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Engineering TME-activated CD47-specific CAR macrophage via Arg1 promoter for safe and effective solid tumor immunotherapy.

BACKGROUND: Chimeric antigen receptor macrophage (CAR-Mφ) therapy has promising therapeutic potential in solid tumors, yet challenges remain in target compatibility and systemic toxicity. METHODS: In this study, we screened the CD47-scFv sequence of CAR-Mφ as the extracellular structure. We then constructed a classical CD47 CAR-Mφ incorporated the costimulatory domain of the α1β1 integrin-mediated Fc-gamma receptor I (FcγRI) signaling component. Subsequently, we developed a tumor microenvironment (TME)-responsive CAR macrophage platform by the arginase 1 (Arg1) promoter to target CD47, a highly expressed but clinically challenging immune checkpoint in solid tumors. RESULTS: We found that anti-CD47-scFv-mediated macrophages can effectively kill tumor cells both in vivo and in vitro. Furthermore, by integrating an α1β1 integrin-mediated FcγRI signaling domain, CD47 CAR-Mφ exhibited superior antitumor activity in hCD47+4T1 and SGC-7901 cells in vitro, which demonstrated that the CD47 CAR-Mφ was effective against solid tumors. Subsequently, Arg1-mediated activated pArg1 CD47 CAR-Mφ exhibited strong cytotoxicity against target cancer cells. We further demonstrated TME-controllable CAR gene expression in situ and induced a significant regression of established tumors in vivo. Besides, TME-dependent activation of CD47 CAR Mφ reduced the cytotoxic killing effect on erythrocytes. CONCLUSIONS: Our findings confirmed that the TME-specific activation mechanism of pArg1 CD47 CAR-Mφ based on intrinsic Arg1 promoter reprogramming endowed CAR-Mφ to effectively mitigate erythrocyte toxicity while enabling safe multidose administration regimens. This Trojan horse-like CAR-Mφ system achieves tumor-specific activation while minimizing systemic toxicity, offering a novel strategy to expand CAR-Mφ applications for solid tumors.

Animals↗

Mice with duplications and deletions at the Tme locus have altered MnSOD activity.

Superoxide radicals that result from normal cellular metabolism have been implicated as a cause of multiple age-related degenerative diseases (Halliwell, B., and Gutteridge, J. M. (1990) Methods Enzymol. 186, 1-85; Harman, D. (1988) Mol. Cell. Biochem. 84, 155-161; Ames, B. N., Shigenaga, M. K., and Hagen, T. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7915-7922). Manganese superoxide dismutase (MnSOD) is thought to be the sole enzymic scavenger of superoxide in mammalian mitochondria. We have investigated MnSOD activity and gene dose in mice with deletions and a duplication of the Tme (t-associated maternal effect) locus on chromosome 17. We find that MnSOD activity is significantly correlated with gene dose in these animals; animals with heterozygous deletions of Tme have 50% of normal activity, and animals with a heterozygous duplication of Tme have 150% of normal activity. These ratios of activity appear to be systemic, as they were observed in brain, heart, skeletal muscle and liver. The results support the model that basal MnSOD activity is regulated solely by cis elements, in that variation in MnSOD activity caused by altered gene dose on one chromosome is not compensated by gene activity on the other. Since gene knockouts of MnSOD have not yet been generated, the tlub2 and Thp animals may become useful models for those studying the role of mitochondrial superoxide in pathophysiological processes. A model for the maternal-lethal effect of Tme deletions is proposed.

Animals↗

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer.

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Adult↗

Ring-testing and field-validation of a terrestrial model ecosystem (TME)--an instrument for testing potentially harmful substances: conceptual approach and study design.

During spring and summer 1999 a ring-test and field-validation study with an open, intact Terrestrial Model Ecosystem (TME) was conducted at four different European sites (Amsterdam, The Netherlands; Bangor, U.K.; Coimbra, Portugal; Flörsheim, Germany). The objective of the study was to establish a standardised method which allows the impact of chemical stressors on terrestrial compartments at ecosystem level to be investigated and possible uses of such data in existing Environmental Risk Assessments (ERAs) for chemicals to be evaluated. This issue of Ecotoxicology presents in a series of papers the results of the TME ring-test and field-validation study. Additionally, results derived from an open-homogeneous terrestrial microcosm (Integrated Soil Microcosm, ISM) are included in this series as a separate paper. In this first paper of the series background information on the planning and organisation of the study are given. The conceptual approach and the design of the study with TMEs are briefly outlined, based on the scientific discussion on the use of terrestrial microcosms in ecology and applied environmental sciences during the last 25 years. Further, some suggestions are presented on the selection of measurement endpoints to quantify structural and functional aspects of terrestrial ecosystems. Finally, the main results of the TME-study are summarised and conclusions are drawn on the technical feasibility of TMEs, their comparability with field studies and the potential use of TMEs in ERA.

Animals↗

Is pre-operative radiotherapy necessary in T-T rectal cancer with TME?

OBJECTIVE: The indications for pre-operative radiotherapy in rectal cancer are still unclear with the exception of T4 tumours. The aim of this study was to assess local and overall recurrence in patients with T1-T3 rectal cancers undergoing total mesorectal excision (TME). METHODS: Prospective data was collected from 150 patients with rectal cancer treated in one surgical centre between July 1997 and July 2002. One hundred and twenty-nine primary resections were carried of which 102 were with curative intent. Seventy-nine patients with T1-T3 tumours were included in the analysis. Nine had local resections and 70 underwent TME; 19 of the 70 patients were node positive and 51 were node negative. RESULTS: At a median follow-up of 37 months (range 19-79 months) there were 3 (4.3%) isolated local recurrences. One node positive patient developed isolated local recurrence compared with 2 node negative patients. The node positive patient died from a myocardial infarction while the two node negative patients died as a consequence of local recurrence. Three (4.3%) of 70 patients developed systemic relapse all of whom were node positive. The cancer specific mortality rate over the same follow-up period was 3/19 for node positive patients and 2/51 for node negative patients. Of 9 patients who had local resections, none developed local recurrence or systemic relapse. CONCLUSIONS: With TME the rate of local recurrence in T1-T3 tumours is low. Our results do not support the use of pre-operative radiotherapy for these patients.

Adult↗

Total mesorectal excision (TME)--twenty years on.

INTRODUCTION: The results of total mesorectal excision (TME) for rectal cancer were first reported 20 years ago. The superior outcome in the original two papers was attributed to the complete excision of the mesorectum, preference for anterior resection over abdominoperineal resection, application of cytotoxic solutions to eradicate exfoliated tumour cells and specialisation in rectal cancer surgery. A review was conducted to examine the evidence from the literature accumulated over the past 20 years in support of this thesis. METHODS: A Medline search of all studies was carried out pertaining to the issues of mesorectal metastases, anterior resection versus abdominoperineal resection, exfoliated tumour cells in rectal cancer and specialisation in rectal cancer surgery. RESULTS: Mesorectal metastases can be found up to 5 cm from the apparent distal edge of a rectal cancer. They occur in pT3 and pT4 tumours. Their presence indicates a poorer prognosis. There is evidence that TME improves outcomes in mid- and low-rectal cancers but its role in upper rectal and rectosigmoid cancers is controversial. It has been difficult to demonstrate the superiority of anterior resection over abdominoperineal resection as comparative studies report similar outcomes. Exfoliated tumour cells have been demonstrated to contribute to anastomotic recurrence and this probability may be reduced by the use of cytotoxic agents to irrigate the rectal stump. Multiple studies have shown that specialisation in rectal cancer surgery result in lower postoperative morbidity and mortality, local and distant recurrence rates and higher rates of sphincter saving resections. CONCLUSION: The majority of tenets espoused in the original papers on TME have found support in follow-up studies since their publication.

Disease-Free Survival↗

Ring-testing and field-validation of a terrestrial model ecosystem (TME)--an instrument for testing potentially harmful substances: effects of carbendazim on soil microbial parameters.

The effects of carbendazim on substrate induced respiration (SIR), dehydrogenase activity (DHA), phosphatase activity and thymidine incorporation by bacteria were evaluated in an experiment with an open intact Terrestrial Model Ecosystem (TME) and in a simultaneous field-validation study. Experiments were performed on four different European soils in Germany, The Netherlands, United Kingdom and Portugal. Data analysis focused on (i) detecting differences between experiments, especially in control values, (ii) checking similarity in data variability at each treatment level between experiments and (iii) analysing the resemblance of response to the model chemical in both experiments. Results obtained showed that control values from TME experiments were similar to those obtained on the respective field site, in most of the comparisons made for SIR, DHA and thymidine incorporation. Phosphatase activity revealed more differences, but values of both experiments had the same order of magnitude. At least part of the variation could be explained from the correlation of the microbial parameters with soil moisture content. Comparisons on data variability also revealed the absence of significant differences between experiments in all parameters in most cases, indicating that TMEs were able to represent the spatial variability found in the field. Effects of carbendazim, when occurring, were observed at treatment levels exceeding the highest recommended application rate of 0.36 kg a.i./ha. Effects on SIR and DHA were observed early in time, but effects on phosphatase activity and thymidine incorporation rate were found 8 or 16 weeks after chemical application. These effects were mild, and rarely a 50% inhibition on any of these parameters was seen at carbendazim dosages up to 87.5 kg a.i./ha. The response to the model chemical in TMEs and field plots was similar in most cases. These results give promising prospects for the use of TMEs as an integrative tool in higher tier levels of different assessment schemes.

Bacterial Physiological Phenomena↗

The Pelican Cancer Foundation and The English National MDT-TME Development Programme.

The formation of The Pelican Cancer Foundation in 2000 was based around the pioneering work of Professor Bill Heald and colleagues, and the development of Total Mesorectal Excision (TME) for rectal cancer. A series of surgical workshops in Scandinavia in the mid 1990s and, later, six further workshops in the Trent region culminated in the commissioning of the fully multidisciplinary National MDT-TME Development Programme by the National Cancer Director, Professor Mike Richards, in March 2003.

Charities↗

Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in mice.

In the mouse the insulin-like growth factor receptor type 2 gene (Igf2r) is imprinted and maternally expressed. Igf2r encodes a trans-membrane receptor that transports mannose-6-phosphate tagged proteins and insulin-like growth factor 2 to lysosomes. During development the receptor reduces the amount of insulin-like growth factors and thereby decreases embryonic growth. The dosage of the gene is tightly regulated by genomic imprinting, leaving only the maternal copy of the gene active. Although the function of Igf2r in development is well established, the function of imprinting the gene remains elusive. Gene targeting experiments in mouse have demonstrated that the majority of genes are not sensitive to gene dosage, and mice heterozygous for mutations generally lack phenotypic alterations. To investigate whether reduction of Igf2r gene dosage by genomic imprinting has functional consequences for development we generated a non-imprinted allele (R2Delta). We restored biallelic expression to Igf2r by deleting a critical element for repression of the paternal allele (region 2) in mouse embryonic stem cells. Maternal inheritance of the R2Delta allele has no phenotype; however, paternal inheritance results in biallelic expression of Igf2r, which causes a 20% reduction in weight late in embryonic development that persists into adulthood. Paternal inheritance of the R2Delta allele rescues the lethality of a maternally inherited Igf2r null allele and a maternally inherited Tme (T-associated maternal effect) mutation. These data show that the biological function of imprinting Igf2r is to increase birth weight and they also establish Igf2r as the Tme gene.

Alleles↗

[Laparoscopic rectal excision for cancer using total mesorectaol excision (TME). Long term outcome of a series of 179 patients].

BACKGROUND: The purpose of this study was to evaluate the outcomes and the five-year survival of 179 consecutive patients with rectal carcinoma operated with a laparoscopic procedure between April 1992 and April 2003. METHODS: Patients with obstructing, bulky cancers were excluded from this study. Tumor stage was defined according to the TNM classification. Preoperative radiation therapy was offered to T(3) N(0) or N(+) patients (45 Gy). The laparoscopic-assisted technique included total mesorectal excision (TME), primary high vascular ligation, centrifugal dissection of the mesentery, and "no touch" technique. All the N+ patients received adjuvant chemotherapy. The outcomes were defined as five-years recurrence (local recurrence and distant metastasis) and the diseases-free survival. The survival rates were calculated with the Kaplan-Meier test. RESULTS: There were 108 males and 71 females, median age was 67 (range 39-88). There were 61 upper rectum localizations (34%), 68 middle rectum (38%) and 50 low rectum (28%). Twenty-nine patients required open conversion (16%). Surgical operative morbidity was 24% and medical morbidity was 4%. There were 60 stage I (40%), 25 stage II (16%), 49 stage III (32%), and 16 stage IV (10%). Ninety patients (71%) are alive and disease free, ten (5%) are alive with disease recurrence, and 37 patients (20%) are deceased. Only one case of trocar site implantation occurred after curative resection during an average follow up of 76 months. Five-year observed survival rate were 85% for stage I, 70% for stage II, and 63% for stage III. CONCLUSION: In our experience laparoscopic rectal resection could be done safely. The oncologic outcome was similar to that of open surgery. Further randomized trials will be necessary to confirm the value of this technique.

Adult↗

Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial.

BACKGROUND: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. METHOD: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n=1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. RESULTS: Normal pre-operative CEA values were present in 63% (CEA<5.0) and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. CONCLUSION: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

Adult↗

Ring-testing and field-validation of a terrestrial model ecosystem (TME)--an instrument for testing potentially harmful substances: effects of carbendazim on organic matter breakdown and soil fauna feeding activity.

Organic matter (OM) decomposition and soil fauna feeding activity were integrated as functional endpoints into ecotoxicological tests with intact-soil-core Terrestrial Model Ecosystems (TMEs). Cellulose filter paper served as standardized OM and was either inserted into the top soil or placed on the soil surface for a period of up to 16 weeks. Faunal feeding activity was assessed by the bait-lamina method. The fungicide carbendazim, applied at six dosages ranging from 0.36 kg/ha to 87.5 kg a.i./ha, served as a model chemical. To validate the results from the TME test, a field study was run in parallel. In TMEs the cellulose paper inserted into the soil was decomposed faster than under field conditions. The carbendazim-induced effects on OM decomposition in TMEs and in the field were comparable and followed a clear dose-response relationship. The calculated EC50 values after 8 weeks of incubation were 9.5, 7.1 and 2.1 kg carbendazim/ha for grassland TMEs, grassland field and arable TMEs, respectively. The feeding activity of the soil fauna showed a large variability. The EC50 values for the effect of carbendazim on bait-lamina consumption ranged between 2.0 and 56 kg a.i./ha. Effects on decomposition were correlated with effects on enchytraeids and earthworms but not with effects on bait-lamina consumption.

Animals↗

Does perifascial rectal excision (i.e. TME) when combined with the autonomic nerve-sparing technique interfere with operative radicality?

OBJECTIVE: The lymphatic drainage from the rectum was studied to evaluate if the autonomic nerve sparing dissection may interfere with the operative radicality and might result in metastatic lymph nodes being overlooked and left in situ. PATIENTS AND METHODS: 50 consecutive patients had an extended extrafascial rectal excision resection for cancer. In 19 of the 50 patients activated carbon particles (CH40) were injected preoperatively into the rectum. The autonomic nerves with surrounding connective tissue were serially dissected from the resected specimen, carefully sliced at 5-mm intervals and collected for histological study. Lymph nodes along the axial and lateral drainage routes were examined, and the inclusion of CH40 in the nodes was microscopically studied according to the site of CH40 injection. RESULTS: Lymph nodes within the connective tissue along the dissected autonomic nerves were demonstrated in 47 of the 50 cases. Two of 50 cases had positive nodes along preaortic plexus or pelvic plexus, and a case with nodal involvement along the pelvic plexus had poor prognosis in spite of nerve excision. CH40 when injected into the rectum above the peritoneal reflection was demonstrated in the vast majority of the axial nodes, while in only one lymph node along the preaortic plexus when injected in the rectum above the peritoneal reflection. On the other hand when injected in the rectum below the peritoneal reflection, CH40 was demonstrated both in axial and lateral nodes as well as in lymph nodes along bilateral pelvic plexuses, right hypogastric nerve, superior hypogastric plexus, preaortic plexus and mesenteric plexus as well. CONCLUSIONS: When located above the peritoneal reflection a rectal carcinoma will spread preferentially along the upper axial route, while a carcinoma located below the peritoneal reflection will also spread laterally and along the autonomic nerves. It was inferred that lymphatic flow along the autonomic nerves came up from the rectum below the peritoneal reflection mainly through a so-called lateral ligament but its clinical significance was negligible. Therefore doing TME with autonomic nerve preservation does not imply a less radical surgery from the point of lymphatic spread.

Journal Article↗

Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective randomised trial with standard operative and histopathological techniques. Dutch ColoRectal Cancer Group.

OBJECTIVE: To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy. DESIGN: Prospective randomised study. SETTING: Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals. SUBJECTS: The first 500 randomised Dutch patients with primary rectal cancer. MAIN OUTCOME MEASURES: Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life. RESULTS: Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups. CONCLUSIONS: The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Adult↗

Total mesorectal exsicion (TME).

For almost twenty years the concept of total mesorectal excision (TME) has featured in the medical literature. It remains however the object of ongoing controversy and sometimes of downright antagonism. At the present time there are at least four other names for exactly the same technique being championed by different authorities. 1. Circumferential Mesorectal Excision (Enker); 2. Sharp Mesorectal Excision (Cohen); 3. Extrafascial Excision of the Rectum (Hill); 4. Total Anatomical Dissection (Boley). As Shakespeare said "A rose by any other name would smell as sweet".

Digestive System Surgical Procedures↗

[Controversy about treatment of colorectal cancer in view of surgeon--lymph node dissection for colorectal surgery (lateral lymph node dissection and TME)].

Lateral lymph node dissection is technique for reducing local recurrence rate after resection of rectal cancer. In this study, we will report a decade experience for lateral lymph node dissection of rectal cancer in 491 cases. Lateral lymph node metastases occurred in 15.4% of rectal cancer which was below peritoneal reflection and through muscularis propria into non-peritoneal. It is a problem that it has never been well designed study of lateral lymph node dissection for rectal cancer. On the other hand, TME has also contributed reducing local recurrence rate. But, distant margin for resection of rectal cancer is controversial.

Colorectal Neoplasms↗

Teaching efforts to spread TME surgery in Sweden.

The whole infrastructure of rectal cancer treatment in Sweden has changed dramatically due to the awareness of the local recurrence rate, good surgical technique, and selective use of radiotherapy. Surgeons have been trained in a proper way, and it has been proven that the outcome has improved enormously in our country [14]. Due to repeated reports from the SRCR to each unit, it is possible for every surgeon to follow the process. It has been shown that the outcome for not only colon cancer but also rectal cancer has improved dramatically during the last 40 years, and there is a marked improvement in survival from approximately 40% in the early 1960s to almost 60% in the late 1990s [15]. An interesting phenomenon is that the relative 5-year survival rate has, during the 5-year cohort, been better for patients with colon cancer compared to those with rectal cancer. For the last two 5-year cohorts in Sweden, 1990-1995 and 1996-2000, the results for rectal cancer patients have improved, and in the most recent cohort, rectal cancer patients are actually doing better than colon cancer patients in terms of relative survival [16]. This increase has been interpreted to be a result of much better surgery, a more selective use of radiotherapy, but most of all an awareness of the results and focus on good auditing. This quality assurance and quality control of rectal cancer surgery is important and will be mandatory in the future for all units to not only know the results but also be able to present them in a way that patients can understand. We are facing a new generation of young patients who are familiar with the Internet and find all types of information before having surgery. It is obvious that only the best units will survive in such a competition, and the only way to be able to compete is to show good results within a good and validated population-based quality registration, as is the situation for many different diseases in Sweden today. A tremendous change has been seen in our country over the last two decades, and it is in part a result of registration and quality auditing, where the results are displayed to the surgeons.

Colorectal Surgery↗

Laparoscopic TME: better vision, better results?

One of the most controversial discussions on laparoscopic surgery deals with the question of whether to apply this technique to malignant disease and specifically to rectal cancer. The four major issues are the adequacy of oncologic resection, recurrence rates and patterns, long-term survival and quality of life. There is evidence, from nonrandomized studies, suggesting that margins of excision and lymph node harvest achieved laparoscopically reached comparable results to those known from conventional open resection. Our own experience of laparoscopic surgery on rectal cancer is based on 52 patients treated with curative intent. Focusing on the postoperative long-term run, we gained the following results: The median age of patients was 66.7 years and ranged from 42-88. Anastomotic leakage was seen in 6.1% of cases. In a median follow-up of 48 months (36-136), we reached an overall 3-year survival rate of 93% and a 5-year survival rate of 62%. Local recurrence was 1.9%, distant metastasis occurred in 11.5% of cases. We saw no port-site metastasis. To evaluate functional results following laparoscopic surgery a matched pair analysis was carried out. Matching of patients after laparoscopic and conventional open surgery was performed according to sex, age, type of resection, time period of surgery, and stage of disease classified by UICC. Regarding bladder and sexual dysfunction, using the EORTC QLQ CR38 score we found no statistical significant difference between the examined groups. As far as can be seen, laparoscopic surgery in rectal carcinoma may achieve the same or, in selected patients, even better results than open surgery. However, at present no published study has shown much evidence. Many more studies are necessary to define the place of laparoscopic technique in rectal cancer surgery, regarding appropriate selection of patients and evaluating adjuvant or neoadjuvant treatment in combination with the laparoscopic approach.

Adult↗