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1.  Transanal endoscopic microsurgery: what indications in 2013? 
Gastroenterology Report  2013;1(2):75-84.
Thanks to major advances in the field of surgical techniques and neoadjuvant chemoradiation therapy, along with more accurate pre-operative staging tools and the widespread introduction of population-based screening programs, treatment of rectal cancer has been evolving over the past few decades, moving towards a more tailored approach. This has brought a shift in the treatment algorithm of benign rectal lesions and selected early rectal cancers, for which today transanal endoscopic microsurgery (TEM) is accepted as an effective alternative to abdominal surgery.
In 2013, topics of controversy are the role of TEM in the treatment of more advanced rectal cancers, in cases of complete pathological response after chemoradiation therapy and the role of TEM as a platform for single-port surgery and NOTES. This article reviews the current indications for TEM and the future perspectives of this approach in the treatment of rectal tumors.
PMCID: PMC3938006  PMID: 24759812
transanal endoscopic microsurgery; full-thickness excision; rectal adenoma; early rectal cancer; chemoradiation; NOTES
2.  Transanal Endoscopic Microsurgery for the Treatment of Well-Differentiated Rectal Neuroendocrine Tumors 
Recently, an increase in well-differentiated rectal neuroendocrine tumors (WRNETs) has been noted. We aimed to evaluate transanal endoscopic microsurgery (TEM) for the treatment of WRNETs.
Between December 1995 and August 2009, 109 patients with WRNETs underwent TEM. TEM was performed for patients with tumors sizes of up to 20 mm and without a lymphadenopathy. These patients had been referred from other clinics after having been diagnosed with WRNETs by using a colonoscopic biopsy; they had undergone a failed endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) and exhibited an involved resection margin and remaining tumor after ESD or EMR, regardless of the distance from the anal verge. This study included 38 patients that had more than three years of follow-up.
The mean age of the patients was 51.3 ± 11.9 years, the mean tumor size was 8.0 ± 3.9 mm, and no morbidity occurred. Thirty-five patients were asymptomatic. TEM was performed after a colonoscopic resection in 13 cases because of a positive resection margin, a residual tumor or a non-lifting lesion. Complete resections were performed in 37 patients; one patient with a positive margin was considered surgically complete. In one patient, liver metastasis and a recurrent mesorectal node occurred after five and 10 years, respectively.
TEM might provide an accessible and effective treatment either as an initial or as an adjunct after a colonoscopic resection for a WRNET.
PMCID: PMC3440489  PMID: 22993706
Well-differentiated rectal neuroendocrine tumors; Transanal endoscopic microsurgery; Colonoscopic resection; Treatment
3.  A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma 
Neoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC.
Methods and materials
Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 b.i.d. d1–5 weekly). One cycle of capecitabine (1000 mg/m2 b.i.d. d1–14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation.
Between October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2–3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3–4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1–2.
Our study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical complications. Treatment response was an early surrogate marker and correlated to oncologic prognosis.
PMCID: PMC3680166  PMID: 23718210
Rectal cancer; Intensity-modulated radiation therapy; Neoadjuvant chemoradiotherapy
4.  Transanal endoscopic microsurgery: a review 
Canadian Journal of Surgery  2014;57(2):127-138.
Rectal adenomas and cancers occur frequently. Small adenomas can be removed colonoscopically, whereas larger polyps are removed via conventional transanal excision. Owing to technical difficulties, adenomas of the mid- and upper rectum require radical resection. Transanal endoscopic microsurgery (TEM) was first designed as an alternative treatment for these lesions. However, since its development TEM has been also used for a variety of rectal lesions, including carcinoids, rectal prolapse and diverticula, early stage carcinomas and palliative resection of rectal cancers. The objective of this review is to describe the current status of TEM in the treatment of rectal lesions. Since the 1980s, TEM has advanced substantially. With low recurrence rates, it is the method of choice for resection of endoscopically unresectable adenomas. Some studies have shown benefits to its use in treating early T1 rectal cancers compared with radical surgery in select patients. However, for more advanced rectal cancers TEM should be considered palliative or experimental. This technique has also been shown to be safe for the treatment of other uncommon rectal tumours, such as carcinoids. Transanal endoscopic microsurgery may allow for new strategies in the treatment of rectal pathology where technical limitations of transanal techniques have limited endoluminal surgical innovations.
PMCID: PMC3968206  PMID: 24666451
5.  Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial 
Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery.
To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine.
Patients and methods
This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique.
Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively.
In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.
PMCID: PMC2699338  PMID: 19508705
6.  Transanal endoscopic microsurgery combined with endoscopic posterior mesorectum resection in the treatment of patients with T1 rectal cancer – 3-year results 
Rectum-sparing transanal endoscopic microsurgery (TEM) is a well-established treatment for T1 rectal cancer (RC). However, it is associated with an increased rate of local recurrence in comparison with extended resection. In most cases this failure is linked to inappropriate case selection and the presence of clinically non-detectable metastases in the regional lymph nodes. Endoscopic posterior mesorectal resection (EPMR) makes it possible to remove the relevant lymphatic drainage of the lower third of the rectum in a minimally invasive way, which in turn can help in adequate tumor staging.
To evaluate the long-term clinical results and influence of combined TEM and EPMR treatment on the anorectal functions.
Material and methods
Ten consecutive patients with T1 RC were operated on using TEM and EPMR as a two-stage procedure between 2007 and 2009.
After a median follow-up of 42.6 (range: 36–80) months, none of our patients complained of symptoms of incontinence apart from one female patient with gas incontinence diagnosed preoperatively. There was no statistically significant difference in basal anal pressure, squeeze anal pressure, high pressure zone length or fecal continence assessed using the Fecal Incontinence Severity Index before and in follow-up months after the procedure. Postoperative morbidity consisted of one hematoma formation and one male patient complaining about sexual dysfunction until 6 months postoperatively. There was no evidence of locoregional recurrence.
Endoscopic posterior mesorectal resection in combination with TEM appears to be safe, feasible and with no impact on the basic anorectal functions in the 3-year follow-up.
PMCID: PMC3983548  PMID: 24729808
transanal endoscopic microsurgery; rectal cancer; endoscopic posterior mesorectal resection
7.  Current experience and future directions of completely NOTES colorectal resection 
Clinical implementation and widespread application of natural orifice translumenal surgery (NOTES) has been limited by the lack of specialized endoscopic equipment, which has prevented the ability to perform complex procedures including colorectal resections. Relative to other types of translumenal access, transanal NOTES using transanal endoscopic microsurgery (TEM) provides a stable platform for endolumenal and direct translumenal access to the peritoneal cavity, and specifically to the colon and rectum. Completely NOTES transanal rectosigmoid resection using TEM, with or without transgastric endoscopic assistance, was demonstrated to be feasible and safe in a swine survival model. The same technique was successfully replicated in human cadavers using commercially available TEM, with endoscopic and laparoscopic instrumentation. This approach also permitted complete rectal mobilization with total mesorectal excision to be performed completely transanally. As in the swine model, transgastric and/or transanal endoscopic assistance extended the length of proximal colon mobilized and overcame some of the difficulties with TEM dissection including limited endoscopic visualization and maladapted instrumentation. This extensive laboratory experience with NOTES transanal rectosigmoid resection served as the basis for the first human NOTES transanal rectal cancer excision using TEM and laparoscopic assistance. Based on this early clinical experience, NOTES transanal approach using TEM holds significant promise as a safe and substantially less morbid alternative to conventional colorectal resection in the management of benign and malignant colorectal diseases. Careful patient selection and substantial improvement in NOTES instrumentation are critical to optimize this approach prior to widespread clinical application, and may ultimately permit completely NOTES transanal colorectal resection.
PMCID: PMC2999239  PMID: 21160873
Colorectal diseases; Transanal endoscopic microsurgery; Natural orifice translumenal endoscopic surgery
8.  Transanal Endoscopic Microsurgery for Rectal Tumors: A Review 
The Permanente Journal  2012;16(2):45-50.
Since its introduction in 1983, transanal endoscopic microsurgery (TEM) has emerged as a safe and effective method to treat rectal lesions including benign tumors, early rectal cancer, and rectal fistulas and strictures. This minimally invasive technique offers the advantages of superior visualization of the lesion and greater access to proximal lesions with lower margin positivity and specimen fragmentation and lower long-term recurrence rates over traditional transanal excision. In addition, over two decades of scientific data support the use of TEM as a viable alternative to radical excision of the rectum with less morbidity, faster recovery, and greater potential cost savings when performed at specialized centers.
PMCID: PMC3383161  PMID: 22745615
9.  Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer 
Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.
Materials and Methods
A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m2 capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.
Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.
Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.
PMCID: PMC2843876  PMID: 20368828
Rectal cancer; Preoperative; Chemoradiotherapy; Capecitabine
10.  Transanal endoscopic microsurgery--impact on the practice of a colorectal surgeon in a district general hospital. 
INTRODUCTION: The objective was to assess the impact on the management of colorectal patients treated in a district general hospital within the first year after the introduction of transanal endoscopic microsurgery (TEM). PATIENTS AND METHODS: Data were collected for consecutive unselected patients who underwent TEM. Comparative data were derived from a matched group of patients who underwent anterior resection, peranal procedures (PAR) or transanal resection (TAR) in this unit. RESULTS: Twenty-two patients underwent TEM (11 men and 11 women; aged, 29-87 years; median, 75 years). Eighteen patients had a pre-operative diagnosis of benign rectal neoplasms; three were found to have invasive carcinoma, which might have been missed during TAR. Four patients had a pre-operative diagnosis of rectal cancer and TEM provided local tumour control in three cases. The operating time ranged between 20-150 min (mean, 65 min; median, 57 min). Hospital stay ranged between 0-10 days (mean, 3.7 days; median, 3 days), with a total of 97 in-patient days for the entire group of patients. Twenty-four operations were performed (22 TEM and two salvage anterior resections), with an estimated cost of 1544 pounds sterling for consumables used. Alternative treatments in the absence of TEM were considered to involve 10 anterior resections, 5 closures of ileostomy, 30 TAR procedures and one PAR procedure, with an estimated 306 days of in-patient admission, 46 operations and 6245 pounds sterling spent on consumables. CONCLUSIONS: Availability of TEM allows more efficient treatment for a significant number of patients with rectal tumours. The cost of the equipment is offset by a significant decrease in the length of in-patient admissions.
PMCID: PMC1964132  PMID: 16263010
11.  Transanal endoscopic microsurgery in treatment of rectal adenomas and T1 low-risk carcinomas 
Transanal endoscopic microsurgery as a local therapy option for rectal neoplasms is a tissue-sparing technique that protects the anal sphincter. The present retrospective analysis reports the course of observation after local excision of adenomas and T1 low-risk carcinomas using transanal endoscopic microsurgery.
In a retrospective analysis we examined data on 279 patients for local recurrence. A total of 144 patients had a rectal adenoma (n = 103) or a R0 resection of low-risk T1 carcinomas (n = 41). In this collective, we also examined parameters concerning perioperative management, complications, intraoperative blood loss and duration of hospital stay.
Patients with adenoma were on average 64.9 (range 37 to 90) years old; 83.5% of the adenomas were located 3 to 11 cm from the anocutaneous line. In adenoma patients the recurrence rate was 2.9% for an observation period of 21.8 months. The postoperative course was without any complications in 98.1% of patients.
Patients with T1 low-risk carcinoma were 64.6 (range 30 to 89) years old. In all cases, an R0 resection could be performed. The recurrence rate was 9.8% for an observation period of 34.4 months. In this group the postoperative course was free of complications in 97.6% of patients.
The high efficacy of transanal endoscopic microsurgery ensures minimally invasive treatment of adenomas and low-risk T1 carcinomas with low complication rates and a low rate of therapeutic failure.
PMCID: PMC3556112  PMID: 23181563
Transanal endoscopic microsurgery; Rectal adenoma; Rectal carcinoma; Local excision; Endoscopic surgery
12.  RTOG 0247: A Randomized Phase II Study of Neoadjuvant Capecitabine and Irinotecan or Capecitabine and Oxaliplatin with Concurrent Radiation Therapy for Patients with Locally Advanced Rectal Cancer 
To evaluate rate of pathologic complete response (pCR) and toxicity of two neoadjuvant chemoradiation (chemoRT) regimens for T3/T4 rectal cancer in a randomized phase II study.
Methods and Materials
Patients with T3 or T4 rectal cancer < 12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8 Gy fractions) with (1) concurrent capecitabine (1200 mg/m2/d M-F) and irinotecan (50 mg/m2 weekly × 4 doses) (arm 1), or (2) concurrent capecitabine (1650 mg/m2/d M-F) and oxaliplatin (50 mg/m2 weekly × 5 doses) (arm 2). Surgery was performed 4–8 weeks after chemoRT, and adjuvant chemotherapy 4–6 weeks after surgery. The primary endpoint was pCR rate, requiring 48 evaluable patients per arm.
146 patients were enrolled. Protocol chemotherapy was modified due to excessive GI toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint—final regimen described above. Patient characteristics were similar for both arms. Following chemoRT, tumor downstaging was 52% and 60%, and nodal downstaging (excluding N0 patients) was 46% and 40%, for arms 1 and 2, respectively. The pCR rate for arm 1 was 10% and for arm 2 was 21%. For arms 1 and 2, respectively, preop chemoRT grade 3/4 hematologic toxicity was 9% and 4%, and grade 3/4 non-hematologic toxicity was 26% and 27%.
Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10/48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a phase III randomized trial (NSABP R04).
PMCID: PMC3208721  PMID: 21775070
Neoadjuvant; chemotherapy; radiation; rectal; cancer
13.  Transanal polypectomy using single incision laparoscopic instruments 
Transanal excision of rectal polyps with laparoscopic instrumentation and a single incision laparoscopic port is a novel technique that uses technology originally developed for abdominal procedures from the natural orifice of the rectum. Transanal endoscopic microsurgery (TEM) is a well established surgical approach for certain benign or early malignant lesions of the rectum, under specific indications. Our technique is a hybrid technique of transanal surgery, a reasonable method for polyp resection without the need of the sophisticated and expensive instrumentation of TEM which can be applied whenever endoscopic or conventional transanal surgical removal is not feasible.
PMCID: PMC3083502  PMID: 21528096
Polypectomy; SILS; Transanal endoscopic microsurgery; Laparoscopy; Endoscopy
14.  Anorectal functional outcome after repeated transanal endoscopic microsurgery 
AIM: To evaluate the status of anorectal function after repeated transanal endoscopic microsurgery (TEM).
METHODS: Twenty-one patients undergoing subtotal colectomy with ileorectal anastomosis were included. There were more than 5 large (> 1 cm) polyps in the remaining rectum (range: 6-20 cm from the anal edge). All patients, 19 with villous adenomas and 2 with low-grade adenocarcinomas, underwent TEM with submucosal endoscopic excision at least twice between 2005 and 2011. Anorectal manometry and a questionnaire about incontinence were carried out at week 1 before operation, and at weeks 2 and 3 and 6 mo after the last operation. Anal resting pressure, maximum squeeze pressure, maximum tolerable volume (MTV) and rectoanal inhibitory reflexes (RAIR) were recorded. The integrity and thickness of the internal anal sphincter (IAS) and external anal sphincter (EAS) were also evaluated by endoanal ultrasonography. We determined the physical and mental health status with SF-36 score to assess the effect of multiple TEM on patient quality of life (QoL).
RESULTS: All patients answered the questionnaire. Apart from negative RAIR in 4 patients, all of the anorectal manometric values in the 21 patients were normal before operation. Mean anal resting pressure decreased from 38 ± 5 mmHg to 19 ± 3 mmHg (38 ± 5 mmHg vs 19 ± 3 mmHg, P = 0.000) and MTV from 165 ± 19 mL to 60 ± 11 mL (165 ± 19 mL vs 60 ± 11 mL, P = 0.000) at month 3 after surgery. Anal resting pressure and MTV were 37 ± 5 mmHg (38 ± 5 mmHg vs 37 ± 5 mmHg, P = 0.057) and 159 ± 19 mL (165 ± 19 mL vs 159 ± 19 mL, P = 0.071), respectively, at month 6 after TEM. Maximal squeeze pressure decreased from 171 ± 19 mmHg to 62 ± 12 mmHg (171 ± 19 mmHg vs 62 ± 12 mmHg, P = 0.000) at week 2 after operation, and returned to normal values by postoperative month 3 (171 ± 19 vs 166 ± 18, P = 0.051). RAIR were absent in 4 patients preoperatively and in 12 (χ2 = 4.947, P = 0.026) patients at month 3 after surgery. RAIR was absent only in 5 patients at postoperative month 6 (χ2 = 0.141, P = 0.707). Endosonography demonstrated that IAS disruption occurred in 8 patients, and 6 patients had temporary incontinence to flatus that was normalized by postoperative month 3. IAS thickness decreased from 1.9 ± 0.6 mm preoperatively to 1.3 ± 0.4 mm (1.9 ± 0.6 mm vs 1.3 ± 0.4 mm, P = 0.000) at postoperative month 3 and increased to 1.8 ± 0.5 mm (1.9 ± 0.6 mm vs 1.8 ± 0.5 mm, P = 0.239) at postoperative month 6. EAS thickness decreased from 3.7 ± 0.6 mm preoperatively to 3.5 ± 0.3 mm (3.7 ± 0.6 mm vs 3.5 ± 0.3 mm, P = 0.510) at month 3 and then increased to 3.6 ± 0.4 mm (3.7 ± 0.6 mm vs 3.6 ± 0.4 mm, P = 0.123) at month 6 after operation. Most patients had frequent stools per day and relatively high Wexner scores in a short time period. While actual fecal incontinence was exceptional, episodes of soiling were reported by 3 patients. With regard to the QoL, the physical and mental health status scores (SF-36) were 56.1 and 46.2 (50 in the general population), respectively.
CONCLUSION: The anorectal function after repeated TEM is preserved. Multiple TEM procedures are useful for resection of multi-polyps in the remaining rectum.
PMCID: PMC3484352  PMID: 23155324
Familial adenomatous polyposis; Repeated transanal endoscopic microsurgery; Anorectal function; Anorectal manometry; Subtotal colectomy
15.  The prognostic impact of extracapsular lymph node involvement in rectal cancer patients: Implications for staging and adjuvant treatment strategies 
Oncology Letters  2012;3(4):825-830.
Limited data suggest that extracapsular lymph node involvement (LNI) has a negative prognostic impact in gastrointestinal malignancies. The aim of this study was to assess the prevalence and prognostic impact of LNI in patients with primary resected rectal cancer. Between 1997 and 2007, 243 rectal cancer patients underwent surgical therapy without neoadjuvant treatment at our Department. Of these, 12 (5%) patients received transanal endoscopic microsurgery and were not included for further analyses. In the remaining patients, a (low) anterior resection was performed in 79% and an abdominoperineal rectal amputation in 21%. The total number of analyzed lymph nodes and the number of metastatic lymph nodes with/without extracapsular LNI were determined and the prognostic impact of LNI was assessed. The median number of analyzed lymph nodes was 14. In total, 59% of patients were node-negative, 18% of patients were node-positive without extracapsular LNI and 23% of patients were node-positive with extracapsular LNI. A positive lymph node status with extracapsular LNI was significantly correlated with a poorer T-, N- and M-category, grading and more frequent lymphatic vessel infiltration compared with node-negative or node-positive without extracapsular LNI patients (p<0.001). The overall 5-year survival rate of node-negative patients was 75%, for node-positive without extracapsular LNI patients 69% and for node-positive with extracapsular LNI patients 36% (p<0.001). By multivariate analysis, the N-category with extracapsular LNI was characterized as an independent prognostic factor. Extracapsular lymph node involvement reveals an independent negative prognostic impact in patients with rectal cancer undergoing surgical therapy. Staging systems for rectal cancer should include the implementation of extracapsular lymph node involvement.
PMCID: PMC3362417  PMID: 22741001
rectal cancer; prognostic factors; extracapsular lymph node involvement; adjuvant therapy
16.  Short–term effects of neoadjuvant chemoradiation therapy on anorectal function in rectal cancer patients: a pilot study 
Neoadjuvant chemoradiation therapy followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. However, deterioration of anorectal function after long-course neoadjuvant chemoradiation therapy combined with surgery for rectal cancer is poorly defined. The aim of this study was to evaluate the physiological and clinical change of anorectal function after neoadjuvant chemoradiation therapy for rectal cancer.
We analyzed 30 patients on whom preoperative anorectal manometry data were available both before and after chemoradiation from October 2010 to September 2011. All patients underwent long-course neoadjuvant chemoradiation therapy. We compared manometric parameters between before and after neoadjuvant chemoradiation therapy.
Of 30 patients, 20 were males and 10 females. The mean age was 64.9 ± 9.9 years (range, 48-82). Before nCRT, the rectal compliance was higher in patients with ulceroinfiltrative type (P = 0.035) and greater involvement of luminal circumference (P = 0.017). However, there was the tendency of increased rectal sensory threshold for desire to defecate when the patient had decreased circumferential ratio of the tumor (P = 0.099), down-graded T stage (P = 0.016), or reduced tumor volume (P = 0.063) after neoadjuvant chemoradiation.
Neoadjuvant chemoradiation therapy did not significantly impair overall sphincter function before radical operation. The relationship between tumor response of chemoradiation and sensory threshold for desire to defecate may suggest that neoadjuvant chemoradiation may be helpful for defecatory function as well as local disease control, at least in the short-term period after the radiation in locally advanced rectal cancer patients.
PMCID: PMC3766044  PMID: 23961877
Anorectal function; Neoadjuvant chemoradiation; Manometry; Rectal cancer
17.  Management of anastomotic leak after low anterior resection with transanal endoscopic microsurgical (TEM) debridement and repair 
Anastomotic leak after low anterior resection (LAR) in patients with rectal cancer who have received neoadjuvant chemoradiation can be challenging to treat and can lead to the creation of a permanent stoma. We report the case of a post-operative anastomotic leak after a Baker-type anastomosis during a low anterior resection was successfully managed with transanal endoscopic microsurgical (TEM) debridement and repair. TEM can be a successful endoluminal alternative treatment in the management of anastomotic leak after LAR and can prevent the morbidity associated with re-exploration and colostomy.
PMCID: PMC3649630
18.  Outcomes in Patients Treated by Laparoscopic Resection of Rectal Carcinoma After Neoadjuvant Therapy for Rectal Cancer 
We analyzed the effect of neoadjuvant chemoradiation on feasibility and outcomes in rectal cancer patients undergoing laparoscopic resection of the rectum.
This was a retrospective analysis of a consecutive series of laparoscopic resections for rectal cancer from 1998 to 2004 (N=60).
Eight patients received preoperative chemoradiation therapy (neoadjuvant group) for rectal cancer and 52 patients did not (primary surgical group). The conversion rate was higher in the neoadjuvant group, but this did not reach statistical significance (3/8, 37% in the neoadjuvant group vs. 7/52, 13% in the primary surgical group, P=0.12). Operative time was longer in the neoadjuvant group (170±60 vs 228±70 min, P=0.03). Complication rates (3/52, 5.7% in the primary surgical vs. 0% in the neoadjuvant group, P=1.0), and a median number of resected lymph nodes (14.5 in the primary surgical vs. 16.0 in the neoadjuvant group, P=0.81) were similar between groups.
Laparoscopic resection of rectal cancer in patients after preoperative chemoradiation treatment seems to be associated with a higher conversion rate and a longer duration of surgery. No change in mortality and morbidity was detected. We encourage further investigation of laparoscopic rectal surgery for treatment of rectal cancer.
PMCID: PMC3015728  PMID: 17761081
Rectal cancer; Laparoscopic resection; Neoadjuvant chemoradiation
19.  Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study) 
BMC Surgery  2009;9:4.
Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.
The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas.
Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment.
Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures.
Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group.
The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas.
Trial registration number
( NTR1422
PMCID: PMC2664790  PMID: 19284647
20.  Transanal Endoscopic Video-Assisted Excision: Application of Single-Port Access 
Transanal endoscopic video-assisted excision of benign and malignant rectal lesions with pneumorectal distension appears to optimize the visual field and avert several of the pitfalls commonly associated with transanal endoscopic microsurgery.
Transanal endoscopic microsurgery is a safe and efficacious surgical approach for local excision of benign adenomas and early-stage rectal cancer. However, utilization of the technique has been limited due to the unavailability of high-priced specialized instrumentation at many institutions and the technically demanding training required. To avoid these obstacles, we have explored an alternative approach called Transanal Endoscopic Video-Assisted excision, which combines the merits of single-port access and local transanal excision.
A disposable single-incision port is inserted into the anal canal for transanal access. The port contains 3 cannulae for introducing instrumentation into the rectal lumen, and a supplementary cannula for carbon dioxide insufflation. Pneumorectum results in rectal distention and optimizes the visual field during the procedure. Standard laparoscopic instrumentation is utilized for visualization and transanal excision of rectal pathologies.
Transanal endoscopic video-assisted excision is an innovative approach to local excision of benign and malignant rectal lesions. The approach averts several of the pitfalls commonly experienced with transanal endoscopic microsurgery. Continued investigation and development of this novel modality will be important in establishing its role in minimally invasive surgery.
PMCID: PMC3134696  PMID: 21902943
Anal canal; Laparoscopy; Microsurgery; Rectal neoplasms
21.  Transanal endoscopic micro-surgery (TEMS) for the management of large or sessile rectal adenomas: a review of the technique and indications 
In this review article the surgical technique of Transanal Endoscopic Microsurgery (TEMS) is examined. A number of techniques have been used to treat adenomas of the rectum. The treatment of large adenomas which occupy a large surface of the rectal lumen or adenomas which are flat and grow in a "carpet-like" fashion is particularly challenging. Major rectal surgery carries a risk of morbidity and mortality, particularly in elderly and unfit patients. Although local excision with transanal resection (TAR) and the Kraske sacral operation have been used in the past, during the last twenty years TEMS has become the method of choice for those lesions. TEMS is efficient and minimally invasive. The technique allows the patient to recover rapidly and the incidence of complications is much lower than that of major surgery. In case of recurrence the option of repeat TEMS or major surgery remain available. TEMS has been slow to gain popularity mainly for reasons of cost and steep learning curve but it is now an established procedure and a valuable therapeutic option which is particularly useful for elderly and unfit patients. Gastroenterologists should be aware of the nature and indications of TEMS in order to advise and refer selected patients with rectal adenomas accordingly.
PMCID: PMC1468413  PMID: 16674824
22.  Using GIS for spatial analysis of rectal lesions in the human body 
Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features.
In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes.
Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure.
This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process.
PMCID: PMC1839078  PMID: 17362510
23.  Endoscopic ultrasound and magnetic resonance imaging for re-staging rectal cancer after radiotherapy 
AIM: To compare the sensitivity and specificity of two imaging techniques, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI), in patients with rectal cancer after neoadjuvant chemoradiation therapy. And we compared EUS and MRI data with histological findings from surgical specimens.
METHODS: Thirty-nine consecutive patients (51.3% Male; mean age: 68.2 ± 8.9 years) with histologically confirmed distal rectal cancer were examined for staging. All patients underwent EUS and MRI imaging before and after neoadjuvant chemoradiation therapy.
RESULTS: After neoadjuvant chemoradiation, EUS and MRI correctly classified 46% (18/39) and 44% (17/39) of patients, respectively, in line with their histological T stage (P > 0.05). These proportions were higher for both techniques when nodal involvement was considered: 69% (27/39) and 62% (24/39). When patients were sorted into T and N subgroups, the diagnostic accuracy of EUS was better than MRI for patients with T0-T2 (44% vs 33%, P > 0.05) and N0 disease (87% vs 52%, P = 0.013). However, MRI was more accurate than EUS in T and N staging for patients with more advanced disease after radiotherapy, though these differences did not reach statistical significance.
CONCLUSION: EUS and MRI are accurate imaging techniques for staging rectal cancer. However, after neoadjuvant RT-CT, the role of both methods in the assessment of residual rectal tumors remains uncertain.
PMCID: PMC2785059  PMID: 19938195
Endoscopic ultrasound; Magnetic resonance imaging; Rectal cancer; Neoadjuvant chemoradiation therapy; Diagnostic accuracy
24.  Impact of transanal endoscopic microsurgery on functional outcome and quality of life 
Transanal endoscopic microsurgery (TEM) is a minimal invasive technique for local excision of rectal tumours. The procedure is performed via a rectoscope with a diametre of 4 cm. The aim of this prospective study was to assess both functional outcome and quality of life after TEM.
Patients and methods
Between 2004 and 2006, 47 patients were studied prior to and at least 6 months after TEM. Demographics, operative details and post-operative complications were recorded. Functional outcome was determined using the Faecal Incontinence Severity Index (FISI). Quality of life was measured using the EuroQol EQ-5D questionnaire and the Faecal Incontinence Quality of Life (FIQL) score.
Six months after surgery, median FISI score was found to be decreased (p  < 0.01), depicting an improvement in faecal continence. This improvement was most significant in tumours within 7 cm from the dentate line (p = 0.01). From the patients’ perspective, post-operative quality of life was found to be higher (p  < 0.02). A significant improvement was observed in two of the four FIQLS domains (embarrassment, p = 0.03; lifestyle, p = 0.05). The domains of lifestyle, coping and behaviour and embarrassment were correlated with the FISI (all p < 0.05).
This study indicates TEM has no deteriorating effect on faecal continence. Moreover, once the tumour has been excised using TEM, quality of life is improved.
PMCID: PMC2386752  PMID: 18379797
Rectal neoplasms; TEM; Local excision; Quality of life; Functional outcome
25.  Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer 
BMC Surgery  2014;14:4.
Complete pathological response occurs in 10–20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis.
Case presentation
A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence.
The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy alone in patients with stages II-III rectal adenocarcinoma (without metastasis).
PMCID: PMC3900671  PMID: 24438090
Pathological complete response; Stage iv rectal cancer; Preoperative chemotherapy; Oxaliplatin

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