Rate Of Sphincter-sparing Surgery Research Articles

Contemporary, national patterns of surgery after preoperative therapy for stage II/III rectal adenocarcinoma.

BACKGROUNDContemporary treatment of stage II/III rectal cancer combines chemotherapy, chemoradiation, and surgery, though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery (MIS) is debated. AIMTo describe patterns of surgical approach for stage II/III rectal cancer in relation to neoadjuvant therapies.METHODSA retrospective cohort was created using the National Cancer Database. Primary outcome was rate of sphincter-sparing surgery after neoadjuvant therapy. Secondary outcomes were surgical approach (open, laparoscopic, or robotic), surgical quality (R0 resection and 12+ lymph nodes), and overall survival. RESULTSA total of 38927 patients with clinical stage II or III rectal adenocarcinoma underwent surgical resection from 2010-2016. Clinical stage II patients had neoadjuvant chemoradiation less frequently compared to stage III (75.8% vs 84.7%, P < 0.001), but had similar rates of total neoadjuvant therapy (TNT) (27.0% vs 27.2%, P = 0.697). Overall rates of total mesorectal excision without sphincter preservation were similar between clinical stage II and III (30.0% vs 30.3%) and similar if preoperative treatment was chemoradiation (31.3%) or TNT (30.2%). Over the study period, proportion of cases approached laparoscopically increased from 24.9% to 32.5% and robotically 5.6% to 30.7% (P < 0.001). This cohort showed improved survival for MIS approaches compared to open surgery (laparoscopy HR 0.85, 95%CI 0.78-0.93, and robotic HR 0.82, 95%CI 0.73-0.92).CONCLUSIONSphincter preservation rates are similar across stage II and III rectal cancer, regardless of delivery of preoperative chemotherapy, chemoradiation, or both. At a national level, there is a shift to predominantly MIS approaches for rectal cancer, regardless of whether sphincter sparing procedure is performed.

Neoadjuvant tyrosine kinase inhibitors in rectal gastrointestinal stromal tumours: a provision for enhanced oncological and functional outcomes

BackgroundThe role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs.MethodsA retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared.ResultsPatients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1–3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group.ConclusionsNeoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.

Effect of combined neoadjuvant chemoradiation on overall survival for patients with locally advanced rectal cancer.

657 Background: Prospective randomized trials have demonstrated that neoadjuvant chemoradiation improves local control and results in a higher rate of sphincter-sparing surgery for patients with locally advanced rectal cancer. However, neoadjuvant therapy utilization and population-based outcomes are not well defined. Methods: Adults with stage II/III rectal adenocarcinoma within the National Cancer Data Base undergoing surgery between 2006-2012 were analyzed. Patients were grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only, or concomitant chemoradiation. Multivariable modeling was used to compare perioperative outcomes and overall survival between groups. Results: Among 32,978 patients included, 9,714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1,170 (3.5%) radiotherapy only, and 21,204 (64.3%) concomitant chemoradiation. 5-year overall survival among groups was 62%, 69%, 71%, and 74%, respectively. Compared to no therapy, chemotherapy or radiotherapy alone was not associated with any differences in perioperative or oncologic outcomes (all p &gt; 0.05). With adjustment for patient and disease characteristics, neoadjuvant chemoradiation was associated with a lower likelihood of margin positivity (OR 0.74, p &lt; 0.001), need for permanent colostomy (OR 0.77, 95% CI 0.70-0.85, p &lt; 0.001), 30-day mortality (OR 0.67, p = 0.003), and overall survival (HR 0.69, p &lt; 0.001). When compared to chemotherapy or radiotherapy alone, neoadjuvant chemoradiation was still associated with improved overall survival (vs. chemotherapy: HR 0.83, p = 0.04; vs. radiotherapy: HR 0.75, p &lt; 0.001). Conclusions: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter-preservation and survival for patients with locally advanced rectal cancer. Despite this finding, one third of patients with locally advanced rectal cancer are failing to receive this therapy in the United States.

Is There a Role for Adjuvant Chemotherapy in Rectal Cancer?

Adjuvant chemoradiotherapy trials demonstrated a reduction in local failure and an increase in survival of patients with locally advanced rectal cancer submitted to upfront surgery. The standard-of-care shifted to neoadjuvant chemoradiotherapy when the German Rectal Cancer Study Group Trial demonstrated the benefit of neoadjuvant compared to adjuvant fluoropyrimidine chemoradiotherapy in lower rates of local failure, lower toxicity in patients optimally resected with total mesorectal excision (TME), and higher rate of sphincter-sparing surgery. Overall survival (OS) was equivalent in both arms. The benefit of adjuvant chemotherapy after preoperative chemoradiotherapy has not been clearly demonstrated in randomized trials. This review will discuss the role of fluoropyrimidine-based and oxaliplatin-based adjuvant chemotherapy in patients treated with neoadjuvant chemoradiotherapy.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone

Purpose: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer.Methods: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60 min. Total mesorectal excision was performed routinely.Results: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n = 40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8 cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p = 0.077).Conclusion: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.

Rates of pathologic complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with or without regional pelvic hyperthermia for locally advanced rectal cancer.

622 Background: Regional pelvic hyperthermia is frequently added to neoadjuvant radiochemotherapy for locally advanced rectal cancer. The present retrospective study is the first to evaluate the impact of hyperthermia on rates of complete pathologic response and sphincter-sparing surgery in the context of a standard up-to-date neoadjuvant radiochemotherapy scheme. Methods: Between 2007 and 2010, 85 consecutive patients with locally advanced cancer (cT3, cT4, cN+) of the middle and lower rectum received neoadjuvant radiochemotherapy at our institution. 45 of 85 patients (“RCT group”) received standard treatment consisting of radiotherapy to the pelvis with 5040 cGy in 28 fractions of 180 cGy and 5-fluorouracil as a continuous infusion with 1000 mg/m² over 120 hours during the first and fifth week of treatment. 40 of 85 patients (“HRCT group”) received the same treatment with at least four treatments of weekly regional hyperthermia. Target temperature was 40.5°C for at least 60 minutes. Total mesorectal excision was routinely performed. Results: No significant difference in the distribution of age, gender, clinical stage and tumor grade was observed between both groups. Complete pathologic response was seen in 6.7% of patients in the RCT group and 22% of patients in the HRCT group (p=0.034). Overall rates of sphincter-sparing surgery were 64% in the RCT group and 65% in HRCT. However for deep seated tumors located within 4 cm of the anal verge (based on initial staging), sphincter sparing surgery was achieved in only 11.1% of patients in the RCT group but 35.7% of patients in the HRCT group (p = 0.19). Conclusions: The addition of regional hyperthermia to neoadjuvant radiochemotherapy significantly increases the rate of complete pathologic response, with a tendency towards higher rates of sphincter-sparing surgery for deep seated tumors.

Can Performance of Sphincter-Sparing Surgery Serve as an Outcome Measure for Rectal Cancer?

In the appropriate clinical scenario, sphincter-sparing surgery is a marker of high-quality surgical care for rectal cancer. Improvements in anesthesia, medical care, surgical technique, bowel stapling devices, and better understanding of the pathophysiology of rectal cancer have led to expanding use of sphincter-sparing surgery in rectal cancer treatment. Despite an increased interest in sphincter-sparing surgery techniques for resectable rectal cancers in the past two decades, recent national trends in sphincter preservation indicate that there has been no net change in the use of this technique. Although it is not entirely clear why national sphincter salvage rates remain lower than those reported by “Centers of Excellence,” further research is needed to better delineate the modifiable factors that contribute to low rates of sphincter-sparing surgery. Future improvements in rectal cancer surgery can be achieved with a concerted effort by clinicians at the local or societal level.

Improved Rate of Sphincter Sparing Surgery Following Preoperative Chemoradiotherapy for Rectal Cancer With 5-FU/Oxaliplatin (5FU/OX) Compared to 5-Fluorouracil (5-FU) Alone

Improved Rate of Sphincter Sparing Surgery Following Preoperative Chemoradiotherapy for Rectal Cancer With 5-FU/Oxaliplatin (5FU/OX) Compared to 5-Fluorouracil (5-FU) Alone

Early analysis of toxicity and surgery in patients treated with cetuximab single agent followed by 5-fu, cetuximab and pelvic radiotherapy as neo-adjuvant treatment for operable, locally advanced rectal cancer (rc)

14531 Background: Pre-operative chemo-radiotherapy in locally advanced RC has been used to improve local control and to facilitate sphincter-sparing surgery for distal tumors. Cetuximab, an anti EGFR monoclonal antibody, has proved efficacy in advanced colorectal cancer. Methods: Study design provided: 1) tumor biopsy to confirm diagnosis and to measure tumor biomarkers (EGFR, TS, p53, MAP kinase, Ki 67, p21, bcl-2; immunological cell profile at the tumor level: CD45RO, CD68, CD56 CD4+/CD25+, CD31, HLA-A, -B and -C), 2) Cetuximab single agent (400 mg/sqm loading dose, then 250 mg/sqm weekly) for 3 doses, 3) a second biopsy to evaluate tumor biomarkers, 4) Cetuximab 250 mg/sqm weekly plus 5FU (225 mg/sqm in continuous infusion) concomitantly with RT (50 Gy), 5) surgery. Tumor biomarkers are measured again on tumor specimen in non pCR patients (pts). 66 pts with resectable uT3/uT4 N0/+ RC will enter the study. Primary aim is: toxicity and activity (pathologic complete response). Secondary aim is: evaluation of biological parameters, rates of sphincter sparing surgery and disease free survival. Results: Up to now 29 pts are valuable for toxicity (M/F= 22/5; median age: 61; range: 35–74). Ultrasound staging at diagnosis is: uT3N0: 7; uT3N1: 20; uT4N1: 2. Four pts (14%) withdrew neo-adjuvant treatment after 1 administration of Cetuximab: 2 for hypersensitivity reactions (1 G3; 1 G4), 1 for progression and 1 for purulent arthritis. Twenty-two pts (75%) presented acne-like rash; treatment with Cetuximab was interrupted or reduced in 4 pts (14%): in 2 for acne-like rash grade 3 (NCI-CTC) and in 2 pts for refuse. Grade 1–2 gastro-intestinal toxicity (unrelated to Cetuximab) was observed in 13 pts (proctitis: 4; diarrhoea: 9); in 1 case: diarrhoea G4. Twenty pts are valuable for surgery: 18 pts (90%) underwent conservative surgery. Two pts (10%) experienced post-surgical complications: 1 anastomotic fistula and 1 colonic necrosis. Conclusions: Pre-operative treatment with 5FU, Cetuximab and pelvic RT is well tolerated and does not increase surgical complication rate. An update on efficacy data and biological markers evaluation will be presented at the meeting. No significant financial relationships to disclose.

The Status of Radical Proctectomy and Sphincter-Sparing Surgery in the United States

Worldwide, "centers of excellence" in rectal cancer surgery report high rates of anal sphincter-sparing surgery (70-90 percent) after proctectomy. The rate of sphincter-sparing surgery with reestablishment of intestinal continuity in the general population of the United Stares is unknown. We used data from the Nationwide Inpatient Sample, a 20 percent stratified random sample of patients admitted to hospitals in the United States. We identified patients with rectal cancer from 1988 through 2003 who underwent sphincter-sparing surgery with reestablishment of intestinal continuity or proctectomy with colostomy. To determine predictors of sphincter-sparing surgery with reestablishment of intestinal continuity, we constructed a multivariate model that analyzed patients' age, gender, race, insurance status, and income level. During our 16-year study period, radical extirpative procedures were performed in 41,631 patients: 16,510 (39.7 percent) sphincter-sparing surgery with reestablishment of intestinal continuity, and 25,121 (60.3 percent) sphincter-sacrificing procedures. The proportion of sphincter-sparing procedures increased from 26.9 percent in 1988 to 48.3 percent in 2003 (P < 0.001). There has been no significant change in the rate of sphincter-sparing surgery since 1999 (P = not significant). Logistic regression revealed that patients who were older, male, black, used Medicaid insurance, or lived in lower-income zip codes were less likely to have sphincter-sparing surgery with reestablishment of intestinal continuity (P < 0.001). Despite a significant increase in the rate of sphincter-sparing surgery with reestablishment of intestinal continuity, most radical resections for rectal cancer in hospitals in the United States result in a colostomy. Patients vulnerable to proctectomy without sphincter preservation were older, male, black, used Medicaid insurance, or lived in lower income zip codes.

Preoperative Tegafur Suppositories for Resectable Rectal Cancer: Phase II Trial

Preoperative radiochemotherapy for rectal cancer causes a high rate of moderate-to-severe toxicities and is associated with only moderate survival benefits. A simpler, safer, and more convenient treatment would be preferable. Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were piloted. A total of 129 patients with resectable rectal cancer were enrolled. The primary end points were pathologic response, adverse events, rate of sphincter-sparing surgery, recurrence, and survival. The total dose of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in 60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic leakage in 9 percent of cases. Pathologic responses were observed in 70 percent of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total dose that patients showing complete or two-thirds or more necrosis received was 42.8 +/- 6.4 g (P = 0.01) compared with 31.6 +/- 1.2 g administered to patients showing less than two-thirds necrosis. Adverse events were observed in 15.6 percent of patients overall, and Grade III or IV events were observed in 2.3 percent of patients. During a median follow-up of 48 months, distant metastasis occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent of patients. The four-year, disease-free and overall survival rates were 67.6 and 80.1 percent, respectively. Preoperative tegafur suppositories are associated with low toxicity and may lead to anal sphincter-sparing surgery with acceptable postoperative complications and favorable local and distal control.