Long-Term Outcome of Patients with Complete Pathologic Response after Neoadjuvant Chemoradiation for cT3 Rectal Cancer: Implications for Local Excision Surgical Strategies

Background

Neoadjuvant chemoradiotherapy (CRT) followed by radical surgery including total mesorectal excision (TME) is standard treatment in patients with locally advanced rectal cancer. Emerging data indicate that patients with complete pathologic response (ypCR) after CRT have favorable outcome, suggesting the possibility of less invasive surgical treatment. We analyzed long-term outcome of cT3 rectal cancer treated by neoadjuvant CRT in relation to ypCR and type of surgery.

Methods

The study population comprised 139 patients (93 men, 46 women; median age 62 years) with cT3N0–1M0 mid and distal rectal adenocarcinoma treated by CRT and surgery (110 TME and 29 local excision) at our institution between 1996 and 2008. At pathology, ypCR was defined as no residual cancer cells in the primary tumor.

Results

Tumors of 42 patients (30.2%) were classified as ypCR. After a median follow-up of 55.4 months, comparing patients with ypCR to patients with no ypCR, 5-year disease-specific survival was 95.8% versus 78.0% (P = 0.004), and 5-year disease-free survival was 90.1% vs. 64.0% (P = 0.004). In patients with ypCR, no statistically significant outcome difference was observed between TME and local excision. In patients treated by local excision, comparing patients with ypCR to patients with no ypCR, 5-year disease-free survival was 100% vs. 65.5% (P = 0.024), and 5-year local recurrence-free survival was 92.9% vs. 66.7% (P = 0.047).

Conclusions

With retrospective analysis limitations, our data confirm favorable long-term outcome of cT3 rectal cancer with ypCR after CRT and warrant clinical trials exploring local excision surgical strategies.     

Comparison of tumor recurrence between laparoscopic total mesorectal excision with sphincter preservation and laparoscopic abdominoperineal resection for low rectal cancer

Background

By traditional open surgery, the tumor recurrence rate of total mesorectal excision with sphincter-preserving procedure was lower than that of abdominoperineal resection (APR) for the treatment of low rectal cancer. The present study aimed to rescrutinize whether the same conclusion can be drawn when both surgical procedures are performed laparoscopically.

Methods

We retrospectively reviewed the prospectively recorded clinicopathologic data of 344 consecutive patients with low rectal cancer, in which 170 patients underwent preoperative chemoradiotherapy followed by laparoscopic total mesorectal excision (TME), whereas 174 patients underwent laparoscopic TME directly without chemoradiotherapy. Such patients were further stratified according to the pathologic tumor, node, metastasis stage (stage II or III disease) and surgical strategy (APR or sphincter-preserving operation [SPO]). The surgical procedures are presented in supplemental videos. The disease-free survival, recurrence patterns, and functional recovery of patient groups stratified as appropriate were compared.

Results

In patients who received preoperative chemoradiotherapy, the estimated recurrence rate were similar between laparoscopic TME with SPO and laparoscopic APR with 10.6 %, 7 of 66, versus 18.5 %, 5 of 27, in stage II disease (p = 0.811, log-rank test); and 19.3 %, 11 of 57, versus 20 %, 4 of 20, in stage III disease (p = 0.980). In patients without preoperative chemoradiotherapy, the recurrence rate was significantly higher in laparoscopic APR than in the laparoscopic TME with SPO group of patients with stage III disease (45 %, 9 of 20, vs. 19.3 %, 16 of 83, p = 0.025), whereas the recurrence rate of the two procedures was similar (21.4 %, 3 of 14, vs. 17.5 %, 10 of 57, p = 0.702) in stage II disease.

Conclusions

When low rectal cancer was operated on by laparoscopic approach, the poorer prognosis of APR compared to SPO was only observed in stage III patients without preoperative chemoradiotherapy.     

Selective Lateral Pelvic Lymph Node Dissection in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy Based on Pretreatment Imaging

Background

The significance of lateral pelvic lymph node (LPLN) metastasis in advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) remains unclear. The objective of this study was to evaluate the outcomes of selective LPLN dissection (LPLD) based on the pretreatment imaging in patients with advanced low rectal cancer treated with preoperative CRT.

Methods

We reviewed 127 consecutive patients with clinical stage II–III low rectal cancer below the peritoneal reflection who underwent preoperative CRT and curative resection. LPLD was performed in patients with suspected LPLN metastasis based on MDCT or MRI before CRT (LPLD group, N = 38), and only total mesorectal excision (TME) was performed in patients without suspected LPLN metastasis (TME group, N = 89). Clinical characteristics and the oncological outcome were compared between groups.

Results

The median tumor-to-anal verge distance was 40 mm in both groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3 patients (3.4 %) in the TME group and in none (0 %) of the LPLD group. Multivariate analysis showed that only ypN was an independent prognostic factor for relapse-free survival (RFS), but LPLN metastasis was not associated with poor RFS.

Conclusions

The incidence of LPLN metastasis is high even after preoperative CRT, and LPLD might improve local control and survival of patients with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.     

What is the Incidence of Metastatic Lymph Node Involvement After Significant Pathologic Response of Primary Tumor Following Neoadjuvant Treatment for Locally Advanced Rectal Cancer?

Background

In locally advanced rectal cancer (LARC) patients, major response to neoadjuvant radiotherapy (NR) has been associated with favorable long-term outcomes. Positive pathologic nodal status was recently proven to be associated with poor prognosis even after total regression of primary tumor (ypT0). The aim of this study was to evaluate the rate of lymph node (LN) involvement in patients with complete (ypT0) or major (TRG1: very few viable tumor cells) response.

Methods

Included were patients with complete or major response after radiotherapy followed by surgery and histological examination of the whole specimen.

Results

From 1996 to 2010, 245 patients with LARC were treated by NR. We collected clinical data for 53 patients (21.6 %) with ypT0 (n = 26, 49 %) or TRG1 (n = 27, 51 %) response. Sphincter-preserving surgery was performed in 40 patients (75 %). Overall, nine patients (16.9 %) presented LN involvement: 2 (7.7 %) in the ypT0 group and 7 (25.9 %) in the TRG1 group (NS). Patients with ypT3 tumors had significantly more invaded LN than patients with ypT1–T2 tumors (6 of 13 [46 %] vs 1 of 14 [7 %], p = .032). After median follow-up of 30 months (range, 1–160 months), 5-year disease-free and overall survivals were 88.2 and 89.0 %, respectively.

Conclusions

There was a clear cutoff between patients with ypT0–T2 (3 of 40, 7.5 %) and ypT3 (6 of 13, 46 %) concerning the incidence of metastatic LN in patients achieving pathologic complete or major response after NR. In patients with good clinical response, local full-thickness resection of the residual tumor could be a first step, followed by standard rectal resection in cases of ypT3.     

Clinically-Staged T3N0 Rectal Cancer: Is Preoperative Chemoradiotherapy the Optimal Treatment?

Background

Preoperative chemoradiotherapy has been widely adopted as the standard of care for stage II–III rectal cancers. However, patients with T3N0 lesions had been shown to have a better prognosis than other categories of locally advanced tumor. Thus, neoadjuvant chemoradiation is likely to be overtreatment in this subgroup of patients. Nevertheless, the low accuracy rate of preoperative staging techniques for detection of node-negative tumors does not allow to check this hypothesis. We analyzed a group of patients with cT3N0 low rectal cancer who underwent neoadjuvant chemoradiotherapy with the purpose of evaluating the incidence of metastatic nodes in the resected specimens.

Methods

Between January 2002 and February 2008, 100 patients with low rectal cancer underwent clinical staging by means of endorectal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging. All patients received preoperative 5-fluorouracil-based chemoradiotherapy and surgical resection with curative aim.

Results

Of 100 patients with locally advanced rectal cancer, 32 were clinically staged as T3N0M0. Pathological analysis showed the presence of lymph node metastases in nine patients (28%) (node-positive group). In the remaining 23 cases, clinical N stage was confirmed at pathology (node-negative group). Node-positive and node-negative groups differ only in the number of ypT3 tumors (P < .01).

Conclusions

Our results indicate that immediate surgery for patients with cT3N0 rectal cancer represents an undertreatment risk in at least 28% of cases, making necessary the use of postoperative chemoradiotherapy. Preoperative chemoradiotherapy should be the therapy of choice on the grounds of the principle that overtreatment is less hazardous than undertreatment for cT3N0 rectal cancers.     

Evaluation of 18F-FDG-PET for Early Detection of Suboptimal Response of Rectal Cancer to Preoperative Chemoradiotherapy: A Prospective Analysis

Background

Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT.

Methods

A total of 27 prospectively accrued patients with locally advanced rectal cancer (T_3–4/N₁) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8–14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV_max, SUV_avg, and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis.

Results

Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV_max, SUV_avg, and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%.

Conclusions

In this pilot study, FDG-PET at 8–14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.     

What is the Significance of the Circumferential Margin in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy?

Background

The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.

Methods

Review of a single institution’s prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.

Results

The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and <0.001, respectively).

Conclusion

In this dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.     

Comparison of Magnetic Resonance Imaging and Histopathological Response to Chemoradiotherapy in Locally Advanced Rectal Cancer

Background

Magnetic resonance imaging (MRI) methods for chemoradiotherapy (CRT) response assessment of rectal cancer include posttreatment T staging (ymrT), tumor regression grading (mrTRG), volume reduction posttreatment, and modified RECIST measurement. We compared these methods in identifying good versus poor responders with the histopathological standards of T stage (ypT) and tumor regression grading (TRG).

Methods

A total of 86 patients underwent CRT in a prospective phase II trial for MRI-defined locally advanced rectal cancer. Two readers independently assessed MRIs for ymrT, mrTRG, volume change, and RECIST. Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression.

Results

A total of 83 patients had evaluable imaging, and 78 had final pathology (five did not undergo surgery). Of these, 34 patients had good response (ypT0-3a) and 44 had poor response (>ypT3a). Also, 27 patients had favorable pathologic TRG (predominant fibrosis) and 51 had unfavorable TRG (predominant tumor). Good mrTRG and ymr P?=?0.001) associated with favorable pathology odds ratio [OR]?=?16.11 (95?% confidence interval [95?% CI]: 3.36?C77.29) and 17.50 (95?% CI: 5.38?C56.89), respectively. RECIST measurements and volume reduction of >80?% showed an OR of 3.23 (95?% CI: 1.14?C9.17), 4.25 (95?% CI: 0.92?C15.45), respectively, for a good ypT score (P?=?0.028), but there was no association for histopathological TRG.

Conclusion

Favorable and unfavorable histopathology are predicted by both ymrT and mrTRG, and we recommend these parameters for post-treatment assessment of rectal cancers treated with CRT.     

Prognostic Implications of the Number of Retrieved Lymph Nodes of Patients with Rectal Cancer Treated with Preoperative Chemoradiotherapy

Background

The impact of the number of retrieved lymph nodes (LNs) on oncological outcomes in patients with rectal cancer remains unclear. This study was designed to evaluate the prognostic implications of the number of retrieved LNs in patients with rectal cancer receiving preoperative chemoradiotherapy (CRT).

Methods

The study cohort consisted of 859 patients with locally advanced (cT3-4 or cN+) mid to low rectal cancer that had been treated with preoperative CRT and radical resection between 2000 and 2009. Multivariate analysis and the Kaplan-Meier method were used to evaluate the influence of the number of retrieved LNs on disease-free survival (DFS).

Results

The median number of LNs retrieved from included patients was 13 (interquartile range [IQR] 9–17). Multivariate analysis confirmed the independent prognostic importance of the number of retrieved LNs on DFS (hazard ratio?=?0.97, 95 % confidence interval?=?0.95–0.99, p?=?0.029). The 3-year DFS rate in patients with yp stage II rectal cancer was associated with the total number of retrieved LNs.

Conclusions

DFS was associated with the number of LNs retrieved from patients with rectal cancer who received preoperative CRT, especially among patients with ypT3-4 N0 stage tumors. The oncological importance of the number of retrieved LNs should be considered when treating these patients.     

Laparoscopic-assisted versus open total mesorectal excision with anal sphincter preservation for mid and low rectal cancer: a prospective, randomized trial

Background

This single-center, prospective, randomized trial was designed to compare the short-term clinical outcome between laparoscopic-assisted versus open total mesorectal excision (TME) with anal sphincter preservation (ASP) in patients with mid and low rectal cancer. Long-term morbidity and survival data also were recorded and compared between the two groups.

Methods

Between August 2001 and August 2007, 80 patients with mid and low rectal cancer were randomized to receive either laparoscopic-assisted (40 patients) or open (40 patients) TME with ASP. The median follow-up time for all patients was 75.7 (range 16.9–115.7) months for the laparoscopic-assisted group and 76.1 (range 4.7–126.6) months for the open group. The primary endpoint of the study was short-term clinical outcome. Secondary endpoints included long-term morbidity rate and survival. Data were analyzed by intention-to-treat principle.

Results

The demographic data of the two groups were comparable. Postoperative recovery was better after laparoscopic surgery, with less analgesic requirement (P < 0.001), earlier mobilization (P = 0.001), lower short-term morbidity rate (P = 0.043), and a trend towards shorter hospital stay (P = 0.071). The cumulative long-term morbidity rate also was lower in the laparoscopic-assisted group (P = 0.019). The oncologic clearance in terms of macroscopic quality of the TME specimen, circumferential resection margin involvement, and number of lymph nodes removed was similar between both groups. After curative resection, the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and 91.3 %, respectively (P = 0.912). The respective probabilities of being disease-free were 83.3 and 74.5 % (P = 0.114).

Conclusions

Laparoscopic-assisted TME with ASP improves postoperative recovery, reduces short-term and long-term morbidity rates, and seemingly does not jeopardize survival compared with open surgery for mid and low rectal cancer (http://ClinicalTrials.gov Identifier: NCT00485316).     

A pilot study of natural orifice transanal endoscopic total mesorectal excision with laparoscopic assistance for rectal cancer

Background

The objective of this pilot study was to evaluate the feasibility and safety of natural orifice endoscopic transanal total mesorectal excision (TME) with laparoscopic assistance in a cohort study of five patients with stage I and IIA rectal cancer.

Methods

Five eligible patients with node-negative rectal cancer located 4–12 cm from the anal verge were enrolled in an IRB-approved pilot study. All patients underwent transanal endoscopic TME with laparoscopic assistance, hand-sewn coloanal anastomosis, and a diverting loop ileostomy. Primary and secondary end points included adequacy of the mesorectal excision and 30-day postoperative complications, respectively.

Results

Between November 2011 and May 2012, three males and two females underwent transanal endoscopic TME with laparoscopic assistance. Patient mean age and BMI were 48.6 ± 9.8 years and 25.7 ± 2.3 kg/m², respectively. Tumors were located an average of 5.7 ± 2.4 cm from the anal verge and preoperatively staged as T1N0M0 (2), T2N0M0 (1), and T3N0M0 (2). Mean operative time was 274.6 ± 85.4 min with no intraoperative complications. Partial intersphincteric resection was performed in conjunction with transanal endoscopic TME in three patients. Pathologic examination of TME specimens demonstrated complete mesorectal excision in all cases with negative proximal, distal, and radial margins. Mean length of hospital stay was 5.2 ± 2.6 days and three minor complications occurred, including one ileus and two cases of transient urinary dysfunction. At a mean early follow-up of 5.4 ± 2.3 months, all patients remain disease-free.

Conclusions

In this pilot study of five patients with rectal cancer, transanal endoscopic TME with laparoscopic assistance is feasible and safe, and is a promising alternative to open and laparoscopic TME. Evaluation of long-term functional and oncologic outcomes of this approach is needed before widespread adoption can be recommended.     

Is the Outcome of a Salvage Surgery for T4 Thoracic Esophageal Squamous Cell Carcinoma Really Poor?

Background

Among patients with T4 thoracic esophageal squamous cell carcinoma (TESCC), it is unclear whether the outcomes of late responders who undergo high-dose chemoradiotherapy (CRT) followed by salvage esophagectomy differs from those of early responders who undergo low-dose CRT followed by esophagectomy.

Methods

A total of 153 patients with T4 TESCC were treated with CRT. The first evaluation was performed after 40 Gy of CRT for downstaging. Of these, 28 patients could be downstaged, and underwent subsequent surgery (early responders). For the remaining patients, additional CRT was administered, and patients were re-evaluated after treatment and underwent salvage surgery. In total, 40 patients (early + late responders) were analyzed.

Results

The primary tumors exhibited a grade 3 response in six (21.4 %) of the early responders and two (16.7 %) of the late responders (p = 1.000). The rate of residual tumor in the primary tumor was 80 % (32/40 patients). The proportions of resected lymph nodes and positive metastatic nodes were similar between early and late responders (p = 0.406 and p = 0.859, respectively). The 5-year overall survival rates among the early and late responders were 25.9 and 36.5 %, respectively, and the median survival times were 24.8 and 24.3 months (p = 0.925), respectively. The 5-year cause-specific survival rates in the early and late responder groups were 61.5 and 72.9 % (p = 0.425), respectively.

Conclusion

The outcomes of both early and late responders to CRT were similar, and salvage surgery for T4 TESCC outweighs the risks in patients with T4 TESCC.     

Does Intramesorectal Proctectomy with Rectal Eversion Affect Postoperative Complications Compared to Standard Total Mesorectal Excision in Patients with Ulcerative Colitis?

Introduction

Proctectomy for ulcerative colitis (UC) can be performed via intramesorectal proctectomy with concomitant rectal eversion (IMP/RE) or total mesorectal excision (TME). No data exists comparing the outcomes of the two techniques.

Methods

All UC patients undergoing J-pouch surgery at a single institution over 10.5 years were included. Postoperative complications with IMP/RE vs. TME were analyzed using univariable and multivariable statistics.

Results

One hundred nineteen of 201 (59 %) patients underwent IMP/RE. Demographic and disease characteristics were similar between groups. On univariable analysis, IMP/RE had fewer total perioperative complications than TME (p?=?0.02), but no differences in postoperative length of stay or readmissions. Multivariable regression accounting for patient age, comorbidities, disease severity, preoperative medications, operative technique, and follow-up time (mean 5.5?±?0.2 years) suggested that both anastomotic leak rate (OR 0.32; p?=?0.04) and overall postoperative complications (2.10?±?0.17 vs. 2.60?±?0.20; p = 0.05) were lower in the IMP/RE group.

Conclusions

IMP/RE may be associated with fewer overall postoperative complications compared to TME. However, further studies on functional and long-term outcomes are needed.     

Safety and Feasibility of Laparoscopic Intersphincteric Resection for Very Low Rectal Cancer

Background

Laparoscopic surgery has been reported to be one of the approaches for total mesorectal excision (TME) in rectal cancer surgery. Intersphincteric resection (ISR) has been reported as a promising method for sphincter-preserving operation in selected patients with very low rectal cancer.

Methods

From July 2005 to December 2008, 35 patients with very low rectal cancer underwent laparoscopic TME with ISR. The results were compared retrospectively with those of previous open TME with ISR.

Results

Conversion to open surgery was necessary in one (3%) patient. The median operation time was 293 min and median estimated blood loss was 40 ml. The pelvic plexus was completely preserved in 32 patients. There was no mortality. Postoperative complications occurred in three (9%) patients. The median length of postoperative hospital stay was 17 days. Macroscopic complete mesorectal excision was achieved in all cases. Complete resection (R0) was achieved in 34 patients. Clinical lymph node stage, operation time, and blood loss were significantly different between the laparoscopic group and open group, but the differences of other factors were not statistically significant.

Conclusions

Laparoscopic TME with ISR is technically feasible and a safe alternative to laparotomy with favorable short-term postoperative outcomes.     

Chronological Improvement in Survival Following Rectal Cancer Surgery: A Large-Scale, Single-Center Study

Background

Total mesorectal excision (TME) and preoperative chemoradiation therapy (PCRT) for rectal cancer are used sequentially in our center. The aim of this study was to evaluate survival of patients with stage II/III rectal cancer chronologically and to determine whether therapeutic advances associated with TME and PCRT have improved patient survival.

Methods

A retrospective review of 2,197 patients from July 1989 to December 2006 was conducted. The time period (P) for this study was divided into three groups: P1 (1989–1995), P2 (1996–2001) for TME, P3 (2002–2006) for PCRT. Cancer-specific survival (CSS), disease-free survival (DFS), and recurrences among the three periods were investigated.

Results

A total of 293 patients in P1, 836 patients in P2, and 1,068 patients in P3 were enrolled. The 5-year CSS in stages II and III was statistically different between P1/P2 and P3 (stage II, p = 0.008; stage III, p < 0.001). The 5-year DFS was significantly different between P1/P2 and P3 for stage III (p = 0.001). The local recurrence and systemic recurrence rates decreased during P3, but there was no significant difference between the three periods for stage II. For stage III, local recurrence was significantly different between the three periods (P1 vs. P2, p = 0.002; P1 vs. P3, p < 0.001; P2 vs. P3, p = 0.008).

Conclusions

We identified an improvement in survival for stage II/III rectal cancer and a decrease in local recurrence for stage III rectal cancer during P3, the most recent period. This may be due to frequent application of PCRT based on the TME.     

Prognostic Factors for Postoperative Morbidity and Tumour Response After Neoadjuvant Chemoradiation Followed by Resection for Rectal Cancer

Background and Purpose

In patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by rectal resection, postoperative morbidity is a significant clinical problem. Pathologic complete tumour response seems to give the best prognosis in the long term. Little is known about the factors that are associated with postoperative complications and pathologic complete response. The aim of this retrospective study was to identify and describe these factors.

Methods

Ninety-nine consecutive patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation (50 Gy and capecitabine) followed by surgery at our institute between January 2007 and May 2012 were identified. Postoperative complications were graded according to the Clavien-Dindo classification. Pathologic tumour response was categorized as complete response or no/partial response.

Results

Postoperative complications occurred in 68 patients (69 %) and grade 3–5 complications in 25 patients (25 %). The 30-day and 90-day mortality were 1 % (n?=?1) and 2 % (n?=?2), respectively. A young age (p?=?0.021) and a preoperative or postoperative blood transfusion (p?=?0.015) independently predicted complications. Intraoperative or postoperative blood transfusion (p?=?0.007) and ypT0-1 stage (p?=?0.037) were independent predictors for grade 3–5 complications. Complete response rate was 22 % (n?=?22); 4 % (n?=?4) of patients showed no response. No independent factors predicting complete response were found.

Conclusions

Neoadjuvant chemoradiation followed by rectal resection is associated with significant postoperative morbidity but minimal postoperative mortality. A complete response rate of 22 % was achieved.     

Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer

Purpose

To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan.

Methods

Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2–123 months).

Results

A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %.

Conclusions

This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

     

Transanal endoscopic microsurgery for rectal tumors: experience at Korea’s National Cancer Center

Background

Transanal endoscopic microsurgery (TEM) is a minimally invasive alternative to transanal excision, enabling complete local excision of selected benign or malignant rectal tumors. This study aimed to determine the surgical and oncologic results for rectal tumors excised by TEM.

Methods

From November 2001 to October 2007, 45 patients underwent TEM for excision of adenoma (13 patients), carcinoid tumor (6 patients), and carcinoma (26 patients). The patients included 27 men and 18 women with a median age of 52 years (range, 22–72 years).

Results

The median tumor distance from the anal verge was 7 cm (range, 3–15 cm), and the median tumor size was 17 mm (range, 2–60 mm). There was no procedure-related morbidity or mortality. However, one patient with rectal carcinoma died of lung cancer during the follow-up period. Of 13 patients with adenomas, 1 patient (7.7%, 1/13) experienced local recurrence 5 months after surgery. No recurrence occurred for six patients with carcinoid tumors. Histologic examination of the carcinomas showed pathologic tumor (pT) stage 0 (ypT0) in 2 patients, pT1 in 17 patients (including ypT1 in 1 patient), pT2 in 6 patients, and pT3 in 1 patient. Immediate salvage surgery was performed for five patients (19%, 5/26). During a median follow-up period of 37 months (range, 5–72 months), one patient (3.8%, 1/26) experienced local recurrence. The overall and disease-free 5-year survival rates for patients with carcinoma were 96.2% and 88.5%, respectively.

Conclusions

The TEM procedure is a safe and appropriate surgical treatment option for benign rectal tumors. With strict patient selection, it is oncologically safe for early-stage rectal carcinomas.     

Preoperative therapy of esophagogastric cancer: the problem of nonresponding patients

Introduction

Preoperative treatment is nowadays standard for locally advanced esophagogastric cancer in Europe. Surprisingly, little attention has been paid to nonresponders so far. The aim of our retrospective exploratory study was the comparison of responder, nonresponder, and primary resected patients in respect of outcome considering the tumor entity.

Patients and methods

From 2001–2011, 607 patients with locally advanced esophagogastric carcinoma (adenocarcinoma of the esophagogastric junction (AEG), n?=?293; squamous cell cancer (SCC), n?=?111; gastric cancer, n?=?203) after preoperative treatment (n?=?281) or primary resection (n?=?326) were included. Histopathological response evaluation (Becker criteria) was available for 263.

Results

A total of 76/263 (28.9 %) were responders (<10 % residual tumor). There was an association of response with increased R0 resections (p?<?0.001) but also with a higher complication rate (p?=?0.008) compared to nonresponse and primary surgery. Mortality was not influenced. Increased R0 resections after response were confirmed in every tumor entity (AEG, p?=?0.010; SCC, p?=?0.023; gastric cancer, p?=?0.006). Median survival was best for responders with 43.5 months [95 % confidence interval (CI), 27.9–59.1], followed by nonresponders with 24.3 months (95 % CI, 21.6–27.0) and primary resected patients with 20.8 months (95 % CI, 17.7–23.9; p?=?0.002). AEG (p?=?0.012) and gastric cancer (p?=?0.017) revealed identical results, but in the subgroup of SCC, the survival of nonresponders (median, 11.6 months; 95 % CI, 6.9–16.3) was even worse than for primary resected patients (median, 23.8 months; 95 % CI, 1.7–46.0; p?=?0.012).

Conclusion

The histopathological response rate was low. Generally, nonresponding patients with AEG or gastric cancer seem not to have a disadvantage compared to primary resected patients, but nonresponders with SCC have a worse prognosis, which strengthens the demand for a critical patient selection in surgery for this tumor entity.     

Previous transanal endoscopic microsurgery for rectal cancer represents a risk factor for an increased abdominoperineal resection rate

Background

Transanal endoscopic microsurgery (TEM) represents a surgical option in the treatment of selected early rectal cancers. However, when definitive histopathology shows negative prognostic factors, rectal resection with total mesorectal excision (TME) is recommended to reduce the risk of recurrence. No studies have yet analyzed the impact of previous TEM on the perioperative outcomes of immediate laparoscopic TME (LTME) for rectal cancer. The aim of this study was to evaluate the perioperative outcomes of LTME after TEM for rectal cancer.

Methods

This study was a retrospective analysis of a prospective database. All patients undergoing LTME within 8 weeks after full-thickness TEM for rectal cancer between January 2001 and December 2011 were included. Each patient was matched on the basis of demographic and clinical characteristics with two patients undergoing primary LTME for rectal cancer during the same period. Age, gender, body mass index, tumor distance from the anal verge, tumor size, neoadjuvant chemoradiation, previous TEM, rectal wall defect size created during TEM, and intraoperative complications were included in a multivariate analysis to identify risk factors for abdominoperineal resection (APR).

Results

A total of 17 patients undergoing TEM followed by LTME were compared to 34 patients undergoing primary LTME. Mean operative time of LTME after TEM was significantly higher (206 vs. 188 min, P = 0.025). APR was more frequently performed after TEM [odds ratio (OR) 5.25, P = 0.028] and in male patients (OR 9.04, P = 0.034). On multivariate analysis, a previous TEM was the only independent predictor of APR (OR 4.13, P = 0.046). The incidence and severity of postoperative complications were similar in both groups. Mesorectum integrity was complete in all cases.

Conclusions

LTME after TEM is a challenging procedure, with a significantly higher risk of APR compared to primary LTME. Future improvements in preoperative patient selection for TEM are needed to reduce this risk.