Guidelines recommend MRI as part of the staging work-up of patients with rectal cancer because it can identify high-risk groups requiring preoperative treatment. Phenomenal tumour responses have been ...observed with current chemoradiotherapy regimens-even complete regression in 25% of patients. For these patients, the options of organ-saving treatment as an alternative to surgery are now discussed, and critical for this approach is the availability of tools that can accurately measure response. The value of MRI in rectal cancer staging is established, but the role of MRI for the selection of patients for organ-saving treatment is debatable, because MRI is not able to accurately assess tumour response to preoperative chemoradiotherapy (owing to its reliance on morphological changes). Functional MRI is emerging in the field of oncology. It combines information on detailed anatomy with that of tumour biology, providing comprehensive information on tumour heterogeneity and its changes as a result of treatment. This Review provides knowledge on the strengths and weaknesses of MRI for response assessment after chemoradiotherapy in rectal cancer and on its ability to predict tumour response at the time of primary diagnosis. It elaborates on new functional magnetic resonance technology and discusses whether this and new postprocessing approaches have the potential to improve prediction and assessment of response.
Diffusion-weighted imaging (DWI) tumor volumetry is promising for rectal cancer response assessment, but an important drawback is that manual per-slice tumor delineation can be highly time consuming. ...This study investigated whether manual DWI-volumetry can be reproduced using a (semi)automated segmentation approach.
Seventy-nine patients underwent magnetic resonance imaging (MRI) that included DWI (highest b value b1000 or b1100) before and after chemoradiation therapy (CRT). Tumor volumes were assessed on b1000 (or b1100) DWI before and after CRT by means of (1) automated segmentation (by 2 inexperienced readers), (2) semiautomated segmentation (manual adjustment of the volumes obtained by method 1 by 2 radiologists), and (3) manual segmentation (by 2 radiologists); this last assessment served as the reference standard. Intraclass correlation coefficients (ICC) and Dice similarity indices (DSI) were calculated to evaluate agreement between different methods and observers. Measurement times (from a radiologist's perspective) were recorded for each method.
Tumor volumes were not significantly different among the 3 methods, either before or after CRT (P=.08 to .92). ICCs compared to manual segmentation were 0.80 to 0.91 and 0.53 to 0.66 before and after CRT, respectively, for the automated segmentation and 0.91 to 0.97 and 0.61 to 0.75, respectively, for the semiautomated method. Interobserver agreement (ICC) pre and post CRT was 0.82 and 0.59 for automated segmentation, 0.91 and 0.73 for semiautomated segmentation, and 0.91 and 0.75 for manual segmentation, respectively. Mean DSI between the automated and semiautomated method were 0.83 and 0.58 pre-CRT and post-CRT, respectively; DSI between the automated and manual segmentation were 0.68 and 0.42 and 0.70 and 0.41 between the semiautomated and manual segmentation, respectively. Median measurement time for the radiologists was 0 seconds (pre- and post-CRT) for the automated method, 41 to 69 seconds (pre-CRT) and 60 to 67 seconds (post-CRT) for the semiautomated method, and 180 to 296 seconds (pre-CRT) and 84 to 91 seconds (post-CRT) for the manual method.
DWI volumetry using a semiautomated segmentation approach is promising and a potentially time-saving alternative to manual tumor delineation, particularly for primary tumor volumetry. Once further optimized, it could be a helpful tool for tumor response assessment in rectal cancer.
Objective
The aim of this study was to evaluate whether magnetic resonance imaging (MRI) can accurately identify poor responders after chemoradiotherapy (CRT) who will need to go straight to surgery, ...and to evaluate whether results are reproducible among radiologists with different levels of expertise.
Methods
Seven independent readers with different levels of expertise retrospectively evaluated the restaging MRIs (T2-weighted + diffusion-weighted imaging T2W + DWI) of 62 patients and categorized them as (1) poor responders – highly suspicious of tumor; (2) intermediate responders – tumor most likely; and (3) good – potential (near) complete responders. The reference standard was histopathology after surgery (or long-term follow-up in the case of a watch-and-wait program).
Results
Fourteen patients were complete responders and 48 had residual tumor. The median percentage of patients categorized by the seven readers as ‘poor’, ‘intermediate’, and ‘good’ responders was 21% (range 11–37%), 50% (range 23–58%), and 29% (range 23–42%), respectively. The vast majority of poor responders had histopathologically confirmed residual tumor (73% ypT3-4), with a low rate (0–5%) of ‘missed complete responders’. Of the 14 confirmed complete responders, a median percentage of 71% were categorized in the MR-good response group and 29% were categorized in the MR-intermediate response group.
Conclusions
Radiologists of varying experience levels should be able to use MRI to identify the ± 20% subgroup of poor responders who will definitely require surgical resection after CRT. This may facilitate more selective use of endoscopy, particularly in general settings or in centers with limited access to endoscopy.
We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our ...objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR. A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR. Secondary outcome parameters were operative time, blood loss, 90-day mortality and length of hospital stay. Following pancreatic surgery, 63% of the patients experienced one or more postoperative complications. There was no significant difference in incidence or severity of complications between patients undergoing pancreatic surgery with (70%) or without (60%, P = 0.7) jejunal IR. Following colorectal surgery, 60% of the patients experienced one or more postoperative complication. Complication rate and severity were similar in patients with (50%) and without (65%, P = 0.46) colonic IR. Operative time, amount of blood loss, postoperative C-reactive protein, length of hospital stay or mortality were equal in both intervention and control groups for jejunal and colon IR. This study showed that human experimental intestinal IR models are safe in patients undergoing pancreatic or colorectal surgery.
Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases.
...This study aimed to investigate risk factors for distant metastases using time-dependent analyses.
Data from an international watch and wait database were retrospectively reviewed. Cox regression analysis was used to determine risk factors for worse distant metastases-free survival. Conditional survival modeling was used to investigate the impact of risk factors on the development of distant metastases.
Retrospective, multicenter database.
A total of 793 patients (47 institutions) with rectal cancer and clinical complete response to neoadjuvant treatment from the International Watch & Wait Database were included.
Distant metastases-free survival.
Of the 793 patients managed with watch and wait (median follow-up 55.2 mo)' 85 patients (10.7%) had distant metastases. Fifty-one of 85 patients (60%) had local regrowth at any time. Local regrowth was an independent factor associated with worse distant metastases-free survival in the multivariable model. Using conditional estimates, patients with local regrowth without distant metastases for 5 years (from decision to watch and wait) remained at higher risk for development of distant metastases for 1 subsequent year compared to patients without local regrowth (5-year conditional distant metastases-free survival 94.9% vs 98.4%).
Lack of information on adjuvant chemotherapy, salvage surgery for local regrowth, and heterogeneity of individual surveillance/follow-up strategies used may have affected results.
In patients with clinical complete response managed by watch and wait, development of local regrowth at any time is a risk factor for distant metastases. The risk of distant metastases remains higher for 5 years after development of local regrowth. See Video Abstract at http://links.lww.com/DCR/C53.
ANTECEDENTES:Casi el 30 % de los pacientes con cáncer de recto desarrollan un nuevo crecimiento local después de la respuesta clínica completa inicial manejada por watch and wait. Estos pacientes podrían tener un mayor riesgo de metástasis a distancia.OBJETIVO:Investigar los factores de riesgo de metástasis a distancia mediante análisis dependientes del tiempo.DISEÑO:Se revisó retrospectivamente los datos de la base de datos internacional de Watch and Wait. Se utilizó el análisis de regresión de Cox para determinar los factores de riesgo de peor sobrevida libre de metástasis a distancia. Se utilizó un modelo de sobrevida condicional para investigar el impacto de los factores de riesgo en el desarrollo de metástasis a distancia. El tiempo transcurrido hasta el evento se calculó utilizando la fecha de decisión para watch and wait y la fecha del nuevo crecimiento local para el diagnóstico de metástasis a distancia.ESCENARIOBase de datos multicéntrica retrospectiva.PACIENTES:Se incluyeron un total de 793 pacientes (47 instituciones) con cáncer de recto y respuesta clínica completa al tratamiento neoadyuvante de la base de datos internacional de Watch and Wait.PRINCIPALES MEDIDAS DE RESULTADO:Desarrollo de metástasis a distancia.RESULTADOS:De los 793 pacientes tratados con watch and wait (mediana de seguimiento de 55,2 meses), 85 (10,7%) tenían metástasis a distancia. 51 de 85 (60%) tuvieron recrecimiento local en algún momento. El recrecimiento local fue un factor independiente asociado a una peor supervivencia libre de metástasis a distancia en el modelo multivariable. Además, al usar estimaciones condicionales, los pacientes con recrecimiento local sin metástasis a distancia durante 5 años (desde la decisión de watch and wait) permanecieron en mayor riesgo de desarrollar metástasis a distancia durante un año subsiguiente en comparación con los pacientes sin recrecimiento local (sobrevida libre de metástasis a distancia a 5 años: recrecimiento local 94,9% frente a no recrecimiento local 98,4%).LIMITACIONES:La falta de información relacionada con el uso de quimioterapia adyuvante, las características específicas de la cirugía de rescate para el nuevo crecimient o local y la heterogeneidad de las estrategias individuales de vigilancia/seguimiento utilizadas pueden haber afectado los resultados observados.CONCLUSIONES:En pacientes con respuesta clínica completa manejados por Watch and Wait, el desarrollo de recrecimiento local en cualquier momento es un factor de riesgo para metástasis a distancia. El riesgo de metástasis a distancia sigue siendo mayor durante 5 años después del desarrollo de un nuevo crecimiento local. Consulte Video Resumen en http://links.lww.com/DCR/C53. (Traducción-Dr. Felipe Bellolio).
The aim of this work was to investigate the value of rectal cancer T-staging on MRI after chemoradiotherapy (ymrT-staging) in relation to the degree of fibrotic transformation of the tumour bed as ...assessed using the pathological tumour regression grade (pTRG) of Mandard as a standard of reference.
Twenty two radiologists, including five rectal MRI experts and 17 'nonexperts' (general/abdominal radiologists), evaluated the ymrT stage on the restaging MRIs of 90 rectal cancer patients after chemoradiotherapy. The ymrT stage was compared with the final ypT stage at histopathology; the percentages of correct staging (ymrT = ypT), understaging (ymrT < ypT) and overstaging (ymrT > ypT) were calculated and compared between patients with predominant tumour at histopathology (pTRG4-5) and patients with predominant fibrosis (pTRG1-3). Interobserver agreement (IOA) was computed using Krippendorff's alpha.
Average ymrT/ypT stage concordance was 48% for the experts and 43% for the nonexperts; ymrT/ypT stage concordance was significantly higher in the pTRG4-5 subgroup (58% vs. 41% for the pTRG1-3 group; p = 0.01), with the best results for the MRI experts. Overstaging was the main source of error, especially in the pTRG1-3 subgroup (average overstaging rate 38%-44% vs. 13%-55% in the pTRG4-5 subgroup). IOA was higher for the expert versus nonexpert readers (α = 0.67 vs. α = 0.39).
ymrT-staging is moderately accurate; accuracy is higher in poorly responding patients with predominant tumour but low in good responders with predominant fibrosis, resulting in significant overstaging. Radiologists should shift their focus from ymrT-staging to detecting gross residual (and progressive) disease, and identifying potential candidates for organ preservation who would benefit from further clinical and endoscopic evaluation to guide final treatment planning.
Seroma formation is a common complication after breast cancer surgery and can lead to delayed wound healing, infection, patient discomfort and repeated visits to the outpatient clinic. Mastectomy ...combined with flap fixation is becoming standard practice and is currently combined with closed-suction drainage. There is evidence showing that closed-suction drainage may be insufficient in preventing seroma formation. There is reasonable doubt whether there is still place for closed-suction drainage after mastectomy when flap fixation is performed. We hypothesize that mastectomy combined with flap fixation and closed suction drainage does not cause a significant lower incidence of seroma aspirations, when compared to mastectomy and flap fixation alone. Furthermore, we expect that patients without drainage will experience significantly less discomfort and comparable rates of surgical site infections.
This is a randomized controlled trial in female breast cancer patients undergoing mastectomy and flap fixation using sutures with or without sentinel lymph node biopsy (SLNB). Patients will be eligible for inclusion if they are older than 18 years, have an indication for mastectomy with or without sentinel procedure. Exclusion criteria are modified radical mastectomy, direct breast reconstruction, previous history of radiation therapy of the unilateral breast, breast conserving therapy and inability to give informed consent. A total of 250 patients will be randomly allocated to one of two groups: mastectomy combined with flap fixation and closed-suction drainage or mastectomy combined with flap fixation without drainage. Follow-up will be conducted up to six months postoperatively. The primary outcome is the proportion of patients undergoing one or more seroma aspirations. Secondary outcome measures consist of the number of invasive interventions, surgical site infection, quality of life measured using the SF-12 Health Survey, cosmesis, pain and number of additional outpatient department visits.
To our knowledge, no randomized controlled trial has been conducted comparing flap fixation with and without closed-suction drainage with seroma aspiration as the primary outcome. This study could result in finding evidence that supports performing mastectomy without closed-suction drainage.
This trial was approved by the medical ethical committee of Zuyderland Medical Center METC-Z on 20 March 2019 (METCZ20190023). The SARA Trial was registered at ClinicalTrials.gov as per July 2019, Identifier: NCT04035590 .
Background
Response Evaluation Criteria In Solid Tumors (RECIST) are known to have limitations in assessing the response of colorectal liver metastases (CRLMs) to chemotherapy.
Objective
The ...objective of this article is to compare CT texture analysis to RECIST-based size measurements and tumor volumetry for response assessment of CRLMs to chemotherapy.
Methods
Twenty-one patients with CRLMs underwent CT pre- and post-chemotherapy. Texture parameters mean intensity (M), entropy (E) and uniformity (U) were assessed for the largest metastatic lesion using different filter values (0.0 = no/0.5 = fine/1.5 = medium/2.5 = coarse filtration). Total volume (cm3) of all metastatic lesions and the largest size of one to two lesions (according to RECIST 1.1) were determined. Potential predictive parameters to differentiate good responders (n = 9; histological TRG 1–2) from poor responders (n = 12; TRG 3–5) were identified by univariable logistic regression analysis and subsequently tested in multivariable logistic regression analysis. Diagnostic odds ratios were recorded.
Results
The best predictive texture parameters were Δuniformity and Δentropy (without filtration). Odds ratios for Δuniformity and Δentropy in the multivariable analyses were 0.95 and 1.34, respectively. Pre- and post-treatment texture parameters, as well as the various size and volume measures, were not significant predictors. Odds ratios for Δsize and Δvolume in the univariable logistic regression were 1.08 and 1.05, respectively.
Conclusions
Relative differences in CT texture occurring after treatment hold promise to assess the pathologic response to chemotherapy in patients with CRLMs and may be better predictors of response than changes in lesion size or volume.
One concern after rectal cancer surgery is the high local recurrence rate. Randomized trials have shown that the best local control rate for rectal cancer patients as a group is achieved after a ...short course of radiation therapy followed by optimal surgery. It is debatable, however, whether all patients with rectal cancer should undergo preoperative radiation therapy. Preoperative identification of those most likely to benefit from neoadjuvant therapy is important. Therefore, the challenge for preoperative imaging in rectal cancer is to determine subgroups of patients with different risks for recurrence: those with superficial tumors, who can be treated with surgery alone; those with operable tumors and a wide circumferential resection margin, who can be treated with a short course of radiation therapy followed by total mesorectal excision; and those with advanced cancer and a close or involved resection margin, who require a long course of radiation therapy, with or without chemotherapy, and extensive surgery. So far, there is no consensus on the role of diagnostic imaging (endorectal ultrasonography, computed tomography, and magnetic resonance MR imaging) in the care of patients with primary rectal cancer. Preoperative staging has long relied on digital examination alone, which indicates that it has been difficult to achieve accuracy levels high enough for clinical decision making with preoperative imaging. In this review, the relevance of preoperative imaging in staging the local extent of primary rectal cancer will be discussed. Research on various imaging modalities, with an emphasis on MR, will be discussed under four main headings that address the most relevant aspects of local spread of rectal tumors: T stage, circumferential resection margin, locally advanced rectal cancer, and N stage.
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