Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Investigation of a Novel Decision Support Metric for Head and Neck Adaptive Radiation Therapy Using a Real-Time In Vivo Portal Dosimetry System.

In adaptive radiation therapy of head and neck cancer, any significant anatomical changes observed are used to adapt the treatment plan to maintain target coverage without elevating the risk of xerostomia. However, the additional resources required for adaptive radiation therapy pose a challenge for broad-based implementation. It is hypothesized that a change in transit fluence is associated with volumetric change in the vicinity of the target and therefore can be used as a decision support metric for adaptive radiation therapy. This was evaluated by comparing the fluence with volumetric changes in 12 patients. Transit fluence was measured by an in vivo portal dosimetry system. Weekly cone beam computed tomography was used to determine volume change in the rectangular region of interest from condyloid process to C6. The integrated transit fluence through the region of interest on the day of the cone beam computed tomography scan was calculated with the first treatment as the baseline. The correlation between fluence change and volume change was determined. A logistic regression model was also used to associate the 5% region of interest volume reduction replanning trigger point and the fluence change. The model was assessed by a chi-square test. The area under the receiver-operating characteristic curve was also determined. A total of 46 pairs of measurements were obtained. The correlation between fluence and volumetric changes was found to be -0.776 (P value <.001). The negative correlation is attributed to the increase in the photon fluence transport resulting from the volume reduction. The chi-square of the logistic regression was found to be 17.4 (P value <.001). The area under the receiver-operating characteristic curve was found to be 0.88. Results indicate the change in transit fluence, which can be measured without consuming clinical resources or requiring additional time in the treatment room, can be used as a decision support metric for adaptive therapy.

Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients.

BACKGROUND: De novo malignancy is not uncommon after liver transplantation (LT). Gastric cancer is one of the most common malignancies in both the Korean general population and LT recipients, and colorectal cancer prevalence is gradually increasing. METHODS: Among 3690 adult recipients who underwent LT from January 1999 and December 2013, the screening patterns and prognosis of 26 cases of gastric cancer and 22 cases of colorectal cancer were analyzed. RESULTS: For gastric cancer, the mean patient age was 54.6 ± 6.2 years at LT and 59.5 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 60.2 ± 29.8 months. Patients were divided into regular (n = 18) and non-regular (n = 8) screening groups, with early cancer found in 14 and 0 patients; their 2-year survival rates after cancer diagnosis were 93.1% and 33.3% (P = .006), respectively. Endoscopic resection was successfully performed in 8 patients, all in the regular screening group. For colorectal cancer, the mean patient age was 53.3 ± 6.1 years at LT and 58.1 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 54.3 ± 38.0 months. Patients were divided into regular (n = 19) and non-regular (n = 3) screening groups, with early cancer found in 12 and 0 patients; their 2-year survival rates after cancer diagnosis of 92.3% and 33.3% (P = .003), respectively. Endoscopic resection was successfully performed in 6 patients, all in the regular screening group. CONCLUSIONS: LT recipients are strongly advised to undergo regular screening studies for various de novo malignancies, especially cancers common in the general population. Regular endoscopic screening contributes to the timely detection of gastric and colorectal cancers, improving post-treatment survival outcomes.

Late anastomotic leakage after low anterior resection in rectal cancer patients: clinical characteristics and predisposing factors.

AIM: The purpose was to examine the clinical characteristics and predisposing factors of late anastomotic leakage following low anterior resection for rectal cancer. METHOD: We retrospectively evaluated the clinicopathological features of patients who experienced anastomotic leakage after low anterior resection for rectal cancer. Patients were divided into two groups according to the time to leakage: early leakage (within 30 days postoperatively) and late leakage (after 30 days postoperatively). Clinicopathological characteristics were compared between the two groups. RESULTS: Anastomotic leakage occurred in 141 patients. Anastomotic leakage was diagnosed at a median of 17 (range 0-886) days postoperatively; 85 (60.3%) and 56 (39.7%) were categorized as the early and late leakage groups, respectively. Radiotherapy (hazard ratio 5.007; 95% CI 2.208-11.354; P < 0.0001) was the only significant independent predisposing factor for late leakage. Diverting stoma did not protect against late leakage. The late leakage group more frequently had the fistula type (46.4% vs. 10.6%; P < 0.001) and less frequently needed laparotomy (55.4% vs. 78.8%; P = 0.001). The rate of long-term stoma over 1 year was greater in the late leakage than the early leakage group (51.8% vs. 29.4%; P = 0.009). CONCLUSION: Late anastomotic leakages that develop after 30 days following low anterior resection are not uncommon and may be associated with the use of radiotherapy. Late leakage should be a different entity from early leakage in terms of the type of leakage, methods of management and subsequent sequelae.

Prevalence and clinical significance of cellular and acellular mucin in patients with locally advanced mucinous rectal cancer who underwent preoperative chemoradiotherapy followed by radical surgery.

AIM: The frequent presence of acellular mucin in specimens showing pathological complete response to preoperative chemoradiotherapy (CRT) and the poor response to preoperative CRT in mucinous rectal cancer have been reported. However, the prevalence and prognostic significance of cellular and acellular mucin have not been evaluated in resected specimens from patients with mucinous rectal cancer who undergo preoperative CRT. METHOD: We retrospectively evaluated the clinicopathological features and prognostic significance of mucin in resected specimens from 59 consecutive patients with mucinous rectal cancer who underwent long-course CRT followed by resection between January 2000 and December 2009. Patients were categorized according to the presence of mucin, as identified by pathological analysis. The clinicopathological findings and oncological results were compared. RESULTS: Mucin was identified in 25 of 59 patients with mucinous rectal cancer (42.4%). Mucin was more frequent in men (hazard ratio = 23.94, 95% confidence interval = 1.875-305.504, P = 0.015) and in specimens showing a good tumour response grade (hazard ratio = 64.26, 95% confidence interval = 6.940-595.045, P < 0.001). With a median follow-up of 67.7 (range 8.6-133.2) months, the 5-year overall survival (60.7% without mucin vs 51.4% with mucin, P = 0.898) and disease-free survival (59.9% without mucin vs 56.9% with mucin, P = 0.813) did not differ between the groups. CONCLUSION: The presence of mucin in rectal cancer with mucinous differentiation after preoperative CRT and resection is associated with male gender and a good tumour response grade, without significant impact on oncological outcome.

The psychometric properties of the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) as a measure of autistic traits in a community sample of Singaporean infants and toddlers.

BACKGROUND: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. METHODS: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). RESULTS: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. CONCLUSIONS: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Clinical implications of mucinous components correlated with microsatellite instability in patients with colorectal cancer.

AIM: Colorectal cancer (CRC) with microsatellite instability (MSI) is characterized by frequent poor differentiation or mucinous histology. The purpose of this study was to evaluate the association of MSI with clinicopathological features and the oncological outcome in patients with a mucinous component. METHOD: CRC tissue samples were analysed for histology and MSI. Patients were grouped according to the mucinous content of the tumour, as follows: > 50%, mucinous adenocarcinoma (MA); ≤ 50%, adenocarcinoma with mucinous component (AMC); none, nonmucinous adenocarcinoma (NMA). Clinicopathological parameters and survival were compared between patient groups. RESULTS: Of 2025 patients, 84 (4%) had MA and 124 (6%) had AMC. In addition, 202 (10%) had MSI. Patients with MA and AMC tended to have a younger age of onset, right-colon predilection, large-sized tumour and high frequency of MSI compared with those with NMA (P < 0.001). MA and AMC patients with MSI showed a trend towards right-colon predilection and infrequent lymph-node metastasis compared with those with microsatellite stability (MSS; P = 0.005-0.03). There were no survival differences between the three groups, but patients with MSI-MA demonstrated lower 4-year recurrence and better overall survival rates than those with MSS-MA (P = 0.018 and P = 0.046, respectively). CONCLUSION: Clinicopathological features of AMC and MA were similar and closely associated with MSI status. Although the prognoses of AMC and MA were no different from that of NMA, survival of patients with an MSI-MA tumour was significantly better than for those with MSS-MA tumours.

Childhood intermittent exotropia from a different angle: does severity affect quality of life?

BACKGROUND: Few studies have explored the relationship between health-related quality of life (HRQOL) and clinical severity of childhood intermittent exotropia (IXT) measured by angle of deviation, control and stereoacuity. METHODS: Sixty-eight consecutive children aged 5-17 years with childhood IXT who attended the paediatric eye clinic were recruited. One accompanying parent was recruited concurrently. Child, parent and proxy (parent about the child) HRQOL was measured using the IXT questionnaire (IXTQ). Angle of deviation, control and stereoacuity of the children were measured and correlated with IXTQ scores using Spearman's correlation coefficient and paired t test for differences in child and proxy IXTQ mean scores. RESULTS: The mean age of the children was 9.0±2.6 years. Child HRQOL was not correlated to any strabismus measurements. Poorer parent HRQOL was correlated with poorer distance control (surgery subscale, r=-0.24 p=0.049), poorer near control (surgery subscale, r=-0.30, p=0.013), poorer office near control (mean, r=-0.24, p=0.047; psychological subscale, r=-0.27, p=0.025; surgery subscale, r=-0.28, p=0.020) and larger angle of deviation (psychological subscale, r=-0.30, p=0.013). Poorer proxy HRQOL was correlated with poorer home control (r=-0.28, p=0.022) and larger angle of deviation (r=0.33, p=0.0061). CONCLUSIONS: It is difficult to predict child HRQOL based on clinical measurements. However, parent HRQOL tends to be worse with poorer control and larger angle of deviation. Perhaps HRQOL should be routinely assessed in clinic alongside clinical measurements in order to tailor management appropriately.

Nomogram to predict ypN status after chemoradiation in patients with locally advanced rectal cancer.

BACKGROUND: Pelvic lymph node (LN) status after preoperative chemoradiotherapy (CRT) is an important indicator of oncologic outcome in patients with locally advanced rectal cancer. The purpose of this study was to develop a nomogram to predict LN status after preoperative CRT in locally advanced rectal cancer patients. METHODS: The nomogram was developed in a training cohort (n=891) using logistic regression analyses and validated in a validation cohort (n=258) from a prospectively registered tumour registry at Asan Medical Center. The model was internally and externally validated for discrimination and calibration using bootstrap resampling. Model performance was evaluated by the concordance index (c-index) and calibration curve. RESULTS: Pretreatment ypT stage, patient age, preCRT tumour differentiation, cN stage, lymphovascular invasion, and perineural invasion were reliable predictors of LN metastasis after preoperative CRT. The nomogram developed using these parameters had c-indices of 0.81 (training) and 0.77 (validation). The calibration plot suggested good agreement between actual and nomogram-predicted LN status after preoperative CRT. CONCLUSIONS: This nomogram improves prediction of LN status after preoperative CRT in patients with locally advanced rectal cancer. It will be useful for counselling patients as well as for the design and stratification of patients in clinical trials.

Validation of the seventh edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging in patients with stage II and stage III colorectal carcinoma: analysis of 2511 cases from a medical centre in Korea.

AIM: The sixth and seventh editions of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system for patients with stage II and stage III colorectal carcinoma (AJCC-6 and AJCC-7) were compared. METHOD: Between 2000 and 2007, 2511 stage II/III colorectal carcinoma patients received primary surgical resection at the Asan Medical Center (Seoul, Korea). All patients were staged using AJCC-6 and AJCC-7 TNM systems. Patients with synchronous or other cancers, those given preoperative chemotherapy or radiotherapy and those in whom fewer than 12 lymph nodes were resected, were excluded. Overall survival (OS) and disease-free survival (DFS) were compared. RESULTS: Of 2511 patients, 255 (10.2%) had different stages in the AJCC-6 and AJCC-7. For the AJCC-7, the 5-year OS by stage was 94.2% for stage IIA, 88.8% for stage IIB, 83.5% for stage IIC, 91.8% for stage IIIA, 81.8% for stage IIIB and 72.0% for stage IIIC. The OS and the DFS were not significantly different for the new substages IIB (n = 57) and IIC (n = 34) (P = 0.34 and P = 0.87, respectively). For the 187 patients with stage T3N2a cancer, the OS and the DFS were significantly different from stage IIIB other than T3N2a (P = 0.008 and P = 0.01, respectively) and there were no statistically significant differences in OS between the T3N2a group and the IIIC group (P = 0.46). CONCLUSION: The study indicates that AJCC-7 has better prognostic validity than AJCC-6 for staging of patients with stage II and stage III colorectal carcinoma.

Outcomes of colorectal anastomoses during pelvic exenteration for gynaecological malignancy.

BACKGROUND: Although pelvic exenteration is frequently indicated during surgery for gynaecological malignancy, performing a colorectal anastomosis remains contentious because of concern about leakage. This study evaluated the safety of performing a low colorectal anastomosis during pelvic exenteration for gynaecological malignancy. METHODS: Between April 2001 and December 2006, 145 consecutive patients underwent low colorectal anastomosis without (122) or with (23) a stoma after pelvic exenteration for advanced primary or recurrent gynaecological malignancy. Subjects were assessed in terms of five patient-, four disease- and two surgery-related variables. The proportion of patients with each risk factor for leakage was found, and the rate of symptomatic anastomotic leakage was determined. RESULTS: The mean age of the patients was 53.5 (range 10-77) years and the most common diagnosis was ovarian cancer (77.9 per cent). The mean operating time was 453 (range 145-845) min and the mean blood loss was 1080 (range 110-10 500) ml; 95 patients (65.5 per cent) required a blood transfusion. Of the 145 patients, 81 (55.9 per cent) had patient-related, 94 (64.8 per cent) had disease-related and 67 (46.2 per cent) had surgery-related variables associated with a risk of leakage. Symptomatic anastomotic leakage developed in three patients (2.1 per cent). CONCLUSION: Although patients with gynaecological malignancy carry considerable risks associated with anastomotic leakage, carefully executed low colorectal anastomosis during pelvic exenteration was found to be safe.

The usefulness of preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for localization in laparoscopic colorectal surgery.

BACKGROUND: Laparoscopic surgery for colorectal neoplasm requires precise tumor localization. The authors have assessed the safety and efficacy of colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for tumor localization in laparoscopic colorectal surgery. METHODS: Between July 2004 and January 2007, 63 patients underwent colonoscopic tattooing using prepackaged sterile India ink before laparoscopic surgery of colorectal tumors. Patient medical records and operation videos were retrospectively assessed. RESULTS: Tattoos were visualized intraoperatively in 62 (98.4%) of the 63 patients, and colorectal tumors were accurately localized in 61 patients (96.8%). In one patient, the tattoo could not be detected, whereas in another patient, it was visualized but the serosal surface of the rectosigmoid colon was stained diffusely. Both of these patients underwent intraoperative colonoscopy. Localized leakages of ink were identified in six patients (9.5%) during surgery. However, five of these patients had no symptoms, and the sixth patient, who underwent polypectomy and tattooing simultaneously, felt mild chilling without fever or abdominal pain. CONCLUSIONS: Preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink is a safe and effective method for tumor localization in laparoscopic colorectal surgery.

Synchronous gastric cancer in primary sporadic colorectal cancer patients in Korea.

BACKGROUND AND AIMS: Colorectal cancer has been reported to be the malignancy most frequently associated with gastric cancer in Korea. The aim of this study was to define the frequency and clinical characteristics of synchronous gastric cancer detected at preoperative esophagogastroduodenoscopy (EGD) in colorectal cancer patients. MATERIALS AND METHODS: This prospective study analyzed the EGD results from 1,542 consecutive colorectal cancer patients who underwent surgery from January 2003 to December 2005 at the Center for Colorectal Cancer, National Cancer Center, Korea. RESULTS: Of the 1,542 cases, 1,155 (74.9%) underwent EGD at our center and 387 underwent EGD at other hospitals within 6 months before surgery. Of the 1,542 cases, synchronous gastric cancers were detected in 31 cases (2.0%). Of these 31 cases, 26 had early gastric cancer (EGC; 83.9%) and 5 had advanced gastric cancer. Ten (38.5%) of the 26 EGC cases were managed using endoscopic mucosal resection. Compared to colorectal cancer patients without synchronous gastric cancer, the group of patients with synchronous gastric cancer was older (65.5+/-9.6 vs 58.4+/-11.3 years, p=0.001) and had a greater proportion of males (77.4 vs 59.4%, p=0.043). CONCLUSION: This study found that 2% of Korean sporadic colorectal cancer patients had synchronous gastric cancer. A preoperative EGD for colorectal cancer patients is likely to greatly assist in the diagnosis of synchronous gastric cancer at an early stage and the implementation of appropriate minimally invasive treatment.

Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro.

Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and in vitro invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.

Pre-operative chemo-radiotherapy improves the sphincter preservation rate in patients with rectal cancer located within 3 cm of the anal verge.

AIMS: To evaluate whether pre-operative chemo-radiotherapy (CRT) improves the sphincter preservation rate for distal rectal cancers within 3 cm of the anal verge. METHODS: Between January 2001 and December 2004, 49 patients underwent surgery with or without pre-operative CRT for primary rectal adenocarcinoma within 3 cm of the anal verge. Clinical data were retrospectively reviewed, including stage workups, surgical records and pathology records to determine sphincter preservation rate and the factors influencing sphincter preservation. RESULTS: Of 49 patients with rectal tumours within 3 cm of the anal verge, 31 underwent pre-operative CRT followed by surgery (CRT group), and 18 underwent surgery alone (non-CRT group). Sphincter preservation was possible in 11 of 31 CRT patients, and only one of 18 non-CRT patients (p=0.036). The factors most influencing sphincter preservation were reduction in tumour size (p=0.005) and downstaging (p=0.001) following pre-operative CRT. CONCLUSION: We could observe that sphincter preservation was improved in CRT group with statistical significance when compared to non-CRT group in our study patients with rectal cancer within 3 cm of the anal verge.

Universal newborn hearing screening in Singapore: the need, implementation and challenges.

With about 1 in 1000 born with severe to profound hearing loss and about 5 in 1000 with lesser degrees of loss, congenital deafness is the commonest major birth defect. It is the recommended standard that hearing loss in newborns be detected by 3 months of age and intervention implemented by 6 months of age. Delayed detection and intervention may affect speech, language and psychosocial development, resulting in poor academic achievements. Universal newborn hearing screening (UNHS) is the only effective way of detecting all babies with hearing loss, within the recommended time frame. A survey in Singapore revealed that traditional childhood hearing screening programmes resulted in late detection (mean age, 20.8 months; range, 0 to 86 months) and late intervention (mean age, 42.4 months; range, 1 to 120 months). Increasingly, UNHS is becoming standard medical care in developed countries. In Singapore, UNHS has been implemented in all hospitals with obstetric services. Although a screening rate of more than 99% has been achieved in public hospitals, private hospitals have a screening rate of only about 77%. Parents' awareness and acceptance of early detection is still lacking, and this needs to be addressed by appropriate public education. Support from obstetricians and paediatricians will significantly contribute towards this objective. Effective programme management is essential; this includes the use of data management systems, the maintenance of a team of experienced screeners, and efficient coordination between screening and diagnostic services. Early detection of childhood deafness, together with early and effective intervention, maximises the chances of successful integration into mainstream education and society.

Changes in outcome with sphincter preserving surgery for rectal cancer in Korea, 1991-2000.

AIM: To report the clinical and oncological data of patients operated on for rectal cancers 3-5 cm from the AV over a 10 year period, including the Sphincter preservation (SP) rate. METHODS: We reviewed medical records of 304 patients with rectal cancers 3-5 cm from the AV who underwent surgical resection from January 1991 through December 2000. The 10 years were divided into three periods based on the introduction of new surgical techniques, specifically, ultralow anterior resection (ULAR) with double stapling in March 1994 and ULAR with coloanal anastomosis in April 1997. The rates of SP, complications and patient survival during these periods were compared. RESULTS: The SP rate increased significantly over the 10 years, from 16.4% in period I (January 1991-February 1994), to 53.0% in period II (March 1994-March 1997), to 86.5% in period III (April 1997-December 2000) (p<0.001). Over time, the age of the patients increased (p=0.004), the length of the distal resection margin became shorter (p=0.005), and the rate of lymph node metastasis increased (p=0.016). The factors significantly influencing SP were the period (p<0.001) and the distance from the AV (p<0.001). Over time, morbidity did not increase, and overall and disease free survival rates did not decrease. In contrast, the overall survival of N2 cases significantly increased over time (p=0.0492). CONCLUSION: Over 10 years, the SP rate in rectal cancers 3-5 cm from the AV was significantly increased by the introduction of the double stapling and coloanal anastomosis techniques. These surgical methods, however, had no effect on morbidity, disease free survival and overall survival rates.