Objective
The aim of the paper is to provide an overview of intraoperative sampling methods for frozen section (FS) analysis and of surgical techniques for a secondary neurovascular bundle (NVB) ...resection, as the method of surgical margin (SM) sampling and the management of a positive SM (PSM) at the nerve‐sparing (NS) area are under evaluated issues. FS analysis during radical prostatectomy (RP) can help to tailor the plane of dissection based on cancer extension and thus extend the indications for NS surgery.
Evidence Acquisition
We performed a PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Web of Science, Cochrane Library, and Elton B. Stephens Co. (EBSCO)host search to include articles published in the last decade, evaluating FS analysis in the NS area and surgical attempts to convert a PSM to a negative status.
Evidence Synthesis
Overall, 19 papers met our inclusion criteria. The ways to collect samples for FS analysis included: systematic (analysing the whole posterolateral aspect of the prostate specimen, i.e., neurovascular structure‐adjacent frozen‐section examination NeuroSAFE); magnetic resonance imaging (MRI)‐guided (biopsies from MRI‐suspicious areas, retrieved by the surgeon in a cognitive way); and random biopsies from the soft periprostatic tissues.
Techniques to address a PSM in the NS area included: full resection of the spared NVB, from its caudal to cranial aspect, often including the rectolateral part of the Denonvilliers’ fascia; partial resection of the NVB, in cases where sampling attempts to localise a PSM; incremental approach, meaning a partial or full resection that extends until no prostate tissue is found in the soft periprostatic environment.
Conclusions
There is no homogeneity in prostate sampling for FS analysis, although most recent evidence is moving toward a systematic sampling of the entire NS area. The management of a PSM is variable and can be affected by the sampling strategy (difficult localisation of the persisting tumour at the NVB). The difficult identification of the exact soft tissue location contiguous to a PSM could be considered as the critical point of FS analysis and of spared‐NVB management.
The prognosis of patients with colorectal liver metastases (LMs) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LMs ...which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDCs) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LMs has been barely analyzed thus far. We assessed PDC presence in the histological slides of surgically resected and synchronous LMs in 63 patients with CRC who had been not submitted to any neoadjuvant treatments. Then, we analyzed its association with patients’ cancer-specific survival (CSS) or progression-free survival. The presence of PDCs (P = .016) and PDC localization at tumor edge of LMs (P = .0004) were significantly associated with shorter CSS. PDC presence at the periphery of LMs and positive resection margin were independent prognostic variables for CSS. PDC localization at the tumor edge of LMs was a significant (P = .0079) and independent prognosticator of shorter progression-free survival. Our data suggest that PDC presence and peripheral localization in LMs may be relevant to predict outcome and useful for clinical decision making in patients with colorectal synchronous LMs.
•The prognosis of patients with colorectal LM is commonly established on clinical features.•Low attention is given to histopathological features of LM as prognostic factors.•The number of PDCs in primary CRC is correlated with prognosis and metastatic disease.•This study shows that PDC presence and peripheral localization in synchronous colorectal LMs are associated with bad prognosis.•Assessment of PDC counting in synchronous LMs may be useful to assess prognosis and for clinical decision making in patients with stage IV CRC.
mutations are grouped in activating
-independent signaling as monomers (class 1-V600E) or as dimers (class 2-codons 597/601), and
-dependent with impaired kinase activity (class 3-codons 594/596). ...Although clinical, pathologic, and molecular features of
-mutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes.
Data from 117 patients with
(92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540
wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan-Meier and log-rank test.
Class 3
-mutated mCRC was more frequently left sided (
= 0.0028), pN0 (
= 0.0159), and without peritoneal metastases (
= 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with
wt, was 2.38 95% confidence interval (CI), 1.61-3.54 for class 1, 1.90 (95% CI, 0.85-4.26) for class 2, and 0.93 (95% CI, 0.51-1.69) for class 3 (
< 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in
-mutated class 2 (
= 0.033) compared with class 3 cases.
For the first time, different clinical and pathologic features and outcome data were reported according to the three
mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients.
Robot-assisted radical prostatectomy (RARP) involves a tradeoff between oncological control and functional outcomes. Intraoperative control of surgical margins (SMs) may help in ensuring the safety ...of the dissection. Fluorescence confocal microscopy (FCM) is an effective method for interpretation of prostate tissue and provides digital images with an appearance similar to hematoxylin-eosin staining.
To describe an alternative technique to NeuroSAFE for intraoperative evaluation of neurovascular-adjacent margins shaved from ex vivo specimens using FCM analysis.
This was a prospective study of 24 patients undergoing RARP with intraoperative FCM control of margin status.
After surgical dissection, SMs are sectioned from the fresh prostate using the Mohs technique (shaving): three slices from the apex and the right and left posterolateral aspects are obtained. Digital images of the shavings are immediately acquired via FCM and shared with a remote pathologist. In the case of a positive SM, a focal secondary resection of the bundle can be performed owing to the ability of FCM to locate a region of interest on the flat sample.
The primary outcome measure was the rate of negative margins at neurovascular-adjacent sites. Oncological and functional outcomes for patients with 1 yr of follow-up are also reported.
All patients had negative SMs in shavings from neurovascular-adjacent areas at final histopathology; four underwent a secondary resection with final conversion to negative SM status. Nine of ten patients with 1-yr follow-up are free of biochemical recurrence (prostate-specific antigen persistence in one pN1 case), nine are fully continent, and four of the five with preoperative potency have recovered their sexual function.
Digital frozen sections with FCM during RARP may represent an alternative to NeuroSAFE for possible optimization of functional outcomes without compromising oncological safety.
We developed a technique to ensure complete removal of cancer tissue during surgical removal of the prostate. Tissue specimens are examined via digital microscopy in real time during the operation. This allows the surgeon to remove more tissue if cancer is detected at the margins of a specimen, while avoiding unnecessary removal of healthy tissue.
Fluorescence confocal microscopy analysis of areas adjacent to neurovascular bundles in freshly shaved prostate specimens represents a feasible and easy procedure to control surgical margin status during prostatectomy. The ability to create digital images without conventional processing and to allow remote reporting is a major strength. In the future, the technique could be used to guide functional tissue sparing and reduce positive margins at final histopathology.
Ex vivo fluorescence confocal microscopy (FCM) is an innovative imaging tool that can be used intraoperatively to obtain real‐time images of untreated excised tissue with almost histologic ...resolution. As inflammatory diseases often share overlapping clinical features, histopathology evaluation is required for dubious cases, delaying definitive diagnoses, and therefore therapy. This study identifies key‐features at ex vivo FCM for differential diagnoses of cutaneous inflammatory diseases, in particular, psoriasis, eczema, lichen planus and discoid lupus erythematosus. Retrospective ex vivo FCM and histological evaluations with relevant diagnoses were correlated with prospectively reported histopathologic diagnoses, to evaluate agreement and the level of expertise required for correct diagnoses. We demonstrated that ex vivo FCM enabled the distinction of the main inflammatory features in most cases, providing a substantial concordance to histopathologic diagnoses. Moreover, ex vivo FCM and histological evaluations reached a substantial agreement with histopathologic diagnoses both for all raters and for each operator. After a yet to be defined learning curve, these preliminary results suggest that dermatologists may be able to satisfactorily interpret ex vivo FCM images for correct real‐time diagnoses. Despite some limitations mainly related to the equipment of FCM with a single objective lens, our study suggests that ex vivo FCM seems a promising tool in assisting diagnoses of cutaneous inflammatory lesions, with a level of accuracy quite close to that offered by histopathology. This is the first study to investigate ex vivo FCM application in cutaneous inflammatory lesions, and to evaluate the diagnostic capability of this technology.
Poor histological differentiation is currently considered among the adverse histopathological factors associated with unfavourable clinical course of colorectal carcinoma (CRC). At present, the ...histological grade of CRC is assessed based on the percentage of glandular differentiation in the tumor according to the World Health Organization (WHO) criteria. However the prognostic value of the WHO grading system is limited by significant inter-observer variability in its assessment. In addition, the prognostic significance of WHO grading seems to depend on the microsatellite instability (MSI) status of the tumor. Finally, this grading does not apply to rarer histotypes of colorectal adenocarcinomas, such as the micropapillary, medullary, mucinous and signet ring cell variants. Recently a novel grading system based on the counting of clusters of five or more cells lacking a glandular structure (poorly differentiated clusters) and set in the tumor stroma or at invasive edge has been proposed in CRC. There is evidence that grading based on poorly differentiated clusters (PDC) is more reproducible and has more robust prognostic significance compared to WHO grading in CRC. In the present review we discuss the morphological features, criteria for the assessment, prognostic significance and correlation with biomolecular profiles of grading based on PDC counting in CRC.
AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and ...surgery.METHODS Tumor regression grade(TRG) according to the Dworak system and yT NM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced(c TNM stage Ⅱ and Ⅲ) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival(DFS) and cancer specific survival(CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTS cN + status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response(low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified twotiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The twotiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with c N+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
Ulcerative colitis UC patients are at an increased risk of developing colorectal cancer due to chronic inflammation. Endoscopic submucosal dissection ESD allows removal of non-invasive neoplastic ...lesions in the colon, but few data are available on its efficacy in UC patients.
Data from consecutive UC patients diagnosed with visible dysplastic lesions in the colon who underwent ESD were evaluated. The en bloc removal, R0 resection and complication rates were calculated. Local recurrence and metachronous lesions during follow-up were identified. A systematic review of the literature with pooled data analysis was performed.
A total of 53 UC patients age: 65 years; range 30-74; M/F: 31/22 underwent ESD. The en bloc resection rate was 100%, and the R0 resection rate was 96.2%. Bleeding occurred in seven 13.2% patients, and perforation in three 5.6% cases, all treated at endoscopy. No recurrence was observed, but two metachronous lesions were detected. Data from six other studies three Asian and three European were available. By pooling data, en bloc resection was successful in 88.4% (95% confidence interval CI = 83.5-92) of 216 lesions and in 91.8% 95% CI = 87.3-94.8 of 208 patients. R0 resection was achieved in 169 ESDs, equivalent to a 78.2% 95% CI = 72.3-83.2 rate for lesions and 81.3% 95% CI = 75.4-86 rate for patients. No difference between European and Asian series was noted.
This pooled data analysis indicated that ESD is a suitable tool for safely and properly removing non-invasive neoplastic lesions on colonic mucosa of selected UC patients.
Summary Mucinous adenocarcinoma (MAC) of the colon and rectum is a histological entity with still indefinite prognostic significance. Although it was previously designated as poorly differentiated by ...convention, the most recent World Health Organization guidelines indicate that the level of maturation of the epithelium determines differentiation in MAC and that microsatellite instability status should be taken into account for its histological grading. Nonetheless, precise criteria for grading are not provided, and the prognostic value of histological grading in MAC still remains unclear. In the present study we aimed to investigate the prognostic value of a grading system based on the counting of poorly differentiated clusters (PDC) of neoplastic cells in 108 colorectal MACs and to compare its reproducibility and significance with those of a grading system based on glandular differentiation. We found that PDC grade was more reproducible and significantly associated with disease progression ( P = .0089) as well as with death from colorectal cancer ( P = .0035) in our MACs, as compared to the grade based on glandular differentiation, which was not associated with any of the clinicopathologic variables. Moreover, PDC grade emerged as a significant, independent prognostic factor of recurrence-free survival ( P = .0198) and cancer-specific survival ( P = .0293) in MAC. Interestingly, the prognostic value of PDC grade was unaltered following incorporation of mismatch repair system status in grading. In conclusion, we demonstrated for the first time that PDC grading is feasible, reproducible, and prognostically relevant in MAC, which may support its use in routine practice.
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