Robot-assisted techniques in vascular and endovascular surgery.

For thousands of years, robots have inspired the imagination of humans, but it was only about 35 years ago that a robot was used for the first time in medicine. Since then, robot-assisted procedures have become increasingly popular in urology, general surgical specialties, and gynecology. Robot-assisted vascular surgery was first introduced in 2002 and was thought to overcome the limitations of laparoscopy. However, it did not gain widespread popularity, and its usage is still limited to a few centers worldwide. Robot-assisted endovascular procedures, on the other hand, while still in its infancy, have become a promising alternative to existing techniques. The improvements of the robotic systems promote better surgical performance and reduce occupational hazards for vascular and endovascular surgeons. A comprehensive review of literature was performed using the search terms "robotic," "robot assisted," "vascular surgery," and "aortic" for surgical procedures or "robotic," "robot assisted," and "endovascular" for endovascular procedures. Full text articles that were published between January 1990 and March 2021 were included. This review summarizes the development of the techniques for robot-assisted vascular and endovascular surgery in recent years, its outcomes, advantages, disadvantages, and perspectives.

Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer.

BACKGROUND: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data. METHODS: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data. RESULTS: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008). CONCLUSIONS: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.

Duodenal intussusception of the remnant stomach after biliopancreatic diversion: a case report.

BACKGROUND: We present a rare case of an antegrade intussusception of the remnant stomach four years after a biliopancreatic diversion. CASE PRESENTATION: A 55-year-old female patient presented with epigastric pain in our emergency room. Laboratory parameters showed an anemia as well as elevated transaminases and hyperbilirubinemia. The CT scan showed an intussusception of the remnant stomach into the duodenum followed by cholestasis. At laparotomy the remnant stomach was resected. CONCLUSION: Bowel obstruction and intussusception after bariatric surgery are a rare but often unrecognized complication. Sonography as well as a CT scan should be performed. The exploratory laparoscopy however is the most valuable diagnostic tool in patients with suspected intussusception, due to the high rate of non-specific symptoms and misinterpreted radiographic investigations.

[Robot-assisted vs laparoscopic gastric bypass : First experiences with the DaVinci system in bariatric surgery]. / Roboterassistierter vs. laparoskopischer Magenbypass : Erste Erfahrungen mit dem DaVinci-System in der bariatrischen Chirurgie.

Conventional laparoscopy is the gold standard in bariatric surgery. Internationally, robot-assisted surgery is gaining in importance. Up to now there are only few reports from Germany on the use of the system in bariatric surgery. Since January 2017 we have been performing robot-assisted gastric bypass surgery. It remains unclear whether the use of the robotic system has advantages over the well-established laparoscopic technique. Within a period from January to early August 2017 a total of 53 gastric bypass operations were performed. Of these 16 proximal redo Roux-en-Y gastric bypass operations were performed with the DaVinci Si system versus 29 laparoscopic procedures. A retrospective analysis of the perioperative course was carried out. Body weight, body mass index (BMI), Edmonton obesity staging system (EOSS) and American Society of Anesthesiologists (ASA) classification did not show significant differences. There were also no significant differences in terms of estimated blood loss, intraoperative complications, duration of surgery, postoperative inflammatory parameters and weight loss. There was no mortality and no need for revisional surgery in either group. After laparoscopic surgery there was a delayed occurrence of a leak of the gastrojejunostomy followed by readmission and endoscopic negative pressure wound therapy. The results show that the proximal Roux-en-Y gastric bypass can be performed safely and efficiently using the DaVinci surgical system. Significant differences to the conventional laparoscopic procedure were not found. Larger randomized controlled trials are needed to define the role of the DaVinci system in bariatric surgery.

[Robotic pylorus-preserving pancreaticoduodenectomy : Video article]. / Roboterassistierte pyloruserhaltende Pankreaskopfresektion : Videobeitrag.

Pylorus-preserving pancreaticoduodenectomy is one of the most complex procedures in general surgery. Laparoscopic pancreaticoduodenectomy was initially described in 1994; however, its worldwide distribution is so far limited to only a few specialist centers. Robotic surgery using the DaVinci® system can overcome many limitations of laparoscopic surgery. The system is a promising tool for a more widespread introduction of minimally invasive surgery for pancreatic diseases. Mortality rates of 0-5% and pancreatic fistula rates of 0-35% are described in the literature; therefore, thorough complication management is crucial in the postoperative course. The video presents a robotic pylorus-preserving pancreaticoduodenectomy for periampullary carcinoma in a female patient.

[Robot-assisted rectal surgery: hype or progress?]. / Roboterassistierte Rektumchirurgie: Hype oder Fortschritt?

Minimally invasive laparoscopic surgery for rectal cancer has undergone a significant evolution during the last decades and has become the standard approach in specialized centers with better short-term and comparable oncological outcome to open surgery. The laparoscopic approach remains challenging and has various inherent technical challenges particularly associated with rectal cancer resection. Robotic colorectal surgery using the da Vinci® surgical system has been successfully introduced into clinical practice during recent years and provides specific technical advantages. Studies have shown that the robotic approach in colorectal surgery is safe and feasible with comparable results. It is associated with low conversion rates, more R0 situations for low rectal cancer with larger tumors and more neoadjuvant treatment compared to standard laparoscopy. Robot-assisted surgery is an attractive development of minimally invasive surgery and should also be further evaluated with mandatory monitoring of outcome parameters in registries in Germany.

[Robot-assisted minimally invasive lobectomy with systematic lymphadenectomy for lung cancer]. / Roboterassistierte minimalinvasive Lobektomie mit systematischer Lymphadenektomie zur Behandlung des Bronchialkarzinoms.

BACKGROUND AND INTRODUCTION: Lobectomy for lung cancer is the standard therapy for lung cancer in limited stages. The adoption of minimally invasive lobectomy (video-assisted thoracic surgery or VATS lobectomy) has increased worldwide since its first description more than 15 years ago. However, the VATS technique has a long learning curve and sometimes limitations in terms of precise preparation and presentability of the central structures of the lung hilus due to the limited mobility of the standard thoracoscopic instruments. By using a four-arm robotic platform (DaVinci®), not only the preparation of the hilus structures but also the central lymphadenectomy can be performed in a comfortable and safe way under a clear and precise view. INDICATION: Surgical treatment of locally limited lung cancer in the right lower lobe (squamous cell carcinoma). PROCEDURE: Robot-assisted, minimally invasive right lower lobectomy with systematic lymphadenectomy. CONCLUSION: Robot-assisted minimal invasive lobectomy is feasible with special regard to oncological and technical aspects. Especially the intrathoracic precise dissection of the tissue under a perfect view allow a comfortable and safe operation technique.

Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression.

Does neoadjuvant treatment before oncologic esophagectomy affect the postoperative quality of life? A prospective, longitudinal outcome study.

To evaluate the cancer patients' quality of life (QoL) following esophagectomy the focus was placed on the impact of neoadjuvant treatment before surgery. For patients undergoing oncologic surgery, the QoL is generally accepted as an important outcome parameter in addition to clinical parameters. This prospective nonrandomized study evaluated QoL in patients treated by preoperative chemo(radio)therapy followed by either surgery or surgery alone with special focus on the postoperative course. QoL was assessed in 131 consecutive patients who underwent surgery for esophageal cancer. The EORTC-QLQ-C30 and a tumor-specific module were administered before surgery, at discharge, 3, 6, 12, and 24 months after surgery. Clinical data were collected prospectively and a follow up was performed every 6 months. The histological type of cancer was squamous cell carcinoma in 49.6% and adenocarcinoma in 50.4%. There was no significant difference between patients that were treated neoadjuvantly and those that were first operated on with regard to morbidity, mortality, and survival rates (5-year survival rate of 34%). Most QoL scores dropped significantly below the baseline in the early postoperative period and recovered slowly during the follow-up period to almost preoperative levels in many scores. There was no statistically significant difference in any of the QoL scales between neoadjuvantly treated or primary operated patients. Esophageal resections are associated with significant deterioration of QoL, which slowly recovers during the follow-up period to an almost preoperative level. Neoadjuvant treatment seems to not further negatively affect the QoL deterioration.

[Robotic-assisted minimally invasive abdominothoracal oesophageal resection with intrathoracic anastomosis]. / Roboterassistierte, minimalinvasive abdominothorakale Ösophagusresektion mit intrathorakaler Anastomose.

BACKGROUND: Ivor Lewis oesophagectomy is one of the approaches used worldwide for treating oesophageal cancer. The adoption of minimally invasive oesophagectomy has increased worldwide since its first description more than 15 years ago. However, minimally invasive oesophagectomy with a chest anastomosis has advantages. By using a four-arm robotic platform, not only the preparation of the gastric tube and mobilisation of the oesophagus but also the intrathoracic anastomosis of the oesophagogastrostomy can be performed in a comfortable and safe way. INDICATION: The indication for oesophageal resection is oesophageal cancer. PROCEDURE: The operative procedure comprises robotic-assisted abdominothoracal oesophageal resection with reconstruction by a gastric tube and intrathoracic anastomosis (Ivor Lewis procedure). CONCLUSION: Robotic abdominal and thoracic minimally invasive esophagectomy is feasible, and safe with a complete lymph node dissection. Especially the intrathoracic anastomosis of the oesophagogastrostomy can be performed in a comfortable and safe way.

A mechanistic, model-based approach to safety assessment in clinical development.

Assessing the safety of pharmacotherapies is a primary goal of clinical trials in drug development. The low frequency of relevant side effects, however, often poses a significant challenge for risk assessment. Methodologies allowing robust extrapolation of safety statistics based on preclinical data and information from clinical trials with limited numbers of patients are hence needed to further improve safety and efficacy in the drug development process. Here, we present a generic systems pharmacology approach integrating prior physiological and pharmacological knowledge, preclinical data, and clinical trial results, which allows predicting adverse event rates related to drug exposure. Possible fields of application involve high-risk populations, novel drug candidates, and different dosing scenarios. As an example, the approach is applied to simvastatin and pravastatin and the prediction of myopathy rates in a population with a genotype leading to a significantly increased myopathy risk.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e13; doi:10.1038/psp.2012.14; advance online publication 7 November 2012.

Risk evaluation in cutaneous melanoma patients undergoing lymph node dissection: impact of POSSUM.

INTRODUCTION: When lymphatic metastasis occurs, surgery is the primary treatment modality in melanoma patients. Depending on the tumour stage, patients receive a completion lymph node dissection (CLND) when a positive sentinel node is detected. Patients with clinically evident disease of the regional lymph nodes are recommended to undergo a therapeutic lymph node dissection (TLND). The aim of this study was to assess the morbidity of CLND and TLND and to evaluate the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) for preoperative risk adjustment of postoperative morbidity. METHODS: The hospital files of 143 patients who underwent CLND and TLND for malignant melanoma were analysed. The POSSUM score was used to predict morbidity rates after surgery for the total patient group as well as separated for CLND and TLND patients. RESULTS: The overall complication rate was 28.0% and the mortality rate was 0%. The morbidity rate predicted by POSSUM was 32.9%, the mortality 8.3%. Morbidity in patients undergoing CLND was significantly higher with regard to overall wound complications compared with patients with TLND. In these subgroups, POSSUM failed to predict the rates precisely. CONCLUSIONS: The POSSUM score predicted the morbidity of the total patient group accurately but failed to predict the rates in the TLND and CLND subgroups. Patients receiving CLND showed the highest morbidity rates. Preoperative sentinel lymph node biopsy therefore has more influence on postoperative morbidity than the physiological parameters represented in the POSSUM physiological score.

Palliative partial pancreaticoduodenectomy impairs quality of life compared to bypass surgery in patients with advanced adenocarcinoma of the pancreatic head.

BACKGROUND: Some surgical centres consider palliative resection (PR) to be superior to double loop bypass (DLB) as treatment for advanced carcinoma of the pancreatic head. We performed a retrospective study with prospectively collected data at a single centre to compare PR and DLB in regard to quality of life (QoL). METHODS: From January 1996 to September 2008, 196 patients were given palliative surgery for advanced pancreatic cancer at the University Hospital of Kiel. Forty-two patients underwent PR and 154 underwent DLB. These groups were compared with regard to survival, post-operative morbidity, and QoL. The EORTC QLQ-C30 was used to assess QoL before surgery, at discharge, three months after surgery, and six months after surgery. RESULTS: The median survival time after PR was 7.5 months (95% CI: 4.95-10.05) and after DLB was 6 months (95% CI: 4.98-7.02; log rank test: p = 0.066). There were no significant differences in mortality and morbidity rates (7.1% and 45.2% for PR; 3.9% and 38.3% for DLB, respectively). Assessment of QoL indicated that patients who underwent PR had more impairment of some functional metrics and increased symptoms compared to those who underwent DLB. CONCLUSION: There was no significant difference in survival or morbidity after PR and DLB, but patients who underwent DLB had better QoL than patients who underwent PR. Therefore, clinicians may want to reconsider the use of PR for patients with advanced pancreatic cancer.

Association of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk.

The incidence rates and relative risks for colorectal cancer (CRC) are higher in men than in women. Sex steroids may play a role in this gender-associated difference in CRC risk. This study was conducted to explore the relationship of single nucleotide polymorphisms (SNPs) in steroid hormone signaling (ESR1, ESR2, PGR, NR1I2, and SHBG), phase I- and II-metabolizing enzyme (COMT, HSD17B1, CYP1A1, CYP17A1, CYP1A2, CYP1B1, CYP2C9, CYP3A4, CYP2C19, and GSTP1), and hormone transporter (ABCB1) genes with the risk of CRC in German women and men, separately. From the population-based DACHS study (South Germany), 47 putatively functional SNPs were genotyped in 1798 CRC cases (746 women and 1052 men) and 1810 controls (732 women and 1078 men). Significant allele dose-response associations were observed with ESR2_rs1255998, ESR2_rs928554, HSD17B1_rs605059, and ABCB1_rs2229109 in women (P trend=0.004, 0.05, 0.03, and 0.05 respectively) and with ABCB1_rs1045642, ABCB1_rs9282564, and SHBG_rs6259 in men (P trend=0.01, 0.03, and 0.02 respectively). The ESR2_rs1255998_G allele showed the most significant association with risk for CRC in women, with a per-allele odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.88). This finding was replicated in an independent study from North Germany including 1076 female CRC cases and 1151 controls (OR=0.84, 95% CI 0.71-1.04), yielding a per-allele OR of 0.80 (95% CI 0.69-0.93, P trend=0.003) in the pooled sample. These findings implicate a role of ESR2 in the risk for developing CRC in women and suggest that HSD17B1, ABCB1, and SHBG genes may contribute to sex steroid-mediated effects on CRC development.

TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer.

BACKGROUND: Clinicopathologic stage is still the main parameter to evaluate the prognosis of newly diagnosed colorectal cancer (CRC) patients. Although molecular markers have been suggested for follow up of treated CRC patients, their complete clinical application is still under evaluation. MATERIALS AND METHODS: To evaluate the association of immune-related genes with CRC prognosis and survival, a total of 19 single nucleotide polymorphisms (SNPs) were genotyped in 614 German patients within the Kiel cohort (POPGEN). RESULTS: A promoter variant (rs1800872) in the Interleukin-10 (IL-10) gene was associated with an increased lymph node metastasis involvement [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.03-4.2, for carriers of the TT genotype]. More importantly, among 582 followed up patients the SNP rs3775291 in the toll-like receptor 3 (TLR-3) gene was associated with CRC specific survival (150 events). Patients carrying the TT genotype had a 93% increased risk of death compared with the CC carriers [hazard ratio (HR) = 1.93, 95% CI 1.14-3.28]. The observed effect of the TLR-3 variant was restricted to stage II patients (HR = 4.14, 95% CI 1.24-13.84) and to patients who did not receive adjuvant therapy (HR = 3.2, 95% CI 1.4-7.7). CONCLUSIONS: Our results may provide additional candidates for risk assessment in stage II CRC patients for treatment decision. Further validation of the presented findings is warranted.

Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective pilot study.

BACKGROUND AND STUDY AIMS: Major leakage from an esophageal anastomosis is a life-threatening surgical complication. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is a new method for treating such leakage. PATIENTS AND METHODS: Between June 2007 and June 2009, five patients (mean age 68 years) who developed anastomotic leakage after esophageal surgery were prospectively evaluated. After endoscopic diagnosis of a major leakage, polyurethane sponges were endoscopically positioned in the wound cavity of the anastomosis. Continuous suction was applied via drainage tubes fixed to the sponges. Initially sponges were endoscopically changed three times per week. RESULTS: In all five patients treatment was successful. Median time to reduce levels of inflammation markers by 50 % was 10 days for white blood cell (WBC) count and 7 days for C-reactive protein (CRP). The smallest initial wound cavity size was 42 cm (3) and the largest was 157 cm (3). The median duration of drainage was 28 days, with a median of 9 sponge changes and a median time to total cavity closure of 42 days. Two patients needed anastomotic dilation by Savary-Miller bougienage due to stenosis found on further follow-up. One of these patients died of acute severe hemorrhage from an aortoanastomotic fistula after the dilation procedure. CONCLUSIONS: Endoscopically assisted vacuum therapy is a well-tolerated and effective therapeutic option for treatment of major esophageal leaks after surgery. Additional surgery was avoided in all cases. However, the occurrence of a delayed aortoesophageal fistula calls for careful further investigation of this new technique.

COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer.

It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT.

Increased proteasome subunit protein expression and proteasome activity in colon cancer relate to an enhanced activation of nuclear factor E2-related factor 2 (Nrf2).

An elevated proteasome activity contributes to tumorigenesis, particularly by providing cancer cells with antiapoptotic protection and efficient clearance from irregular proteins. Still, the underlying mechanisms are poorly known. In this study, we report that in colon cancer patients, higher proteasome activity was detected in tumoral tissue compared with surrounding normal tissue, and also that increased levels of proteasomal subunit proteins, such as S5a/PSMD4 and alpha-5/PSMA5, could be detected. Colon tumors showed higher nuclear levels of nuclear factor E2-related factor 2 (Nrf2), a transcription factor supposed to be involved in the control of proteasomal subunit protein expression. The induction or overexpression of Nrf2 led to stronger S5a and alpha-5 expression in the human colon cancer cell lines, Colo320 and Lovo, as well as in NCM460 colonocytes along with higher proteasome activity. The small interfering RNA (siRNA)-mediated Nrf2 knockdown decreased S5a and alpha-5 expression and reduced proteasome activity. Additionally, Nrf2-dependent S5a and alpha-5 expression conferred protection from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, an effect preceded by an increased nuclear factor (NF)-kappaB activation and higher expression of antiapoptotic NF-kappaB target genes. These findings point to an important role of Nrf2 in the gain of proteasome activity, thereby contributing to colorectal carcinogenesis. Nrf2 may therefore serve as a potential target in anticancer therapy.

[Long-term survival of curatively operated gastric cancer: influence of the gender and splenectomy]. / Langzeitüberleben nach kurativer Magenkarzinomoperation: Bedeutung des Geschlechts und der Splenektomie.

BACKGROUND: Despite advances in operative technique long-term survival of curatively operated gastric cancer patients still remains poor with 5-year-survival of 25 %. Gender differences have been recognized in patients with colorectal carcinoma with a higher 5-year-survival of women. The long time-survival of the individual patient is closely dependent on his immunofunction. If a splenectomy has to be carried out, the postoperative immunofunction will be affected considerably. Thus, the question arises as to how far gender and splenectomy influence the long time-survival after curative gastric cancer surgery. METHODS: In a retrospective analysis of 505 patients with gastric cancer who had been treated between the years 1992 and 2002, a curative resection, i. e. R0, could be performed in 243 patients (48.1 %) with a definite classified tumour stadium according to the UICC (1997). The sociodemographic, operative, histomorphologic and postoperative data of each patient were collected, stratified by gender and compared using log-rank-test (survival) and chi-square-test (distribution). Multivariate analysis was performed by cox regression. The level of significance was set at p < 0.05. RESULTS: The sociodemographic, histopathologic and operative data between the two genders were comparable. The morbidity between men and women was not significant. However the rate of postoperative sepsis was higher in men (p < 0.05). With regard to the long-term survival, no difference could be shown between the two groups. However, splenectomy had a significant effect on long time-survival. Women with preserved spleen had a significantly improved five-year-survival rate as compared to women undergoing splencetomy and men with preserved spleen (p < 0.05). Multivariate analysis revealed only the tumour stage as a predictor for long time-survival in men, whereas in women the extend of lymphadenectomy and sepsis also influenced long time-survival. CONCLUSION: Long time-survival of curatively operated gastric cancer patients is gender dependent in terms of splenectomy. Therefore, gender differences should be taken into account in analysing long-term data of oncological patients.