Background
Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival ...after re-resection, RD, and prognostic factors are analyzed.
Methods
Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of re-resected patients were reviewed. Survival and prognostic factors were analyzed.
Results
Overall, 463 patients were included; 24% (
n
= 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval CI 11.6–15.6), compared with 52.6 months (95% CI 36.3–68.8) in re-resected patients (
p
< 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months;
p
< 0.001). In patients who underwent re-resection, RD in the liver (hazard ratio HR 5.54;
p
< 0.001) and lymph nodes (HR 2.35;
p
= 0.005) were the only significant prognostic factors in multivariable analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3;
p
= 0.003) and pN1 stage (HR 23.0;
p
= 0.022).
Conclusion
Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages.
Microscopic colitis presents as chronic watery diarrhoea and leads to a significant disease burden. Specific histological characteristics are key to diagnosing microscopic colitis and to specify its ...subtypes collagenous colitis or lymphocytic colitis. Histological hallmarks of microscopic colitis are an increased inflammatory infiltrate in the lamina propria without significant crypt architectural distortion and intraepithelial lymphocytosis, which is generally more prominent in lymphocytic colitis. Next to these similarities, collagenous colitis is defined by a thickened collagen band underneath the surface epithelium, which is absent or only slightly present in lymphocytic colitis. Besides these two well defined subtypes of microscopic colitis, incomplete forms of microscopic colitis are acknowledged which give the same symptom burden and should be recognized and treated accordingly. Both clinical and histopathological research in the field of microscopic colitis is ongoing. Recent studies have focussed on where to take biopsies to best establish the diagnosis, the implications of supplementary stain usage and interobserver agreement. Furthermore, insight into the potential underlying pathophysiological mechanisms increases. This review aims to provide an overview of the condition of microscopic colitis, with a focus on diagnosis. In addition, it aims to highlight that the increasing incidence and associated significant disease burden imply that this condition is not so ‘microscopic’ at all.
Abstract
Background
Neoadjuvant chemoradiotherapy (nCRT) followed by resection of the tumor with two field lymphadenectomy is a standard treatment for esophageal cancer. After nCRT, however, in more ...than 70% of patients no lymph node metastases are found, suggesting extensive overtreatment. Tumor-targeted fluorescence imaging is a promising technique to detect lymph node metastases intra-operatively and guide personalized resection. The aim of this study is to identify potential viable tumor markers for fluorescence imaging of lymph node metastases in patients with esophageal adenocarcinoma (EAC).
Methods
Immunohistochemistry (IHC) was performed on tissue microarrays from EAC’s patients that underwent surgical resection between 2007 and 2016. Patients were subdivided in five groups, non-pretreated patients with and without metastatic lymph nodes, complete responders, partial responders and non-responders after nCRT. Five membranous markers, c-MET, CAIX, EGFR, EpCAM, HER2, and two cytoplasmic markers, VEGF-A and VEGF-A receptor were included. Tumor marker expression was scored on intensity (none (0), slight (1), moderate (2), strong (3)) and the percentage of positive cells (estimation). Threshold for positive detection rate was defined as an intensity of ≥ 2 in more than 10% the cells.
Results
EpCAM showed the highest expression in metastastic lymph nodes, with a median intensity of 3 (range 2–3) in > 70% of the tumor cells. Expression was found in 37 out of 39 EAC’s (95%). VEGF-A and CAIX expression was observed in 28 of 33 (85%) and 10 of 33 (30%) of metastatic lymph nodes and 34 of 39 (87%) and 17 of 39 (44%) in the primary EAC’s, respectively. For the other tumor biomarkers the detection rate ranged between 0 and 11% for metastatic lymph nodes and primary EAC’s. Only EpCAM and VEGF-A showed weak, non-specific staining in the fibrotic tissue.
Conclusion
High expression rates in primary EAC and metastatic lymph nodes were observed using immunohistochemical antibodies for EpCAM, VEGF-A and CA-IX, making these clinically relevant viable EAC tumor markers. A phase 1 dose finding study targeting VEGF-A by Bevacizumab-800-CW in patient with EAC is in preparation.
Disclosure
All authors have declared no conflicts of interest.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
In operable patients suffering from esophageal cancer, the percentage of patients without metastatic lymph nodes found after neoadjuvant chemoradiotherapy (nCRT) is 69%. Extensive ...lymph node dissections during esophagectomy may be omitted or minimized in these patients, reducing associated morbidity. Recently, MRI with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, ferumoxtran-10) has been reintroduced to detect metastatic lymph nodes in prostate cancer. The aim of this study is to assess the feasibility of USPIO-MRI to detect loco-regional lymph node metastases in patients with esophageal cancer.
Methods
USPIO-nanoparticles are intravenously infused 24 to 36 hours before MRI. USPIO-enhanced MRI is performed before and after nCRT. After nCRT, patients are scanned under general anesthesia immediately prior to surgery in the MR system of the hybrid MITeC operation room with controlled mechanical ventilation. During controlled prolonged apneu, a four-minute iron-sensitive MRI acquisition is used to visualize suspicious esophageal lymph nodes without motion artefacts. Resected specimens, still containing USPIO, are measured ex-vivo in a preclinical 7T MR system before histopathological examination. A radiological assessment of the presence of suspicious lymph nodes in-vivo is matched to the ex-vivo nodes on preclinical MRI, providing the ground truth for the presence of metastases.
Results
Currently, three patients were included in the study of which one patient has been examined before and after nCRT. MRI under anesthesia prior to surgery with controlled mechanical ventilation was possible resulting in a clinically relevant spatial resolution to visualize possible malignant lymph nodes. Suspicious nodes were identified and could be matched using corresponding anatomical landmarks to the ex-vivo MRI, which showed good visual agreement with esophageal specimen after resection.
Conclusion
A successful method was proposed to validate USPIO-enhanced MRI to detect metastatic lymph nodes in patients with esophageal cancer. Matching ex-vivo USPIO-MRI images with histopathology results provides direct information for validation of in vivo USPIO-MRI and characteristics of loco-regional lymph nodes. Final results on the feasibility of USPIO-MRI to detect metastatic lymph nodes after nCRT are still awaited. Feasibility and preliminary values of the accuracy of the technique are the starting point for a phase two study.
Disclosure
All authors have declared no conflicts of interest.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response ...of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations.
The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin area under the curve 2 mg/mL per min plus paclitaxel 50 mg/m2 of body-surface area combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4–6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET–CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed.
Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% 95% CI 17–50) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% 95% CI 4–23) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% 95% CI 17–44). PET–CT missed six of 41 TRG3 or TRG4 tumours (15% 95% CI 7–28). PET–CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas).
After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803).
Dutch Cancer Society.
PDF
