Claus Bisgaard

PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

PurposeThe objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation.MethodsThe study included 30 patients with locally advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral® (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic tumor regression as the “standard.” The pathologic response was quantified by tumor regression grade.ResultsPositron emission tomography/computer tomography correctly identified six of eight patients (specificity 75 percent) with complete pathologic response. However, the sensitivity of positron emission tomography/computer tomography was only 45 percent and the accuracy 53 percent. The positive and negative predictive values were 83 and 33 percent, respectively.ConclusionsWe conclude that positron emission tomography/computer tomography performed seven weeks after the end of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography.

Peritoneal microdialysis. Early diagnosis of anastomotic leakage after low anterior resection for rectosigmoid cancer.

Background: The aim of the present study was to evaluate the efficacy and safety of intraperitoneal microdialysis in early detection of anastomotic leakage after low anterior resection for rectosigmoid cancer. Methods: In a series of 116 consecutive patients scheduled for low anterior resection for rectosigmoid cancer, a total of 50 patients consented to participate. Peritoneal microdialysis was performed by a 1 mm thin catheter anchored in close proximity to the anastomosis. Five patients were excluded due to catheter malfunction. Average microdialysis time in the remaining 45 patients was 177.6 (80–252) hours. Samples were collected every 4-hours, and the concentration of glucose, lactate, pyruvate and glycerol was measured. Results: Four patients developed symptomatic anastomotic leakage. Two patients developed non-abdominal sepsis. In 38 patients the postoperative course was uncomplicated, considering major complications, and they served as controls. In three patients with late (≥ 10 days) anastomotic leakage a significant increase in concentration of lactate and lactate/pyruvate ratio (L/P-ratio) was seen several days prior to development of clinical symptoms. In one patient with early anastomotic leakage it coincided with the development of clinical symptoms. In the two patients with non-abdominal sepsis the values were within normal range. Conclusion: Peritoneal microdialysis is a safe and promising tool in early diagnosis of anastomotic leakage after low anterior resection for rectosigmoid cancer.

Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC)

Background. Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery. Methods. Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days (divided in three doses). Results. From September 2000 to November 2004, 52 patients (median age 60 years (32–83); median PS 0 (0–2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25–49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27–112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6–45.2 months). Twenty-one patients (40%) are still alive June 2007. Conclusions. Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

Transrectal ultrasonography and magnetic resonance imaging in the staging of rectal cancer. Effect of experience.

Objective. To evaluate the effect of experience on preoperative staging of rectal cancer using magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). Material and methods. From January 2002 to May 2006, 134 consecutive patients with biopsy-proven rectal cancer were examined with a 1.5-Tesla MRI unit and TRUS using a 6.5-MHz transducer. An experienced gastrointestinal radiologist (R1) or a general radiologist (R2) performed the evaluations. All patients (78 M, 56 F, mean age 69.1 years, range 38–89) were treated with surgery alone. The mean size of the tumour was 4.0 cm (range 1.1–7.5). A complete postoperative histopathological examination was used as the gold standard. Results. At pathology, 42 of 134 (31%) tumours were classified as T1-T2 and 92 (69%) were classified as T3-T4. The TRUS sensitivity in rectal tumour T-staging was 93% for R1 and 75% for R2 (p<0. 01); specificity was 83% for R1 and 46% for R2 (p<0.05). The MRI sensitivity in rectal tumour T-staging was 96% for R1 and 77% for R2 (p<0. 05); the specificity was 74% for R1 and 40% for R2 (p<0.05). There was no difference in the results of N-staging between R1 and R2 for either TRUS or MRI. Conclusion. Reader experience had a statistically significant positive effect on the preoperative prediction of tumour involvement of the rectal wall. To obtain high-quality preoperative prediction of rectal cancer T-stage, it is suggested that preoperative TRUS and MRI staging should be supervised by an expert in the colorectal cancer team. In addition to this supervision, the person responsible for staging should be trained through a defined training programme.