Piet Pattyn

Prognostic Value of the Lymph Node Ratio in Stage III Colorectal Cancer: A Systematic Review

BackgroundAlthough nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer, marked heterogeneity exists within stage III patients. Recently, the lymph node ratio (LNR), defined as the ratio of the number of positive nodes over the total number of examined nodes, was proposed to stratify outcome in stage III patients.MethodsA systematic search was performed for studies examining the prognostic significance of the LNR in colon or rectal cancer. Individual studies were assessed for methodological quality and summary data extracted. Hazard ratios from multivariate analyses were entered in a fixed-effects meta-analysis model.ResultsIn total, 16 studies were identified including 33,984 patients with stage III colon or rectal cancer. In all identified studies, the LNR was identified as an independent prognostic factor in patients with stage III cancer of the colon or rectum. The prognostic separation obtained by the LNR was superior to that of the number of positive nodes (N stage). The pooled hazard ratios for overall and disease-free survival were 2.36 (95% confidence interval, 2.14–2.61) and 3.71 (95% confidence interval, 2.56–5.38), respectively.ConclusionsThe LNR allows superior prognostic stratification in stage III colorectal cancer and should be validated in prospective studies.Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer, marked heterogeneity exists within stage III patients. Recently, the lymph node ratio (LNR), defined as the ratio of the number of positive nodes over the total number of examined nodes, was proposed to stratify outcome in stage III patients. A systematic search was performed for studies examining the prognostic significance of the LNR in colon or rectal cancer. Individual studies were assessed for methodological quality and summary data extracted. Hazard ratios from multivariate analyses were entered in a fixed-effects meta-analysis model. In total, 16 studies were identified including 33,984 patients with stage III colon or rectal cancer. In all identified studies, the LNR was identified as an independent prognostic factor in patients with stage III cancer of the colon or rectum. The prognostic separation obtained by the LNR was superior to that of the number of positive nodes (N stage). The pooled hazard ratios for overall and disease-free survival were 2.36 (95% confidence interval, 2.14–2.61) and 3.71 (95% confidence interval, 2.56–5.38), respectively. The LNR allows superior prognostic stratification in stage III colorectal cancer and should be validated in prospective studies.

Surgery, wound healing, and metastasis: Recent insights and clinical implications

BACKGROUNDnSurgery-induced acceleration of tumour growth has been observed since several centuries.nnnMETHODSnWe reviewed recent insights from in vitro data, animal experimentation, and clinical studies on how surgery-induced wound healing or resection of a primary cancer influences the tumour-host ecosystem in patients harbouring minimal residual or metastatic disease.nnnRESULTSnMost of the growth factors, chemokines, and cytokines orchestrating surgical wound healing promote tumour growth, invasion, or angiogenesis. In addition, resection of a primary tumour may accelerate synchronous metastatic growth. In the clinical setting, indirect evidence supports the relevance of the above findings. Randomized clinical trials are underway comparing resection versus observation in metastatic breast and colon cancer with asymptomatic primary tumours.nnnCONCLUSIONSnIn depth knowledge of how surgical intervention alters the tumour-host-metastasis communicating ecosystems could have important implications for clinical decision making in patients with synchronous metastatic disease and for the design and timing of multimodality treatment strategies.

Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomy

OBJECTIVESnOesophageal carcinoma (EC) remains an aggressive disease. Despite extensive changes in therapeutic modalities, surgical resection remains the first choice therapy for curable oesophageal cancer patients. Anastomotic sites are prone to serious complications such as leakage, fistula, bleeding and stricture. Leakage of the anastomosis (AL) remains one of the main causes of postoperative morbidity and mortality. The purpose of this study was to identify predictors associated with postoperative leakage after Ivor Lewis oesophagectomy and its consequences in a single centre.nnnMETHODSnWe performed a retrospective analysis of 412 Ivor Lewis oesophageal resections in a single institute between 2005 and 2014. Univariable and multivariable logistic regression have been used to identify predictors of AL and its impact on postoperative outcome and overall survival. Kaplan-Meier curve was used to analyse overall survival and log-rank analysis to determine odds ratio.nnnRESULTSnA total of 412 patients were evaluated. Mean age was 62 ± 11 years (77% male). Overall leak rate was 2.9%. In-hospital or 30-day mortality was 4.4%. Mean intensive care unit (ICU) stay was 1 day and mean hospital stay was 19 days. A history of renal failure, diabetes, higher American Society of Anaesthesiologists score and current cigarette and corticosteroid use were identified as predictors of AL on univariable analysis. Multivariable analysis identified active smoking [P = 0.05, odds ratio (OR) 4.34, 95% confidence interval (CI): 0.98-19.28] and active corticosteroid use (P < 0.001, OR 15.8, 95% CI: 3.25-76.7) as independent significant predictors. A history of diabetes tended to be associated with a higher leakage rate but failed to reach statistical significance. AL was associated with a longer ICU and hospital stay and a significantly higher mortality (42% in the AL group vs 3% in the control group, P < 0.0001).nnnCONCLUSIONSnAnastomotic leakage after oesophagectomy is a major cause of postoperative morbidity and mortality. Identifying risk factors preoperatively can contribute to the prevention of postoperative complications.

Use of bone anchors in perineal hernia repair: a practical note.

BackgroundBone anchoring systems are used extensively in orthopaedic surgery but have scarcely been reported as useful in abdominal wall or perineal hernia repair. After coccygectomy or sacrectomy the development of bowel herniation is not uncommon. Considering repair of such a perineal hernia, adequate fixation of the prosthetic mesh is difficult and, therefore, recurrence is rather frequent, mostly due to insufficient anchoring of the mesh to the bony structures.MethodsWe discuss a patient in which the Mitek GII anchoring system was used to overcome the problem of soft-tissue-to-bone attachment in such cases.ConclusionBone anchoring systems seem to be an efficient method to overcome the problems of soft-tissue-to bone attachment in both abdominal and perineal hernia repair.

Isolation of Enterococcus avium from bile and blood in a patient with acute cholecystitis.

The isolation of Enterococcus avium from bile fluid and blood of an uncompromised patient with acute cholecystitis is reported. As advanced identification of Enterococcus sp. by biochemical and physiological tests is not routinely done, the occurrence of E. avium infections may be underestimated.

Functional outcome after Ivor Lewis esophagectomy for cancer.

Little is known on functional outcome after Ivor Lewis esophagectomy (ILE) with intrathoracic anastomosis.

Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer

Most patients with rectal cancer receive neoadjuvant radiochemotherapy (RCT), causing a variable decrease in tumor mass. We evaluated the prognostic impact of pathologic parameters reflecting tumor response to RCT, either directly or indirectly. Seventy-six rectal cancer patients receiving neoadjuvant RCT between 2006 and 2009 were included. We studied the association between disease-free survival (DFS) and the “classical” clinicopathologic features as well as tumor deposits, circumferential resection margin (CRM), Dworak regression grade, and tumor and nodal downstaging. Patients with tumor downstaging had a longer DFS (pu2009=u20090.05), indicating a more favorable prognosis when regression was accompanied by a decrease in tumor infiltrative depth, referred to as tumor shrinkage. Moreover, tumor downstaging was significantly associated with larger CRM and nodal downstaging (pu2009=u20090.02), suggesting that shrinkage of the primary tumor was associated with a decreased nodal tumor load. Higher Dworak grade did not correlate with tumor downstaging, nor with higher CRM or prolonged DFS. This implies that tumor mass decrease was sometimes due to fragmentation rather than shrinkage of the primary tumor. Lastly, the presence of tumor deposits was clearly associated with reduced DFS (pu2009=u20090.01). Assessment of tumor shrinkage after RCT via tumor downstaging and CRM is a good way of predicting DFS in rectal cancer, and shrinkage of the primary tumor is associated with a decreased nodal tumor load. Assessing regression based on the amount of tumor in relation to stromal fibrosis does not accurately discern tumor fragmentation from tumor shrinkage, which is most likely the reason why Dworak grade had less prognostic relevance.

Functional Outcome Following Colon Interposition in Total Pharyngoesophagectomy with or without Laryngectomy

Our study compares deglutition between a group who had undergone total esophagopharyngolaryngectomy and a group who had esophagectomy and partial pharyngectomy with preserved larynx, after reconstruction of the upper digestive tract with pedicled colon interposition. In four patients the laryngeal structures could be preserved (three caustic burns and one proximal esophageal tumor). Six patients underwent a total laryngopharyngectomy for large pharyngeal tumors. Swallowing was assessed by a questionnaire, clinical examination, and videofluoroscopy. All patients had normal intake of semisolid foods and fluids. All patients but three experienced some feeling of “narrowing” of the tract: four at the level of the hypopharynx, two at the oropharyngeal level, one at the oral level. In the laryngectomy group, solid food caused some degree of delayed swallowing in three patients. Dumping occurred in one case out of the nonlaryngectomy group. On clinical examination a tense motility in all laryngectomy patients appeared, food remnants in five and repeated swallowing movements in four. The videofluoroscopy confirmed repeated swallowing movements and presence of residual food in the oral cavity. Temporal stagnation occurred at the anastomosis site in all patients and in two patients at a place of colon redundancy. Colon interposition is a reliable reconstruction and gives the possibility of a good functional outcome. Although preservation of the larynx facilitates swallowing even in this reconstructive procedure, it may be better to perform a total laryngopharyngectomy and colon interposition in oncological cases where the pharyngeal remnant is borderline for primary closure.

Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer

Abstract Introduction : Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. Methods : From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). Results : 147 patients were evaluated: 109 received 36 Gy, while 38 received 41–50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). Conclusions : In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.INTRODUCTIONnNeoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined.nnnMETHODSnFrom a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1).nnnRESULTSn147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001).nnnCONCLUSIONSnIn patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

The VEGFR Inhibitor Cediranib Improves the Efficacy of Fractionated Radiotherapy in a Colorectal Cancer Xenograft Model

Background/Purpose: Radiotherapy (RT) increases local tumor control in locally advanced rectal cancer, but complete histological response is seen in only a minority of cases. Antiangiogenic therapy has been proposed to improve RT efficacy by “normalizing” the tumor microvasculature. Here, we examined whether cediranib, a pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, improves microvascular function and tumor control in combination with RT in a mouse colorectal cancer (CRC) model. Methods: CRC xenografts (HT29) were grown subcutaneously in mice. Animals were treated for 5 consecutive days with vehicle, RT (1.8 Gy daily), cediranib (6 mg/kg po), or combined therapy (cediranib 2 h prior to radiation). Tumor volume was measured with calipers. Vascular changes were analyzed by dynamic contrast-enhanced MRI, oxygenation and interstitial fluid pressure probes and histology. To investigate vascular changes more in detail, a second set of mice were fitted with titanium dorsal skinfold window chambers, wherein a HT29 tumor cell suspension was injected. In vivo fluorescence microscopy was performed before and after treatment (same treatment protocol). Results: In vivo microscopy analyses showed that VEGFR inhibition with cediranib led to a “normalization” of the vessel wall, with decreased microvessel permeability (p < 0.0001) and tortuosity (p < 0.01), and a trend to decreased vessel diameters. This seemed to lead to lower tumor hypoxia rates in the cediranib and combination groups compared to the control and RT groups. This led to an increased tumor control in the combination group compared to controls or monotherapy (p < 0.0001). Conclusions: The combination of RT with cediranib enhances tumor control in a CRC xenograft mouse model. Microvascular analyses suggest that cediranib leads to vascular normalization and improved oxygenation.