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.     

Endorectal ultrasound of T3 and T4 rectal cancers after preoperative chemoradiation

PURPOSE: This study was undertaken to assess the accuracy and ability of endorectal ultasound (ERUS) to predict changes in rectal tumor stage after a preoperative chemoradiation protocol. METHODS: Since December 1990, all rectal malignancies at our institution have been preoperatively staged with ERUS. ERUS has been an essential tool in preoperative staging of rectal cancer patients, possessing an overall accuracy of 84 percent for T stage and 81 percent for lymph node status in our hands (Williamson PR, unpublished data). Beginning in July 1992, all patients staged with T3 or T4 lesions on initial ERUS have been entered into a protocol consisting of preoperative chemoradiation therapy (CRT). This protocol consists of patients receiving 4,500 to 5,040 rads for five to eight weeks and concomitantly receiving sensitizing doses of 5-fluorouracil and/or leucovorin. All patients were scheduled for sphincter-saving or abdominoperineal resections six to eight weeks following completion of CRT. A repeat ERUS was performed on each patient one week before surgery. RESULTS: The study group consisted of 15 patients who completed CRT, including 12 males and 3 females. Evidence of tumor shrinkage via ERUS measurement was seen in all patients. Average tumor shrinkage as assessed by ERUS was 16 percent by width and 32 percent by depth of invasion. Sonographic level of invasion and nodal status were each downstaged in 38 percent of patients. Pathologic evaluation comparison revealed that the level of invasion was downstaged in 47 percent and nodal status in 88 percent compared with initial ERUS staging. Of those patients downstaged, 4 of 11 (36 percent) revealed no tumor in the pathology specimen. CONCLUSIONS: We conclude from our early experience that although ERUS offers a method for assessing degree of shrinkage and downstaging of T3 and T4 lesions after CRT, presently it does not closely predict the pathologic results. Results are strongly related to the experience of the ultrasonographer. The ability to distinguish tumor from radiation-induced changes to perirectal tissues is under continued investigation, and a new method of interpreting the data obtained by ERUS after CRT will need to be established.     

A Pathologic Complete Response to Preoperative Chemoradiation Is Associated With Lower Local Recurrence and Improved Survival in Rectal Cancer Patients Treated by Mesorectal Excision

PURPOSE: Preoperative chemoradiation reduces tumor size and nodal metastasis in patients with rectal cancer. Tumor downstaging has been associated with an increased probability of a sphincter-saving procedure and with improved local control. However, pathologic complete response to chemoradiation has not been correlated with local control and patient survival. We studied the prognostic value of pathologic complete response to preoperative chemoradiation in rectal cancer patients. METHODS: We have prospectively followed up 168 consecutive patients with ultrasound Stages II (46) and III (122) rectal cancer treated by preoperative chemoradiation followed by radical resection with mesorectal excision; 161 had a curative resection. Recurrence and survival were compared with tumor characteristics and pathologic complete response. Average follow-up was 37 months. RESULTS: Tumor downstaging occurred in 97 (58 percent) patients, including 21 (13 percent) patients who had a pathologic complete response. None of the clinical or pathologic variables was associated with pathologic complete response. The estimated 5-year rate of local recurrence was 5 percent; of distant metastasis, 14 percent. None of the patients with pathologic complete response has developed disease recurrence. We found no difference in survival among patients with pathologic Stages I, II, or III tumors. CONCLUSIONS: A pathologic complete response to preoperative chemoradiation is associated with improved local control and patient survival. For patients without pathologic complete response, the pathology stage does not have prognostic significance.     

Primary vs. secondary anastomosis after sigmoid colon resection for perforated diverticulitis (Hinchey Stage III and IV): a prospective outcome and cost analysis

PURPOSE: Our hypothesis was that in patients with perforated sigmoid colon diverticulitis and peritonitis (Hinchey Stage III and IV) a one-stage sigmoid colon resection is safe and cost effective when performed by an experienced colorectal surgeon. We evaluated outcome and cost of one-stage vs. two-stage sigmoid colon resection after diverticulitis perforation and peritonitis. METHODS: Patients undergoing emergency resection for perforated sigmoid colon diverticulitis and peritonitis (Hinchey Stage III and IV). Outcome, costs, and insurers reimbursement were compared between 13 patients undergoing sigmoid colon resection and primary anastomosis (Group A) and 42 patients undergoing sigmoid colon resection with Hartmann's procedure and secondary descendorectostomy (Group B). RESULTS: Group A patients were comparable to Group B patients in age, gender, preoperative risk and severity of peritonitis (Mannheim Peritonitis Index and C-reactive protein). Operating room time for sigmoid colon resection with primary anastomosis (3.3 +/- 1.2 hours) was identical to the time for sigmoid colon resection with colostomy (3.3 +/- 1 hour), and morbidity and mortality, intensive care unit, and in-hospital stay were not significantly different between the two groups. In Group B patients' intestinal continuity was restored 169 +/- 74 days after the primary resection in 32 of 42 patients only (78 percent). The second procedure took on average 1.4 hours longer than the first procedure. Patients in Group B received more antibiotics (2.2 vs. 2) albeit for a shorter period of time (4.5 vs. 5.7 days, P = not significant). Overall expenses for restoration of intestinal continuity were between 74 and 229 percent higher for Group B patients than for Group A patients. Reimbursement was 18,191 +/- 16,761 SFr (Group A) and 41,321 +/- 26,983 SFr (Group B) respectively. CONCLUSION: With meticulous surgical technique and extensive intraoperative lavage, perforated sigmoid colon diverticulitis with peritonitis can be treated by a one-stage sigmoid colon resection and anastomosis with a low mortality and morbidity. A one-stage procedure is considerably cheaper and patients are rehabilitated faster and to a higher percentage.     

肝细胞癌放疗降期——从姑息走向根治

肿瘤分期是为了指导按分期治疗,某一期别的治疗方案不是一成不变的,应根据病情变化适时调整,尽可能朝有利疾病控制的方向转化。肝癌治疗进程需要随访和再分期,目的是为患者创造更好的治疗方案,特别是根治机会。局限肝内的大肝癌不能手术切除,经过介入栓塞化疗结合放疗,肿瘤缩小降期,部分转化为可手术切除,从不可治愈转化为可治愈。伴有门静脉癌栓的肝癌患者,经过新辅助放疗,癌栓缩小后再予手术切除,生存期较未新辅助放疗者显著延长。大肝癌经过综合治疗后降期为小肝癌,转化为立体定向放疗或射频消融,也可从姑息走向根治。肝癌放疗降期的临床报道渐多,循证级别逐渐提高,值得在临床实践中借鉴。     

A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum

PURPOSE: National Surgical Adjuvant Breast and Bowel Project Protocol R-03 was designed to determine the worth of preoperative chemotherapy and radiation therapy in the management of operable rectal cancer. METHODS: Thus far, 116 patients of an eventual 900 with primary operable rectal cancer have been randomized to receive multimodality therapy to begin preoperatively (59 patients) or identical therapy beginning after curative surgery (57). All patients received seven cycles of 5-fluorouracil (FU)/leucovorin (LV) chemotherapy. Cycles 1 and 4 through 7 used a high-dose weekly FU regimen. In Cycles 2 and 3, FU and low-dose LV chemotherapy was given during the first and fifth week of radiation therapy (5,040 cGy). The preoperative arm (Group 1) received the first three cycles of chemotherapy and all radiation therapy before surgery. The postoperative arm (Group 2) received all radiation and chemotherapy after surgery. Primary study end points included disease-free survival and survival. Secondary end points included local recurrence, primary tumor response to combination therapy, tumor downstaging, and sphincter preservation. RESULTS: Overall treatment-related toxicity was similar in both groups. Although seven preoperative patients had events after randomization that precluded surgery, eight events occurred during an equivalent follow-up period in the postoperative group. No patient was deemed inoperable because of progressive local disease. Sphincter-saving surgery was intended in 31 percent of Group 1 patients and 33 percent of Group 2 patients at the time of randomization. Such surgery was actually performed in 50 percent of the preoperatively treated patients and 33 percent of the postoperatively treated patients. The use of protective colostomy in patients undergoing sphincter-sparing surgery and the development of perioperative complications in all surgical patients were similar in both groups. There was evidence of tumor downstaging in evaluable patients under-going preoperative therapy, with 8 percent of Group 1 patients having had a pathologic complete response. CONCLUSION: These data do suggest that the preoperative chemotherapy and radiation therapy regimen used are, at least, as safe and tolerable as standard postoperative treatment. There is presently a trend to tumor downstaging and sphincter preservation in the preoperative arm. Whether this arm will have greater or lesser survival and long-term toxicity awaits the completion of this relevant study.Supported by National Cancer Institute Grants U10-CA-12027 and U10-CA-37377 and American Cancer Society Grant R-13.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Primaryvs. secondary anastomosis after sigmoid colon resection for perforated diverticulitis (Hinchey Stage III and IV)

PURPOSE: Our hypothesis was that in patients with perforated sigmoid colon diverticulitis and peritonitis (Hinchey Stage III and IV) a one-stage sigmoid colon resection is safe and cost effective when performed by an experienced colorectal surgeon. We evaluated outcome and cost of one-stagevs. two-stage sigmoid colon resection after diverticulitis perforation and peritonitis. METHODS: Patients undergoing emergency resection for perforated sigmoid colon diverticulitis and peritonitis (Hinchey Stage III and IV). Outcome, costs, and insurers reimbursement were compared between 13 patients undergoing sigmoid colon resection and primary anastomosis (Group A) and 42 patients undergoing sigmoid colon resection with Hartmann's procedure and secondary descendorectostomy (Group B). RESULTS: Group A patients were comparable to Group B patients in age, gender, preoperative risk and severity of peritonitis (Mannheim Peritonitis Index and C-reactive protein). Operating room time for sigmoid colon resection with primary anastomosis (3.3±1.2 hours) was identical to the time for sigmoid colon resection with colostomy (3.3±1 hour), and morbidity and mortality, intensive care unit, and in-hospital stay were not significantly different between the two groups. In Group B patients' intestinal continuity was restored 169±74 days after the primary resection in 32 of 42 patients only (78 percent). The second procedure took on average 1.4 hours longer than the first procedure. Patients in Group B received more antibiotics (2.2vs. 2) albeit for a shorter period of time (4.5vs. 5.7 days,P = not significant). Overall expenses for restoration of intestinal continuity were between 74 and 229 percent higher for Group B patients than for Group A patients. Reimbursement was 18,191±16,761 SFr (Group A) and 41,321±26,983 SFr (Group B) respectively. CONCLUSION: With meticulous surgical technique and extensive intraoperative lavage, perforated sigmoid colon diverticulitis with peritonitis can be treated by a one-stage sigmoid colon resection and anastomosis with a low mortality and morbidity. A one-stage procedure is considerably cheaper and patients are rehabilitated faster and to a higher percentage.Presented in part at the Mittelrheinischer Chirurgenkongress, Pforzheim, Germany, September 22 to 23, 2000.     

Interval to surgery after neoadjuvant treatment for colorectal cancer

The current standard treatment of low-lying locally advanced rectal cancer consists of chemoradiation followed by radical surgery.The interval between chemoradiation and surgery varied for many years until the1999 Lyon R90-01 trial which compared the effects of a short(2-wk)and long(6-wk)interval.Results showed a better clinical tumor response(71.7%vs 53.1%)and higher rate of positive and pathologic tumor regression(26%vs 10.3%)after the longer interval.Accordingly,a 6-wk interval between chemoradiation and surgery was set to balance the oncological results with the surgical complexity.However,several recent retrospective studies reported that prolonging the interval beyond 8or even 12 wk may lead to significantly higher rates of tumor downstaging and pathologic complete response.This in turn,according to some reports,may improve overall and disease-free survival,without increasing the surgical difficulty or complications.This work reviews the data on the effect of different intervals,derived mostly from retrospective analyses using a wide variation of treatment protocols.Prospective randomized trials are currently ongoing.     

Preoperative Chemoradiotherapy and Total Mesorectal Excision Surgery for Locally Advanced Rectal Cancer: Correlation With Rectal Cancer Regression Grade

PURPOSE Preoperative long-course chemoradiotherapy is recommended for rectal carcinoma when there is concern that surgery alone may not be curative. Downstaging of the tumor can be measured as rectal cancer regression grade (1-3) and may be of importance when estimating the prognosis. The aim of this study was to look at the long-term results of tumor regression in patients receiving long-course chemotherapy before surgical resection of rectal cancer.METHODS We reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinoma of the mid rectum or distal rectum found to be stage T3/4 between January 1995 and November 1999. Patients received 45 to 50 Gy irradiation in 2-Gy fractions and an infusion of 5-fluorouracil. Surgical specimens were assessed for rectal cancer regression grade. Patients were followed up routinely with clinical examination, computed tomography, and colonoscopy.RESULTS Sixty-five patients with a mean age 65 (range, 32–83) years underwent chemoradiotherapy before surgical resection. Thirty patients (46 percent) were classified as rectal cancer regression Grade 1, with 9 patients (14 percent) having complete sterilization of the tumor. Fifty-three patients (82 percent) underwent a curative resection. Overall survival, with a median follow-up of 39 (range, 24–83) months, was 67 percent and was associated with tumor downstaging. The local recurrence rate was 5.8 percent in those patients who underwent a curative resection and was significantly lower with rectal cancer regression Grade 1 tumors (P = 0.03). Eight of nine patients (89 percent) whose tumor had been sterilized were alive and well with no recurrence of tumor at a median follow-up of 41 (range, 24–70) months.CONCLUSIONS Preoperative chemoradiotherapy resulted in significant regression of tumor. Overall survival was high and was associated with downstaging of tumor. The local recurrence rate was significantly lower with rectal cancer regression Grade 1 tumors and was not seen in patients with sterilized tumors.Presented at the Association of Coloproctology of Great Britain and Ireland, Manchester, United Kingdom, July 2002.Reprints are not available.     

Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer: preliminary results

PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer may improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chemoradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anorectal function. METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative staging was based on digital rectal examination, endorectal ultrasound, and computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed with the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery was performed 46 (range, 24-63) days after completion of adjuvant therapy. RESULTS: Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-induced toxic reactions. Four patients developed intercurrent distant metastases or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty-eight patients underwent surgical resection: abdominoperineal resection, anterior resection, and Hartmann's procedure were performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma), and 5 percent, respectively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deterioration, after chemoradiation and surgery, in the quality of life on all subscales assessed, with physical, role, and social function being most severely affected. The symptoms most adversely affected were micturition, defecation, and gastrointestinal problems. Body image and sexual enjoyment deteriorated in both men and women. Chemoradiation alone led to prolonged pudendal nerve terminal motor latency in 57 percent of 7 patients assessed. CONCLUSION: Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rate, and adverse effects on quality of life and anorectal function.     

Preoperative induction therapy for locally advanced thymic tumors: a retrospective analysis using the ChART database

Background

To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies.

Methods

Between 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery directly after preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III–IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis.

Results

Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs. 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs. 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P=0.000), although R0 resection were similar (76.4% vs. 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P=0.000).

Conclusions

Preoperative neoadjuvant therapy have been used only occasionally in locally advanced thymic malignances. Effective induction therapy leading to tumor downstaging may be beneficial for potentially unresectable diseases, especially in patients with thymomas. These findings would be helpful to related studies in the future.     

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgery-first strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.     

elderly patients with unresectable pancreatic headcancer

AIM: To determine if surgical biliary bypass would provide improved quality of residual life and safe palliation in elderly patients with unresectable pancreatic head cancer. METHODS: Nineteen patients, 65 years of age or older, were managed with surgical biliary bypass (Group A). These patients were compared with 19 patients under 65 years of age who were managed with surgical biliary bypass (Group B). In addition, the results for group A were compared with those obtained from 17 patients, 65 years of age or older (Group C), who received percutaneous transhepatic biliary drainage to evaluate the quality of residual life. RESULTS: Five patients (26.0%) in Group A had complications, including one intraabdominal abscess, one pulmonary atelectasis, and three wound infections. One death (5.3%) occurred on postoperative day 3. With respect to morbidity, mortality, and postoperative hospitalization, no statistically significant difference was noted between Groups A and B. The number of readmissions and the rate of recurrent jaundice were lower in Group A than in Group C, to a statistically significant degree ( P = 0.019, P = 0.029, respectively). The median hospital-free survival period and the median overall survival were also significantly longer in Group A ( P = 0.001 and P < 0.001, respectively). CONCLUSION: Surgical palliation does not increase the morbidity or mortality rates, but it does increase the survival rate and improve the quality of life in elderly patients with unresectable pancreatic head cancer.     

Surgery for Locally Recurrent Rectal Cancer

PURPOSE Resection of locally recurrent rectal cancer after curative resection represents a difficult clinical problem and a surgical challenge. The aim of this study was to assess the outcome of a series of patients who underwent resection of locally recurrent rectal cancer with curative intent.METHODS A retrospective review was performed of 64 patients who underwent surgical exploration with a view to cure for locally recurrent rectal cancer under the care of one surgeon between April 1997 and April 2004. Details were obtained on the primary tumor and the operation, the indication for investigation of recurrence, preoperative imaging, operative findings, morbidity and mortality, and histopathology.RESULTS The median time interval between resection of primary tumor and surgery for locally recurrent disease was 31 (interquartile range, 21 to 48) months. Twenty-three patients had central disease, 10 patients had sacral involvement, 21 patients had pelvic sidewall involvement, and 10 patients had both sacral and sidewall involvement. Fifty-seven patients underwent resection of the tumor. Thirty-nine of the 57 patients underwent wide resection (abdominoperineal excision of rectum, anterior resection, or Hartmanns procedure) whereas 18 patients (31.6 percent) required radical resection (pelvic exenteration or sacrectomy). Curative, negative resection margins were obtained in 21 of 57 patients who had tumor excision (36.8 percent). Perioperative mortality was 1.6 percent. Significant postoperative morbidity occurred in 40 percent of patients.CONCLUSIONS This study has shown that a significant proportion of patients with locally recurrent rectal cancer can undergo resection with negative margins.     

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China

BackgroundThe downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging.MethodsWe performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China.ResultsRecipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.ConclusionsCompared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.     

Preoperative chemoradiation with capecitabine in locally advanced rectal cancer

BACKGROUND: Preoperative radiation therapy in combination with 5-fluoracil (5-FU) improves local tumour control in locally advanced rectal cancer. The aim of our study was to evaluate the toxicity and efficacy of preoperative chemoradiation using the oral 5-FU prodrug capecitabine in locally advanced rectal cancer. METHODS: Sixty patients with locally advanced rectal cancer were treated with preoperative chemoradiation. Radiotherapy consisted of a total dose of 50 Gy delivered in 25 fractions to the pelvis. Chemotherapy was concurrently administered and consisted of oral capecitabine only on radiotherapy days. Surgery was performed six to ten weeks after completion of chemoradiation. RESULTS: The patient population consisted of 19 females and 41 males, with a median age of 61 years. All but two patients received the full dose of chemoradiation. No grade 3 or 4 haematological toxicities developed. Two patients (3%) developed grade 3 radiation dermatitis and one a grade 3 diarrhoea. All patients underwent definitive surgery; 19 patients underwent an abdominal perineal resection (APR), 25 a low anterior resection (LAR) and 16 patients a Hartmann's procedure. One patient with a low anterior resection developed an anastomotic leakage (4%). Final pathology demonstrated eight patients (13%) with a complete pathological response. Primary tumour and nodal downstaging occurred in 67 and 84% of the patients, respectively. Two patients (3%) had an R1 resection, one after an APR and one after an LAR. CONCLUSION: Preoperative chemoradiation with oral capecitabine is safe and well tolerated in locally advanced rectal cancer patients. This preoperative treatment has a considerable downstaging effect on the tumour and lymph nodes.     

Rate of Pathologic Complete Response With Increased Interval Between Preoperative Combined Modality Therapy and Rectal Cancer Resection

INTRODUCTION Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy. Prolongation of the interval between preoperative combined modality therapy and surgery (RT-surgery interval) as a means of increasing pathologic complete response rate has not been fully examined.METHODS One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified. All patients had endorectal ultrasound prior to combined modality therapy. Final pathology reports were reviewed for ypT and ypN stage and margin status. Medical records were reviewed for sphincter preservation, operative time, estimated blood loss, hospital stay, and morbidity (overall, anastomotic, and perineal).RESULTS A pathologic complete response (ypT0N0) occurred in 24 patients (15 percent). Median RT-surgery interval was 44 (range, 15-206) days. A pathologic complete response occurred in 19 percent of patients with an interval >44 days, vs. 12 percent in those with an interval 44 days (P = 0.27). Downstaging by three stages occurred more frequently in the long-interval group (15 percent vs. 6 percent, P = 0.11). The rates of sphincter preservation, positive margins, estimated blood loss, and operative time were not significantly different. Overall morbidity was similar between groups.CONCLUSIONS Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval. However, sphincter preservation is not increased. Until prospective analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome, the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear.Supported by the National Cancer Institute, RO1 CA 82534-01 (J.G.G.).Read at the Meeting of the American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Reoperative rates for Crohn's disease following strictureplasty

Background: In Crohn's disease, ten-year reoperative recurrence rates after resection range from 30 to 53 percent. To determine the effect of strictureplasty on reoperative “recurrence” rates, experience at a single tertiary care institution was reviewed. PATIENTS AND MATERIALS: Records of all patients who underwent strictureplasty for Crohn's disease from June 1984 to July 1994 at a tertiary care institution were reviewed. Data collected included duration of disease, medical and surgical history related to Crohn's disease, indications for strictureplasty, and longterm outcome. RESULTS: One hundred sixty-two patients (87 male) underwent 191 operations for a total of 698 strictureplasties (Heineke-Mikulicz, 617; Finney's, 81). Mean number of strictureplasties was three, and mean patient age was 36 years. No mortality occurred. Cumulative five-year incidence of reoperative recurrence was 28 percent (95 percent confidence interval, 18.8–37.2 percent), with a median follow-up of 42 (range, 1–120) months. Obstructive symptoms were relieved in 98 percent of patients. To determine whether any difference in reoperative rates exists between patients who have strictureplasty alone and those who have strictureplasty with bowel resection, we divided patients in two groups, those receiving strictureplasty alone and those undergoing strictureplasty plus resection. For patients treated by strictureplasty alone (Group A, n=52; 32 percent), cumulative reoperative rate at five years was 31±9.6 (±standard error) and for patients with concomitant bowel resection (Group B, n=110; 68 percent), it was 27.2±5.4 (±standard error). No statistical difference was present between these two groups. Of patients undergoing strictureplasty alone (Group A), operative recurrence was managed by new strictureplasty in seven, by restrictureplasty in two, and by bowel resection in one. Among patients in Group B (strictureplasty and concomitant bowel resection), new strictureplasty was performed in 11, restrictureplasty in 6, and bowel resection in 9. CONCLUSION: Strictureplasty is a safe and effective procedure for Crohn's disease in selected patients. Reoperative rates are comparable with resective surgery, and most recurrences occur at new sites.     

Interpretation of Magnetic Resonance Imaging for Locally Advanced Rectal Carcinoma After Preoperative Chemoradiation Therapy

PURPOSE: Neoadjuvant concomitant chemoradiotherapy has been used in cases of locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. Preoperative staging is essential for planning and providing optimal therapy. The purpose of this study is to determine the accuracy of staging with magnetic resonance imaging and to define any factors that interfere in interpretation of images obtained after preoperative chemoradiation therapy.METHODS: Thirty-six patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed six to eight weeks later by radical surgery. Preoperative magnetic resonance images were reinterpreted by one radiologist and the results compared with histopathologic staging.RESULTS: T-level downstaging occurred in 10 of 36 patients (28 percent), and N-level downstaging occurred in 29 of 36 patients (80 percent) after completion of chemoradiation therapy. Pathologic complete remission after chemoradiotherapy occurred in five patients (12 percent). Of the 36 patients, 17 (47 percent) were overstaged and 2 (6 percent) were understaged in T-level, whereas 10 patients (28 percent) were overstaged and 3 patients (8 percent) were understaged in N-level. The accuracy of magnetic resonance imaging for determining depth of wall invasion was 47 percent, with 64 percent accuracy for nodal staging.CONCLUSIONS: Magnetic resonance imaging is commonly used in staging of pelvic malignancies because of its fine resolution, but chemoradiotherapy may decrease its accuracy. Thickening of the rectal wall after radiation by marked fibrosis, and peritumoral infiltration of inflammatory cells and vascular proliferation may contribute to overestimation of stage. By contrast, pathologic residual cancer beneath normal mural structure after chemoradiation therapy may result in understaging of rectal cancer.Presented at the Scientific Meeting of the Taiwan Surgical Association, Taipei, Taiwan, March 27 to 28, 2004.     

Perioperative outcomes after ultra low anterior resection in the era of neoadjuvant chemoradiotherapy

Purpose

Data on perioperative outcomes of sphincter preserving ultra low anterior resections (ULAR) following neoadjuvant chemoradiotherapy (NA-CTRT) is sparsely reported in literature.

Methods

Prospective data of 68 patients was reviewed retrospectively. Patients who received preoperative chemoradiotherapy (CTRT, Group A, n?=?45) were compared with those who were operated upfront (Group B, n?=?23).

Results

Overall, mean distance of the tumor from anal verge was 5.1 cm (range 3–8). In Groups A and B, it was 5.2 and 5.1 cm, respectively. In Group A, 3 patients had complete response, 40 had partial response and 2 had progressive disease. Overall, the mean distance of the anastomosis performed from the anal verge was 2.8 cm (range 1–4). In Groups A and B, it was 2.7 and 2.9 cm, respectively (NS). Mean blood loss in Groups A and B was 510.5 (range 200–2,200) and 345 mL (range 50–800), respectively (p?=?0.037). Two patients in Group A required blood transfusion (range 1–2) compared to none in Group B. The overall complication rate was 26.5 % (18/68); in Groups A and B, it was 22.2 % and 34.8 %, respectively. There was no postoperative mortality. Postoperative stay for Groups A and B was 8 and 9.5 days (p?=?0.009), respectively. In Group A, 23/45 patients, earlier planned for abdominoperineal resection, ultimately received sphincter–preserving ULAR.

Conclusion

ULAR can be performed safely without added morbidity or mortality after neoadjuvant chemoradiation. In some cases, earlier deemed to be suitable for APR, the neoadjuvant approach improved chances of sphincter conservation.