Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature

<p>Abstract</p> <p>Background</p> <p>Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome.</p> <p>Methods</p> <p>Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection).</p> <p>Results</p> <p>Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent.</p> <p>Conclusion</p> <p>The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.</p

The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

<p>Abstract</p> <p>Background</p> <p>The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0_micro+patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0_micro+) and evaluate the benefits from adjuvant chemotherapy in pN0_micro+CC patients.</p> <p>Methods/design</p> <p>EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an <it>ex vivo </it>sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0_micro+) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).</p> <p>Discussion</p> <p>The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 _micro+CC patients by reducing disease recurrence by adjuvant chemotherapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01097265">NCT01097265</a></p

One Step Nucleic Acid Amplification (OSNA) - a new method for lymph node staging in colorectal carcinomas

<p>Abstract</p> <p>Background</p> <p>Accurate histopathological evaluation of resected lymph nodes (LN) is essential for the reliable staging of colorectal carcinomas (CRC). With conventional sectioning and staining techniques usually only parts of the LN are examined which might lead to incorrect tumor staging. A molecular method called OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the metastatic status of the complete LN and therefore improve staging.</p> <p>Methods</p> <p>OSNA is based on a short homogenisation step and subsequent automated amplification of cytokeratin 19 (CK19) mRNA directly from the sample lysate, with result available in 30-40 minutes. In this study 184 frozen LN from 184 patients with CRC were investigated by both OSNA and histology (Haematoxylin & Eosin staining and CK19 immunohistochemistry), with half of the LN used for each method. Samples with discordant results were further analysed by RT-PCR for CK19 and carcinoembryonic antigen (CEA).</p> <p>Results</p> <p>The concordance rate between histology and OSNA was 95.7%. Three LN were histology+/OSNA- and 5 LN histology-/OSNA+. RT-PCR supported the OSNA result in 3 discordant cases, suggesting that metastases were exclusively located in either the tissue analysed by OSNA or the tissue used for histology. If these samples were excluded the concordance was 97.2%, the sensitivity 94.9%, and the specificity 97.9%. Three patients (3%) staged as UICC I or II by routine histopathology were upstaged as LN positive by OSNA. One of these patients developed distant metastases (DMS) during follow up.</p> <p>Conclusion</p> <p>OSNA is a new and reliable method for molecular staging of lymphatic metastases in CRC and enables the examination of whole LN. It can be applied as a rapid diagnostic tool to estimate tumour involvement in LN during the staging of CRC.</p

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology