Aims
Interobserver agreement for dysplasia in Barrett's oesophagus (BO) is low, and guidelines advise expert review of dysplastic cases. The aim of this study was to assess the added value of p53 ...immunohistochemistry (IHC) for the homogeneity within a group of dedicated gastrointestinal (GI) pathologists.
Methods and results
Sixty‐single haematoxylin and eosin (HE) slide referral BO cases 20 low‐grade dysplasia (LGD); 20 high‐grade dysplasia (HGD); and 20 non‐dysplastic BO reference cases were digitalised and independently assessed twice in random order by 10 dedicated GI pathologists. After a ‘wash‐out’ period, cases were reassessed with the addition of a corresponding p53 IHC slide. Outcomes were: (i) proportion of ‘indefinite for dysplasia’ (IND) diagnoses; (ii) interobserver agreement; and (iii) diagnostic accuracy as compared with a consensus ‘gold standard’ diagnosis defined at an earlier stage by five core expert BO pathologists after their assessment of this case set. Addition of p53 IHC decreased the mean proportion of IND diagnoses from 10 of 60 to eight of 60 (P = 0.071). Mean interobserver agreement increased significantly from 0.45 to 0.57 (P = 0.0021). The mean diagnostic accuracy increased significantly from 72% to 82% (P = 0.0072) after p53 IHC addition.
Conclusion
Addition of p53 IHC significantly improves the histological assessment of BO biopsies, even within a group of dedicated GI pathologists. It decreases the proportion of IND diagnoses, and increases interobserver agreement and diagnostic accuracy. This justifies the use of accessory p53 IHC within our upcoming national digital review panel for BO biopsy cases.
Background
A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens ...in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence.
Methods
Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5‐fluorouracil and oxaliplatin‐containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval.
Results
Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015).
Conclusion
The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.
Promising responses
Background
Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction ...chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes.
Methods
All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS).
Results
A pathologic complete response was observed in 22 patients (17%), a “good” response (Mandard 2–3) in 74 patients (56%), and a “poor” response (Mandard 4–5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (
p
= 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (
p
= 0.004,
p
= 0.003, and
p
= 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (
p
= 0.020 and
p
= 0.028, respectively).
Conclusions
Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.
Aim
Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients ...without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases.
Method
All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis.
Results
Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3‐year metastasis‐free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98–2.11).
Conclusion
LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis‐free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.
Background and Aim
Although endoscopic recognition of dysplasia in Barrett’s esophagus is difficult, experience in recognition of early neoplastic lesions is supposed to increase the detection of ...early neoplastic lesions. The aim of this study was to assess the significance of dysplasia in random biopsies in Barrett’s esophagus, in the absence of reported visible lesions as well as the difference in final outcome of pathology.
Methods
We retrospectively identified all patients with Barrett’s esophagus with suspicion of dysplasia or early adenocarcinoma who were referred to our center between February 2008 and April 2016. We analyzed all endoscopy reports, pathology reports, and referral letters from 19 different hospitals. Patients were divided into two groups, based on the presence or absence of visible lesions reported upon referral.
Results
In total, 170 patients diagnosed with dysplasia or adenocarcinoma were referred to our tertiary center. Ninety-one of these referred patients were referred with dysplasia or adenocarcinoma in random biopsies, without a reported lesion during endoscopy in the referral center. During endoscopic work-up at our center, a visible lesion was detected in 44 of these 91 patients (48.4%). After endoscopic work-up and treatment, adenocarcinoma was found in an additional 21 patients. Two of these patients were initially referred with low-grade dysplasia, and 19 patients were initially referred with high-grade dysplasia. The final pathology was upstaged in 35.8% of the patients.
Conclusions
The presence of any grade of dysplasia in random biopsies during surveillance in referral centers is a marker for more severe final pathology. Training in recognition of early neoplastic lesions in Barrett’s esophagus imaging is recommended for endoscopists performing Barrett’s surveillance.
Molecular markers in colon cancer are needed for a more accurate classification and personalized treatment. We determined the effects on clinical outcome of the BRAF mutation, microsatellite ...instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.
Stage II colon carcinoma patients (n = 106) treated with surgery only and 258 stage III patients all adjuvantly treated with 5-fluorouracil chemotherapy were included. KRAS mutations in codons 12 and 13, V600E BRAF mutation and MSI status were determined.
Older patients (P < 0.001), right-sided (P = 0.018), better differentiated (P = 0.003) and MSI tumors (P < 0.001) were significantly more frequent in stage II than stage III. In both groups, there was a positive association between mutated BRAF and MSI (P = 0.001) and BRAF mutation and right-sided tumors (P = 0.001). Mutations in BRAF and KRAS were mutually exclusive. In a multivariate survival analysis with pooled stage II and stage III data, BRAF mutation was an independent prognostic factor for overall survival (OS) and cancer-specific survival hazards ratio (HR) = 0.45, 95% confidence interval (CI) 0.25–0.8 for OS and HR = 0.47, 95% CI 0.22–0.99. KRAS mutation conferred a poorer disease-free survival (HR = 0.6, 95% CI 0.38–0.97).
The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.
Aim
Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally ...recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes.
Methods
All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post‐treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1–2), partial (TRG 3) or poor (TRG 4–5). The PET/CT and TRG categories were compared, and possible confounders were analysed.
Results
A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post‐treatment PET/CT and surgery negatively influenced the predictive value.
Conclusion
Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients.
The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient ...selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.
All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.
Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).
Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.
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