Ignazio Tarantino

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

OBJECTIVEnTo assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival.nnnBACKGROUNDnThere is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease.nnnMETHODSnStage 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.nnnRESULTSnOverall, 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.nnnCONCLUSIONSnOn 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.

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

BackgroundThe 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.MethodsPatients 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.ResultsOverall, 91,416 patients (51,937 [56.8xa0%] with right-sided, 39,479 [43.2xa0%] with left-sided colon cancer; median follow-up 38xa0months) were eligible. In univariable analysis, patients with right-sided cancer had worse overall (hazard ratio [HR]u2009=u20091.32, 95 % CI:1.29–1.36, Pu2009<u20090.001) and cancer-specific survival (HRu2009=u20091.26, 95 % CI:1.21–1.30, Pu2009<u20090.001) compared to patients with left-sided cancer. After propensity score matching, the prognosis of right-sided carcinomas was better regarding overall (HRu2009=u20090.92, 95 % CI: 0.89u2009−u20090.94, Pu2009<u20090.001) and cancer-specific survival (HRu2009=u20090.90, 95 % CI:0.87u2009−u20090.93, Pu2009<u20090.001). In stage I and II, the prognosis of right-sided cancer was better for overall (HRu2009=u20090.89, 95 % CI:0.84–0.94 and HRu2009=u20090.85, 95 % CI:0.81–0.89) and cancer-specific survival (HRu2009=u20090.71, 95 % CI:0.64u2009−u20090.79 and HRu2009=u20090.75, 95 % CI:0.70–0.80). Right- and left-sided colon cancer had a similar prognosis for stage III (overall: HRu2009=u20090.99, 95 % CI:0.95–1.03 and cancer-specific: HRu2009=u20091.04, 95 % CI:0.99–1.09).ConclusionsThis 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.

Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis

PurposeThere is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival.MethodsPatients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis.ResultsA total of 442 stage IV P-NET patients were identified, of whom 75 (17.0xa0%) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of deathu2009=u20090.41, 95xa0% confidence interval [CI] 0.25–0.66, pu2009<u20090.001) and cancer-specific survival (HR of deathu2009=u20090.41, 95xa0% CI 0.25–0.67, pu2009<u20090.001) in unadjusted multivariate Cox regression analysis; the benefit persisted after propensity score adjustment.ConclusionsThis population-based analysis of stage IV P-NET patients provides compelling evidence that palliative resection of the primary tumor is associated with significant survival benefit. Thus, the recent recommendations judging resection of the primary as inadvisable and the accompanying trend towards fewer palliative resections of the primary tumor have to be contested.

Comparative Outcomes of Neoadjuvant Treatment Prior to Total Mesorectal Excision and Total Mesorectal Excision Alone in Selected Stage II/III Low and Mid Rectal Cancer

AbstractBackgroundCurrent guidelines advocate that nall rectal cancer patients with American Joint Committee on Cancer (AJCC) stages II and III disease should be subjected to neoadjuvant therapy. However, improvements in surgical technique have resulted in single-digit local recurrence rates with surgery only.MethodsOperative, postoperative, and oncological outcomes of patients with and without neoadjuvant therapy were compared between January 2002 and December 2013. For this purpose, all patients resected with low anterior rectal resection (LAR) and total mesorectal excision (TME) who had or had not been irradiated were identified from the authors’ prospectively maintained database. Patients who were excluded were those with high rectal cancer or AJCC stage IV disease; in the surgery-only group, patients with AJCC stage I disease or with pT4Nx rectal cancer; and in the irradiated patients, patients with ypT4Nx or cT4Nx rectal cancer.ResultsOverall, 454 consecutive patients were included. A total of 342 (75xa0%) patients were irradiated and 112 (25xa0%) were not irradiated. Median follow-up for all patients was 48xa0months. Among patients with and without irradiation, pathological circumferential resection margin positivity rates (2.9 vs. 1.8xa0%, pxa0=xa00.5) were not different. At 5xa0years, in irradiated patients compared with surgery-only patients, the incidence of local recurrence was decreased (4.5 vs. 3.8xa0%, pxa0=xa00.5); however, systemic recurrences occurred more frequently (10 vs. 17.8xa0%, pxa0=xa00.2). Irradiation did not affect overall or disease-free survival (neoadjuvant treatment vs. surgery-only: 84.9 vs. 88.2xa0%, pxa0=xa00.9; 76 vs. 79.1xa0%, pxa0=xa00.8).ConclusionsThe current study adds to the growing evidence that suggests a selective rather than generalized indication for neoadjuvant treatment in stages II and III rectal cancer.

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

BackgroundThe objective of the present population-based analysis was to assess survival patterns in patients with resected and metastatic GIST.MethodsPatients 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.ResultsOverall, 5138 patients were included. Median age was 62xa0years (range: 18–101 years), 47.3xa0% were female, 68.8xa0% Caucasians. GIST location was in the stomach in 58.7xa0% and small bowel in 31.2xa0%. Lymph node and distant metastases were found in 5.1 and 18.0xa0%, respectively. For non-metastatic GIST, three-year overall survival increased from 68.5xa0% (95 % CI: 58.8–79.8xa0%) in 1998 to 88.6xa0% (95 % CI: 85.3–92.0xa0%) in 2008, cancer-specific survival from 75.3xa0% (95 % CI: 66.1–85.9xa0%) in 1998 to 92.2xa0% (95 % CI: 89.4–95.1xa0%) in 2008. For metastatic GIST, three-year overall survival increased from 15.0xa0% (95 % CI: 5.3–42.6xa0%) in 1998 to 54.7xa0% (95 % CI: 44.4–67.3xa0%) in 2008, cancer-specific survival from 15.0xa0% (95 % CI: 5.3–42.6xa0%) in 1998 to 61.9xa0% (95 % CI: 51.4–74.5xa0%) in 2008 (all PTrendu2009<u20090.05).ConclusionsThis 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.

Anastomotic leakage after curative rectal cancer resection has no impact on long-term survival: a propensity score analysis

PurposeAnastomotic leakage (AL) is a severe and frequent complication of rectal cancer resection, with an incidence rate of approximately 9xa0%. Although the impact of AL on morbidity and short-term mortality has been established, the literature is contradictory regarding its influence on long-term, cancer-specific survival. The present investigation assessed the long-term survival of 584 patients with stage I–III rectal cancer.MethodsThe 10-year overall survival and cancer-specific survival were analyzed in 584 patients from a single tertiary center. All patients had undergone curative rectal cancer resection between 1991 and 2010. Patients with and without AL were compared using both a multivariate Cox hazards model and propensity score analysis.ResultsA total of 64 patients developed AL (11.0xa0%, 95xa0% confidence interval (CI)u2009=u20098.7 to 13.8xa0%). The median follow-up was 5.2xa0years for all patients; and 7.4xa0years for patients still alive at the end of the investigated period. AL did persistently not impair cancer-specific survival based on unadjusted Cox regression (hazard ratio of death (HR)u2009=u20091.27, 95xa0% CIu2009=u20090.65 to 2.48, Pu2009=u20090.489); risk-adjusted Cox regression (HRu2009=u20091.10, 95xa0% CIu2009=u20090.54 to 2.20, Pu2009=u20090.799); and propensity score matching (HRu2009=u20091.18, 95xa0% CIu2009=u20090.57 to 2.43, Pu2009=u20090.660).ConclusionsBased on the present propensity score analysis, the oncologic outcomes in patients undergoing curative rectal cancer resections were not impaired by the development of anastomotic leakage.

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

BackgroundAn 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.MethodsPatients 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.ResultsWe identified 8249 patients with stage IV gastric cancer. The rate of metastatic disease increased from 31.0xa0% in 1998 to 37.5xa0% in 2009 (Pxa0<xa00.001). The palliative gastrectomy rate dropped from 18.8 to 10.2xa0% (Pxa0=xa00.004). The median survival for patients who underwent palliative gastrectomy (Nxa0=xa01445, 17.4xa0%) and for patients who did not undergo palliative gastrectomy (Nxa0=xa06804, 82.4xa0%) was 7 and 3xa0months, respectively. There was an increase in median overall survival from 2xa0months (1998) to 3xa0months (2009) in the no-gastrectomy group, and from 6.5 to 8xa0months in the gastrectomy group. The 3-year cancer-specific survival rates were 2.1xa0% (95xa0% confidence interval 1.7–2.5xa0%) for patients who did not undergo palliative gastrectomy and 9.4xa0% (95xa0% confidence interval 7.8–11.2xa0%) for patients who underwent palliative gastrectomy (Pxa0<xa00.001). Palliative gastrectomy was associated with an increased cancer-specific survival in propensity-score-adjusted Cox regression analyses (hazard ratio 0.50, 95xa0% confidence interval 0.46–0.55, Pxa0<xa00.001).ConclusionOn 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.

Impact of Anatomic Location on Locally Recurrent Rectal Cancer: Superior Outcome for Intraluminal Tumour Recurrence

BackgroundLocal recurrence of rectal cancer after curative surgery predicts patients’ prognosis. The correlation between the exact anatomic location of tumour recurrence and patients’ survival is still under debate. Thus, this study aimed to investigate the impact of the exact location of recurrent rectal cancer on post-operative morbidity and survival.MethodsThis is a retrospective study including 90 patients with locally recurrent rectal cancer. The location of tumour recurrence was classified into intraluminal and extraluminal recurrence. Univariate and multivariable Cox regression analyses were used to determine the impact on post-operative morbidity and survival.ResultsPatients’ survival with intraluminal recurrence was significantly longer compared to patients with extraluminal recurrence (pu2009=u20090.027). Curative resection was associated with prolonged survival in univariate and multivariable analyses (pu2009=u20090.0001) and was more often achieved in patients with intraluminal recurrence (pu2009=u20090.024). Survival of curative resected patients with intraluminal recurrence was significantly longer compared to curatively resected patients with extraluminal recurrence (pu2009=u20090.0001). The rate of post-operative morbidity between intraluminal and extraluminal recurrence was not statistically different (pu2009=u20090.59).ConclusionBased on the present investigation, intraluminal recurrence is associated with superior outcome. Post-operative morbidity did not differ significantly between both groups.

Predictors for regional lymph node metastasis in T1 rectal cancer: a population-based SEER analysis.

BackgroundLocal resection of early-stage rectal cancer significantly reduces perioperative morbidity compared with radical resection. Identifying patients at risk of regional lymph node metastasis (LNM) is crucial for long-term survival after local resection.MethodsPatients after oncological resection of T1 rectal cancer were identified in the Surveillance, Epidemiology, and End Results register 2004–2012. Potential predictors of LNM and its impact on cancer-specific survival were assessed in logistic and Cox regression with and without multivariable adjustment.ResultsIn total, 1593 patients with radical resection of T1 rectal cancer and a minimum of 12 retrieved regional lymph nodes were identified. The overall LNM rate was 16.3xa0% (Nxa0=xa0260). A low risk of LNM was observed for small tumor size (Pxa0=xa00.002), low tumor grade (Pxa0=xa00.002) and higher age (Pxa0=xa00.012) in multivariable analysis. The odds ratio for a tumor size exceeding 1.5xa0cm was 1.49 [95xa0% confidence interval (CI) 1.06–2.13], for G2 and G3/G4 carcinomas 1.69 (95xa0%xa0CI 1.07–2.82) and 2.72 (95xa0%xa0CI 1.50–5.03), and for 65- to 79-year-old and over 80-year-old patients 0.65 (95xa0%xa0CI 0.43–0.96) and 0.39 (95xa0% CI 0.18–0.77), respectively. Five-year cancer-specific survival for patients with LNM was 90.0xa0% (95xa0%xa0CI 85.3–95.0xa0%) and for patients without LNM 97.1xa0% (95xa0%xa0CI 95.9–98.2xa0%, hazard ratioxa0=xa03.21, 95xa0%xa0CI 1.82–5.69, Pxa0<xa00.001).ConclusionsIn this population-based analysis, favorable cancer-specific survival rates were observed in nodal-negative and nodal-positive T1 rectal cancer patients after primary radical resection. The predictive value of tumor size, grading and age for LNM should be considered in medical decision making about local resection.

Sphincter-Preserving Surgery for Low Rectal Cancer: Do We Overshoot the Mark?

PurposeIntersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for a selected subset of patients with low rectal cancer, combining equivalent oncological outcome and sphincter preservation. However, functional results are heterogeneous and often imperfect. The aim of the present investigation was to determine the long-term functional results and quality of life after ISR.MethodsOne hundred forty-three consecutive patients who underwent surgery for low rectal cancer were analysed. Sixty patients received ISR and 83 patients APR, respectively. Kaplan-Meier estimate was used to analyse patients’ survival. The EORTC QLQ-C30, -C29 and the Wexner score were used to determine functional outcome and quality of life.ResultsISR and APR were both associated with comparable morbidity and no mortality. Patients’ disease- and recurrence-free survival after ISR and APR were similar (pu2009=u20090.2872 and pu2009=u20090.4635). Closure of ileostomy was performed in 73% of all patients after ISR. Long-term outcome showed a rate of incontinence (Wexner score ≥10) in 66% of the patients. Despite this, patients’ quality of life was significantly better after ISR compared to APR in terms of abdominal complaints and psycho-emotional functioning.ConclusionsISR is technically feasible with acceptable postoperative morbidity rates. Functional results following ISR are compromised by incontinence as the most important complication. However, long-term quality of life is superior to APR, which should be considered when selecting patients for ISR.