Contrast-enhanced ultrasound can guide the therapeutic strategy by improving the detection of colorectal liver metastases.

BACKGROUND & AIMS: CT may miss up to 30% of cases of colorectal liver metastases (CRLMs). We assessed the impact of contrast-enhanced ultrasound (CEUS) on the detection of CRLMs and on changes to the therapeutic strategy; additionally, we assessed the accuracy of CEUS in differentiating unclear focal liver lesions (FLLs) compared to staging-CT. METHODS: We prospectively analyzed all patients with newly diagnosed and histologically confirmed colorectal cancer (CRC) at our tertiary gastroenterological center between December 2015 and May 2019. CEUS was performed in a total of 296 patients without CRLMs after staging-CT using the contrast agent (SonoVue®). Standard of reference was obtained by MRI or histology to diagnose CRLMs missed by CT. Benign FLLs were confirmed by MRI or follow-up CT (mean follow-up interval: 18 months). RESULTS: Eight additional CRLMs were detected by CEUS (overall 2.7%; sensitivity 88.9%, specificity 99.0%, positive predictive value 100%, negative predictive value 99.6%). All patients with CRLMs detected only by CEUS were in tumor stage T3/T4 (4.0% additionally detected CRLMs). The number needed to screen to detect 1 additional CRLM by CEUS was 37 in all patients and 24.5 in T3/T4-patients. When results were reviewed by a board-certified radiologist and oncologist, the therapeutic strategy changed in 6 of these 8 patients. Among the 62 patients (20.9%) with unclear FLLs after staging-CT, CEUS determined the dignity (malignant vs. benign) of 98.4% of the FLLs. CONCLUSION: Overall, CEUS detected 2.7% additional CRLMs (including 4.0% in tumor stage T3/T4) with a significant impact on the oncological therapeutic strategy for 75% of these patients. Patients with tumor stage T3/T4 would particularly benefit from CEUS. We propose CEUS as the first imaging modality for CT-detected lesions of unknown dignity. LAY SUMMARY: In patients with newly diagnosed colorectal cancer, contrast-enhanced ultrasound (CEUS) detected additional liver metastases after computed tomography (CT). In the majority of these patients, the oncological therapy was changed after obtaining the CEUS results. After staging-CT, 21% of hepatic lesions remained unclear. In these cases, CEUS was accurate to either reveal or exclude liver metastasis in nearly all patients and could reduce costs (e.g., number of MRI scans).

Molecular Lymph Node Staging with One-Step Nucleic Acid Amplification and its Prognostic Value for Patients with Colon Cancer: The First Follow-up Study.

BACKGROUND: Molecular lymph node workup with one-step nucleic acid amplification (OSNA) is a validated diagnostic adjunct in breast cancer and also appealing for colon cancer (CC) staging. This study, for the first time, evaluates the prognostic value of OSNA in CC. PATIENTS AND METHODS: The retrospective study includes patients with stage I-III CC from three centres. Lymph nodes were investigated with haematoxylin and eosin (H&E) and with OSNA, applying a 250 copies/µL threshold of CK19 mRNA. Diagnostic value of H&E and OSNA was assessed by survival analysis, sensitivity, specificity and time-dependent receiver operating characteristic curves. RESULTS: Eighty-seven patients were included [mean follow-up 53.4 months (± 24.9)]. Disease recurrence occurred in 16.1% after 19.8 months (± 12.3). Staging with H&E independently predicted worse cancer-specific survival in multivariate analysis (HR = 10.77, 95% CI 1.07-108.7, p = 0.019) but not OSNA (HR = 3.08, 95% CI 0.26-36.07, p = 0.197). With cancer-specific death or recurrence as gold standard, H&E sensitivity was 46.7% (95% CI 21.3-73.4%) and specificity 84.7% (95% CI 74.3-92.1%). OSNA sensitivity and specificity were 60.0% (95% CI 32.3-83.7%) and 75.0% (95% CI 63.4-84.5%), respectively. CONCLUSIONS: In patients with CC, OSNA does not add relevant prognostic value to conventional H&E contrasting findings in other cancers. Further studies should assess lower thresholds for OSNA (< 250 copies/µL).

Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases.

BACKGROUND: Approximately one third of all patients with CRC present with, or subsequently develop, colorectal liver metastases (CRLM). The objective of this population-based analysis was to assess the impact of resection of liver only, lung only and liver and lung metastases on survival in patients with metastatic colorectal cancer (mCRC) and resected primary tumor. METHODS: Ten thousand three hundred twenty-five patients diagnosed with mCRC between 2010 and 2015 with resected primary were identified in the Surveillance, Epidemiology and End Results (SEER) database. Overall, (OS) and cancer-specific survival (CSS) were analyzed by Cox regression with multivariable, inverse propensity weight, near far matching and propensity score adjustment. RESULTS: The majority (79.4%) of patients had only liver metastases, 7.8% only lung metastases and 12.8% metastases of lung and liver. 3-year OS was 44.5 and 27.5% for patients with and without metastasectomy (HR = 0.62, 95% CI: 0.58-0.65, P < 0.001). Metastasectomy uniformly improved CSS in patients with liver metastases (HR = 0.72, 95% CI: 0.67-0.77, P < 0.001) but not in patients with lung metastases (HR = 0.84, 95% CI: 0.62-1.12, P = 0.232) and combined liver and lung metastases (HR = 0.89, 95% CI: 0.75-1.06, P = 0.196) in multivariable analysis. Adjustment by inverse propensity weight, near far matching and propensity score and analysis of OS yielded similar results. CONCLUSIONS: This is the first SEER analysis assessing the impact of metastasectomy in mCRC patients with removed primary tumor on survival. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in OS and CSS for liver resection but not for metastasectomy of lung or both sites.

The prognostic value of signet ring cell histology in stage I/II colon cancer-a population-based, propensity score-matched analysis.

BACKGROUND: Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer. METHODS: Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods. RESULTS: Eighty-eight thousand nine hundred fifty-eight stage I-II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p < 0.001; CSS, p < 0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82-1.12%) p = 0.616; CSS: HR, 1.01 (95% CI, 0.79-1.28%) p = 0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82-1.14%) p = 0.669 and CSS: HR: 1.09 (95% CI: 0.84-1.40%) p = 0.529), a survival disadvantage was found for signet ring cell histology. CONCLUSION: This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes.

BACKGROUND: The lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN. METHODS: One hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3 months. RESULTS: Fifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8-54). DFS and OS were significantly shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and 4.5 (p = 0.054). CONCLUSIONS: LNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

Revisiting a dogma: similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis.

BACKGROUND: The objective of the present analysis was to assess whether small bowel gastrointestinal stromal tumor (GIST) is associated with worse cancer-specific survival (CSS) and overall survival (OS) compared with gastric GIST on a population-based level. PATIENTS AND METHODS: Data on patients aged 18 years or older with histologically proven GIST was extracted from the SEER database from 1998 to 2011. OS and CSS for small bowel GIST were compared with OS and CSS for gastric GIST by application of adjusted and unadjusted Cox regression analyses and propensity score analyses. RESULTS: GIST were located in the stomach (n = 3011, 59 %), duodenum (n = 313, 6 %), jejunum/ileum (n = 1288, 25 %), colon (n = 139, 3 %), rectum (n = 172, 3 %), and extraviscerally (n = 173, 3 %). OS and CSS of patients with GIST in the duodenum [OS, HR 0.95, 95 % confidence interval (CI) 0.76-1.19; CSS, HR 0.99, 95 % CI 0.76-1.29] and in the jejunum/ileum (OS, HR 0.97, 95 % CI 0.85-1.10; CSS, HR = 0.95, 95 % CI 0.81-1.10) were similar to those of patients with gastric GIST in multivariate analyses. Conversely, OS and CSS of patients with GIST in the colon (OS, HR 1.40; 95 % CI 1.07-1.83; CSS, HR 1.89, 95 % CI 1.41-2.54) and in an extravisceral location (OS, HR 1.42, 95 % CI 1.14-1.77; CSS, HR = 1.43, 95 % CI 1.11-1.84) were significantly worse than those of patients with gastric GIST. CONCLUSIONS: Contrary to common belief, OS and CSS of patients with small bowel GIST are not statistically different from those of patients with gastric GIST when adjustment is made for confounding variables on a population-based level. The prognosis of patients with nongastric GIST is worse because of a colonic and extravisceral GIST location. These findings have implications regarding adjuvant treatment of GIST patients. Hence, the dogma that small bowel GIST patients have worse prognosis than gastric GIST patients and therefore should receive adjuvant treatment to a greater extent must be revisited.

Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial.

BACKGROUND: Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS: A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS: SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS: This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.

A population-based analysis of secondary malignancies in breast cancer patients receiving breast reconstruction.

BACKGROUND: There is an ongoing debate about the relationship between breast implants and secondary malignancies. METHODS: Breast cancer patients undergoing surgical reconstruction after mastectomy by either implants or autologous flap were identified in the Surveillance, Epidemiology and End Results registry between 1998 and 2002. The occurrence of secondary malignancies at least 1 year after diagnosis was compared between breast reconstruction with implants vs autologous flap. RESULTS: Of 7955 women, 3727 underwent reconstruction using implants and 4228 using autologous flap. The incidence of secondary tumours was similar in both the groups (hazards ratio (HR)=1.02, 95% confidence interval (CI): 0.82-1.26, P=0.880). For lung cancer, a significantly increased risk for implants (HR=2.51, 95% CI: 1.28-4.95, P=0.005) was observed. CONCLUSIONS: Except for lung cancer, no association between implants and secondary malignancies including lymphomas was observed.

Predictive value of mucinous histology in colon cancer: a population-based, propensity score matched analysis.

BACKGROUND: This investigation aimed to assess whether mucinous histology impacts overall (OS) and cancer-specific survival (CSS) in colon cancer. METHODS: Colon cancer patients who underwent surgery between 2004 and 2011 were identified in the Surveillance, Epidemiology, and End Results database. OS and CSS were assessed using Cox regression and propensity score methods. RESULTS: Out of 121 628 patients, 12 863 (10.6%) had a mucinous histology. Five-year OS and CSS for mucinous adenocarcinoma were 54.4% (95% CI: 53.4-55.5%) and 66.5% (95% CI: 65.5-67.5%) compared with 60.2% (95% CI: 59.8-60.5%) and 71.9% (95% CI: 71.5-72.2%) for non-mucinous adenocarcinoma (P<0.001). This survival disadvantage disappeared in multivariable analyses (hazard ratio (HR)=1.02, 95% CI: 0.99-1.05, P=0.269 and HR=1.03, 95% CI: 0.99-1.06, P=0.169), and after propensity score matching (OS: HR=0.99, 95% CI: 0.93-1.04, P=0.606 and CSS: HR=0.99, 95% CI:0.92-1.06, P=0.783). CONCLUSIONS: In this population-based investigation, a mucinous histology did not negatively impact survival. Hence, the present study does not provide evidence to change treatment strategies in patients with mucinous adenocarcinoma of the colon.

Improved Survival After Primary Tumor Surgery in Metastatic Breast Cancer: A Propensity-adjusted, Population-based SEER Trend Analysis.

BACKGROUND: There is ongoing debate about nonpalliative primary tumor surgery in metastatic breast cancer patients. This issue has become even more relevant with the introduction of increasingly sensitive imaging modalities. METHODS: Metastatic breast cancer patients were identified in the SEER registry between 1998 and 2009. The effect of primary tumor surgery on overall and cancer-specific mortality using risk-adjusted Cox proportional hazard regression modeling and stratified propensity score matching was assessed. RESULTS: Overall, 16,247 women with metastatic breast cancer were included. Of those 7600 women underwent primary tumor surgery although 8647 did not have any surgery at all. Primary tumor surgery decreased from 62.0% in 1998 to 39.1% in 2009 (P < 0.001). Primary tumor surgery was associated with decreased overall mortality (hazard ratio (HR) = 0.53, 95% CI 0.50-0.55, P < 0.001) and cancer-specific mortality (HR = 0.51, 95% CI 0.48-0.54, P < 0.001) in the propensity score-matched model. The benefit of primary tumor surgery increased from 1998 to 2009 for overall mortality (1998: HR = 0.72, 95% CI 0.59-0.89, 2009: HR = 0.42, 95% CI 0.35-0.50) and cancer-specific mortality (1998: HR = 0.72, 95% CI 0.58-0.89, 2009: HR = 0.40, 95% CI 0.33-0.48). CONCLUSIONS: The present study-the first population-based analysis using propensity score methods-provides evidence of a favorable impact of primary tumor surgery on mortality in metastatic breast cancer patients. Most importantly, the benefit of primary tumor surgery increased over time from 1998 to 2009. Although the final results of ongoing randomized studies are awaited, currently available evidence should be discussed with metastatic breast cancer patients.

Better survival in right-sided versus left-sided stage I - III colon cancer patients.

BACKGROUND: The distinction between right-sided and left-sided colon cancer has recently received considerable attention due to differences regarding underlying genetic mutations. There is an ongoing debate if right- versus left-sided tumor location itself represents an independent prognostic factor. We aimed to investigate this question by using propensity score matching. METHODS: Patients with resected, stage I - III colon cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2012). Both univariable and multivariable Cox regression as well as propensity score matching were used. RESULTS: Overall, 91,416 patients (51,937 [56.8 %] with right-sided, 39,479 [43.2 %] with left-sided colon cancer; median follow-up 38 months) were eligible. In univariable analysis, patients with right-sided cancer had worse overall (hazard ratio [HR] = 1.32, 95 % CI:1.29-1.36, P < 0.001) and cancer-specific survival (HR = 1.26, 95 % CI:1.21-1.30, P < 0.001) compared to patients with left-sided cancer. After propensity score matching, the prognosis of right-sided carcinomas was better regarding overall (HR = 0.92, 95 % CI: 0.89 - 0.94, P < 0.001) and cancer-specific survival (HR = 0.90, 95 % CI:0.87 - 0.93, P < 0.001). In stage I and II, the prognosis of right-sided cancer was better for overall (HR = 0.89, 95 % CI:0.84-0.94 and HR = 0.85, 95 % CI:0.81-0.89) and cancer-specific survival (HR = 0.71, 95 % CI:0.64 - 0.79 and HR = 0.75, 95 % CI:0.70-0.80). Right- and left-sided colon cancer had a similar prognosis for stage III (overall: HR = 0.99, 95 % CI:0.95-1.03 and cancer-specific: HR = 1.04, 95 % CI:0.99-1.09). CONCLUSIONS: This population-based analysis on stage I - III colon cancer provides evidence that the prognosis of localized right-sided colon cancer is better compared to left-sided colon cancer. This questions the paradigm from previous research claiming a worse survival in right-sided colon cancer patients.

Modest overall survival improvements from 1998 to 2009 in metastatic gastric cancer patients: a population-based SEER analysis.

BACKGROUND: An increasing fraction of gastric cancer patients present with distant metastases at diagnosis. The objective of the present 11-year population-based trend analysis was to assess the survival rates in patients who underwent and in patients who did not undergo palliative gastrectomy. METHODS: Patients with metastatic gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2009. Time trend and impact of palliative gastrectomy on survival were assessed by both a multivariate Cox proportional hazards model and propensity score matching. RESULTS: We identified 8249 patients with stage IV gastric cancer. The rate of metastatic disease increased from 31.0 % in 1998 to 37.5 % in 2009 (P < 0.001). The palliative gastrectomy rate dropped from 18.8 to 10.2 % (P = 0.004). The median survival for patients who underwent palliative gastrectomy (N = 1445, 17.4 %) and for patients who did not undergo palliative gastrectomy (N = 6804, 82.4 %) was 7 and 3 months, respectively. There was an increase in median overall survival from 2 months (1998) to 3 months (2009) in the no-gastrectomy group, and from 6.5 to 8 months in the gastrectomy group. The 3-year cancer-specific survival rates were 2.1 % (95 % confidence interval 1.7-2.5 %) for patients who did not undergo palliative gastrectomy and 9.4 % (95 % confidence interval 7.8-11.2 %) for patients who underwent palliative gastrectomy (P < 0.001). Palliative gastrectomy was associated with an increased cancer-specific survival in propensity-score-adjusted Cox regression analyses (hazard ratio 0.50, 95 % confidence interval 0.46-0.55, P < 0.001). CONCLUSION: On a population-based level, only modest improvements in prognosis for metastatic gastric cancer were observed in patients who underwent and in patients who did not undergo palliative gastrectomy. Considering the low rate of midterm survivors in both groups, only a small subgroup of patients benefits from palliative gastrectomy.

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis.

OBJECTIVE: To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND: There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS: Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS: Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS: On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor.

BACKGROUND: The objective of the present population-based analysis was to assess survival patterns in patients with resected and metastatic GIST. METHODS: Patients with histologically proven GIST were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1998 through 2011. Survival was determined applying Kaplan-Meier-estimates and multivariable Cox-regression analyses. The impact of size and mitotic count on survival was assessed with a generalized receiver-operating characteristic-analysis. RESULTS: Overall, 5138 patients were included. Median age was 62 years (range: 18-101 years), 47.3% were female, 68.8% Caucasians. GIST location was in the stomach in 58.7% and small bowel in 31.2%. Lymph node and distant metastases were found in 5.1 and 18.0%, respectively. For non-metastatic GIST, three-year overall survival increased from 68.5% (95 % CI: 58.8-79.8%) in 1998 to 88.6% (95 % CI: 85.3-92.0%) in 2008, cancer-specific survival from 75.3% (95 % CI: 66.1-85.9%) in 1998 to 92.2% (95 % CI: 89.4-95.1%) in 2008. For metastatic GIST, three-year overall survival increased from 15.0% (95 % CI: 5.3-42.6%) in 1998 to 54.7% (95 % CI: 44.4-67.3%) in 2008, cancer-specific survival from 15.0% (95 % CI: 5.3-42.6%) in 1998 to 61.9% (95 % CI: 51.4-74.5%) in 2008 (all PTrend < 0.05). CONCLUSIONS: This is the first SEER trend analysis assessing outcomes in a large cohort of GIST patients over a 11-year time period. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in overall and cancer-specific survival from 1998 to 2008, both for resected as well as metastatic GIST.

Intranodal Mapping Using Carbon Dye Results in More Accurate Lymph Node Staging in Colon Cancer Patients.

INTRODUCTION: Small nodal tumor infiltrates (SNTI)-defined as isolated tumor cells and micrometastases-are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients. MATERIALS AND METHODS: Isosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin-eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI. RESULTS: Of a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9 %). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (p < 0.001). In 52 out of 59 LN (88.1 %), phagocytosed carbon dye was in close proximity to SNTI. CONCLUSIONS: In the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping-which has been previously described for melanoma-can be extended to colon cancer patients.

Perioperative blood transfusions do not impact overall and disease-free survival after curative rectal cancer resection: a propensity score analysis.

OBJECTIVE: To assess the putative impact of perioperative blood transfusions on overall and disease-free survival in patients undergoing curative resection of stage I-III rectal cancer by applying propensity-scoring methods. BACKGROUND: Whether perioperative blood transfusions negatively impact survival remains a matter of great debate. METHODS: In a single-center study, 401 patients undergoing open curative resection of stage I-III rectal cancer between 1996 and 2008 were assessed. The median follow-up was 34.2 months. Patients who did and did not receive perioperative blood transfusions were compared using Cox regression and propensity score analyses. RESULTS: Overall, 217 patients (54.1%) received blood transfusions. Patients' characteristics were highly biased concerning transfusions (propensity score 0.77±0.23 vs. 0.28±0.25; P<0.001). In unadjusted analysis, blood transfusions were associated with a 119% increased risk of mortality [hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.34-3.57, P=0.001]. In propensity score-adjusted Cox regression (HR: 1.02, 95% CI: 0.65-1.58, P=0.970), blood transfusions did not increase the risk of overall survival. Similarly, in propensity score-adjusted Cox regression (HR: 0.86, 95% CI: 0.60-1.23, P=0.672), blood transfusions were not associated with an increased risk of recurrence. CONCLUSIONS: This is the first propensity score-based analysis providing compelling evidence that worse oncological outcomes after curative rectal cancer resection in patients receiving perioperative blood transfusions are caused by the clinical circumstances requiring transfusions, not due to the blood transfusions themselves. Therefore, concerns about overall and disease-free survival should be no issue in the decision-making regarding perioperative blood transfusions in patients undergoing curative rectal cancer resection.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

BACKGROUND: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. METHODS: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. RESULTS: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). CONCLUSIONS: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Blue dye injection does not induce dissemination of epithelial cells during SLN procedure in colon cancer patients.

INTRODUCTION: The sentinel lymph node (SLN) procedure for colon cancer patients has been increasingly performed over the past decade and has shown advantages regarding lymph node staging. However, there are concerns that the manipulation of the colon, particularly the blue dye injection, results in isolated tumor cell dissemination to lymph nodes. Therefore, the objective of the present study was to evaluate whether the blue dye injection during the SLN procedure for colon cancer induces epithelial cell dissemination to the regional lymph nodes using a fake SLN procedure as a model. METHODS: One hundred seventy-four colon cancer patients underwent open oncologic colon resection and SLN procedure according to a standardized protocol. For the fake SLN procedure, blue dye was injected ex vivo, into the subserosa of a nontumor-bearing segment of the resected colon in 37 unselected patients. Three levels of each SLN were stained with H&E and with the pancytokeratin marker AE1/AE3 and were analyzed for the presence of cytokeratin positive cells. RESULTS: Identification of fake SLN was successful in 32 of the 37 patients (86 %). Seventy fake SLN were histologically confirmed. The median number of fake SLN was 2 per patient (range 1-8). None of the fake SLN showed any disseminated epithelial cells. CONCLUSIONS: The present prospective study provides compelling evidence that blue dye injection during sentinel lymph node procedure for colon cancer does not induce epithelial cell dissemination to the sentinel lymph nodes. Therefore, isolated tumor cells in sentinel lymph nodes result from a true metastatic process.

High risks for adverse outcomes after gastric bypass surgery following failed gastric banding: a population-based trend analysis of the United States.

OBJECTIVES: The objectives of this investigation were to (1) compare short-term outcomes for patients undergoing primary gastric bypass surgery with those who had gastric bypass procedures performed as a rescue procedure after failed gastric banding and (2) study trends in the frequency of reoperations between 2005 and 2008 for patients who had prior gastric banding. BACKGROUND: The use of gastric banding to treat obesity has increased drastically in the United States. However, the frequency of reoperations related to gastric banding and associated short-term outcomes are unknown. METHODS: The Nationwide Inpatient Sample from 2005 to 2008 was used for this population-based study. Descriptive statistics as well as unadjusted and risk-adjusted generalized linear models were performed to assess adverse short-term outcomes. RESULTS: A total of 66,303 patients were included in the analysis, 63,171 (95.3%) underwent a primary gastric bypass procedure and 3132 patients (4.7%) underwent a gastric band-related reoperation. Patients undergoing a gastric bypass procedure concomitant with a band-related reoperation had more intraoperative complications [risk-adjusted odds ratio (OR): 2.3, P = 0.002] and postoperative complications (risk-adjusted OR: 8.0, P < 0.001), were at higher risk of reoperations/reinterventions (risk-adjusted OR: 6.0, P < 0.001), increased length of hospital stay (adjusted mean difference: 0.89 days, P < 0.001), and higher hospital charges (adjusted mean difference: $13,257, P < 0.001). The number of gastric band-related reoperations increased from 579 in 2005 to 1132 in 2008 (196%). CONCLUSIONS: The number of reoperations after gastric banding is rapidly increasing in the United States. To our knowledge, this is the first population-based study providing strong evidence that patients undergoing gastric bypass procedure after failed gastric banding have more adverse outcomes than those undergoing gastric bypass alone. The broad indication for gastric banding should be reaffirmed for the US population.

Relative survival is an adequate estimate of cancer-specific survival: baseline mortality-adjusted 10-year survival of 771 rectal cancer patients.

BACKGROUND: The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. METHODS: Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. RESULTS: The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). CONCLUSIONS: Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported.