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Subcapsular liver metastasis resected after preoperative treatment combining chemotherapy and bevacizumab. Typical well-limited lesion with central infarct-like necrosis (*), surrounded by fibrosis and residual tumour (arrows).
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Citations
... Tumor cells get replaced by fibrotic scar tissue comprising of fibroblasts and bundles of collagen. The presence of foamy macrophages may help to distinguish chemotherapyinduced fibrosis from fibrous stromal tissue/ fibroinflammatory changes that could be confused with a chemotherapy response [19,20]. Fibroinflammatory changes may be seen around the tumor in absence of any treatment [21]. ...
Peritoneal surface oncology has emerged as a subspecialty of surgical oncology, with the growing popularity of surgical treatment
of peritoneal metastases comprising of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
Pathological evaluation plays a key role in multidisciplinary management but there are still many areas where there are no
guidelines or consensus on reporting. Some tumors presenting to a peritoneal surface oncology unit are rare and pathologists my
not be familiar with diagnosing and classifying those. In this manuscript, we have reviewed the evidence regarding various
aspects of histopathological evaluation of peritoneal tumors. It includes establishing a diagnosis, appropriate classification and
staging of common and rare tumors and evaluation of pathological response to chemotherapy. In many instances, the information
captured is of prognostic value alone with no direct therapeutic implications. But proper capturing of such information is vital for
generating evidence that will guide future treatment trends and research. There are no guidelines/data set for reporting
cytoreductive surgery specimens. Based on the authors’ experience, a format for handling/grossing and synoptic reporting of
these specimens is provided
... The appearance of ILN was classified into central ILN, speckled ILN, or neither. Central ILN was present in the center of the tumor, and tumor cells surrounded the circumference with or without intervening fibrosis [27]. Speckled ILN produced a number of lumps in the tumor with fibrosis (Fig. 3). ...
... We evaluated the histologic findings of necrotic characteristics in CRLM after preoperative chemotherapy, such as the shape of ILN and the dominant type of necrosis. With regard to the shape of ILN, central ILN was mentioned in a figure of a previous report [27]. In addition, we classified ILN into central and speckled ILN. ...
... Necrotic characteristics, not only the dominant type of necrosis but also the shape of ILN, may be related with an overall attenuation in CRLM after preoperative chemotherapy. Meanwhile, it was reported that ILN in CRLM after preoperative chemotherapy was associated with patients treated with a regimen including bevacizumab [22,27]. Our study showed that the frequency of central and speckled ILN was 29.8% (14/47) and 23.4% (11/47), respectively, in the all preoperative chemotherapy group, whereas it was 42.3% (11/26) and 23.1% (6/ 26), respectively, in the FOLFOX or FOLFIRI with bevacizumab group. ...
PurposeRadiological evaluation of the efficacy of preoperative chemotherapy for colorectal liver metastasis (CRLM) is the most important tool for determining treatment strategies. The aim of this study was to identify a correlation between morphologic appearance on computed tomography (CT) and histologic findings of CRLM after preoperative chemotherapy. Methods
We examined 47 patients who had undergone a first hepatic resection for CRLM after preoperative chemotherapy and had received contrast-enhanced CT scans. We assessed the morphologic appearance of the overall attenuation based on metastases changing from heterogeneous to mixed and homogenous lesions, the tumor–liver interface, and the peripheral rim enhancement on CT. Histologic parameters included usual necrosis (UN), infarct-like necrosis (ILN), three-zonal change, dangerous halo, mucous lake, shape of ILN, dominant type of necrosis, and presence of viable tumor cells. The relationship between morphologic appearance and histologic findings was evaluated. ResultsCT overall attenuation revealed that UN predominance was more common in the heterogeneous group than in the mixed and homogeneous groups (P = 0.011). The frequency of ILN increased sequentially from ill-defined to variable and sharp at the tumor–liver interface (P = 0.038), and the frequency of UN decreased sequentially from present to partially resolved and completely resolved in the peripheral rim enhancement (P = 0.023). The histologic presence of viable tumor cells was closely associated with the tumor–liver interface (P = 0.0003) and the peripheral rim enhancement (P = 0.004). ConclusionsCT morphologic appearance of CRLM after preoperative chemotherapy is correlated with histologic findings regarding necrosis.
... ILN was only observed in preoperatively treated patients and not in untreated patients, and it significantly correlated with improved DFS (log-rank p = 0.047) [48]. The association between bevacizumab and ILN was also confirmed in larger series retrospectively eval- uated [49]. Based on this observation, ILN was incorporated by Chang et al. in a modified TRG (mTRG) which considers the presence of ILN a form of therapeutic effect equivalent to fibrosis. ...
... We would like to thank Bibeau et al (2013) for their constructive comment on our article. We acknowledge that the question raised is of crucial interest and, as the evaluation of infarct-like necrosis (ILN) was not planned in our analyses, we went back to our samples in order to investigate it. ...
... In conclusion, we definitely agree with the proposal from Bibeau et al (2013) to include the evaluation of ILN in future studies assessing pathologic response of colorectal liver metastases to preoperative treatments. ...
The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
Cytoreductive surgery with or without HIPEC is a potentially curative approach for a small percentage of patients with colorectal peritoneal metastases. In patients undergoing surgery, the survival is significantly prolonged over systemic chemotherapy alone. Locoregional recurrence and disease progression which occurs in over 80% of the patients remains a problem. Completeness of cytoreduction and the surgical peritoneal cancer index (PCI) are the two most important prognostic factors determining treatment outcomes. Even in patients with a low PCI and complete cytoreduction, recurrence is common. Clinical research is focused on searching for molecular markers that can identify poor candidates for the procedure. Some aspects of disease biology and evolution of peritoneal metastases are still poorly understood which could be used to determine patient prognosis and develop different therapeutic approaches. Not all patients benefit from HIPEC, there may be some in whom systemic chemotherapy is not required and prophylactic approaches have failed to prevent PM in clinical trials so far. Neoadjuvant chemotherapy is offered to many patients with both resectable and unresectable disease. The pathological response to chemotherapy has prognostic value but has not been utilized for therapeutic decision making. This chapter focuses on routine histopathological findings that could be further exploited to better evaluate prognosis and treat patients.
This experimental study evaluated the histological response of peritoneal metastases (PM) from colorectal cancer (CRC) after preoperative systemic chemotherapy (pCT). The results demonstrated that the Peritoneal Regression Grade Score could be used in medical practice.
Aim:
The aim was to evaluate the histological criteria used by the tumour regression grade (TRG) and Peritoneal Regression Grade Score (PRGS) for determining the response to chemotherapy (CT), in a mouse model of peritoneal metastases (PM) from colorectal cancer (CRC).
Methods:
Twenty immunocompetent BALB/c mice were randomized into four groups at day (D) 10 after intraperitoneal (ip) injection with bioluminescent CRC tumour cells (CT26-luc). A histology before treatment group was obtained by sacrifice on D10; the other groups all received one of the following ip treatments over 15 days: 5% glucose (control, G5); 5-fluorouracil (5FU, 0.03 mg/g); or 5FU with oxaliplatin (Ox, 0.006 mg/g). The histological response (HR) was analysed by comparing the histology of PM before and after treatment, using both scores: TRG and PRGS.
Results:
All mice showed limited PM as visualised by bioluminescence and confirmed at the time of sacrifice in the histology before treatment group. The mean peritoneal carcinomatosis index (PCI) was = 8 [6-10], The rate of complete HR was significantly higher in the Ox-5FU group (83.3%) than 5FU group (0%) and G5 group (0%) (p = 0.016). Fibrosis was present only in CT-treated groups (p = 0.05). PCI, ascites volume and haemorrhagic ascites were significantly higher in the G5 group than CT groups (p < 0.05).
Conclusions:
The TRG score can be used in practice when we want to compare the HR between the primary tumour and the PMs. The PRGS is a good measure of HR and is correlated with the efficacy of CT.
Purpose
To investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival.
Methods
Sixty-two out of 301 patients presenting with synchronous CRLM underwent LFA between 2007 and 2016. All patients underwent neoadjuvant chemotherapy. After neoadjuvant treatment patients were re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Liver resection was scheduled after 4–6 weeks. Changes in non-tumoral parenchyma and the tumor response according to the Tumor Regression Grade score (TRG) were assessed on surgical specimens. Primary tumor resection was scheduled 4–8 weeks following hepatectomy.
Results
Five patients out of 62 (8.1%) showed “Progressive Disease” at re-evaluation after neoadjuvant chemotherapy, 22 (35.5%) showed “Stable Disease” and 35 (56.5%) “Partial Response”; of these latter, 29 (82%) showed histopathologic downstaging. The 5-year survival (OS) rate was 55%, while the 5-year disease-free survival (DFS) rate was 16%. RECIST criteria, T-stage, N-stage and TRG were independently associated with OS. Bilobar presentation of disease, RECIST criteria, R1 margin and TRG were independently associated with DFS. Patients with response to neoadjuvant chemotherapy had better survival than those with stable or progressive disease (radiological response 5-y OS: 65% vs. 50%; 5-y DFS: 20% vs. 10%; pathological response 5-y OS: 75% vs. 56%; 5-y DFS: 45% vs. 11%).
Conclusions
LFA is an oncologically safe strategy. Selection is a critical point, and the best results in terms of OS and DFS are observed in patients having radiological and pathological response to neoadjuvant chemotherapy.
: Multimodal therapeutic strategies have improved the outcome of peritoneal metastases (PM). However, objective assessment of therapy response remains difficult in PM, since radiological studies have a poor accuracy for low-volumetric disease. There is an obvious need for a histological gold standard allowing assessment of tumor response to treatment in PM.
: We propose to perform peritoneal punch biopsies with a diameter of 3 to 5 mm in all four abdominal quadrants. We propose a four-tier Peritoneal Regression Grading Score (PRGS), defined as Grade 1: complete response (absence of tumor cells), Grade 2: major response (major regression features, few residual tumor cells), Grade 3: minor response (some regressive features but predominance of residual tumor cells), Grade 4: no response (tumor cells without any regressive features). Acellular mucin and infarct-like necrosis should be regarded as regression features. We recommend reporting the mean and the worst value of the regression grades obtained. When complete tumor response is suspected intraoperatively, a peritoneal cytology should be sampled.
: A generic, unique score for the assessment of histological tumor response to chemotherapy in PM makes sense because of the clinical impact of histological response to therapy and because the organ of metastasis (peritoneum) is the same. By adopting PRGS, different centers will be able to use a uniform terminology and grading that will allow meaningful comparison of their results.
: PRGS has now to be validated in several gastrointestinal and gynecological cancer types and may be useful both in clinical and research settings.
The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy (N = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68-0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63-1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.
La prise en charge du cancer colorectal a changé ces quinze dernières années. Ces changements reposent en partie sur des évolutions dans le domaine de l’anatomie pathologique, tant morphologique que moléculaire. Elles se déclinent aux plans pronostique et prédictif. Le but de cet article est de souligner quelques changements majeurs ayant eu lieu dans le domaine de l’anatomie pathologique des cancers colorectaux depuis le dernier millénaire. Abstract Colorectal cancer management has been modified these last fifteen years. It is notably linked to the evolutions of anatomic pathology, both at the morphological and molecular levels, which have prognostic and predictive relevance. The goal of this article is to underline some major changes which occurred in colorectal malignant tumor pathology since the last millennium.
