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1.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371860

RESUMO

Identification of low muscle mass becomes increasingly relevant due to its prognostic value in cancer patients. In clinical practice, mid-upper arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) are often used to assess muscle mass. For muscle-mass assessment, computed tomography (CT) is considered as reference standard. We investigated concordance between CT, BIA, and MAMC, diagnostic accuracy of MAMC, and BIA to detect low muscle mass and their relation with the clinical outcome malnutrition provided with the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). This cross-sectional study included adult patients with advanced esophageal and gastrointestinal cancer. BIA, MAMC, and PG-SGA-SF were performed. Routine CT-scans were used to quantify psoas muscle index (PMI) and skeletal muscle area. Good concordance was found between CTPMI and both BIAFFMI (fat free mass index) (ICC 0.73), and BIAASMI (appendicular skeletal muscle index) (ICC 0.69) but not with MAMC (ICC 0.37). BIAFFMI (94%), BIAASMI (86%), and MAMC (86%) showed high specificity but low sensitivity. PG-SGA-SF modestly correlated with all muscle-mass measures (ranging from -0.17 to -0.43). Of all patients with low muscle mass, 62% were also classified with a PG-SGA-SF score of ≥4 points. Although CT remains the first choice, since both BIA and MAMC are easy to perform by dieticians, they have the potential to be used to detect low muscle mass in clinical practice.


Assuntos
Antropometria/métodos , Impedância Elétrica , Músculo Esquelético/fisiopatologia , Avaliação Nutricional , Sarcopenia/diagnóstico , Idoso , Braço/diagnóstico por imagem , Braço/fisiopatologia , Índice de Massa Corporal , Estudos Transversais , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/fisiopatologia , Feminino , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Masculino , Desnutrição/complicações , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estado Nutricional , Estudos Prospectivos , Reprodutibilidade dos Testes , Sarcopenia/etiologia , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
3.
Ann Surg Oncol ; 28(9): 5194-5204, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34023946

RESUMO

BACKGROUND: There is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied. METHODS: Between January 2010 and December 2018, 61 locally advanced RRC patients were treated and analyzed retrospectively. Patients received radiotherapy at a dose of 30.0-30.6 Gy (reCRT) or 50.0-50.4 Gy chemoradiotherapy (CRT) in cases of no prior irradiation because of low-risk primary rectal cancer. In both groups, patients received capecitabine concomitantly. RESULTS: In total, 60 patients received the prescribed neoadjuvant (chemo)radiotherapy followed by surgery, 35 patients (58.3%) in the reRCT group and 25 patients (41.7%) in the long-course CRT group. There were no significant differences in overall survival (p = 0.82), disease-free survival (p = 0.63), and local recurrence-free survival (p = 0.17) between the groups. Patients in the long-course CRT group reported more skin toxicity after radiotherapy (p = 0.040). No differences were observed in late toxicity. In the long-course CRT group, a significantly higher cCR rate was observed (p = 0.029); however, there was no difference in the pCR rate (p = 0.66). CONCLUSIONS: The treatment of RRC patients with re-irradiation is comparable to treatment with long-course CRT regarding toxicity and oncological outcomes. In the reCRT group, less cCR was observed, although there was no difference in pCR. The findings in this study suggest that it is safe and feasible to re-irradiate RRC patients.


Assuntos
Reirradiação , Neoplasias Retais , Quimiorradioterapia , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Estudos Retrospectivos , Resultado do Tratamento
4.
JAMA Surg ; 156(8): 710-720, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009291

RESUMO

Importance: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). Objective: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. Design, Setting, and Participants: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. Interventions: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. Main Outcomes and Measures: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). Results: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. Conclusions and Relevance: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02758951.

5.
Int J Integr Care ; 21(1): 8, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33664641

RESUMO

Introduction: The reorganisation of the structure of a Gastro-Intestinal Oncology Multidisciplinary Team Meeting (GIO-MDTM) in a tertiary centre with three care pathways is evaluated on added value. Methods: In a mixed method investigation, process indicators such as throughput times were analysed and stakeholders were interviewed regarding benefits and drawbacks of the reorganisation and current MDTM functioning. Results: For the hepatobiliary care pathway, the time to treatment plan increased, but the time to start treatment reduced significantly. The percentage of patients treated within the Dutch standard of 63 days increased for the three care pathways. From the interviews, three themes emerged: added value of MDTMs, focus on planning integrated care and awareness of possible improvements. Discussion: The importance of evaluating interventions in oncology care pathways is shown, including detecting unexpected drawbacks. The evaluation provides insight into complex dynamics of the care pathways and contributes with recommendations on functioning of an MDTM. Conclusions: Throughput times are only partly determined by oncology care pathway management, but have influence on the functioning of MDTMs. Process indicator information can help to reflect on integration of care in the region, resulting in an increase of patients treated within the Dutch standard.

6.
Radiother Oncol ; 159: 91-97, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33741470

RESUMO

BACKGROUND AND PURPOSE: A radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT. MATERIALS AND METHODS: Between February 2007 and May 2018, 132 LARC/RRC patients who were scheduled for surgery with IOBT standby, were evaluated. By intra-operative inspection of the resection margin and MR imaging, it was determined whether a resection was presumed to be radical. Frozen sections were taken on indication. In case of a suspected R1 resection, IOBT (1 × 10 Gy) was applied. Histopathologic evaluation, treatment and toxicity data were collected from medical records. RESULTS: Tumour was resected in 122 patients. IOBT was given in 42 patients of whom 54.8% (n = 23) had a histopathologically proven R1 resection. Of the 76 IOBT-omitted R0 resected patients, 17.1% (n = 13) had a histopathologically proven R1 resection. In 4 IOBT-omitted patients, a clinical R1/2 resection was seen. In total, correct clinical judgement occurred in 72.6% (n = 88) of patients. In LARC, 58.3% (n = 14) of patients were overtreated (R0, with IOBT) and 10.9% (n = 5) were undertreated (R1, without IOBT). In RRC, 26.5% (n = 9) of patients were undertreated. CONCLUSION: In total, correct clinical judgement occurred in 72.6% (n = 88). However, in 26.5% (n = 9) RRC patients, IOBT was unjustifiedly omitted. IOBT is accompanied by comparable and acceptable toxicity. Therefore, we recommend IOBT to all RRC patients at risk of an R1 resection as their salvage treatment.


Assuntos
Braquiterapia , Neoplasias Retais , Braquiterapia/efeitos adversos , Humanos , Recidiva Local de Neoplasia/radioterapia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Reto , Terapia de Salvação
7.
J Surg Case Rep ; 2020(7): rjaa122, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32665838

RESUMO

Treatment of stage II-IV nonseminomatous testicular germ cell tumors (NSTGCTs) consists of cisplatin-based combination chemotherapy and, when present, resection of residual retroperitoneal tumor mass (RRTM) by conventional laparotomy or laparoscopy. In case of a retroperitoneal recurrence, a second conventional or laparoscopic procedure may be challenging. A case of late relapse after prior conventional resection of a RRTM and tailor-made surgical management with a posterior retroperitoneoscopic resection (PRR) is reported. A posterior retroperitoneoscopic RRTM resection was performed in a 26-year-old male with a history of stage IIC NSTGCT, presenting with a late left-sided retroperitoneal relapse, 6 years after initial treatment. Postoperative course was uneventful and at 1-year follow-up the patient had no evidence of disease. Reoperative surgery by a minimal invasive retroperitoneoscopic approach should be considered as an alternative for patients with a recurrent retroperitoneal tumor mass of a NSTGCT.

8.
JAMA Oncol ; 6(8): e202701, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32672798

RESUMO

Importance: To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases. Objective: To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases. Design, Setting, and Participants: In this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates. Exposures: Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively. Main Outcomes and Measures: Overall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity. Results: Of 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95). Conclusions and Relevance: Findings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.


Assuntos
Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Conduta Expectante
9.
Surg Oncol ; 33: 135-140, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32561078

RESUMO

BACKGROUND: Despite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic laparoscopy to CT when assessing patient eligibility for CRS + HIPEC. METHODS: This was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic laparoscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method. RESULTS: We identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an "open-and-close" procedure. In contrast to diagnostic laparoscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures. CONCLUSIONS: Adding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic laparoscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach.


Assuntos
Carcinoma/terapia , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Técnicas de Diagnóstico por Cirurgia , Quimioterapia Intraperitoneal Hipertérmica , Laparoscopia , Seleção de Pacientes , Neoplasias Peritoneais/terapia , Adulto , Idoso , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Estudos de Coortes , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Ann Surg Oncol ; 27(10): 3973-3983, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32335752

RESUMO

BACKGROUND: Previous studies have shown that, overall, quality of life (QoL) decreases within the first 3-6 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), returning to baseline levels by 6-12 months. This systematic review aims to evaluate the factors affecting QoL after CRS + HIPEC within 12 months of surgery. METHODS: Electronic databases were investigated searching for articles reporting QoL with validated questionnaires up to September 2019. Risk of bias was assessed with the methodological index for non-randomized studies tool. The primary outcomes were short-term (< 6 months after surgery) and medium-term (6-12 months after surgery) determinants of QoL after CRS + HIPEC. Secondary outcomes were QoL and reported symptoms over time. RESULTS: We included 14 studies that used 12 different questionnaires. The reported data were collected prospectively or retrospectively for 1556 patients (dropout < 50% in four studies). Overall, studies showed diminished QoL within 3 months after surgery and a recovery to baseline or greater by 12 months. QoL was negatively influenced by higher age, female sex, prolonged operation time, extensive disease, residual disease, adjuvant chemotherapy, complications, stoma placement, and recurrent disease. QoL results were comparable between studies, with dropout rates above and below 50%. CONCLUSIONS: QoL returns to baseline levels within 12 months after CRS + HIPEC provided the disease does not recur, and this recovery process is influenced by several factors.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Atividades Cotidianas , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Recidiva Local de Neoplasia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/terapia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos
11.
Ann Surg Oncol ; 27(8): 2997-3008, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32052304

RESUMO

BACKGROUND: The extent of surgery (ES) during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is a well-known risk factor for major postoperative morbidity. Interestingly, the reliability of surgeons to predict the ES prior to CRS + HIPEC is unknown. METHODS: In this prospective, observational cohort study, five surgeons predicted the ES prior to surgery in all consecutive patients with peritoneal metastases (PM) who were scheduled for CRS + HIPEC between March 2018 and May 2019. After the preoperative work-up for CRS + HIPEC was completed, all surgeons independently predicted, for each individual patient, the resection or preservation of 22 different anatomical structures and the presence of a stoma post-HIPEC according to a standardized ES form. The actual ES during CRS + HIPEC was extracted from the surgical procedure report and compared with the predicted ES. Overall and individual positive (PPV) and negative predictive values (NPV) for each anatomical structure were calculated. RESULTS: One hundred and thirty-one ES forms were collected from 32 patients who successfully underwent CRS + HIPEC. The number of resections was predicted correctly 24 times (18.3%), overestimated 57 times (43.5%), and underestimated 50 times (38.2%). Overall PPVs for the different anatomical structures ranged between 33.3 and 87.8%. Overall, NPVs ranged between 54.9 and 100%, and an NPV > 90% was observed for 12 anatomical structures. CONCLUSIONS: Experienced surgeons seem to be able to better predict the anatomical structures that remain in situ after CRS + HIPEC, rather than predict the resections that were necessary to achieve a complete cytoreduction.


Assuntos
Quimioterapia Intraperitoneal Hipertérmica , Idoso , Quimioterapia do Câncer por Perfusão Regional , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Estudos Prospectivos , Reprodutibilidade dos Testes , Cirurgiões
12.
J Nucl Med ; 61(5): 655-661, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31628218

RESUMO

Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2-3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence-guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 ± 2.5 (mean ± SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM.


Assuntos
Bevacizumab , Margens de Excisão , Imagem Óptica , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Cirurgia Assistida por Computador , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/cirurgia , Resultado do Tratamento
13.
Ann Surg Oncol ; 27(4): 1084-1093, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31641950

RESUMO

OBJECTIVE: The aim of this study was to evaluate the introduction of diagnostic laparoscopy (DLS) in patients with colorectal peritoneal metastases (PM) to prevent non-therapeutic laparotomies during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: Patients with histologically proven colorectal PM who underwent a laparotomy for potential CRS + HIPEC from January 2006 to January 2019 were retrospectively identified from a prospectively maintained database. In 2012, DLS was introduced in the preoperative work-up for CRS + HIPEC in our academic center. The rates of non-therapeutic laparotomies, major postoperative complications (Clavien-Dindo grade III or higher), and survival outcomes were investigated for patients who underwent a laparotomy before (cohort A) and after (cohort B) the introduction of DLS. In cohort B, the reasons to refrain from DLS were retrospectively explored from medical records. RESULTS: Overall, 172 patients were included [cohort A: 48 patients (27.9%); cohort B: 124 patients (72.1%)]. A significant drop in the rate of non-therapeutic laparotomies occurred in cohort B compared with cohort A (21.0 vs. 35.4%: p = 0.044), despite only 85 patients (68.5%) from cohort B undergoing DLS in our academic center. The most important reason to refrain from DLS was a recently performed DLS or laparotomy in the referring hospital (48.7%). Major postoperative complications, in-hospital mortality, and survival outcomes were similar for both cohorts. CONCLUSIONS: Performing DLS during the preoperative work-up for CRS + HIPEC prevents non-therapeutic laparotomies in patients with colorectal PM. We recommend performing this laparoscopic screening in an experienced HIPEC center.


Assuntos
Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Laparoscopia/métodos , Neoplasias Peritoneais/diagnóstico , Complicações Pós-Operatórias/etiologia , Idoso , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Peritônio/patologia , Peritônio/cirurgia , Cuidados Pré-Operatórios/efeitos adversos , Estudos Retrospectivos
14.
Eur J Surg Oncol ; 46(4 Pt A): 590-599, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31806520

RESUMO

BACKGROUND: The peritoneal cancer index (PCI) calculated during exploratory laparotomy is a strong prognostic factor for overall survival (OS) in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Progression of the PCI between diagnostic laparoscopy (DLS) and potential CRS + HIPEC (ΔPCI) might be a more dynamic prognostic factor for OS after CRS + HIPEC. MATERIALS AND METHODS: Between 2012 and 2018, all colorectal PM patients who underwent an exploratory laparotomy for potential CRS + HIPEC after DLS were retrospectively identified from a prospectively maintained database. Patients were divided into stable disease (ΔPCI 0-3), mild progression (ΔPCI 4-9), or severe progression (ΔPCI ≥10). Kaplan-Meier analysis and a multivariate Cox regression were performed. RESULTS: Eighty-four patients (ΔPCI 0-3, n = 35; ΔPCI 4-9, n = 34; and ΔPCI ≥10, n = 15) were analysed. Median OS after CRS + HIPEC was significantly decreased in patients with a ΔPCI of 4-9 (35.1 [95% CI 25.5-44.6]) or ΔPCI ≥10 (24.1 [95% CI 11.7-36.5]) compared to patients with a ΔPCI of 0-3 (47.9 [95% CI 40.0-55.7], p = 0.004). In multivariate regression analysis, ΔPCI remained an independent risk factor for OS: ΔPCI 4-9 HR 3.1 (95% CI 1.4-7.2, p = 0.007) and ΔPCI ≥10 HR 4.4 (95% CI 1.5-13.1, p = 0.007). CONCLUSION: A high ΔPCI is an independent dynamic prognostic factor for OS and might reflect a more aggressive tumour biology in patients with colorectal PM. HIPEC surgeons should be aware of a high-ΔPCI-associated diminished prognosis and should reconsider CRS + HIPEC when confronted with a ΔPCI ≥10.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma/secundário , Neoplasias Colorretais/patologia , Mitomicina/uso terapêutico , Neoplasias Peritoneais/secundário , Idoso , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Progressão da Doença , Feminino , Humanos , Hipertermia Induzida , Estimativa de Kaplan-Meier , Laparotomia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Carga Tumoral
15.
Lancet Gastroenterol Hepatol ; 4(10): 761-770, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31371228

RESUMO

BACKGROUND: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer. METHODS: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0-2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m2) for 30 min at 42°C, delivered simultaneously or within 5-8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086. FINDINGS: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3-88·5] for the experimental group vs 76·2% [68·0-84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis. INTERPRETATION: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial. FUNDING: Organization for Health Research and Development and the Dutch Cancer Society.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Hipertermia Induzida/métodos , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Colectomia/efeitos adversos , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Complicações Intraoperatórias , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias
16.
Ann Surg Oncol ; 26(7): 2210-2221, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30877495

RESUMO

BACKGROUND: Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. METHODS: Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien-Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan-Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. RESULTS: The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18-2.26). CONCLUSIONS: Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Segunda Neoplasia Primária/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
17.
BMC Cancer ; 19(1): 254, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898098

RESUMO

BACKGROUND: Approximately 20-30% of patients with pT4 colon cancer develop metachronous peritoneal metastases (PM). Due to restricted accuracy of imaging modalities and absence of early symptoms, PM are often detected at a stage in which only a quarter of patients are eligible for curative intent treatment. Preliminary findings of the COLOPEC trial (NCT02231086) revealed that PM were already detected during surgical re-exploration within two months after primary resection in 9% of patients with pT4 colon cancer. Therefore, second look diagnostic laparoscopy (DLS) to detect PM at a subclinical stage may be considered an essential component of early follow-up in these patients, although this needs confirmation in a larger patient cohort. Furthermore, a third look DLS after a negative second look DLS might be beneficial for detection of PM occurring at a later stage. METHODS: The aim of this study is to determine the yield of second look DLS and added value of third look DLS after negative second look DLS in detecting occult PM in pT4N0-2 M0 colon cancer patients after completion of primary treatment. Patients will undergo an abdominal CT at 6 months postoperative, followed by a second look DLS within 1 month if no PM or other metastases not amenable for local treatment are detected. Patients without PM will subsequently be randomized between routine follow-up including 18 months abdominal CT, or an experimental arm with a third look DLS provided that PM or incurable metastases are absent at the 18 months abdominal CT. Primary endpoint is the proportion of PM detected after a negative second look DLS and will be determined at 20 months postoperative. DISCUSSION: Second look DLS is supposed to result in 10% occult PM, and third look DLS after negative second look DLS is expected to detect an additional 10% of PM compared to routine follow-up alone in patients with pT4 colon cancer. Detection of PM at an early stage will likely increase the proportion of patients eligible for curative intent treatment and subsequently improve survival, given the uniformly reported direct association between the extent of peritoneal disease and survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03413254 , January 2018.


Assuntos
Neoplasias do Colo/patologia , Detecção Precoce de Câncer/métodos , Laparoscopia/métodos , Neoplasias Peritoneais/diagnóstico , Cirurgia de Second-Look/métodos , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/diagnóstico por imagem , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Peritônio/diagnóstico por imagem , Peritônio/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
18.
J Surg Oncol ; 118(2): 332-343, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29938400

RESUMO

Patients with peritoneal carcinomatosis (PC) from colorectal origin may undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a curative approach. One major prognostic factor that affects survival is completeness of cytoreduction. Molecular Fluorescence Guided Surgery (MFGS) is a novel intraoperative imaging technique that may improve tumor identification in the future, potentially preventing over- and under-treatment in these patients. This narrative review outlines a chronological overview of MFGS development in patients with PC of colorectal origin.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Imagem Molecular/métodos , Imagem Óptica/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Cirurgia Assistida por Computador/métodos , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Monitorização Intraoperatória/métodos , Invasividade Neoplásica , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia
19.
J Surg Oncol ; 117(2): 260-268, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28940461

RESUMO

BACKGROUND: Incidence of, and baseline characteristics associated with delirium in patients after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), were subject of investigation. METHODS: The study was conducted among a consecutive series of prospectively included patients who underwent CRS-HIPEC at the University Medical Center Groningen, Groningen, the Netherlands, between February 2006 and January 2015. A chart-based instrument for delirium during hospitalization was used to identify patients with symptoms of delirium who were not diagnosed by a psychiatrist during admission. Uni- and multivariate logistic regression analyses were performed. RESULTS: Data of 136 patients were included in the analysis. Median age was 60 years (range: 18-76) and 50 (37%) patients were male. During hospitalization, 38 (28%) patients were diagnosed with delirium. Factors that differed significantly between the patients with and without delirium by univariate analysis were included in multivariate analysis. Multivariate analysis showed that after adjustment for age and complications other than delirium, having three or more organs resected and the CRP serum levels were independent predictors for delirium (OR: 3.97; 95% 1.24-12.76; OR: 1.01; 95% 1-1.01, respectively). CONCLUSIONS: This report shows an incidence of 28% of delirium, occurring after CRS-HIPEC and suggests a role for systemic inflammation in the development of postoperative delirium.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Delírio/epidemiologia , Hipertermia Induzida/efeitos adversos , Neoplasias/terapia , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Delírio/diagnóstico , Delírio/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Países Baixos/epidemiologia , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
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