Thomas Borschitz

Local excision for more advanced rectal tumors.

Over the past 20 years, local excision (LE) of T1 rectal cancer was increasingly established and represents an oncologically established technique. In contrast, the situation for T2 tumors is less clear and has only been investigated in small patient collectives. LE for T2 tumors is thus discussed controversially. Materials and Methods. In addition to our own patients with T2 rectal cancer treated locally (n=40), we have analysed the local recurrence (LR) rates after LE alone (n=124), after immediate conventional radical reoperation (n=29), after adjuvant (chemo)-radiotherapy (n=294) and those after neoadjuvant chemoradiotherapy (nCRT) (n=269) using a PubMed search. Results. LR rates of low-grade T2 tumors after R0 resection by LE alone was 19%. If additional prognostically unfavorable findings were present, the LR rate rose to 52%. By immediate radical reoperation the LR rate was decreased to 7%, whereas that after adjuvant therapy was 16%. In contrast, LE of more advanced tumors after nCRT resulted in LR rates of 9%. Discussion. LE alone of T2 rectal cancer should not be performed, and after adjuvant chemoradiotherapy the risk of developing LR was also high. In cases with unexpected T2 finding after LE, immediate conventional reoperation can represent an adequate oncological therapy, because it reveals comparable results to those obtained by primary radical resection. First results after nCRT followed by LE showed favorable results with low LR rates. If the indication for LE of T2 cancers can be extended to patients after nCRT in the future will have to be determined in prospective mutlticentre studies.

Confocal chromolaser endomicroscopy: a supplemental diagnostic tool prior to transanal endoscopic microsurgery of rectal tumors?

PurposeDue to diagnostic advancements, preoperative staging of rectal tumors was significantly improved. However, difficulties in obtaining accurate results can sometimes be observed in the staging of adenomas and early rectal carcinomas (pT1/2). The aim of this study was to test if confocal chromolaser endomicroscopy (cCLEM) can help minimize this diagnostic gap.MethodscCLEM generates optical transversal sections at ×1,000 magnification and allows for evaluation of the mucosal microarchitecture and differentiation of normal mucosa from adenomas and carcinomas. Cases with conflicting preoperative findings (adenoma vs. ≥uT2 categories), undetectable tumors after inadequate (R1/RX) snare polypectomy of carcinomas, and extremely flat adenoma areas were studied.ResultsBy cCLEM, in ≥uT2 carcinomas with an adenoma histology, malignoma-suspicious areas were identified and selected biopsies were done. In addition, re-epithelialized polypectomy areas of carcinomas were visualized and targeted reoperations could be carried out. Furthermore, the dignity and extension of extremely flat adenomas were determined and marked by clips for additional therapy.ConclusionsIn cases with rectal tumors, conflicting or unclear findings, and flat extending adenomas, the utilization of cCLEM should be considered. Especially in cases with early rectal carcinomas, unnecessary second operations and also recurrences can be minimized or even avoided by selective usage of cCLEM.

In Reply: Local Excision as an Optional Tool to Individualize Treatment of Rectal Cancer

We are grateful for the opportunity to answer the letter of Dr. Ziogas and colleagues, in which the authors pointed towards the increasing trend for individualized surgical therapy anddiscussed this issue critically. In addition, they highlighted the importance of and advancements made in preoperative diagnostic measures in tumor patients and indicated the existence of diagnostic gaps. We thank the authors for their supplemental remarks; we fully agree with their statements and would like to pick these up for a final discussion. Differentiated staging with high sensitivity and experiences from clinical studies are critically important to avoid possibly therapeutically wrong decisions, especially in tumor patients. In patients who receive therapy with curative intent using minimally invasive procedures to achieve a higher quality of life (QOL) the avoidance of tumor recurrences is still most important. Experiences gained from adjuvant therapy, and the recently even more often utilized neoadjuvant chemoradiotherapy (nCRT), as well as regionally already established multimodal therapies with additional antibody administration have shown that not all patients benefit from such maximal therapy. Instead, each strategy should be used selectively and dependent on the expected response. As such, the response of rectal cancers to nCRT in terms of tumor downsizing and/or downstaging may already represent a selection for further adjuvant measures. Patients with a measurable tumor response to nCRT may benefit from continued postoperative adjuvant chemotherapy, whereas nonresponders will not. These experiences from clinical studies point to the necessity to further extend our pretherapeutic diagnostics. Meanwhile we have learned that therapeutic results can be influenced by, e.g., certain angiogenetic factors epidermal-growth-factor-receptor/vascular endothelial growth factor (EGFR/VEGF) and, in addition, that molecules inducing or inhibiting tumor cell apoptosis (Survivin/bax/bcl-2), or genetic mutations (K-ras) determine the outcome. These and novel markers to be identified in the future may add to the current discussion about the overtreatment of patients with rectal carcinomas using nCRT. Studies which determine prognostic markers and the evidence levels for both conventional and minimally invasive surgical strategies thus need a high statistical power. Results from previous studies form the basis for studies with randomization. Usually, as in our study, these come from smaller collectives and retrospective studies. In addition, unexpected results from studies originally performed with another intent may be the reason for a randomization. The aim of our study was to critically analyze our own first results in light of those presented in the literature, both obtained from a highly selected patient collective. We wanted to assess the possibility of extending the indication for local excision (LE) to T2–3 rectal tumors after combined nCRT. Both our data as well as the initial findings of the other investigators did not reveal a local recurrence after LE of ypT0 findings and 2% local recurrences for ypT1 situations. Some studies have already proven an only low remaining risk for persisting lymph node metastases for these findings. However, since this problem deals with a novel therapeutic concept, patients should only be treated in controlled and prospective settings. In addition, the evidence for such treatment options will have to be proven within a randomized study. Analogous to radical surgery, further development of prognostic markers may be helpful to additionally narrow down what adds to the best and optimized therapy.

Spezielle Aspekte des Vorgehens beim frühen Rektumkarzinom

Grundlage für eine lokale Exzision von pT1-Rektumkarzinomen ist das niedrige lymphogene Metastasierungsrisiko und das damit verbundene niedrige Lokalrezidivrisiko von bestimmten Formen dieser Frühkarzinome. Der präoperativen Beurteilung des Tumor- und Lymphknotenstatus kommt somit eine entscheidende Bedeutung zu. Zur Diagnostik stehen Endosonographie, MRT-Spule, CT- und MRT-Untersuchung als bildgebende Methoden zu Verfügung. Die größte Sensitivität zur Abklärung besitzt unverändert die Endosonographie, wobei sich durch eine Zusammenführung der Befunde der Endosonographie und der präoperativen Biopsie eine Steigerung der Sensitivität erreichen lässt. Die Rezidivraten nach lokaler Exzision von pT1-Tumoren werden nicht einheitlich berichtet, wobei neben dieser Spanne eine Diskrepanz im operativen Vorgehen, im Patientengut und in der histologischen Aufarbeitung mit damit verbundener Rezidiveinschätzung vorliegt. Kontrovers wird weiterhin die Bedeutung einer Nachbehandlung beim unerwarteten Vorliegen einer so genannten «High risk»-Situation oder einem über die Submukosa hinausreichenden Tumor diskutiert. Neben verschiedenen Optionen (Nachoperation, Bestrahlung, Radiochemotherapie) liegen hierfür unterschiedliche zeitliche Konzepte wie eine frühe Nachoperation versus dem Abwarten bis zum Rezidivauftritt zugrunde. Diese Übersichtsarbeit soll den wissenschaftlichen Wert der präoperativen Diagnostik, das zu erwartende Rezidivrisiko für bestimmte Formen des frühen Rektumkarzinoms und den Stand weiterführender onkologischer Maßnahmen aufzeigen.

Transanale endoskopische mikrochirurgische Exzision von pT2-Rektumkarzinomen

ZusammenfassungFragestellung und Hintergrund:In früheren Studien wurde die lokale Exzision vorwiegend als Eingriff bei „low-risk“ pT1-Rektumkarzinomen propagiert. Die Ergebnisse bei T2-Tumoren sind unklar; es wurden Rezidivraten von 0–67% berichtet. Diese Studie wurde durchgeführt, um den Wert der lokalen Exzision bei T2-Rektumkarzinomen, prognostische Faktoren sowie die Notwendigkeit von Nachoperationen zu bestimmen.Patienten und Methodik:Nach einer lokalen Exzision bei 649 Patienten mit Rektumkarzinomen wurden bei 44 Patienten pT2-Karzinome gefunden. Im Allgemeinen wurde eine sofortige Nachoperation empfohlen; allerdings lehnten 24 Patienten eine weitere Operation ab oder wurden aufgrund von Begleiterkrankungen nicht operiert. Die Ergebnisse wurden getrennt analysiert für lokale R0-Resektionen von „low-risk“ Karzinomen sowie für prognostisch ungünstige Kriterien (R1/RX/R ≤ 1 mm/G3–4/L1/V1). Nachoperationen wurden innerhalb von 4 Wochen durchgeführt. Rezidive wurden außerdem entsprechend einer vorausgehenden lokalen R0-Resektion von „low-risk“ Tumoren wie auch ungünstiger Ergebnisse differenziert und in einer Langzeit-Follow-up-Studie analysiert. Patienten mit palliativer Therapie wurden ausgeschlossen, das Follow-up wurde bei 90% erreicht (20 ausschließlich transanale endoskopische mikrochirurgische Exzisionen, 17 transanale endoskopische mikrochirurgische Exzisionen und Nachoperationen).Ergebnisse:Die lokalen Rezidivraten nach ausschließlicher lokaler R0-Resektion von „low-risk“ T2-Karzinomen betrugen 29%, wohingegen Patienten mit ungünstigen Kriterien zu 50% Rezidive entwickelten. Nach einer sofortigen Nachoperation war das lokale Rezidivrisiko bei Patienten ohne Lymphknotenmetastasen signifikant reduziert auf 7%.Schlussfolgerung:Die lokale R0-Resektion bei „low-risk“ pT2-Karzinomen stellt eine unzureichende Therapie dar. Bei pT2N0M0-Rektumkarzinomen kann die Rezidivrate durch sofortige Nachoperation auf ein Level ähnlich einer primären Radikaloperation reduziert werden. Ein primär schlechtes lokales Resektionsergebnis (R1/RX/R ≤ 1 mm/ G3–4/L1/V1) hat keinen negativen Einfluss auf das weitere onkologische Ergebnis.AbstractPurpose:In previous studies, local excision was predominantly established for “low-risk” pT1 rectal cancer. The results obtained with T2 tumors are unclear; recurrence rates of 0 to 67 percent were reported. This study was designed to determine the value of local excision for T2 rectal carcinomas, prognostic factors, and the need for reoperation.Methods:After local excision of 649 patients with rectal tumors, pT2 carcinoma was found in 44 patients. In general, immediate reoperation was recommended; however, 24 patients declined further surgery or were not reoperated because of comorbidities. The results were analyzed separately for local R0 resection of low-risk carcinomas and for prognostically unfavorable criteria (R1/RX/R ≤ 1 mm/G3–4/L1/V1). Reoperation was performed within four weeks. Recurrences also were divided by previous local R0 resection of low-risk tumors as well as by unfavorable results and were analyzed in a long-term, follow-up study. Patients with palliative therapy were excluded, and follow-up was obtained in 90 percent (20 transanal endoscopic microsurgical excision alone, 17 transanal endoscopic microsurgical excision and reoperation).Results:Local recurrence rates after local R0 resection alone of low-risk T2 carcinomas were 29 percent, whereas patients with unfavorable criteria developed recurrences in 50 percent. After immediate reoperation, the local recurrence risk in patients without lymph node filiae was significantly reduced to 7 percent.Conclusions:Local R0 resection of low-risk pT2 carcinomas represents an inadequate therapy. In pT2N0M0 rectal carcinomas, the recurrence rate can be reduced through immediate reoperation to a level similar to primary radical surgery. An initial poor local resection result (R1/RX/R ≤ 1 mm/G3–4/L1/V1) has no negative influence on further oncologic outcome.