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Featured researches published by Christof Hottenrott.
Surgical Endoscopy and Other Interventional Techniques | 2011
Christof Hottenrott
Innovation in technology is crucial for improving healthcare. Robotic technology in surgical practice [1] and nextgeneration sequencing (NGS) platforms in genomics research [2] represent the most promising technological advances for improving clinical outcomes of patients with complex diseases such as cancer. However, technological innovation in healthcare is an important driver of cost growth. Very often, physicians and patients seeking the best treatment embrace new modes of treatment before there is evidence-based clinical utility of new medical devices. It is obvious that comparative-effectiveness research (CER) is required before new medical devices, diagnostics or novel drugs are incorporated into clinical practice [3]. Robotic surgical devices allow a surgeon at a console to operate remote-controlled robotic arms, which may facilitate the performance of laparoscopic procedures. Laparoscopic surgery, in turn, is associated with shorter hospital stays than open surgery, as well as with less postoperative pain and scarring, lower risks of infection and need for blood transfusion, and better aesthetic result. All these advantages can be termed as better short-term quality of life (QOL). Evidence for the superiority of laparoscopic versus open surgery has already been documented for colon cancer, and there is also a trend for similar benefits in patients with rectal cancer and gastric cancer [4–9]. However, there is still no evidence that robotic-assisted surgery significantly improves outcomes and reduces adverse effects as compared with laparoscopic-assisted surgery, while by contrast it appears that it is associated with higher costs. The hypothesis that more appropriate and precise total mesorectal excision (TME) can lead to higher complete cancer resection (R0), lower rates of local and locoregional recurrence, and improved survival with robot-assisted surgery compared with laparoscopic resection [10] requires data from CER, which remain scarce. In the November issue of Surgical Endoscopy, Bianchi and colleagues [11] address the question of potential shortterm benefits of robotic versus laparoscopic surgery in the treatment of patients with middle or lower rectal adenocarcinoma. The authors analysed the data of 50 patients with proven middle/lower rectal adenocarcinoma who all underwent minimally invasive TME either with a four-arm Da Vinci S robot (Intuitive Surgical, Sunnyvale, CA, USA) (n = 25) or with laparoscopic technique (n = 25). The groups were well balanced. Most patients underwent anterior resections (74%) and the remaining underwent abdominoperineal resections (26%), while about half of patients received preoperative (neoadjuvant) chemotherapy. There was no significant difference in median operating time, first bowel movement, median hospital stay or complications between the two groups. Extent of lymphadenectomy as measured by the median number of lymph nodes examined was similar (18 vs. 17). Distal resection margins were disease free in both groups, but circumferential margin was involved in one patient (4%) of the laparoscopic group. There was only one conversion to laparotomy. The authors conclude that robotic TME for rectal cancer is feasible with similar short-term oncologic and QOL outcomes compared with laparoscopic TME. They note that whether the greater manoeuvrability and visibility afforded by the robotic approach can result in better outcomes than those of laparoscopic surgery can be answered by future, more systematic studies considering also the costs of robotic-assisted surgery. C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2010
Christof Hottenrott
Although no survival benefit can be expected, laparoscopic gastrectomy for patients with early gastric cancer has become popular during the last decade. Laparoscopic gastrectomy, compared with open gastrectomy, provides a series of strengths during the early postoperative period
Surgical Endoscopy and Other Interventional Techniques | 2014
Christof Hottenrott
Recent evidence in western countries has confirmed the improvement in survival of open gastrectomy with D2 lymphadenectomy for resectable gastric cancer [1], which has been the standard approach over decades in Japan [2]. Laparoscopic or robotic surgery can improve short-term outcome and quality of life [3], but is laparoscopic D2 gastrectomy safe and effective when performed outside of elite surgeons and hospitals? Targeting gastric adenocarcinoma with human epidermal growth factor 2 (HER2) gene amplification with trastuzumab prolongs survival, but most patients with advanced disease develop recurrence as a consequence of therapeutic resistance and die from the disease. Mutational landscape heterogeneity [4] and highly complex transcriptional regulatory network diversity drive gene expression. This new evidence from sequencing studies and the ENCODE project now shape a much more complex and sophisticated research concept [5]. These latest advances raise for the first time rational hope for the next generation of biomarkers and drugs to improve cancer cure rates. But can enormous challenges be overcome? Using the propensity score matching method, Zhao et al. [6] reported in the August 2013 issue of Surgical Endoscopy the comparative results of D2 gastrectomy between laparoscopic (133 patients) and open (133) distal gastrectomy. There was no significant difference in the number of resected and examined lymph nodes and the postoperative short-term and long-term morbidity and mortality between the two groups. It appears that the only disadvantage of laparoscopic gastrectomy is the longer operating time. However, this report comes from a highly specialized institution with high-volume surgeons and skill in laparoscopic D2 gastrectomy. Laparoscopic D2 lymphadenectomy and laparoscopic total gastrectomy are highly demanding operations and the lack of data from nonspecialized institutions is cause for concern about the safety and efficacy of this approach by low-volume surgeons for whom such an approach cannot be recommended. In contrast to the wide clinical use of minimally invasive surgery such as laparoscopic or robotic resection for other common tumors, e.g., colorectal cancer [7–9], safe and effective laparoscopic D2 gastrectomy for advanced gastric cancer still remains an experimental approach outside of highvolume hospitals [10–13]. Progress in the successful treatment of patients with advanced gastric cancer is very slow. Genomic structural and functional heterogeneity and the complexity of the cancer genome explain the high rate of treatment resistance and the low survival rate for patients with advanced solid tumors, including gastric cancer [4]. Based on this genomic complexity with multiple and still unrecognized genomic subtypes, the disappointing results from current randomized trials using single-gene targeting drugs are not surprising. Trastuzumab for HER2-positive gastric cancer significantly prolongs survival but long-term mortality rates are high among patients with HER2-negative (80 % of all patients) or even HER2-positive disease [14]. Trastuzumab emtansine conjugate is improved treatment for breast cancer and can be similarly effective in HER2overexpressing gastric tumors, but we are still far from achieving high cure rates. We are now shifting from the ‘‘central dogma’’ of the single-gene/protein-phenotype (trait/disease) relationship established by Crick a half century ago to systems biology and genomic medicine. All currently available diagnostics and drugs have been developed based on this reductionist C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2012
Christof Hottenrott
A decade after the approval of the Da Vinci Surgical System (DVSS) by the US Food and Drug Administration (FDA), evidence of its superiority with respect to safety and efficacy for selected types of surgery compared with conventional laparoscopic surgery (CLS) has been accumulated. The potential advantages of the DVSS over CLS include its greater precision, lower error rates, reduced bleeding, shorter hospital stays, more rapid patient recovery, and reduced pain. As a result many surgeons have begun to use the DVSS in daily practice for a wide variety of surgeries, including general, oncological, urological, gynecological, and cardiothoracic [1]. However, because robotic surgery is still in its early stages, comparativeeffectiveness research (CER) evidence is scarce, and costs must be considered in an economical crisis [2], a more critical approach is required [2]. Robotic surgery may not be suitable for specific types of surgical procedures. A paradigm of potential limitations of robotic surgery was published by Scozzari et al. [3] in the February issue of Surgical Endoscopy. Given the difficulties with traditional laparoscopic surgery for morbidly obese patients, the authors thought to use the DVSS to improve the outcomes of these patients. Data from 110 morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass with robot-assisted hand-sewn gastrojejunal anastomosis using the DVSS (DVSS group) were compared with data of 423 patients who underwent standardized CLS group. The patients had a mean weight of 127.5 kg and a mean body mass index (BMI) of 46.7 kg/ m. There were statistically significant differences in favor of the CLS over the DVSS group with respect to the operative time (P \ 0.001) and the cost per patient (P \ 0.001), whereas no differences were found in terms of the intraor postoperative complication rates, revision surgery, or hospital length of stay. The authors concluded that although robot-assisted surgery was safe and intuitive, it did not seem to provide a real advantage over standard laparoscopy in terms of hospital length of stay and complications rates. This study suggests that the use of the DVSS may be indicated for some specific organs and anatomical areas, while it may not be superior to CLS for other disorders and locations. Minimally invasive surgery such as laparoscopyor robot-assisted surgery also has important implications in surgical oncology for a variety of solid tumors. For example, laparoscopic surgery has been the standard approach for colon cancer and promising data have been available for its use in other gastrointestinal cancers, whereas evidence is increasing for the superiority of robotassisted surgery for rectal cancer [4–10]. The age of robotic surgery has dawned and there is still a lot of improvement to be made in the near future. For example, robotic surgery for prostate cancer or rectal cancer is new and has its own learning curve to be overcome. If we remind ourselves of all the debates brought by each new innovative technology, such as laparoscopic surgery, on its first appearance, we believe that further intensive and largescaled studies will answer the upcoming questions about the safety and efficacy of robotic surgery. Translating innovative ideas and concepts into medical practice suggests a key driver to improve health care. However, costs should be considered. A prime paradigm of how costs can drastically be reduced is the competition between biotechnology and pharmaceutical companies and academia regarding next-generation sequencing technology. C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt am Main, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2013
Christof Hottenrott
To the Editor, Discovery of robust biomarkers for more effective management of cancer patients and improved survival is still a grand challenge. Decision on tailoring the best multimodal treatment for patients with colorectal cancer (CRC) is still based on traditional clinicopathologic features and tumor-node-metastasis (TNM) staging system but it is suboptimal. Recurrence in the adjuvant setting often is in stage II and particularly in stage III, whereas disease progression occurs in nearly all patients in the metastatic setting. Current biomedical research is exploring single mutated genes and proteins, gene expression signatures based on multigene assays and more recently integrated genome analysis for identifying markers with prognostic and predictive clinical utility [1–5]. An important finding of a single protein for CRC patients is reported in the October issue of Surgical Endoscopy by Shantha and colleagues [6]. The authors measured and compared preoperative plasma ANGPTL4 levels in patients with CRC and benign colorectal disease (BCD). In addition, they measured ANGPTL4 plasma levels after minimally invasive colorectal resection (MICR) only for CRC. Compared with BCD, preoperative plasma ANGPTL4 levels were lower for patients with CRC. In 80 CRC patients who underwent MICR, ANGPTL4 plasma levels in the postoperative period were significantly lower compared with the preoperative levels. The authors suggest the need for further studies to explain these findings. Although laparoscopic resection of colorectal or gastric tumors has rapidly evolved improving postoperative shortterm outcomes [7–14], decision on adjuvant systemic chemotherapy has not been optimal because of lacking markers to guide personalized treatment with the highest possible response rate. Currently, microsatellite instability (MSI) testing is recommended for adjuvant chemotherapy decision in stage II CRC after complete tumor resection (R0), but for the multigene assays ColoPrint and Oncotype Dx gene expression signatures, no consensus yet exists for their clinical use [1]. Similarly, KRAS testing for treatment decision in patients with stage III KRAS wild-type CRC with the antiepidermal growth factor receptor (EGFR) antibody cetuximab is not recommended, whereas its clinical use in metastatic setting also has been controversial [15]. The recent molecular characterization of CRC applying integrated deep sequencing analysis by using a variety of high-through technologies (HT), such as next-generation sequencing technologies and microarrays, has revealed that genomic heterogeneity and complexity underlying colorectal cancer initiation and metastasis is much more sophisticated than we thought [3, 4]. Based on wholegenome landscape obtained from clinical samples by using HT-NGS and microarrays, exciting network biology-based research is underway to identify genome science and molecular networks-based biomarkers for clinical personalized medicine [2, 16–32]. C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Straße 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2013
Christof Hottenrott
Survival rates after esophageal cancer diagnosis still remain poor despite standardization of surgery and adjuvant treatment for resectable tumors. Currently, the US cancer statistics for patients with regional or stage II/III TNM stage cancer show high mortality rates. Many patients relapse and die after complete tumor resection (R0) and multimodal adjuvant treatment with chemotherapy or chemoradiotherapy, which is associated with toxic side effects. Preoperative or neoadjuvant chemotherapy (NAC) for some cancer types, including esophageal tumor, has been associated with high response rates resulting in wider clinical use of this systemic treatment. However, how can the high relapse and death rates despite the high NAC response rates for esophageal cancer be explained? Currently, a whole-genome sequencing study provides scientific evidence that although most primary tumor cells are sensitive and are killed by initial chemotherapy, a subclone of the founding clone survives, gains additional mutations, and is expanded at relapse. DNA-damaging chemotherapy itself contributes to this treatment failure [1]. Therefore, despite tumor mass reduction in the conventional imaging technology, relapse and death occur, indicating the need for the development of robust prognostic and predictive markers [2, 3]. Considering this latest data on cancer genome and epigenome [4], can endoscopic ultrasound (EUS) be useful in the clinic for monitoring and predicting response to NAC for patients with esophageal cancer? In the February issue of Surgical Endoscopy, Misra et al. [5] evaluated whether EUS is a useful tool for assessing tumor response and staging esophageal cancers after NAC. The authors analyzed 110 patients with esophageal cancer by performing EUS before and after NAC and compared the data with the postsurgical pathologic stage (pTNM). Misra et al. [5] reported an 87 % response rate (n = 96), and among these patients, 39 % had a significant response and 61 % a partial response to NAC. In more than 50 % of the 110 patients there was an overstaging or understaging for T and N status which led the authors to conclude that EUS is an unreliable tool for staging esophageal cancer after NAC. Misra et al. [5] performed a careful study despite its retrospective nature. The data reported suggest caution in using EUS for surgical decision-making after NAC. Surgeons should critically consider the role of EUS or computerized tomography in deciding on tumor resectability and predicting R0 resection, relapse rate, and prognosis. In particular, T stage tumor that is substantially overstaged by EUS after NAC should not lead the surgeon to avoid surgery because T tumors are nonresectable or resection would be incomplete (R1/R2) because T overstaging may have resulted from a NAC-induced inflammatory effect or fibrosis. The clinical data provided by Misra et al. are in accordance with recent whole-genome, exome, transcriptome, epigenome, and functional genomic data for the heterogeneity and high complexity of esophageal and other major cancer types. Surgeons and oncologists need more effective tools than the currently used conventional clinicopathologic and imaging markers for accurately predicting therapeutic response, recurrence, and prognosis. Revolutionary technologies such as next-generation sequencing, living cells imaging using biosensors, and three-dimensional genome resolution now allow for the first time reliable systems computational biology, synthetic genomic biology, C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2013
Christof Hottenrott
Much of the surgical innovation in the treatment of gastric cancer comes from South Korea. After gastric cancer became the most common cancer type in Korea, despite a worldwide reduction in its incidence, the progress in laparoscopic surgery of colleagues from Korea to present and publish the largest series is no surprise. At the same time, objective reports from high-volume Korean hospitals represent a guide for the future trend of gastric cancer laparoscopic surgery worldwide [1]. These advances in clinical practice coupled with a revolution in the exploration of the structure and function of the human genome [2] pave the way for clinical network medicine [3, 4]. All these advances in research and practice currently provide a rational platform for improving the clinical outcomes for gastric cancer patients, particularly in the West, where prognosis still remains poor. Minimally invasive approaches, including laparoscopic and robotic surgery, have been evolved for a safe and effective tumor resection of gastrointestinal cancer. Rapid is the incorporation of these approaches in colorectal cancer and of laparoscopic distal gastrectomy (LDG) in distal gastric cancer [5–12]. But laparoscopic total gastrectomy (LTG), required for oncologic safety for tumors of the upper and middle thirds of the stomach, still remains an experimental approach [5]. To explore the safety and effectiveness of LTG, Jeong et al. [1] reported in the December issue of Surgical Endoscopy the results of their study based on a prospectively constructed database. The authors analyzed the data of 118 patients who underwent LTG for middle or upper gastric cancer from a series of 1,064 patients who underwent laparoscopic gastrectomy between 2007 and 2011. Intraoperative complications occurred. The mean operating time was *5 h, and the mean number of lymph nodes retrieved was 41. To assess the risks of LTG, the authors compared the results with LDG and found not only a significantly longer operation time but also a significantly higher overall morbidity rate for LTG (22.9 %) than for LDG (12.7 %). The most common complications after LTG were anastomosis leakage (n = 9) and luminal bleeding (n = 9). The findings showed D2 lymphadenectomy to be an independent risk factor (odds ratio [OR], 3.87, 95 % confidence interval [CI], 1.30–11.55) for postoperative complications after LTG. The careful analysis of data and the objective report in the study by Jeong et al. [1] provide very useful information for the future trend in laparoscopic total gastrectomy with D2 lymphadenectomy. Based on their experience with about 900 laparoscopic distal gastrectomies, the authors were able to perform a safe and effective LTG. But at the same time, they warn about the potential risks associated with such a demanding surgical procedure and recommend LTG for high-volume surgeons with skill in laparoscopic gastrectomy. Traditional open total gastrectomy, when indicated for gastric cancer, is the standard treatment worldwide outside a few highly specialized institutions. Despite the oncologic safety of D2 lymphadenectomy with either open total gastrectomy or LTG, as reflected by the mean 42 lymph nodes removed by Jeong et al. [1] in this study, many patients after a complete tumor resection (R0) experience peritoneal or hematologic distal recurrence and die of the disease. Recurrence and death rates can be reduced by systemic therapy performed to kill circulating cancer cells or micrometastases using cytotoxic chemotherapeutic agents C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Straße 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2012
Christof Hottenrott
Laparoscopic surgery for the treatment of gastrointestinal cancer has rapidly evolved over the last decade. Although critical analysis of the short-term outcomes of laparoscopic gastrectomy has provided evidence for the safety of this minimally invasive approach, little long-term survival data, particularly for patients with advanced stage II and III gastric cancer, are available [1]. This lack of evidence increases the skepticism about the ability of laparoscopic gastrectomy for advanced gastric cancer to control cancer cell dissemination and prevent recurrence. This gap between expectations of and concerns about the long-term impact of laparoscopic gastrectomy on gastric cancer patients has been bridged by the study of Pak et al. [2] reported in the January issue of Surgical Endoscopy. The authors have analyzed the results of 714 consecutive patients with gastric cancer who underwent laparoscopic gastrectomy in their institution between May 2003 and December 2009. After a median follow-up of 46 months, recurrence was observed in 26 patients (3.7 %), with the secondary tumor located in the peritoneum in seven patients), locoregional in six patients, in distant organs with hematogenous spread in five patients, and other less frequent failures. The 5-year recurrence-free survival rates according to the TNM staging system categories were 95.8 % in stage I patients, 83.4 % in stage II patients, and 46.4 % in stage III patients. This study provides excellent results, similar to those reported by the randomized controlled trials (RCTs) with open D2 gastrectomy for stage II–III disease by Sasako et al. [3]. However, what is the reality from a Western point of view? In contrast to the excellent expertise in laparoscopic gastrectomy of Korean surgeons, a sample size as large as 714 patients treated within 7 years is unrealistic in Western countries, even in specialized hospitals. This lack of high-volume surgeons, which is a predictive factor for safe and effective laparoscopic surgery, raises attention. Indeed, although laparoscopic resection tends to be routinely performed for colorectal cancer, laparoscopic D2 gastrectomy for advanced tumors still remains a grand challenge for Western surgeons [4–11]. Such an approach is less familiar to Western surgeons and can be associated with the reports of increased postoperative complications and mortality. While awaiting the results of confirmatory RCTs for laparoscopic D2 gastrectomy for advanced resectable gastric cancer, biomedical research is focused on novel drugs developed based on the concept of signaling transduction interaction networks. In the era of systems science and biological circuits, there is emerging research based on the latest genome sequencing technology and living-cells networks-based imaging technologies. These advances together with substantial progress in computational systems biology, synthetic biology engineered-based reconstruction of signaling circuits, and mathematical models now shape new horizons in the discovery of innovative biomarkertargeted drug complexes for personalized treatment of cancer patients [12–32].
Surgical Endoscopy and Other Interventional Techniques | 2012
Christof Hottenrott
During the past four decades, open gastrectomy with D2 lymphadenectomy has been the standard approach for resectable gastric cancer in Japan. But only recently with evidence from western phase 3 randomized controlled trials for the safety and survival benefit of D2 versus D1 surgery [1], D2 surgery can be recommended for wide practical implementation when it results in a complete tumor resection (R0). During the past decade, large retrospective studies and small randomized trials, mostly from Korea and Japan, have reported positive results with laparoscopic surgery mainly for early gastric cancer [2]. However, totally laparoscopic D2 gastrectomy particularly for advanced gastric cancer, is a highly demanded, timeconsuming procedure that requires evaluation in clinical trials for its safety and efficacy considering also cost-benefit analysis compared with standard open D2 surgery [3]. The recent report for laparoscopic D2 gastrectomy for gastric cancer by Moisan and colleagues [4] in the March issue of Surgical Endoscopy comes not from Korea, Japan, or specialized hospitals in the United States or European Union but from Chile. In this country, along with Asia and east European countries, incidence of gastric cancer continues to be high, which may explain advances with laparoscopic surgical treatment. Moisan and colleagues [4] compared early and longterm outcomes of 31 gastric cancer patients who underwent totally laparoscopic D2 gastrectomy (LG) with intracorporeal handsewn esophagojejunostomy between 2003 and 2010 with those of 31 patients who received an open D2 gastrectomy (OG) as the standard group. There were major complications with two vs. no duodenal stump leakages in LG and OG respectively and two esophagojejunostomy anastomotic leakages in each group. After a median followup of 3 years, there was no significant difference in recurrence-free survival or overall survival between the two groups. The authors conclude that laparoscopic D2 surgery is feasible, safe, and as effective as open D2 surgery regarding oncological outcomes. This study provides many positive aspects. Totally laparoscopic gastrectomy with total gastrectomy and D2 lymphadenectomy is a highly demanding procedure that is feasible, safe, and effective with respect to long-term survival only when it is performed by high-volume surgeons with expertise and skill in this technique. The 35 retrieved lymph nodes in the laparoscopic group reveals the standardized and completeness of D2 lymphadenectomy that is essential for locoregional tumor control in advanced lymph node-positive disease. However, some questions raise the relatively high rates of leakages in duodenal stump and esophagojejunostomy. Laparoscopic surgery has evolved rapidly and provides evidence for its superiority for the treatment of colon cancer and positive data for rectal cancer treatment [5–7]. However, at present, totally laparoscopic D2 gastrectomy for advanced potentially curable gastric cancer, despite sporadic reports with enhanced results, requires evaluation within clinical trials and cannot be recommended outside highly specialized hospitals [3]. Although laparoscopic surgery can improve quality of life [8–11], the grand challenge remains of how the cancer genome heterogeneity and complexity of cancer cells in individual patient’s tumors can be overcome. Recently, the addition of trastuzumab to chemotherapy in HER2-positive metastatic or advanced gastric cancer has become the new standard, and new phase 3 trials also may establish its use C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt, Germany e-mail: [email protected]
Surgical Endoscopy and Other Interventional Techniques | 2012
Christof Hottenrott
Despite advances with signal transduction inhibitors, such as cetuximab and bevacizumab, as well as small molecules that target tyrosine kinases, surgery and chemoradiotherapy still remain the backbone of therapy of rectal cancer. Laparoscopic rectal cancer surgery has two major goals: to minimize locoregional recurrence and to prevent the sphincter. Total mesorectal excision (TME) is an integral part of surgery, achieving a complete tumor resection (R0) in patients with advanced disease (T2-3N1-2M0). Preoperative chemoradiotherapy results in tumor shrinkage and downstaging and in many cases a sphincter-preserving procedure that could not be possible without neoadjuvant chemoradiotherapy (NCRT). But some patients do not respond because of inherent (primary) resistance or acquired resistance during NCRT. For nonresponder patients, immediate surgery for tumor resection is required. Biomarkers for response prediction or imaging monitoring can help surgeons for the timing of surgery. In the June issue of Surgical Endoscopy, Motson and colleagues [1], in an effort to approach an optimal timing of surgery, describe the results of their study in 30 patients with locally advanced rectal cancer selected for longcourse chemoradiotherapy (LCRT) based on clinical examination and MRI. The median time interval between radiotherapy and surgery was 11 (range, 7–13) weeks. Of 30 patients who received LCRT, 26 patients underwent laparoscopic TME. Of 16 patients who had laparoscopic anterior resection (LAR), anastomotic leak was occurred in 3 (18.7%), which was a fatal complication in one of these patients. The authors conclude that serial MRI helps to determine the optimum timing of laparoscopic TME after LCRT is feasible and safe. Although this is a small, heterogeneous, retrospective analysis with short follow-up, it re-emphasizes the risk of anastomotic leak. TME has been the standard of care for an R0 resection, but it may increase the risk of anastomotic dehiscence through reduced blood flow in the anastomotic area after anterior resection. Despite rapid advances of minimally invasive surgery, including laparoscopic and robotic surgery for colon and gastric cancer, optimal anastomosis after laparoscopic anterior rectal resection remains a pressing challenge [2–9]. Protective temporal ileostoma is suggested to reduce the risks of anastomotic leak. Optimizing the timing of surgery is crucial for the outcomes of patients with rectal cancer. However, despite promising reports with gene expression profiling or other predictor and monitoring disease response during preoperative adjuvant treatment, no robust biomarker or imaging technology has been established for wide clinical use. Recently, high-throughput next-generation sequencing technology provides an unprecedented capacity for identifying all genetic variants underlying cancer through exome and whole genome sequencing. Systematic cancer genome sequencing studies and data from physical and functional genome networks may improve our understanding on gene regulation and how gene expression is dysregulated in cancer, including colorectal cancer. Innovative biomedical research strategies using genome-wide mapping technology are now underway to discover novel biomarkers for optimizing timing of operation and selection of drugs for the individual patient. Furthermore, new more effective targeted drugs can be developed based on understanding of genetic variants, functional deregulation, and tumor heterogeneity [10–29]. C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Straße 3, 60487 Frankfurt, Germany e-mail: [email protected]
