Use of preoperative ultrasound staging for treatment of rectal cancer

INTRODUCTION: Transrectal ultrasound is the standard method for preoperative staging of rectal cancer. This study reviews the accuracy of transrectal ultrasound staging for T3 disease and its use in the selection of patients for neoadjuvant chemoradiation. METHODS: One hundred seventeen patients underwent preoperative transrectal ultrasound evaluation for rectal cancer. Accuracy of transrectal ultrasound was evaluated among 70 patients not receiving preoperative chemoradiation. Forty-seven patients received neoadjuvant chemoradiation based on transrectal ultrasound results. Tumor downstaging and early recurrence were evaluated among 45 of 47 patients receiving neoadjuvant chemoradiation. RESULTS: Among 70 nonirradiated patients, 19 were pathologic Stage pT3. Transrectal ultrasound correctly identified 18 of 19 patients with Stage pT3 (sensitivity, 94.7 percent). Transrectal ultrasound correctly identified 44 of 51 patients with less than pT3 disease (specificity, 86.3 percent). After preoperative chemoradiation in 45 patients with ultrasound Stage uT3 or uT4 tumors, 56 percent of them experienced a reduction in T stage. Residual nodal disease was found in 31 percent of patients. A complete pathologic response with no residual disease at operation was observed in 22 percent of patients. During a median follow-up period of 21 months after diagnosis, seven patients experienced a recurrence of their disease at a median of 12 months after diagnosis. Five of seven patients with recurrence were among a subgroup of ten patients who both failed to downstage T and had residual nodal disease at operation. CONCLUSION: Transrectal ultrasound is an accurate modality for selecting patients for neoadjuvant treatment. Preoperative chemoradiation produced downstaging in 56 percent of patients. Factors related to early recurrence included residual nodal disease and failure to downstage T after neoadjuvant chemoradiation.Presented at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 4 to 8, 1998.     

Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma

Background and aims Preoperative radiotherapy (PRT) for rectal carcinoma has been shown to cause tumour regression and increase local control and patient survival. The aim of this study was to examine the usefulness of tumour regression grading (TRG) in quantifying the effect of PRT.Methods Depending on the tumour stage (uT), as defined by preoperative endorectal ultrasound (ERUS), fixity and distance from the anal verge, 126 patients with rectal cancer underwent either surgery alone, or received short-course 25-Gy radiotherapy or long-course 50-Gy radiotherapy combined with 5-fluorouracil (5-FU) before surgery. TRG in each group was assessed and compared with the downstaging, defined as a change in preoperative uT stage and pathologic stage (pT).Results Complete response (no residual tumour, TRG 1) was seen in 7% of the patients (3/44) and total or major regression (TRG 1–3) in 73% of the patients (32/44) treated with 50-Gy chemoradiation. Of those treated with 25-Gy PRT, 21% (9/42) showed major tumour regression. Of the patients who underwent ERUS and PRT, 32% (26/83) were downstaged when comparing uT with pT, but 53% (14/26) of the downstaged tumours showed no response by TRG. In comparison, 50% (28/57) of the tumours with no downstaging showed a marked response by TRG (p=0.05).Conclusions Tumour regression grading offers detailed information of the effect of PRT and shows that tumour regression is more marked after long-term chemoradiation than after short-course radiotherapy (p=0.02). In contrast, T-stage downstaging was similar in both groups and did not correlate with the TRG results (p=0.05).     

Limitations and pitfalls of transrectal ultrasonography for staging of rectal cancer

PURPOSE: This study was designed to evaluate the accuracy of preoperative staging by transrectal ultrasonography (TRUS) and to clarify the limitations and pitfalls of TRUS by clinicopathologic analysis for staging errors. MATERIALS AND METHODS: Results of TRUS for 164 consecutive patients with rectal cancer were compared prospectively with histopathologic findings according to the newest TNM classification. Clinicopathologic factors that may influence staging errors were analyzed by reviewing both resected specimens and hard copies of TRUS. RESULTS: There were 13 patients histopathologically staged as pTis, 21 as pT1, 34 as pT2, 84 as pT3, 12 as pT4, 73 as pN0, and 91 as pN1–3. Of these, 85, 86, 56, 93, 75, 74, and 77 percent, respectively, were correctly staged by TRUS. Excluding 12 cases with incomplete examinations because of annular constricting tumors, overstaging of tumor invasion depth was mostly caused by tumor invasion close to the deeper uninvolved layer, inflammatory cell aggregation, desmoplastic change, and hypervascularity around the tumor, mimicking tumor invasion on TRUS. The understaging was mostly the result of microscopic invasion beyond the estimated layers and difficulties in examination because of the tumor location being close to the anal canal or on the Houston's valves or the tumor shapes being polypoid or bulky and fungating. Overstaging in lymph node status was caused by reactive lymph node swelling and understaging by the presence of only small involved node and metastasis in the extramesorectal nodes. CONCLUSIONS: An awareness of the limitations and pitfalls of TRUS, as demonstrated by the present study, should improve staging accuracy and contribute to optimum clinical decision-making.     

Colonoscopic ultrasound is associated with a learning phenomenon despite previous rigid probe experience

Colonoscopic ultrasound (CUS) enables total colonoscopic examination combined with staging of tumor. Rigid probe transrectal ultrasound (TRUS) is reliable in assessing rectal cancer. Both the modalities are associated with an initial learning curve. We evaluated the predictability CUS in preoperative staging of rectal cancer during the learning curve, despite experience with TRUS. Forty-four patients with non-obstructing rectal cancer were assessed by colonoscopy and colonic ultrasound using a 7.5 MHz rotating transducer. Accuracy of ultrasound staging was compared with pathological staging. Tumor staging and nodal staging at pathology and ultrasound were named pT, pN and uT, uN, respectively. The pathological staging was pT1 in two (4.5%), pT2 in 16 (36%), pT3 in 21 (48%) and pT4 in five (11.5%) rectal cancer specimens. CUS understaged the tumor in 11 cases and overstaged it in 10 cases. Overall, the positive predictive value was 61%, negative predictive value 73%, sensitivity 61%, and specificity 73%. Lymph nodes were not visualized in 14. The overall un-weighted kappa of CUS staging of RC was 0.18 (poor). The predictive value in tumor staging of CUS is suboptimal in the learning phase, despite previous experience with TRUS.     

Selection criteria for treatment of rectal cancer with combined external and endocavitary radiation

PURPOSE: The aim of this study was to identify factors predictive of recurrence of rectal tumors treated with combined external and endocavitary radiation. METHODS: Seventy-two patients with rectal cancer were evaluated clinically and with transrectal ultrasound before combined external and endocavitary radiation. Ideal lesions were moderately differentiated, mobile, not ulcerated, <3 cm in diameter, and <12 cm from the anal verge. External radiation (4,500 cGy) was given during five weeks followed by endocavitary radiation (3,000 cGy × 2). Median follow-up was 31 (range, 7–93) months. RESULTS: Pretreatment transrectal ultrasound stages were uT1 (6 patients), uT2(27 patients), and uT3 (39 patients). Clinical evaluation identified 26 ideal and 46 nonideal tumors. Overall recurrence was 36 percent; mean time to recurrence was 12 months. Ideal lesions recurred less than nonideal (15vs. 48 percent;P=0.01). Mobile lesions recurred less than tethered lesions (26vs. 52 percent;P=0.048). Transrectal ultrasound stage was predictive of recurrence (0 percent uT1, 22 percent uT2, and 51 percent uT3;P=0.015). Surgery was possible in 14 of 17 patients with pelvic recurrence only; 11 patients (65 percent) had curative surgery. Distant metastases occurred in nine patients; all had pelvic recurrences, and six died of disease. CONCLUSION: Patients with uT3 or nonideal rectal cancers should not be offered combined external and endocavitary radiation for cure. Transrectal ultrasound stage is the only independent predictor of recurrence.Presented at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Comparative study of transrectal ultrasonography, pelvic computerized tomography, and magnetic resonance imaging in preoperative staging of rectal cancer

PURPOSE: The preoperative assessment of rectal cancer wall invasion and regional lymph node metastasis is essential for the planning of optimal therapy. This study was done to determine the accuracy and clinical usefulness of transrectal ultrasonography, pelvic computed tomography, and magnetic resonance imaging in preoperative staging. METHODS: A total of 89 patients with rectal cancer were examined with transrectal ultrasonography (n=89), pelvic computed tomography (n=69), and magnetic resonance imaging with endorectal coil (n=73). The results obtained by these diagnostic modalities were compared with the histopathologic staging of specimens. RESULTS: In staging depth of invasion, the overall accuracy was 81.1 percent (72/89) by transrectal ultrasonography, 65.2 percent (45/69) by computed tomography, and 81 percent (59/73) by magnetic resonance imaging. Overstaging was 10 percent (9/89) by transrectal ultrasonography, 17.4 percent (12/69) by computed tomography, and 11 percent (8/73) by magnetic resonance imaging; and understaging was 8 of 89 (8.9 percent) by transrectal ultrasonography, 12 of 69 (17.4 percent) by computed tomography, and 6 of 73 (8 percent) by magnetic resonance imaging. In staging lymph node metastasis, the overall accuracy rate was 54 of 85 (63.5 percent) in transrectal ultrasonography, 39 of 69 (56.5 percent) in computed tomography, and 46 of 73 (63 percent) in magnetic resonance imaging. The sensitivity was 24 of 45 (53.3 percent) in transrectal ultrasonography, 14 of 25 (56 percent) in computed tomography, and 33 of 42 (78.5 percent) in magnetic resonance imaging; and specificity was 30 of 40 (75.0 percent) in transrectal ultrasonography, 25 of 44 (56.8 percent) in computed tomography, and 13 of 31 (41.9 percent) in magnetic resonance imaging. The accuracy in detection of positive lateral pelvic lymph nodes under magnetic resonance imaging (n=8) was 12.5 percent. The accuracy in detection of posterior vaginal wall invasion was 100 percent in transrectal ultrasonography (n=7) and 100 percent in magnetic resonance imaging (n=3), but 28.5 percent in computed tomography (n=7). CONCLUSIONS: Both transrectal ultrasonography and magnetic resonance imaging with endorectal coil exhibited similar accuracy and were superior to conventional computed tomography in preoperative assessment of depth of invasion and adjacent organ invasion. Because transrectal ultrasonography is a safer and more cost-effective modality than magnetic resonance imaging, transrectal ultrasonography is an appropriate method for preoperative staging of rectal cancer. Further efforts will be needed to provide a better staging of lymph node involvement.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Long-term oncologic results of patients with distal rectal cancer treated by local excision with or without adjuvant treatment

Aim The aim of this study is to review long-term oncologic results of local excision (LE) and to investigate the validity and feasibility of LE as a treatment option for distal rectal cancer. Materials and methods Seventy-six patients who underwent LE for distal rectal adenocarcinoma with curative intent from 1991 to 2000 at Severance Hospital Yonsei University Medical Center, Seoul, Korea were enrolled in this study. Results Preoperative transrectal ultrasonography revealed 3 cases of uT0, 55 cases of uT1 and 18 cases of uT2. Postoperative pathologic examination revealed 10 cases of pT0 (where no residual cancer cells remained), 11 cases of pTis, 37 cases of pT1, 16 cases of pT2, and 2 cases of pT3. Eleven out of 37 patients with pT1 tumors received adjuvant radiation therapy. Among 16 patients with pT2 tumor, 7 undertook salvage operation and 8 received adjuvant therapy. The median follow-up period was 84.9 months. Local recurrence was observed in six patients. The 5-year local recurrence-free survival rate (LFS) was 89.4% in the pT1 group and 75.0% in the pT2 group (p = 0.012). Among the patients with pT1 cancer, those who received adjuvant radiation therapy demonstrated a 5-year LFS of 100%, compared to those who did not, 76.0% (p = 0.038). Conclusion Our results imply a potential role of LE and adjuvant radiation as an option for the treatment of distal rectal cancer, and that even for pT1 carcinoma, LE alone might not be a valid modality.     

T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival

PURPOSE: Preoperative chemoradiation therapy is used widely in the treatment of rectal cancer. The predictive value of response to neoadjuvant remains uncertain. We retrospectively evaluated the impact of response to preoperative and, specifically, of T-level downstaging, nodal downstaging, and complete pathologic response after chemoradiation therapy on oncologic outcome of patients with locally advanced rectal cancer. METHODS: There were 88 patients with ultrasound Stage T3/T4 midrectal (n = 37) and low rectal (n = 51) cancers (63 males; mean age 62.6 years). All patients were treated by preoperative 5-fluorouracil-based chemotherapy and pelvic radiation followed by surgical resection in six weeks or longer (56 sphincter-preserving resections). RESULTS: T-level downstaging after neoadjuvant treatment was demonstrated in 36 (41 percent) of 88 patients, and complete pathologic response was observed in 16 (18 percent) of the 88. Of the 42 patients with ultrasound-positive nodes, 27 had no evidence of nodal involvement on pathologic evaluation (64 percent). The overall response rate (T-level downstaging or nodal downstaging) was 51 percent. At a median follow-up of 33 months, 86.4 percent of patients were alive. The overall recurrence rate was 10.2 percent (three patients had local and six had metastatic recurrences). Patients with T-level downstaging and complete pathologic response were characterized by significantly better disease-free survival (P = 0.03, P = 0.04) and better overall survival (P = 0.07, P = 0.08), according to Wilcoxons test comparing Kaplan-Meier survival curves. None of the patients with complete pathologic response developed recurrence or died during the follow-up period. CONCLUSION: T-level downstaging and complete pathologic response after preoperative chemoradiation therapy followed by definitive surgical resection for advanced rectal cancer resulted in decreased recurrence and improved disease-free survival. Advanced rectal cancers that undergo T-level downstaging and complete pathologic response after chemoradiation therapy may represent subgroups that are characterized by better biologic behavior.     

Preoperative Radiotherapy Combined With Intraoperative Radiotherapy Improve Results of Total Mesorectal Excision in Patients With T3 Rectal Cancer

PURPOSE: The survival advantage of preoperative radiotherapy in patients with rectal cancer is still a matter of debate, because its incremental benefit in the total mesorectal excision setting is unclear. This study was designed to evaluate early and long-term results of preoperative radiotherapy plus intraoperative radiotherapy in a homogeneous population of T₃ middle and lower rectal cancer patients submitted to total mesorectal excision. METHODS: A series of 113 patients with middle and lower T₃ rectal cancer consecutively submitted to total mesorectal excision at a single surgical unit from 1991 to 1997 were divided into two groups according to type of neoadjuvant treatment: preoperative radiotherapy (38 Gy) plus intraoperative radiotherapy (10 Gy; n = 69), and no preoperative treatment (total mesorectal excision; n = 44). Standard statistical analyses were used to evaluate early (downstaging, intraoperative factors, hospital morbidity, and mortality rates) and long-term results (recurrence and survival). RESULTS: Overall, 68.2 percent of patients were downstaged by the preoperative regimens (T₀ specimens in 3 cases). Postoperative complications were comparable in the two groups. Five-year, disease-specific survival was 81.4 and 58.1 percent in preoperative radiotherapy plus intraoperative radiotherapy group and total mesorectal excision group, respectively (P = 0.052). Corresponding figures for disease-free survival were 73.1 and 57.2 percent in the two groups, respectively (P = 0.096). The rates of local recurrence at five years were 6.6 and 23.2 percent in preoperative radiotherapy plus intraoperative radiotherapy and total mesorectal excision groups, respectively (P = 0.017). CONCLUSIONS: Preoperative radiotherapy plus intraoperative radiotherapy associated with total mesorectal excision reduce local recurrence rate and improve survival in T₃ rectal cancer compared with total mesorectal excision alone.     

Influence of tumor position on accuracy of endorectal ultrasound staging

Endorectal ultrasound is a well-established method of preoperative staging of rectal neoplastic lesions. PURPOSE: This study was undertaken to evaluate whether tumor site (in terms of height) and position (with respect to the rectal circumference) have an influence on the reliability of endoluminal ultrasound staging. METHODS: From January 1991 to May 1996, 154 consecutive patients with a total of 162 rectal tumors were examined preoperatively using endorectal ultrasound. Apart from staging all tumors using the uT/uN classification, tumor level and tumor position were recorded prospectively. Neoplasms were subdivided into low rectal (0–6 cm from the anal verge), mid rectal (7–12 cm), and higher lesions (>12 cm). Furthermore, the lumen was divided into an anterior, left lateral, posterior, and right lateral position, and all tumors, apart from circular lesions (n=9), were subclassified accordingly. RESULTS: Overall, we found 40 (25 percent) adenomas, 15 (9 percent) T1, 29 (18 percent) T2, 67 (41 percent) T3, and 11 (7 percent) T4 lesions. Overall accuracy was 78 percent. Staging accuracy for low rectal tumors (n=41) was 68 percent, whereas 76 and 88 percent of mid (n=96) and high (n=25) neoplasms were staged correctly, respectively. The difference was not statistically significant. With regard to position, 47 tumors were situated anteriorly (77 percent accuracy), 42 in the left lateral position (69 percent accuracy), 33 posteriorly (73 percent accuracy), and 31 in the right lateral position (81 percent accuracy). Differences did not reach statistical significance. CONCLUSION: Endorectal ultrasound is currently the best method for preoperative assessment of the depth of infiltration of rectal tumors. However, rectal anatomy seems to affect staging accuracy in the lower rectum because the structure of the ampulla recti renders endosonographic examination more difficult. In addition, endosonographic layers are less well defined at this level. Both factors contribute to a lower reliability and predictive value of endorectal ultrasound staging in the lower rectum, although statistical significance was not reached in this study. On the other hand, tumor position with respect to rectal circumference does not influence the predictive value of endorectal ultrasound.     

Long-Term Results After Neoadjuvant Radiochemotherapy for Locally Advanced Resectable Extraperitoneal Rectal Cancer

Purpose This study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy. Methods Eighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision. Results Median follow-up was 108 (range, 10–169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pTand pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN. Conclusions Long- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis. Presented at the Second Joint Meeting of the European Council of Coloproctology, European Association of Coloproctology, Sociatà Italiana di Chirurgia Colorettale, Bologna, Italy, September 15 to 17, 2005.     

Outcome of patients with clinical stage II or III rectal cancer treated without adjuvant radiotherapy

Background  To clarify the indications for preoperative adjuvant radiotherapy for rectal cancer, the outcome of patients who underwent curative surgery without adjuvant radiotherapy was investigated. Methods  A total of 817 consecutive patients who underwent curative surgery for clinical stage II or III rectal cancer without preoperative adjuvant radiotherapy between 1988 and 2002 were reviewed. Results  The actuarial 5-year local recurrence rate in the examined patients was 6.2%. Univariate analysis showed that sex, pathological T classification (pT), clinical N classification (cN), pathological N classification (pN), tumor site, distance from the anal verge, type of surgery, pathological stage, a positive radical margin, lymphatic invasion, and venous invasion were significantly correlated with local recurrence. Multivariate analysis of preoperative factors identified cN, distance from the anal verge, and sex as statistically significant risk factors for local recurrence. In patients with rectal cancer located less than 5 cm from the anal verge and with positive cN, the local recurrence rate was more than 10%. Conclusions  Patients with rectal cancer located less than 5 cm from the anal verge and with clinically positive lymph nodes should be given preoperative adjuvant radiotherapy.     

Endoluminal ultrasography for rectal tumors: efficacy, sources of error and limitations.

OBJECTIVES: endorectal ultrasound (EUS) is currently accepted as the best technique for the preoperative study of patients with rectal tumors, and surgical decisions depend increasingly on EUS staging. The main pitfalls in staging rectal tumors are over- or understaging as well as errors in imaging lymph nodes. Being aware of such errors and their causes may help to improve the overall results. The aim of the present study was to evaluate the accuracy of EUS in staging rectal neoplasms, and to study potential sources of error. METHODS: from May 1996 to December 1998, 120 patients with rectal tumors were studied preoperatively by EUS. The uTNM classification described by Hildebrandt and coworkers was used. The EUS findings were compared prospectively with the results of pathological examination. When there was no correlation, both the specimen and the EUS findings were carefully reviewed to look for potential sources of error. RESULTS: 41 out of 120 patients were classified as uT1, 10 as uT2, 60 as uT3 and 9 out of 120 as uT4. 31 patients had positive lymph nodes (uN1). On comparing these data with the results of the pathological report, we found 90% accuracy in staging rectal wall penetration, and 70% accuracy in the diagnosis of lymph nodes. Errors were due basically to technical problems, characteristics of the tumor itself, and difficulties in staging lymph nodes. CONCLUSIONS: it is important to identify the potential source of errors as well as the current limitations of EUS to improve the overall results with this technique.     

Apoptosis in rectal cancer

PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53- and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N = 160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P > 0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderately vs. 3.98 percent in poorly differentiated carcinomas; P = 0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1 vs. 3.72 percent in pN2; P = 0.0074), p53 status (mean apoptotic index, 6.26 percent in p53- vs. 4.42 percent in p53+; P = 0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2- vs. 6.51 percent in bcl-2+; P = 0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P = 0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic index vs. 15 percent with high apoptotic index; P > 0.05), and no significant differences were found regarding survival (P > 0.05). On multivariate analysis, International Union Against Cancer stage (P = 0.0002), p53 (P = 0.0002), gender (P = 0.0136), and bcl-2 (P = 0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.     

Long-Term Results of Preoperative Radiotherapy for 113 Cases of UT3 and UT4 Rectal Cancer

PURPOSE: Eighty percent of local recurrence after resection of rectal adenocarcinoma classically occurs within two years of surgery. Pretherapeutic staging is frequently limited to clinical examination, although the accuracy of endoanal ultrasonography has been demonstrated. The aim of this study was to report the long-term results of preoperative radiation therapy and resection of pretherapeutic endoanal ultrasonography–staged T3 and T4 rectal adenocarcinoma. METHODS: This retrospective review analyzed a series of 113 patients who underwent radiation therapy followed by surgery. All patients underwent an endoanal ultrasonography. Median follow-up was 75 months. RESULTS: Fifty-seven percent of patients were pT3 or T4. Thirty-six percent had involvement of lymph nodes. Five-year rates of survival, local recurrence–free survival, and disease-free survival were 79, 73, and 68 percent, respectively. Ten-year rates were 65, 63, and 62 percent, respectively. Median time to detection of local recurrence was 39 months. Eight of ten local recurrences occurred after two years of follow-up. Eight of ten patients with local recurrence had pretherapeutic endoanal ultrasonography–staged N+ tumors. CONCLUSION: These results appear to justify a follow-up program for patients with pretherapeutic endoanal ultrasonography–staged N+ tumor. However, a minimum of seven years of follow-up is needed to obtain an accurate assessment of results.     

Metastasis of rectal cancer to lymph nodes and tissues around the autonomic nerves spared for urinary and sexual function

PURPOSE: To clarify the indications for autonomic nerve-sparing operations for rectal cancer, the presence of lymph nodes and metastasis in the tissue around the autonomic nerve were examined in 28 rectal cancer patients. These were staged as pT2 in 8 patients, pT3 in 19 patients, and pT4 in 1 patient histopathologically. METHODS: The specimens of the autonomic nerve including the inferior mesenteric plexus, preaortic plexus, superior hypogastric plexus, hypogastric nerve, and pelvic plexus were removed with radical abdominopelvic lymphadenectomy after the autonomic nerve-sparing rectal cancer operation. RESULTS: In the tissue around the autonomic nerve, lymph nodes were 11.2±9.6 in number and 2.6±2.4 mm in size (mean ± standard deviation). The frequency of presence of lymph nodes was higher and the number of lymph nodes was larger in the inferior mesenteric plexus (70.4 percent; 3.6) and the preaortic plexus (66.7 percent; 2.1) than in the left and right pelvic plexuses (39.1 percent, 1; 36 percent, 1). Metastasis to the lymph nodes or lymphatic permeation in the tissue around the autonomic nerve were observed in four cases (14.3 percent) of lower rectal cancer, consisting of three with Stage III cancer (pT3, pN1-3, and M0) and one with Stage IV cancer (pT4, pN1, and pM1 (HEP)). CONCLUSION: Radical rectal excision that includes lymph nodes and adjacent tissue around the autonomic nerves may result in metastatic tumor removal that would otherwise be left in situ with nerve-sparing techniques for advanced rectal cancer in Stage III.     

Local excision and adjuvant radiotherapy for rectal adenocarcinoma T1-2 N0

AIM: To study retrospectively the relapse rate, the functional results and the survival rate in patients with rectal carcinoma treated with local excision and adjuvant radiotherapy. METHODS: Between 1980 and 1995, 43 patients were treated. All cancers were infiltrating tumours except 4 high grade dysplasias with positive margins. The pT classification was: pT1 (n=34), pT2 (n=4), pT3 (n=1). In 4 cases the depth of penetration of the tumor into the bowel wall was not evaluable. The endo-anal excision was performed by surgery (n=20) or by endoscopy (n=23). Only the tumor bed was irradiated in 35 cases (contact x-ray therapy: 30, interstitial iridium implant: 5) and in 8 cases the whole rectum was irradiated with external beam radiotherapy (+/- endocavitary irradiation). RESULTS: Median follow-up was 72 months. Four malignant relapses were observed (local: 1, perirectal lymphatic: 2, distant metastasis: 1). The overall 5- and 10-year survival rates were 80 and 68%, respectively. A total of 41 patients preserved a normal sphincter (95%). The anal function was evaluated as excellent or good in all the cases. No severe radiation toxicity was observed. CONCLUSION: Small rectal carcinomas T1 N0 can be effectively treated in most cases by local excision and postoperative radiation therapy. A close multidisciplinary collaboration is necessary to achieve an optimal result.     

Preoperative radiotherapy for locally advanced rectal cancer and prognostic factors influencing outcome

The aim of presented study was to evaluate the impact of different factors on survival, local recurrence and development of metastatic disease in patients with rectal cancer treated with preoperative radiotherapy or 5-fluorouracil (5-FU) based concurrent chemoradiation. Retrospective clinical evaluation was performed in 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period January 1998 - March 2003. Tumor extent was evaluated by CT and/or MRI and/or TRUS examination and tumor biopsy was performed during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. Computed tomography localisation of target volume was used for 3D radiotherapy treatment planning. Accelerated short term regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998-2000 and normofractionated regimen (40-50 Gy/20-25 fractions/4-5 weeks) was performed in 86% of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The 2-year overall survival (OS) was 84% and 5-year OS was 60% following radical resection. The important prognostic factors affecting survival were postradiotherapy determined pathological staging (p=0.005), postradiotherapy tumor grade (p<0.001) and the presence of angioinvasion and/or perineural spread (p=0.023). Prognostic factors for disease-free survival were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy tumor staged T4 (p=0.048) and in presence of angioinvasion and/or perineural spread (0.049). Age, tumor location, histological grade before radiotherapy and tumor downstaging were not statistically significant for survival and/or for local recurrence rate. The best survival rates were obtained in patients with postradiotherapy grade 1 tumors (5-years survival 100%), tumors without angioinvasion and perineural spread (5-years survival 65%) and in patients who obtained complete remission after preoperative radiotherapy (5-years survival 86%).     

Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy

Objective The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection.Patients and methods All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-m paraffin sections were obtained from each lymph node, cut at 50 m apart from each other. The results were reviewed by two independent pathologists.Results Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months.Conclusion Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.     

Extended surgery and early postoperative radiotherapy for undifferentiated thyroid carcinoma.

The current study was devised to evaluate the therapeutic potential of extended surgery for improving survival in undifferentiated thyroid carcinoma (UTC). An institutional retrospective survival analysis (July 1994 to December 1998) of 30 patients who underwent surgery for UTC with locally curative intent was done. Median and 1-year survival was 4 months and 37%, respectively. Primary patients were older (70 vs. 59 years; p = 0.026) and deceased earlier (median survival 4 vs. 20 months; p = 0.027, log-rank test) than their reoperative counterparts, suggesting a referral bias toward younger patients. Survival analysis was restricted to primary pT4 UTC, leaving 18 patients. On univariate analysis, pN and M category, degree of resection (R2 versus R0/1 and radiotherapy (0-30 Gy versus >30 Gy) were identified as parameters suitable for further testing. On multivariate analysis, pN1 was a significant prognosticator of decreased survival (RR = 5.9; p = 0.043), followed by R2 (RR = 4.1, p = 0.088) and M1 (RR = 3.6; p = 0.089). Because of low patient numbers after stratification for radiotherapy, only pN and degree of resection were analyzed on subsequent multivariate analysis. In the incomplete radiotherapy stratum, neither of the two parameters affected survival, whereas R2 and pN1 limited survival in the complete radiotherapy stratum. In primary pT4 UTC, a subset of pN0 patients with R0/1 resections and radiotherapy greater than 30 Gy seemed to benefit from extended surgery. Because pN1 and R2 patients with radiotherapy of 30 Gy or less comprised most UTC patients, only 1-year, but not median, survival improved compared to literature controls.