The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer and B cell chronic lymphocytic leukaemia (CLL) have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another.</p> <p>Case presentation</p> <p>A 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL.</p> <p>Conclusion</p> <p>Whilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.</p

Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons

The accuracy of Multi-detector row CT for the assessment of tumor invasion of the mesorectal fascia in primary rectal cancer

PURPOSE: To evaluate the accuracy of Multi-detector row CT (MDCT) for the prediction of tumor invasion of the mesorectal fascia (MRF). MATERIALS AND METHODS: A total of 35 patients with primary rectal cancer underwent preoperative staging magnetic resonance imaging (MRI) and MDCT. The tumor relationship to the MRF, expressed in 3 categories (1--tumor free MRF = tumor distance > or = 1 mm; 2--threatened = distance < 1 mm; 3--invasion = distance 0 mm) was determined on CT by two observers at patient level and at different anatomical locations. A third expert reader evaluated the MRF tumor relationship on MRI, which served as reference standard. Receiver operating characteristic curves (ROC-curves) and areas under these curves (AUC) were calculated. The inter-observer agreement of CT was determined by using linear weighted kappa statistics. RESULTS: The AUC of CT for MRF invasion was 0.71 for observer 1 and 0.62 for observer 2. The inter-observer agreement was kappa = 0.34. The performance of CT at mid-high rectal levels was statistically significant better compared to low anterior (obs.1: AUC = 0.88 vs. 0.50; obs 2: AUC = 0.84 vs. 0.31; P < or = 0.040). CONCLUSION: Multi-detector row CT has a poor accuracy for predicting MRF invasion in low-anterior located tumors.The accuracy of CT significantly improves for tumors in the mid-high rectum. There is a high inconsistency among readers

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70 – 79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics

Locally advanced and recurrent cancer

A successful treatment of locally advanced and recurrent rectal cancer is based on the responsibility of the surgeon to perform a radical resection. Planning of treatment starts with imaging with a pelvic MRI and a CT scan of chest and the abdomen. Neoadjuvant chemoradiation is given to achieve downstaging and downsizing. After a waiting period of at least 6 weeks, a total mesorectal excision is performed with often an extra-anatomical extension based on the initial imaging. Reconstruction using several types of pedicled flaps is often necessary to close the defect of the pelvic floor.</p

A phase I/II study of oxaliplatin when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group (CCOG) study

The purpose of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of oxaliplatin given synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation for primary unresectable, locally advanced, rectal cancer. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction, and delivered with escalating doses of oxaliplatin in combination with low-dose LV and 5FU. Chemotherapy was given synchronously with radiotherapy in weeks 1 and 5. Escalating doses of oxaliplatin (85, 130 and 150 mg m−2) were given on days 2 and 30, followed by low-dose LV (20 mg m−2) and 5FU (350 mg m−2), both given on days 1–5 and 29–33. Surgery was performed 6–10 weeks later. The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT). Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In all, 32 patients received oxaliplatin at the three dose levels, median age 60 years (range 31–79), 24 males and eight females. The MTD was reached at 150 mg m−2 when four out of six patients experienced DLT. Dose-limiting grade 3 or 4 diarrhoea was reported in two out of six patients at 85 mg m−2, 5 out of 20 at 130 mg m−2 and four out of 6 at 150 mg m−2. Grade 3 neuropathy was reported at 130 mg m−2 (1 out of 20) and at 150 mg m−2 (two out of six), and serious haematological toxicity was minimal; one grade 3 anaemia at 150 mg m−2. In all, 28 out of 32 patients completed all treatments as planned; three had radiotherapy interrupted and three a chemotherapy dose reduction. Four patients did not proceed to surgery due to the presence of metastatic disease (two), unfitness (one) or patient refusal (one). Also, 28 patients underwent surgical resection. Histopathology demonstrated histopathological complete response (pCR) 2 out of 27 (7%), Tmic 3 out of 27 (11%), pCR+Tmic 5 out of 27 (19%), pT0–2 6 out of 27 (22%) and histologically confirmed clear circumferential resection margins in 22 out of 27 (81%). Dose-limiting toxicity with oxaliplatin is 150 mg m−2 given days 2 and 30 when added to the described 5FU LV and 45 Gy radiation preoperatively. The acceptable toxicity and compliance at 130 mg m−2 recommend testing this dose in future phase II studies. The tumour downstaging and complete resection rates are encouragingly high for this very locally advanced group

A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m−2) administered on days 1–5 and 29–33 followed by low dose LV (20 mg m−2) and 5FU (350 mg m−2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6–10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26–75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m−2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m−2 (days 1–5 and 29–33). The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group