166, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31060647

RESUMEN

It is important for surgeons to keep up with improvements both in and outside their field. As medicine evolves, new techniques appear, and oncology is one of the main beneficiaries. "Liquid biopsy" is one of the most recent domains of interest in oncology, as it may provide important details regarding the characteristics of the main tumor and its metastases. Malignant cells are in a continuous dynamic, which makes the initial diagnostic biopsy and the pathological specimen evaluation insufficient in the late evolution of the disease, when relapse or metastases may appear. The fact that the healthcare provider is able to find out additional information about the tumor at a given time, by evaluating a blood sample to obtain a "liquid biopsy" is of utmost importance and gives multiple potentially usable data. There are three means of obtaining biological material that may be used as "liquid biopsy": evaluation of circulating tumor cells, circulating tumor DNA and exosomes. The most intensely studied entity is that of circulating tumor cells, with different applications, amongst which the most important, at present time, is the prognostic value that has important demonstrated implications, not only in breast and prostate cancer, but also in colorectal cancer. Although surgery will, most certainly, not be replaced by other treatments when aiming for a curative approach to rectal cancer, it is important for the surgeon to know information about complementary fields, one of which is comprised by "liquid biopsy".


Asunto(s)
ADN Tumoral Circulante/sangre , Neoplasias Colorrectales/sangre , Exosomas/patología , Biopsia Líquida , Células Neoplásicas Circulantes/patología , Neoplasias Colorrectales/patología , Humanos , Pronóstico , Resultado del Tratamiento
9.
Chirurgia (Bucur) ; 114(2): 207-215, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31060653

RESUMEN

Introduction: In this study, we aim to identify the impact of neoadjuvant radiation treatment upon the number of harvested and positive lymph nodes in the surgical specimen; in addition, we tried to identify the impact of chemotherapy in association with radiotherapy on said structures. Patients and methods: In the study we included patients treated for rectal cancer within a single oncologic surgical Unit serving the north-eastern part of Romania, over a period of 5 and a half years, between May 2013 and April 2018. Firstly, we compared pathologic lymph node status to pretherapeutic staging. Secondly, we compared lymph node values in relation to the treatment scheme. Results: There was a total of 498 patients treated radically through open surgery for low and mid rectal cancer. We saw a decrease in N staging in 218 cases, 65 remaining stationary and 10 increasing their lymph node staging on the surgical specimen. We identified significant differences between the total number of lymph nodes (17.4 vs 24.2, p 0.001), the number of positive lymph nodes (1.4 vs 3.4, p 0.001) and the ratio between positive and total lymph nodes (0.08 vs 0.14, p 0.001) in patients with and without neoadjuvant treatment respectively. However, there was no statistical difference between patients with and without chemotherapy associated to radiotherapy in the neoadjuvant treatment plan (p=0.539, p=0.58, p=0.575). Conclusion: This study shows there are significant variations according to the application of neoadjuvant treatment, between the numbers of positive and total lymph nodes, as well as the positive/total lymph node ratio.


Asunto(s)
Colectomía/métodos , Ganglios Linfáticos/patología , Terapia Neoadyuvante , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Anciano , Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
10.
Chirurgia (Bucur) ; 114(2): 243-250, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31060657

RESUMEN

Introduction: Neuroendocrine tumors of the gastro-entero-pancreatic system have a variety of components, clinical manifestations and prognostic indices according to their anatomical site. Therefore, their diagnostic and management strategies differ a great deal. Prognosis concerning NETs can be poor due to the degree of differentiation, early metastasizing and the high degree of invasiveness. Material and Methods: For the present study, the patient files were evaluated and the parameters of interest were followed. Results: Over the course of 6 years there were 37 patients diagnosed with and treated for NETs, regardless of primary tumor site. There were 9 patients with NETs of the primite mid- and hindgut thusly: 5 cases with colorectal NETs and 4 cases of small bowel NETs. 6 patients benefited from radical surgical treatment, 2 cases with palliative procedures and only one patient with tumor biopsy. The tumors were evaluated according to the 2010 WHO classification based on the number of mitoses and the Ki67 proliferation index. Adjuvant treatment was adapted according to staging and histopathological parameters. Conclusions: Despite recent progress in managing NETs, there are still many controversial aspects regarding the management of these cases, mainly about timing the right sequence of therapy.


Asunto(s)
Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias del Sistema Digestivo/terapia , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Neoplasias del Sistema Digestivo/cirugía , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/cirugía , Pronóstico , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/terapia , Resultado del Tratamiento , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia
11.
Chirurgia (Bucur) ; 113(3): 391-398, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29981670

RESUMEN

Background: Pylorus preserving (PP) pancreaticoduodenectomy (PD) has several advantages in terms of shorter operation time and improved nutritional status but with an increased risk for delayed gastric emptying. Methods: We performed a retrospective study on all patients in which PD was performed from May 2012 to May 2018. It was analyzed early postoperative outcomes and the incidence of delayed gastric emptying (DGE) syndrome for patients with pylorus PP PD technique and pancreaticogastrostomy (PG). Results: There were 47 PD, in which PP technique was performed in 42 cases. The tumour location was in the pancreatic head (n=21, 44.68%), periampullary (ampulla of Vater) (n=14,29.78%), distal bile duct (n=7,14.89%), duodenum (n=2, 4.25%) and advanced right colon cancer (n=3, 6.38%). There were 10 cases (21.2%) of grade III-V complications, grade A pancreatic fistula (PF)8 cases (17%), grade B in 3 cases (6.4%) and grade C in 1 case (2.12%). DGE was encountered in 17 cases (36.17%), grade A 2 cases (4.25%), grade B in 4 cases (8.5%) and grade C in 2 cases (4.25%). Biliary fistula occurred in 3 cases (6.4%) and in 4 cases relaparotomy was needed. Conclusions: The results of our study are concluding with the previous studies, the addition of PG to PP PD does not increase the risk of DGE.


Asunto(s)
Fístula Biliar/etiología , Fístula Biliar/cirugía , Neoplasias del Conducto Colédoco/cirugía , Gastrectomía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Píloro , Anciano , Fístula Biliar/mortalidad , Neoplasias del Conducto Colédoco/mortalidad , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Vaciamiento Gástrico , Humanos , Masculino , Persona de Mediana Edad , Tratamientos Conservadores del Órgano , Neoplasias Pancreáticas/mortalidad , Pancreaticoduodenectomía/métodos , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
12.
Chirurgia (Bucur) ; 111(6): 493-499, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28044951

RESUMEN

Certain combinations of the hematological components, specifically, neutrophils and lymphocytes, named neutrophil to lymphocyte ratio (NLR) or multiplication of neutrophil and monocyte (MNM) have been shown to have prognostic value in a variety of cancers. MATERIAL AND METHODS: Retrospective study which included 133 patients with uterine cervical cancer with or without neoadjuvant therapy based on prognostic factors and correlations between NLR and MNM values, markers that were analyzed as continuous variables. This study aimed to establish the critical value of hematological markers. Results: NLR is significantly lower for preoperative stages I and II (p = 0.0004). There is a significant association between NLR and lymph node metastasis (p = 0.016), parametrial invasion (p = 0.035), lymphovascular space invasion (p = 0.0151) and tumor size (p = 0.0017). Correlational analysis showed that there is a significant association between MNM and lymph node metastasis (p = 0.020), parametrial invasion (p = 0.00010), lymphovascular space invasion materially affecting the value MNM (p = 0.0018), tumor size more than 4 cm (p = 0.0314). NLR and MNM were significantly lower in patients with complete response to neoadjuvant treatment. Discussion: The results of this study outlines the importance of hematological panel and parameters that can be easily used at no extra cost to establish further evolution of patients to treatment.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirugía , Histerectomía , Linfocitos , Neutrófilos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Anciano , Carcinoma de Células Escamosas/sangre , Femenino , Humanos , Histerectomía/métodos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/sangre
13.
J Clin Oncol ; 42(1): 70-80, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37788410

RESUMEN

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.


Asunto(s)
Neoplasias del Recto , Espera Vigilante , Humanos , Neoplasias del Recto/patología , Supervivencia sin Enfermedad , Pronóstico , Quimioradioterapia , Biopsia , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del Tratamiento
14.
J Immunother Cancer ; 8(1)2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32448799

RESUMEN

BACKGROUND: New and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction. METHODS: Immunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538). RESULTS: Optical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II-III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes. CONCLUSION: IS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.


Asunto(s)
Neoplasias del Colon/inmunología , Femenino , Humanos , Masculino , Pronóstico , Reproducibilidad de los Resultados
15.
Clin Cancer Res ; 26(19): 5198-5207, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32669377

RESUMEN

PURPOSE: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). EXPERIMENTAL DESIGN: Biopsies from two independent cohorts (n 1 = 131, n 2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. RESULTS: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). CONCLUSIONS: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.


Asunto(s)
Biopsia , Complejo CD3/inmunología , Linfocitos T CD8-positivos/inmunología , Neoplasias del Recto/tratamiento farmacológico , Anciano , Linaje de la Célula/inmunología , Proliferación Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Inmunidad/efectos de los fármacos , Inmunidad/inmunología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/cirugía , Selección de Paciente , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/inmunología , Neoplasias del Recto/cirugía
16.
Rom J Morphol Embryol ; 60(4): 1175-1182, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32239092

RESUMEN

Pelvic exenteration (PE) is an extensive surgical procedure for locally advanced primary neoplasia (LAPN) or recurrent neoplasia (RN) that consists in the en bloc removal of the pelvic organs (rectum, internal genital organs and bladder) associated with pelvic lymph nodes. PE is classified into anterior, posterior and total, supra or infralevatorian approaches. Our aim was to evaluate the surgical procedure and the resection margins in correlation with postoperative complications and morbidity rates after PE in patients treated in a single surgical unit. The study group comprised patients diagnosed with different malignancies, surgically treated by using PE procedure, during 2012-2018. The cohort included 121 cases with LAPN (n=98, 80.99%) and RN (n=23, 19%), mostly female (n=114, 94.21%), with a mean age of 61.16 (33-85) years. LAPN had predominantly digestive (n=48, 49.98%) and gynecological (n=28, 28.57%) origins, while the majority of RN cases were cervical cancers (n=9, 39.13%). The univariate analysis showed that the gynecological origin of the tumor (p=0.02), urinary stoma (p=0.02) and posterior PE (PPE) (p=0.004) were significant prognostic factors for postoperative complications. After performing the multivariate analysis, only the gynecological origin (p=0.02) of the tumor and PPE (p=0.03) remained determining factors for postoperative complications. PE is a disabling surgical procedure associated with high postoperative mortality and morbidity, although it is often the only solution for advanced cases. The judicious selection of patients who can benefit from such extensive surgery is compulsory. Our study suggests that the gynecological origin of the tumor and PPE are key factors in postoperative complications.


Asunto(s)
Exenteración Pélvica/métodos , Neoplasias Pélvicas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pelvis/patología
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