A. Chiappa

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

BackgroundThis study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.MethodsA consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.ResultsOf the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).ConclusionA prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

PURPOSEnThis study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer.nnnPATIENTS AND METHODSnWe retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied.nnnRESULTSnMedian age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2-73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15).nnnCONCLUSIONSnMore extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer.nnnSYNOPSISnThe impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.

The management of colorectal liver metastases: Expanding the role of hepatic resection in the age of multimodal therapy

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patients treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Epidermal growth factor receptor serum (sEGFR) level may predict response in patients with EGFR-positive advanced colorectal cancer treated with gefitinib?

PurposeEpidermal growth factor receptor-overexpression reported in colorectal cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted a phase II study in 57 patients with EGFR-positive advanced colorectal cancer (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as maintenance. Main biological objective was to assess sEGFR as surrogate marker of tyrosine kinase inhibition and as predictor of response.MethodssEGFR, evaluated by quantitative ELISA, was investigated as predictive factor both taking into account the basal value only, and its whole pattern over time. sEGFR was collected at baseline and at every 2-months assessment in 42 cases. Thirty-three patients reported CR/PR as best objective response (BOR), while nine showed SD/PD.ResultsRetrospectively, on average, the sEGFR values reported by both responders (CR/PR) and not responders (SD/PD) were already different at baseline (49.4xa0±xa06.2 and 42.4xa0±xa08.4xa0ng/ml respectively). This difference was statistically significant (pxa0=xa00.042). Although sEGFR trend over time confirmed the basal difference (pxa0=xa00.032), this result should be taken with caution, due to the small number of patients reporting EGFR values besides the basal one.ConclusionsHigher sEGFR at baseline was associated to BOR and may be considered a significant predictor of outcome in patients with ACC.

Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial

BACKGROUNDnFluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data.nnnPATIENTS AND METHODSnPatients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy.nnnRESULTSnThis trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A.nnnCONCLUSIONnDocetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation

BACKGROUNDnThe role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients.nnnMETHODSnFrom two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS).nnnRESULTSnThe two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the 18FDG PET-CT and age. In the operated patients, surgical morbidity comprised 7 cases of pancreatic fistula. Postoperative mortality was nil. Median OS for patients undergoing left-pancreatectomy was 111 months vs 52 for the non operated patients (pxa0=xa00.003). At multivariate analysis after propensity score adjustment, no surgery as well as liver tumour burden>25% and higher Ki-67 index were associated with an increased risk of death during follow-up. In patients with unresectable primary tumour, OS was similar in comparison to that in the resectable but non-resected patients, and significantly worse than that in the resected patients (pxa0=xa00.032).nnnCONCLUSIONnIn PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic.

Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

Backgroundalthough preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isnt yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up.Methodspatients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3–4/anyN, or anyT/N1–2; ECOG Performance Status 0–2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 ± 2 days after RT completion, adopting the total mesorectal excision technique.Results24 men and 23 women were enrolled; median age was 55 years (r.: 39–77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18–84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence.Conclusionbifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT.