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Recurrence and survival after mesorectal excision for rectal cancer.

BACKGROUND: Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3-11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented. METHODS: Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. RESULTS: The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0.33 (95 per cent confidence interval (c.i.) 0.21 to 0.52); P < 0.001). Multivariate regression analysis showed that only advanced age (HR 0.97 (95 per cent c.i. 0.94 to 1.00); P = 0.048) and tumour in the lower third of the rectum (HR 0.21 (95 per cent c.i. 0.04 to 1.97); P = 0.075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0.58 (95 per cent c.i. 0.43 to 0.77); P < 0.001). Age was the only independent predictor of death after mesorectal excision (HR 1.04 (95 per cent c.i. 1.02 to 1.07); P = 0.001). CONCLUSION: Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Adenocarcinoma↗

Evidence for excision repair-dependent and -independent processes in ara C-induced chromosome rearrangements in G1 human lymphocytes.

1-beta-D-arabinofuranosylcytosine (ara C) enhances the formation of chromosome rearrangements such as translocations or dicentric chromosomes in G1 cells containing DNA lesions. The formation of rearrangements is hypothesized to be the result of inhibition of excision repair. Ara C has also been known to lead to the formation of chromosome rearrangements in G1 cells in the absence of induced DNA lesions. It is not known whether a common mechanism is involved in these two processes. In the present study, we used excision repair-deficient XP cells to investigate whether excision repair is involved in the formation of chromosome rearrangements in G1 cells which do not contain induced DNA lesions. G0 Lymphocytes from an XP patient were either treated with 4-nitroquinoline-1-oxide (4NQO) or left untreated. Cells were then cultured in the presence of ara C for about 18 h. Aphidicolin (APC), which induces chromosome rearrangements in cells containing 4NQO-induced DNA lesions, was used for comparison. The resulting frequency of dicentrics and rings (dic & ring) was determined at the first mitoses after culture initiation. In 4NQO-pretreated XP cells, the frequency of dic & ring was not increased by post-treatment with ara C or with APC. This result is thought to reflect the absence of excision repair in XP cells. However, normal induction of dic & ring was observed in XP cells not pretreated with 4NQO but treated with ara C. Thus, there seems to be two different processes involved in the induction of G1 rearrangements: excision repair-dependent and excision repair-independent. UV-endonuclease is not involved in excision repair-independent rearrangements.

Adolescent↗

Incidence of Wharton's duct stenosis in floor of the mouth cancers excised with scalpel or cautery vs CO2 laser.

Surgery of the floor of the mouth (FOM) using a scalpel or cautery has produced stenosis of Wharton's duct, necessitating further surgery because of painful enlargement to the gland or suspected metastasis. The laser has been proposed as an alternative method that might avoid this complication. A retrospective study comparing these excisional techniques was done at Walter Reed Army Medical Center between 1973 and 1983. Of a total of 58 lesions, 35 were T1N0M0 and 23 were T2N0M0 (two synchronous lesions being present). Of 35 lesions excised with a scalpel, 11 had an associated submandibular gland resection. Of the remaining 25, two developed secondary duct stenosis. Of 10 lesions excised with cautery, three had an associated excision of the submandibular gland. Of the remaining seven, two developed stenosis and one required subsequent excision of the gland. Of 12 lesions excised with laser, four developed stenosis and two required subsequent excision of the gland. Laser excision appears to be of no advantage in avoiding further surgery of the submandibular gland. A submandibular gland resection at the time of the original resection of T1N0 or T2N0 cancers of the FOM does not appear warranted.

Constriction, Pathologic↗

Molecular characterization of two proteins involved in the excision of the conjugative transposon Tn1545: homologies with other site-specific recombinases.

Excision is probably the initial and rate-limiting step of the movements of conjugative transposons of Gram-positive bacteria such as Tn916 and Tn1545. We have shown, by molecular cloning and DNA sequencing, that a 2058 bp Sau3A right-junction fragment of transposon Tn1545 specifies two gene products that are involved in the excision of the element. The DNA sequence of these genes, designated orf1 and orf2, has been determined and the corresponding proteins, ORF1 and ORF2, have been identified in a bacterial cell-free coupled transcription-translation system. These proteins are freely diffusible since they are able to trans-complement in vivo a deletion derivative of Tn1545 defective for excision. Using an in vivo complementation assay, we have demonstrated that ORF2 alone is able to catalyse excision and that ORF1 strongly stimulates the activity of ORF2. We also found that ORF1 and ORF2 display local homology with, respectively, proteins Xis and Int from lamboid phages, which suggests that these excision systems have a common origin. Based on the functional properties of the integrase of bacteriophage lambda, on the analysis of the nucleotide sequence of the junction fragments and of the target before insertion and after excision, a model is proposed for ORF2-catalysed excision of Tn1545 and related conjugative transposons.

Amino Acid Sequence↗

The maize transposable element Ac excises in progeny of transformed tobacco.

To assess the potential of the maize transposable element Ac for gene tagging in heterologous plant species we monitored transcription, excision and transposition of the element in transgenic tobacco plants and their selfed progeny. Ac excised in the majority of primary regenerants and continued to excise in the first-generation progeny plants. In one primary regenerant Ac was transcribed but did not excise. Fourteen of eighteen kanamycin-resistant progeny from this plant showed Ac excision, suggesting that excision of Ac may have been activated during meiosis or in embryo development. This finding, together with the more general observation of continued Ac mobility in the progeny of transformed plants in which Ac had excised, suggests that Ac will be useful for gene tagging.

Blotting, Southern↗

Choroidal hypoperfusion after surgical excision of subfoveal neovascular membranes in age-related macular degeneration.

PURPOSE: To study the choroidal circulation after surgical excision of subfoveal choroidal neovascular membranes (SFCNVM) in age-related macular degeneration (ARMD). METHODS: Twelve eyes of eleven patients with ARMD that underwent surgical excision of SFCNVMs were evaluated with stereoscopic color fundus photography, stereoscopic fluorescein angiography (FA) and scanning laser ophthalmoscope-indocyanine green videoangiography (SLO-ICGv). The patients were followed for a mean of 7.9 months (range 2 to 14 months). RESULTS: Preoperatively, all eyes had angiographic evidence of a SFCNVM, with SLO-ICGv showing the presence of a choriocapillary blush. Postoperatively, stereoscopic color fundus photographs documented that the bed of the surgical excision was characterized by an absence of visible retinal pigment epithelial (RPE) pigmentation in all eyes. Stereoscopic FA of the excision bed revealed choriocapillary hypofluorescence with visible dye perfusion in the underlying medium and large choroidal vessels in all eyes. SLO-ICGv of the excision bed disclosed the presence of perfused medium and large choroidal vessels, but a marked choroidal hypofluorescence with loss of the choriocapillary and small choroidal vascular filling within the excision bed in eleven of the twelve eyes. CONCLUSION: Our results indicate that both choriocapillary and small choroidal vascular filling is frequently abnormal or absent in the bed of surgically excised subfoveal neovascular membranes in ARMD. This finding, which may represent either pathologic or iatrogenic choriocapillary and small choroidal vascular atrophy or occlusion with preservation of perfusion in the underlying medium and large choroidal vessels, may influence structural and visual recovery after submacular surgery for ARMD, despite RPE transplantation or regeneration.

Aged↗

Characterization of eight excision plasmids of Pseudomonas syringae pv. phaseolicola.

Pseudomonas syringae pv. phaseolicola strain LR719 contains a 150 kilobase pair (kb) plasmid pMC7105, stably integrated into its chromosome. Occasionally, single colony isolates of this strain contain an excision plasmid. Eight unique excision plasmids were selected and characterized by BamHI restriction endonuclease and blot hybridization analyses. These plasmids ranged in size from 35 to 270 kb; the largest contained approximately 130 kb of chromosomal DNA sequences. Restriction maps of pMC7105 were developed to deduce the site of integration and to identify the fragments in which recombination occurred to produce each excision plasmid. The eight excision plasmids were arranged into five classes based on the sites where excision occurs. A 20 kb region of pMC7105, which includes BamHI fragment 9 and portions of adjacent fragments, is present in all excision plasmids and thought to contain the origin of replication. The site of integration on pMC7105 maps within BamHI fragment 8. This fragment shows homology with seven other BamHI fragments of pMC7105 and with five chromosomal fragments identified among the excision plasmids. The data strongly suggest that the integration of pMC7105 may have occurred at a repetitive sequence present on the chromosome and on the plasmid.

Cloning, Molecular↗

Effects of radiation on the survival of excision-defective cells from Drosophila melanogaster.

The effect of various doses of ultraviolet light and ionizing radiation on the survival of excision-defective Drosophila cells has been determined by cloning treated and untreated cells in agarose. Although excision-defective cells survive moderate amounts of DNA damage, they display a severe hypersensitivity to both types of radiation relative to excision-proficient cells. Exposure of ultraviolet-irradiated cells to fluorescent light results in a reduction of the density of pyrimidine dimers in cellular DNA and a 10-to 20-fold increase in survival. Parallel analysis of dimer density and survival, however, suggests that much of the lethal effect of ultraviolet light is due to nondimer damage. Cell proliferation was monitored in both excision-proficient and excision-defective cells exposed to doses of ultraviolet light that reduced survival by 90%. Under these conditions excision-proficient cells displayed exponential growth whereas excision-defective cells exhibited no cell proliferation for 12 days.

Animals↗

Calibrated alar base excision: a 20-year experience.

Conflicting guidelines for excisions about the alar base led us to develop calibrated alar base excision, a modification of Weir's approach. In approximately 20% of 1500 rhinoplasties this technique was utilized as a final step. Of these patients, 95% had lateral wall excess ("tall nostrils"), 2% had nostril floor excess ("wide nostrils"), 2% had a combination of these ("tall-wide nostrils"), and 1% had thick nostril rims. Lateral wall excess length is corrected by a truncated crescent excision of the lateral wall above the alar crease. Nasal floor excess is improved by an excision of the nasal sill. Combination noses (e.g., tall-wide) are approached with a combination alar base excision. Finally, noses with thick rims are improved with diamond excision. Closure of the excision is accomplished with fine simple external sutures. Electrocautery is unnecessary and deep sutures are utilized only in wide noses. Few complications were noted. Benefits of this approach include straightforward surgical guidelines, a natural-appearing correction, avoidance of notching or obvious scarring, and it is quick and simple.

Evaluation Studies as Topic↗

High-dose preoperative radiation and full-thickness local excision. A new option for patients with select cancers of the rectum.

Faced with the responsibility of treating patients with invasive distal rectal cancer who were medically unacceptable for the indicated radical surgery, a prospective study was initiated in which high dose preoperative radiation and full-thickness local excision were used. High dose preoperative radiation permitted full-thickness local excision of select cancers, which, by conventional standards, otherwise would have required radical surgery and permanent colostomy. Feasibility was measured on the basis of safety of the technique, control of the cancer, and the quality of anal sphincter function expected. Patients were selected initially because of their predicted inability to tolerate radical surgery, but indications were broadened to include those whose tumors had completely disappeared after irradiation. From 1984 to 1988, 20 patients underwent 21 operative procedures for cancers located between 0 and 7 cm from the anorectal ring. This report is concerned with the 14 patients of this group who were observed for a minimum of 24 months. High-dose preoperative radiation was administered for a total dose of 4500 cGy. Excision and repair were performed 4 to 6 weeks after completion of radiation therapy. Full-thickness disc or hemicircumferential excision was accomplished by transanal, transsphincteric, and transsacral techniques, which included, in several instances, excision of the sphincter mechanism and perineal body, and/or the vaginal wall. Full-thickness local excision after high-dose radiation therapy for rectal cancers has never been reported. Follow-up observation ranged from 24 to 48 months with a median of 31 months. Rectal reservoir function and sphincter control were good in 13 patients. Local recurrence developed in three patients (21 percent), two of whom had postradiation therapy B2 mucinous cancers. Three-year actuarial rate of local recurrence is 23 percent. One (7 percent) patient died of recurrent disease. Actuarial Kaplan-Meier survival at 3 years is 61 percent. Based on the results of this small, select patient group, high-dose radiation therapy followed by full-thickness local excision appears to be a reasonable option for patients who cannot tolerate radical surgery. This bimodal approach also may serve as an option for those who are good medical risks, but for whom sphincter preservation is at stake, and to whom radical surgery offers limited benefits.

Actuarial Analysis↗

Accuracy of AJCC staging for breast cancer patients undergoing re-excision for positive margins. American Joint Committee on Cancer.

BACKGROUND: The current AJCC protocol for breast cancer staging does not include additional tumor found at the time of re-excision in the calculation of tumor size. We hypothesize that the AJCC protocol may result in understaging and undertreatment of breast cancer patients who have additional tumor found at re-excision. METHODS: In a retrospective chart review of breast cancer patients, patients with tumor present at re-excision for positive margins were placed in group 1 (n=72); patients with no tumor present at re-excision, or who underwent a single, negative margin procedure were placed in group 2 (n=147). RESULTS: Patients in group 1 had a higher risk of nodal metastases when compared to patients in group 2. Mean tumor size did not differ significantly between the subgroups. Positive re-excision was strongly associated with lymph node metastases on multivariate analysis after correction for age, grade, stage, and lymphatic invasion (odds ratio=3.13, 95% CI=1.58 6.18, P=.0011). CONCLUSIONS: Current AJCC guidelines may result in undertreatment of breast cancer patients with positive re-excisions. The presence of additional tumor at the time of re-excision should be considered when determining the need for systemic therapy, and may be relevant in determining T stage.

Breast Neoplasms↗

Bile infection contributes to intrahepatic calculi formation after excision of choledochal cysts.

Intrahepatic calculi complicate choledochal cysts in 7-8% of patients. Although congenital stenoses and dilatation of the intrahepatic bile ducts are considered responsible for calculi formation, intrahepatic calculi are usually formed after cyst excision. In this study, bile specimens from patients with choledochal cysts were cultured for bacteria. Results were retrospectively analyzed among the following groups: the primary excision group, consisting of 97 patients undergoing cyst excision as a primary treatment (mean age 5.0 years), the internal drainage group, consisting of 13 patients who had previous cyst-enterostomy at cyst excision (mean age 20.2 years); and the hepatolithiasis group, consisting of 12 patients with postoperative hepatolithiasis (mean age 24.2 years). Bacteria were present in the bile of 10 patients (76.9%) in the internal drainage group and in all patients (100%) in the hepatolithiasis group, but present in only 17 patients (17.5%) in the primary excision group (p<0.01). Polymicrobial infection with Gram-negative enterobacteria such as Escherichia coli and Klebsiella species was predominant in the internal drainage and hepatolithiasis groups, while nonenteric bacteria were found in the primary excision group. Bile infection through bilioenterostomy may play an important role in intrahepatic calculus formation after excision of a choledochal cyst.

Adolescent↗

The pathological assessment of mesorectal excision: implications for further treatment and quality management.

BACKGROUND AND AIMS: Most clinical practice guidelines today recommend total mesorectal excision (TME) for carcinoma of the middle and lower rectal thirds and partial mesorectal excision (PME) for the upper rectal third. However, these procedures may not always fulfill the oncological requirements. The pathological examination of resected rectal carcinomas should always include a visual assessment of the mesorectal excision to ensure oncological adequacy and appropriate quality. The clinical practice guideline of the German Cancer Society recommends reporting of the distal extent of mesorectal excision (total or partial without coning) and the excision in an inviolate fascial envelope. PATIENTS AND METHODS: Reporting schemas of assessment and documentation for daily use and for studies are presented. RESULTS: Careful macroscopic evaluation of the resection specimen should be standardized. This may be supplemented by stain marking after postoperative filling the inferior mesenteric or superior rectal artery with ink or methylene blue solution. Photodocumentation is highly desirable. The pathological assessment of adequacy of mesorectal excision should be taken into account in selection for adjuvant radiotherapy. Objective macro- and microscopic assessment of mesorectal excision by pathologists is essential for quality management throughout patient care and in clinical trials.

Carcinoma↗

Bile duct cancer developed after cyst excision for choledochal cyst.

Oncogenesis after cyst excision for choledochal cyst and suitable surgical procedures for this operation are discussed. The clinical data of 23 patients with cancer of the biliary tree after excision of choledochal cyst reported in the English-language and Japanese literature were reviewed, and data for 1353 Japanese patients with choledochal cyst and/or pancreaticobiliary malunion were analyzed. In the 23 patients reported in the literature, age at cyst excision ranged from 1 to 55 years (average, 23.0 +/- 13.7 years), and cancers were detected at age 18-60 years (average, 32.1 +/- 12.2 years), with intervals between cyst excision and cancer detection of 1-19 years (average, 9.0 +/- 5.5 years). Sites of cancer development were: intrahepatic, six; anastomotic, eight; hepatic side residual cyst, three; and the intrapancreatic duct, six. In the Japanese patients with choledochal cyst and/or pancreaticobiliary malunion, the incidence of cancer associated with primary choledochal cyst and/or pancreaticobiliary malunion was 16.2% (219/1353). The incidence of cancer development after cyst excision in this population, of whom 1291/1353 underwent surgery, was assumed to be 0. 7%. Nearly half of the 23 patients in the literature had undergone inadequate cyst excision. Oncogenesis of cancers after cyst excision is possibly different from that of choledochal cysts.

Adolescent↗

Partial excision of infected fistula results in increased patency at the cost of increased risk of recurrent infection.

Reliable vascular access is often an issue of ongoing frustration for those requiring dialysis. Synthetic arteriovenous fistulae (SAVF) have been widely used to provide vascular access; however, the risk of infection at the SAVF site is significant, especially because the SAVF is potentially exposed to pathogens on a regular basis due to the cannulation required for dialysis. Between 11 and 35% of all SAVF become infected and require surgical removal. The purpose of this investigation was to: (1) compare the risk of recurrent infection with complete versus partial excision of the infected SAVF (ISAVF) and (2) explore the risks and benefits of attempting to preserve patency of noninfected portions of ISAVF. In a retrospective review to determine the risk of recurrent infection after removal of ISAVF, charts of 77 patients undergoing surgery for the removal of an ISAVF from the arm were identified with 84 instances of excision of an ISAVF. Of the 84 ISAVF, 26 (31 %) were treated with complete excision (CE), 30 (35.7%) grafts were partially excised with blood flow restoration through a new interposed PTFE segment (PERF), and 28 (33.3%) grafts were partially excised with no flow restoration (PENF), leaving portions that were not grossly infected. Fourteen of 30 (46.7%) PERF grafts, 4/28 (14.3%) PENF, and 0/26 CE grafts developed further infection at the excision site. These differences were significant when comparing PERF to CE (p < 0.001) and PERF to PENF (p < 0.025), but no significance was found when comparing CE to PENF. Patency was significantly greater for the PERF group at 1 and 2 years than for both CE (p < 0.001) and PENF (p < 0.001). In conclusion, the data suggest that restoring blood flow to the remainder of a partially excised ISAVF significantly increases patency without necessitating catherer placement and a new hemoaccess site, but at the cost of significantly increased risk of recurrent infection.

Adult↗

A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment in Norway. A national audit.

INTRODUCTION: Rectal cancer surgery has been characterized by a high incidence of local recurrence, an occurrence which influences survival negatively. In Norway there was a growing recognition that local recurrence rates were related to surgeon performance and that surgeons applying a standardized surgical technique in the form of total mesorectal excision could achieve better results. This contrasts with the prevailing argument voiced by many opinion leaders that local recurrence rates and possibly survival rates can only be improved by adjuvant or neoadjuvant treatment strategies. The Norwegian Rectal Cancer Project-initiated in 1993-aimed at improving the outcome of patients with rectal cancer by implementing total mesorectal excision as the standard rectal resection technique. METHODS: This observational national cohort study covers all new patients (3,319) with rectal cancer from a population of 4.5 million treated between November 1993 and August 1997. The main outcome measures were local recurrence, survival, and postoperative mortality and morbidity rates. The technique of total mesorectal excision was compared with conventional surgery. RESULTS: The proportion of patients undergoing total mesorectal excision was 78 percent in 1994, increasing to 92 percent in 1997. The observed local recurrence rate for patients undergoing a curative resection was 6 percent in the group treated by total mesorectal excision and 12 percent in the conventional surgery group. Four-year survival rate was 73 percent after total mesorectal excision and 60 percent after conventional surgery. Postoperative mortality rate was 3 percent and the anastomotic dehiscence rate was 10 percent. Radiotherapy was given to 5 percent and chemotherapy to 3 percent of the patients in the curative resection group. CONCLUSION: A refinement of the surgical resection technique for rectal cancer can be achieved on a national level, the technique of total mesorectal excision can be widely distributed, and surgery alone can give good results.

Adolescent↗

Factors affecting circumferential resection margin involvement after rectal cancer excision.

PURPOSE: This study was designed to assess factors affecting rates of circumferential resection margin involvement after rectal cancer excision, the association between circumferential resection margin involvement rates for patients undergoing anterior resection and abdominoperineal excision within the same unit, and trends in outcomes between units. METHODS: Data about patients undergoing rectal cancer excision between 2000 and 2003 were extracted from the Association of Coloproctology of Great Britain and Ireland database. Multivariate logistic regression analysis was used to identify independent predictors of circumferential resection margin involvement. Pearson correlation coefficient was used to evaluate the association between circumferential resection margin involvement for anterior resection and abdominoperineal excision. RESULTS: A total of 1,430 patients satisfied the inclusion criteria. The circumferential resection margin involvement rate for anterior resection (n=794) was 6.7 percent, between hospital variability was 0 to 40 percent, and for abdominoperineal excision (n=521) was 17.6 percent, between hospital variability 0 to 100 percent. Independent predictors of circumferential resection margin involvement were T stage (P<0.001), nodal involvement (P=0.007), and operative procedure (P<0.001). Units with a high circumferential resection margin involvement rate for anterior resection also had a high circumferential resection margin involvement rate for abdominoperineal excision (Pearson correlation=0.349; P=0.01). CONCLUSIONS: Circumferential resection margin involvement is more common in lymph-node-positive tumors and is more common after abdominoperineal excision compared with anterior resection. This relationship was consistent across units irrespective of their individual circumferential resection margin involvement rates.

Aged↗

Self-excision of the antibiotic resistance gene nptII using a heat inducible Cre-loxP system from transgenic potato.

Resistance to antibiotics mediated by selectable marker genes remains a powerful selection tool for transgenic event production. However, regulatory agencies and consumer concerns favor these to be eliminated from food crops. Several excision systems exist but none have been optimized or shown to be functional for clonally propagated crops. The excision of the nptII gene conferring resistance to kanamycin has been achieved here using a gene construct based on a heat-inducible cre gene producing a recombinase that eliminates cre and nptII genes flanked by two loxP sites. First-generation regenerants with the Cre-loxP system were obtained by selection on kanamycin media. Following a heat treatment, second generation regenerants were screened for excision by PCR using nptII, cre, and T-DNA borders primers. Excision efficiency appeared to be at 4.7% depending on the heat treatment. The footprint of the excision was shown by sequencing between T-DNA borders to correspond to a perfect recombination event. Selectable marker-free sprouts were also obtained from tubers of transgenic events when submitted to similar heat treatment at 4% frequency. Spontaneous excision was not observed out of 196 regenerants from untreated transgenic explants. Biosafety concerns are minimized because the expression of cre gene driven by the hsp70 promoter of Drosophila melanogaster was remarkably low even under heat activation and no functional loxP site were found in published Solanum sequence database. A new plant transformation vector pCIP54/55 was developed including a multiple cloning site and the self-excision system which should be a useful tool not only for marker genes in potato but for any gene or sequence removal in any plant.

Anti-Bacterial Agents↗