Non-resection Group Research Articles

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

Background: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies. We previously have shown that SRPT, independent of chemotherapy and performance status, improves survival of stage IV CRC patients. The current study aims to validate our findings in patients with stage IV CRC who were diagnosed during the period of modern chemotherapy. Methods: A cohort of 569 patients with stage IV CRC diagnosed during 2006-2010 in the province of Saskatchewan was evaluated. Cox regression model was used for the adjustment of prognostic variables. Results: Median age was 69 years (59-95) and M: F was 1.4:1. Fifty-seven percent received chemotherapy, 91.4% received FOLFIRI or FOLFOX & 67% received a biologic agent. Median overall survival (OS) of patients who underwent SRPT and received chemotherapy was 27 months compared with 14 months of the non-resection group (p<0.0001). Median OS of patients who received all active agents and had SRPT was 39 months (95%CI: 25.1-52.9). On multivariate analysis, SRPT, hazard ratio (HR):0.44 (95%CI: 0.35-0.56), use of chemotherapy, HR: 0.33 (95%CI: 0.26-0.43), metastasectomy, HR: 0.43 (95%CI: 0.31-0.58), second line therapy, HR: 0.50 (95%CI: 0.35-0.70), and third line therapy, HR: 0.58 (95%CI: 0.41-0.83) were correlated with superior survival. Conclusions: This study confirms our findings and supports a favorable association between SRPT and survival in patients with stage IV CRC who are treated with modern therapy.

The Value of Palliative Gastrectomy for Gastric Cancer Patients With Intraoperatively Proven Peritoneal Seeding.

The aim of this study was to evaluate the survival benefit of palliative gastrectomy for gastric cancer patients with peritoneal seeding proven intraoperatively and to identify positive predictive factors for improving survival.The value of palliative resection for gastric cancer patients with peritoneal metastasis is controversial.From 2006 to 2013, 267 gastric cancer patients with intraoperatively identified peritoneal dissemination were retrospectively analyzed. Patients were divided into resection group and nonresection group according to whether a palliative gastrectomy was performed. Clinicopathologic variables and survival were compared. Subgroup analyses stratified by clinicopathologic factors and multivariable analysis for overall survival were also performed.There were 114 patients in the resection group and 153 in nonresection group. The morbidities in the resection and nonresection groups were 14.91% and 5.88%, respectively (P = 0.014). There, however, was no difference in mortality between the 2 groups. The median survival time of patients in the resection group was longer than in nonresection group (14.00 versus 8.57 months, P = 0.000). The median survivals among the patients with different classifications of peritoneal metastasis were statistically significant (P = 0.000). Patients undergoing resection followed by chemotherapy had a significantly longer median survival, compared with that of patients who had chemotherapy alone, those who had resection alone, or those who had not received chemotherapy or resection (P = 0.000). Results of subgroup analyses showed that except for P3 patients and patients with multisite distant metastases, overall survival was significantly better in patients with palliative gastrectomy, compared with the nonresection group. In multivariate analysis, P3 disease (P = 0.000), absence of resection (P = 0.000), and lack of chemotherapy (P = 0.000) were identified as independently associated with poor survival.Palliative gastrectomy might be beneficial to the survival of gastric cancer patients with intraoperatively proven P1/P2 alone, rather than P3. Postoperative palliative chemotherapy could improve survival regardless of operation and should be recommended.

PWE-335 Colorectal cancer outcomes: what about the also-rans?

<h3>Introduction</h3> Despite advances in non-surgical oncological treatments, surgical resection of the primary tumour is still required to “cure” a patient of colorectal cancer (CRC). Surgeon specific outcome reporting in colorectal cancer surgery focuses on patients who undergo major elective resection, raising a concern that only data for “low risk” patients are included, thus giving an incomplete picture of a Unit’s overall performance in the management of colorectal cancer. The aim of this study was to analyse the frequency, reasons and outcomes of patients who do not undergo resection. <h3>Method</h3> Details of 1093 patients diagnosed with CRC in a single institution between April 2008 and April 2013 were recorded prospectively. Analysis of demographics, staging, treatment, reasons for non-surgical management and survival was performed. Patients who underwent local tumour resection were excluded (n = 40). <h3>Results</h3> 827 (75.6%) patients underwent primary major resection of their tumour, of which 62 patients were stage IV at the time of surgery. 226 (24.4%) patients were treated non-operatively. Of these patients, 143 (63.2%) had Stage IV cancer (37 (25.9%) underwent palliative surgery). 44(19.5%) patients were deemed unfit for surgery, 2 (0.9%) had complete response to chemo-radiotherapy and 23(10.2%) patients declined surgical intervention. During follow up (median 32 months, range 0–78 months), 253 (30.6%) patients who underwent a major resection died, with 175 deaths (69.2%) directly attributed to cancer. For the non-resection group, 182 (68.4%) patients died, with 137 deaths (75.3%) due to cancer. Median survival for patients undergoing major resection was 45 months: 729 (88.1%) and 667 (80.7%) patients were alive at 12 and 24 months respectively. Median survival for non-resection patients was 4 months, with 108 (48.2%) and 84 (37.5%) patients alive at 12 and 24 months respectively, p &lt; 0.0001 (Mann-Whitney U test). Median survival following surgical intervention for Stage IV disease was similar for major resection (12 months) or a palliative procedure (8 months). During the 5 year period studied, the rate of non-resection remained constant at 22.7%, 21.9%, 22.9%, 22.8% and 24.5% year on year respectively, indicating that there was no change is selection criteria for major resection. <h3>Conclusion</h3> To give a complete picture of a unit’s performance for colorectal cancer treatment, data on the rate of non-resection of CRC, together with an analysis of reasons for non-resection should be included in annual Unit or surgeon-specific outcome reports,. Major resection for Stage IV disease does not appear to offer any survival advantage over lesser, palliative procedures. <h3>Disclosure of interest</h3> None Declared.

Detection and cultivation of circulating tumor cells in gastric cancer.

Circulating tumor cells (CTCs) are important targets for treatment and critical surrogate markers when evaluating cancer prognosis and therapeutic response. A sensitive methodology for detecting CTCs in gastric cancer (GC) patients is needed. In this study we demonstrate a device for enrichment and cultivation of CTCs. In total, 22 patients with GC, all candidates for surgery, were enrolled in the study. Peripheral blood samples were collected before surgery, and patients were re-evaluated within operation and divided into two groups: resectable and non-resectable GC. A new size-based separation test for enrichment and cultivation of CTCs was used (MetaCell®). In addition to cytomorphological analysis, gene expression of tumor associated genes (Cytokeratin-18, Cytokeratin-19, Cytokeratin-20, Cytokeratin-7, EPCAM, MUC1, HER2, EGFR) and of leukocyte markers (e.g. CD45, CD68) was tested in enriched CTC fractions. CTCs were detected in 59 % of the patients studied (n = 13/22). CTCs were detected in seven patients of the resection group (7/10, 70 %) and six of the non-resectable group (6/12, 50 %). Enrichment of the viable CTCs allowed subsequent successful cultivation in vitro. The cytomorphological characterization of the CTCs was a prerequisite of random gene expression testing in CTC-positive samples. In CTC-positive samples gene expression of cytokeratin 18 and 19 was elevated in comparison to the whole blood gene expression analysis. CTCs were found to be present in both resectable and non-resectable gastric cancer patients. The size-based separation platform for CTCs may be used for in vitro cultivation, as well as in subsequent molecular analysis if desired. The sensitivity of CTC-detection could be enhanced by the combination of cytomorphological and molecular analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s10616-015-9866-9) contains supplementary material, which is available to authorized users.

Cholangiocarcinoma Risk as Long‐term Outcome After Hepatic Resection in the Hepatolithiasis Patients

Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis. 95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71% (67/95) in resection group and 41% (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3% (6/95) and 7.1% (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4%) than complete stone removal (3.3%) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma. Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis.

Resection of primary tumor in patients who present with stage IV colon cancer may result in improved survival.

726 Background: Resection of the primary cancer in patients with metastatic disease has been shown to result in improved survival in cancers such as renal cell carcinoma. Currently, the impact primary tumor resection has on survival in stage IV colon cancer patients is unknown. Methods: The SEER dataset was queried for patients who presented with histologically confirmed, stage IV colon cancer from 1998-2011. We excluded patients with rectal cancer, multiple primary tumors, age &lt;18 or &gt;90 years, diagnosis upon autopsy/death record, mortality within 30 days of diagnosis, or resection of other tumor sites (regional or distant). Cox proportional hazard models were used to assess demographic and clinical factors predictive of disease specific and overall survival. To limit group differences, a 1:1 matched analysis was also performed on patients who underwent primary resection compared to patients who did not. Results: A total of 28,068 stage IV colon cancer patients were evaluated, of which 70.3% underwent resection. Among the variables studied, multivariate models showed that patients who underwent primary tumor resection were at lower risk of disease-specific and overall mortality, with hazard ratios (HR) of 0.44 (0.43-0.46) and 0.45 (0.43-0.47), respectively. In the matched analysis (n=5,410 in each group), patients who underwent resection of the primary tumor remained at decreased risk of disease-specific and overall mortality, HR 0.48 (0.45-0.52) and 0.49 (0.46-0.53), respectively. The median survival and 3-year survival after matching was 17 and 9 months and 23% and 6% in the resection and nonresection groups, respectively, p&lt;0.0001. Conclusions: The majority (70.3%) of patients in the United States with stage IV colon cancer undergo resection of primary tumors. Analyses of SEER data suggests that resection of the primary tumor may result in improved DSS and OS in patients with stage IV colon cancer. A prospective, randomized trial is warranted to confirm a survival benefit.

A retrospective review of the University Health Network (UHN) multimodal treatment experience with extended resection of pancreatic ductal adenocarcinoma (PDAC) in patients with arterial involvement.

447 Background: Involvement of a major artery with PDAC is a criteria of unresectability. Although major vein resection/reconstruction is now accepted in PDAC resection, the feasibility of arterial resection requires investigation. The response to neoadjuvant therapy (NAT) may be a useful tool for identifying appropriate candidates for extended resection. Methods: We retrospectively reviewed the UHN experience of multimodality therapy in patients (pts) with histologically confirmed PDAC and single vessel arterial involvement (superior mesenteric, celiac or hepatic artery) on CT from Jan 2009 to Dec 2013. These pts received NAT prior to being re-assessed for surgery; pts whose disease was either stable or improved were considered for surgery. Baseline imaging was reviewed independently. Postoperative complications were assessed and oncologic outcomes were analysed with Kaplan-Meier method. Results: We identified a cohort of 57 pts of whom 56 received NAT. On reassessment, 26 (46%) had no evidence of disease progression and were considered operable, while 31 had local or distant progression and were deemed inoperable. Of 26 pts proceeding to surgery, 21 (81%) underwent resection and 5 had a palliative procedure. In the resection group, 10 pts required arterial resection/reconstruction to achieve R0. The post-operative mortality at 90-days was 0% and morbidity was 86% with 33% major complications (Clavien-Dindo III-IV). With a median follow-up of 12,1 months, the median survival for the resection group was 18.7 months (95% CI: 11.2-NA) vs. 13.6 months (95% CI: 11.9-18.1) for the non-resection group, P=0.0246. Conclusions: Our results suggest that a multimodal approach including NAT +/- segmental arterial resection/reconstruction, can be considered but with high post-operative morbidity. The encouraging survival rates of pts after extended resection must be balanced with the morbidity of this surgery. Given the poor prognosis of pts with locally advanced PDAC, there is a rationale for prospective evaluation of this approach to identify pts who are most likely to benefit from this aggressive strategy.

Outcomes of a clinical pathway for borderline resectable pancreatic cancer.

374 Background: While multimodality therapy for borderline resectable pancreatic adenocarcinoma (BPA) is advocated, treatment regimens vary by institution without a standardized approach supported by prospective randomized data. We implemented a multidisciplinary multimodality clinical pathway (CP) for the management of BPA and examined outcomes to investigate optimal therapy. Methods: From January 1, 2006, to December 31, 2013, BPA cases as defined by the NCCN and AHPBA consensus guidelines were managed prospectively along CP. Resection rates, margin status, pathologic response, and overall survival were retrospectively examined. Standard statistical and survival analysis were used. Results: 121 patients were classified as BPA and 101 entered the CP. The neoadjuvant chemoradiation (NT) completion rate was 93.1%. Of those who entered the CP, 55 patients (54.5%) underwent pancreatectomy. R0, R1 and R2 margin rates were 96.3%, 3.7% and 0%, respectively. Of the 55 patients who underwent resection, 22 (40%) required vascular reconstruction, with R0, R1 and R2 margin rates of 95.2%, 4.8%, and 0%, respectively. Pathologic response to treatment was found in 70.8%, with a complete response rate of 15.9%. Median overall survival in the resected group versus the non-resected group was 34.2 months versus 14.7 months, p&lt;0.001. Conclusions: Our series represents one of the largest reports of BPA in the literature and implementation of our CP resulted in a high NT completion rate and pancreatectomy with negative margin rate. Although 41.4% of cases were not resectable after NT, there was a high rate of negative margin resection with &gt;70% pathologic response rate and a favorable median survival.

Surgical resection improves the outcome of the patients with neuroendocrine tumor liver metastases: large data from Asia.

How to properly manage neuroendocrine liver metastasis (NELM) remains debatable, and only limited clinical data have been published from Asian population. The objective of this study is to identify possible prognostic factors affecting overall survival time and to provide a guideline for future clinical practice.A retrospective study was performed on 1286 patients who had neuroendocrine tumors in our specialized center, and data from 130 patients who had NELM were summarized. Demographic and clinicopathologic data, tumor grade, treatment method, and prognosis were statistically analyzed.Most of the NELMs originated from pancreas (65.4%). Important prognostic factors that included tumor location and size were identified with multivariate analysis. Patients with either primary tumor resection or liver metastasis resection showed a 5-year survival of 35.7% or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year survival. More importantly, resection was performed on 7 patients with grade 3 (G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%, and 28.6%, respectively, whereas the other 9 G3 patients without resection died within 3 years. P = 0.49 comparing the resected group with nonresected group in G3 patients. Besides, the overall 5-year survival rates for resected and nonresected patients were 40.5% and 5.4%, respectively.Multiple prognostic factors influenced the overall outcome of NELM including patient age, tumor location, and size, etc. Aggressive surgical approaches could be considered for maximum survival time disregarding the pathological grade of the tumor. Study with larger sample size should be considered to reevaluate the recommendation of the WHO guidelines for G3 neuroendocrine tumors.

Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials

ObjectiveTo evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC). Summary background dataPrimary tumour resection in this setting remains controversial. Patients and methodsWe retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint). ResultsAmongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n=478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n=332 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p<0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53–0.75]; p<0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70–0.95]; p<0.001). ConclusionPrimary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.

The Effect of Prior Pneumonectomy or Lobectomy on Subsequent Lung Transplantation

Lung transplantation in patients with prior lobectomy or pneumonectomy is not well understood. Using the United Network for Organ Sharing (UNOS) database, we address the impact of priormajor lung resection on lung transplantation outcomes. Retrospective review of adult lung transplants from October 1999 to December 2011 in the UNOS database identified 15,300 lung transplants; 102 patients had undergone major lung resection, defined as prior pneumonectomy (n= 22) or lobectomy (n= 80). Propensity match with nonparametric 3:1 nearest-neighbor matching algorithm adjusted for treatment-level differences. After matching, the primary outcome (90-day mortality) and secondary outcome (airway dehiscence, need for dialysis, length of stay more than 25 days) were assessed with univariable and multivariable methods. Subanalysis of pneumonectomy and lobectomy individually compared with matched nonresection patients was done in a similar manner. The Kaplan-Meier method estimated long-term survival. After matching, no significant differences were noted between groups for recipient, donor, or operative characteristics. There were 10 double lung and 12 single lung transplants after pneumonectomy and 51 double lung and 29 single lung transplants after lobectomy. Mortality at 90 days was 13.9% (n= 14) for the resection group and 8.6% (n= 1,247) for the nonresection group (p= 0.09). After matching, a significant increase was noted in 90-day mortality (p= 0.017) and perioperative dialysis (p= 0.039) for the resection versus nonresection patients. Dialysis was significantly higher among pneumonectomy patients (p= 0.03). No long-term survival difference was observed (p= 0.514). After propensity-matching, resection was associated with increased 90-day mortality and dialysis. Careful patient selection is necessary with patients who have undergone prior major lung resection, given their increased risk of perioperative mortality and dialysis.

The role of palliative resection for asymptomatic primary tumor in patients with unresectable stage IV colorectal cancer.

The prognostic role of surgical resection of primary tumors is not well established in patients with asymptomatic unresectable stage IV colorectal cancer. The aims of this study were to reveal the prognostic role of surgical resection of primary tumors and to define prognostic factors affecting long-term oncological outcomes in patients with asymptomatic unresectable synchronous metastases. This study was a retrospective analysis of prospectively collected data. Between 2000 and 2008, a total of 416 patients with asymptomatic unresectable stage IV colorectal cancer were analyzed with propensity score matching. Prematching baseline characteristics were compared by bivariate analysis, and 113 pairs were selected after 1:1 matching with propensity scores estimated from logistic regression. The primary end point was overall survival. Among 416 patients, 218 (52.4%) underwent palliative resection of the primary tumor. Before propensity score matching, palliative resection resulted in a better survival rate than nonresection in univariate analysis (p < 0.001), but not in multivariate analysis (p = 0.08). After matching, the 5-year overall survival rate was significantly lower for patients with peritoneal metastasis and clinical M1b stage tumors in univariate analysis (p = 0.004 and p = 0.02). However, neither peritoneal metastasis nor clinical M1b stage showed any prognostic significance in multivariate analysis. The overall 5-year survival rate of the postmatching group was 4.9% and 3.5% in the palliative resection and nonresection groups. Consequently, palliative resection was not associated with a significant increase in survival compared with nonresection (p = 0.27). A subgroup analysis performed according to the site of metastasis also did not show any significant survival benefit of palliative resection after matching. Selection bias and potential confounders were limitations of this study. Resection of the primary tumor in patients with asymptomatic unresectable stage IV colorectal cancer was not associated with an improvement in overall survival after propensity score matching.

The results of primary chemotherapy of TS-1/cisplatin regimen in unresectable or metastatic gastric cancer patients

Purpose: This study was conducted to evaluate the response rate, side effect and resection rate after primary chemotherapy of TS-1/cisplatin regimen in unresectable or metastatic gastric cancer patients. Methods: From January 2005 to December 2012, 44 patients with unresectable or metastatic gastric cancer were enrolled onto the study. The regimen of primary chemotherapy was TS-1/cisplatin. Results: Unresectable or metastatic lesions were ascertained abdominal computed tomography (CT), positron emission tomography/CT and diagnostic laparoscopy. The factors of inoperability were 26 patients of peritoneal seeding, 8 tumor fixation, 7 mutiple liver metastasis, 15 multiple lymph node metastasis. They received TS-1/cisplatin regimen for primary chemotherapy. The response rates was 40.9% (18/44). The resection rate was 27.2% (12/44). Among 8 patients received curative resection and 4 received palliative resection. Median survival time were 41 months in cutative resection group, 21 months in palliative resection group and 8 months in non-resection group respectively (P=0.000). Conclusion: The response rates was 40.9% (18/44) and the resection rate was 27.2% (12/44). Resection group had longer survival than non-rescetion group. So aggressive treatment was needed to improve survival.

The impact of primary tumor resection on overall survival in patients with colorectal carcinoma and unresectable distant metastases: A prospective cohort study

BackgroundTo compare the patients with primary colorectal carcinoma (CRC) and non-resectable distant metastases with or without primary colorectal tumor resection as a primary treatment in terms of postoperative mortality and overall survival (OS). Patients and methodsThe clinicopathological data of 188 CRC patients with non-resectable distant metastases was analyzed. All patient data were collected prospectively. Colorectal tumor was resected in 121 patients (64.3%). Kaplan–Meier method was used for calculation and plotting of the OS curves of the patient groups, and log-rank test was used for the comparison of the survival curves. The relative importance of the prognostic features was investigated using the Cox proportional hazards model. ResultsIn the whole series and in the patient group undergoing emergency surgical intervention, mortality rate was lower in patients having colorectal tumor resection compared with non-resected patients, with differences approaching the significance level (p = 0.072 and p = 0.076, respectively). Median OS time was significantly longer in resection group (11.0 months), compared with non-resection group (5.5 months) (p < 0.001); in the multivariate Cox analysis colorectal tumor resection had independent prognostic significance (p < 0.001). ConclusionResection of colorectal tumor in primary CRC patients with non-resectable distant metastasis gives significant survival advantage without increasing postoperative mortality compared with non-resection.

Prognostic Significance of Non-curative Gastrectomy for Incurable Gastric Carcinoma

To date, there is no convincing evidence regarding the benefits of non-curative gastrectomy for gastric carcinoma. In the present study, we reviewed the outcomes of patients who underwent surgery for incurable gastric carcinoma and evaluated the prognostic significance of non-curative gastrectomy. Between 2004 and 2011, a total of 197 patients undergoing elective surgery for incurable gastric carcinoma were divided into the gastric resection and non-resection groups. Patient survival was compared between the two groups, and the prognostic significance of non-curative gastrectomy was investigated using multivariate analysis. Overall, 162 (82.2%) patients underwent non-curative gastrectomy with morbidity and mortality of 21.0 and 1.2%, respectively. The median survival of patients undergoing non-curative gastrectomy was significantly longer than that of patients without gastrectomy (12.4 vs. 7.1months, p=0.003). Patients who received postoperative chemotherapy also showed significantly better survival than those without chemotherapy (13.2 vs. 4.3months, p<0.001). Multivariate analysis revealed that non-curative gastrectomy was an independent prognostic factor (hazard ratio 0.61, 95% CI 0.40-0.93, p=0.023) after adjusting for postoperative chemotherapy and other clinical factors. Median survival in patients receiving non-curative gastrectomy combined with postoperative chemotherapy was 13.9months, which was significantly longer than gastrectomy alone (5.4months), chemotherapy alone (9.6months), and no treatment (3.2months) (p<0.001). Primary tumor resection and postoperative chemotherapy are the most important prognostic factors for incurable gastric carcinoma. The survival benefits of non-curative gastrectomy need to be confirmed in a large-scale, randomized trial.

Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer

We evaluated the need for primary tumor resection in patients with colorectal cancer (CRC) and synchronous unresectable metastases who underwent chemotherapy, and identified the associations between the primary tumor characteristics and risk of intestinal obstruction or perforation. We retrospectively analyzed the survival and complication rates of patients with synchronous metastatic CRC treated between April 2005 and December 2011. Of 131 patients, 68 underwent primary tumor resection before chemotherapy, and 63 were treated without resection before chemotherapy. The overall survival (OS) did not significantly differ between the two groups (log-rank P = 0.53). In the resection group, 12 patients (17.6%) developed postoperative complications. In the non-resection group, 16 patients (25.4%) required surgical intervention owing to obstruction or perforation during their treatment. Surgical intervention did not affect the OS. A circumferential tumor was a risk factor for obstruction or perforation of the colorectum in non-resected patients (odds ratio = 11.163; P = 0.006). Resection of primary tumors before chemotherapy is unnecessary in selected patients with synchronous metastatic colorectal cancer. A circumferential tumor is a risk factor for obstruction or perforation during chemotherapy in cases without primary tumor resection.

Who Will Benefit from Noncurative Resection in Patients with Gastric Cancer with Single Peritoneal Metastasis?

The value of noncurative resection for patients with gastric cancer with single peritoneal metastasis is still debatable. This study was undertaken to evaluate the survival benefit of resection in those patients. From 2006 to 2009, 119 patients with gastric cancer with single peritoneal metastasis were identified during surgery. Sixty-three of them had noncurative resection; the remainder had nonresection. Clinicopathological variables and survival were analyzed. Overall survival of patients in the noncurative resection group was longer than that in the nonresection group (14.869 vs 7.780 months). This survival advantage was still significantly better in the P1/P2 patients who underwent noncurative resection (mean survival time 21.164 vs 7.636 months, P = 0.001), but not in the P3 group (P = 0.489). Multivariate analysis indicated that only noncurative resection retained a significant association with better prognosis in P1/P2 patients. The perioperative mortality rate in the resection group was not significantly higher than that of the noncurative group (P = 0.747). Noncurative resection can prolong the survival of patients with gastric cancer with single P1/P2 peritoneal metastasis. This surgical approach should not be taken into account for those patients with P3 gastric cancer.

Effect of Skin Resection on the Improvement of Joint Contractures in Rats

The effect of skin resection on joint contracture was determined by comparing the first measurement of range of motion after cast removal and the second measurement after the skin resection. This study aimed to verify that both the joint movement during the measurement and skin affect range of motion. [Subjects] Twelve female Wistar rats were used. [Methods] The right hind limb ankle of each rat was immobilized in complete plantar flexion in a cast. In the resection group (n = 6), the skin of the right hind limb ankle was removed surgically, but not in the non-resection group (n = 6). In the resection group, the first measurement of the dorsiflexion angle was obtained after the cast was removed, and the second measurement was obtained after skin resection. In the non-resection group, both measurements of the dorsiflexion angle were obtained soon after the cast was removed. [Results] Compared with the non-resection group, the resection group showed a significant increase between the first and second measurements of range of motion. [Conclusion] These results show that range of motion is substantially affected by skin, in addition to joint movement, during measurement.

Prognostic Implications of Primary Tumor Resection in Stage IVB Colorectal Cancer in Elderly Patients.

PurposeThe aim of this study was to identify prognostic factors in stage IVB colorectal cancer in elderly patients, focusing on the influence of treatment modalities, including palliative chemotherapy and primary tumor resection.MethodsA cohort of 64 patients aged over 65 years who presented with stage IVB colorectal cancer at the Gangneung Asan Hospital between July 1, 2001, and December 31, 2009, was analyzed. Demographics, tumor location, tumor grade, performance status, levels of carcinoembryonic antigen (CEA), level of aspartate aminotransferase (AST), and distant metastatic site at diagnosis were analyzed. Using the treatment histories, we analyzed the prognostic implications of palliative chemotherapy and surgical resection of the primary tumor retrospectively.ResultsThe cohort consisted of 30 male (46.9%) and 34 female patients (53.1%); the median age was 76.5 years. Primary tumor resection was done on 28 patients (43.8%); 36 patients (56.2%) were categorized in the nonresection group. The median survival times were 12.43 months in the resection group and 3.58 months in the nonresection group (P < 0.001). Gender, level of CEA, level of AST, Eastern Cooperative Oncology Group performance status, tumor location, and presence of liver metastasis also showed significant differences in overall survival. On multivariate analysis, male gender, higher level of CEA, higher AST level, and no primary tumor resection were independent poor prognostic factors. In particular, nonresection of the primary tumor was the most potent/poor prognostic factor in the elderly-patient study group (P = 0.001; 95% confidence interval, 2.33 to 21.99; hazard ratio, 7.16).ConclusionIn stage IVB colorectal cancer in elderly patients, resection of the primary tumor may enhance survival.

Paradigm Shift in the Treatment of Elderly Patients With Unresectable Stage IV Colorectal Cancer.

See Article on Page 175-181 Colorectal cancer (CRC) is one of the most common malignant tumors that lead to cancer-related death worldwide, and it has an increasing incidence rate. Approximately 20% to 30% of patients with CRC are found to have distant metastases at the time of diagnosis [1]. To date, with recent advances in systemic chemotherapy, nonoperative treatment has become the mainstay of treatment in patients with incurable metastatic CRC [2, 3]. Given the progress in chemotherapy regimens and palliative techniques such as endoluminal stenting and given the high mortality of cancer-directed surgery, the prognostic impact of a primary tumor resection in patients with stage IV CRC has been under debate [4, 5, 6]. A previous analysis of Surveillance Epidemiology and End Results (SEER)-Medicare-linked data between 1991 and 1999 reported a 72% cancer-directed surgery rate in elderly patients (age ≥ 65) with stage IV CRC [6]. However, more recent SEER-Medicare data from 2001 to 2007 demonstrated a statistically significant decrease in the rate of surgical resections of primary tumors from 64.6% in 2001 to 57.1% in 2007 [7]. Similarly, The Netherlands' Cancer Registry also found a significant decrease in primary tumor resection rates from 66% to 56% and an increase in systemic chemotherapy from 2.0% in 1989-1993 to 40% in 2004-2006 in elderly patients with stage IV CRC disease [8]. These treatment trends may indicate that practitioners are rapidly adopting the use of modern combination chemotherapy and that a paradigm shift in the treatment of stage IV CRC is beginning. Current practice guidelines from the National Comprehensive Cancer Network (NCCN) recommend a resection of the primary tumor only if patients are symptomatic or have metastatic sites amenable to a potentially-curative resection. Although the rationale for an up-front primary tumor resection is based on an attempt to resolve potential complications from the primary tumor, such as bowel obstruction, uncontrollable bleeding, or tumor perforation [6, 9], the critical role of surgery for patients with incurable stage IV CRC is still inconclusive, especially for patients with stage IVB CRC. Furthermore, proper prognostic clinical parameters, such as age, performance status, pathological grading, or localization of the primary tumor, should be considered before undertaking surgery in elderly patients with stage IV CRC. Although very limited evidence is available with respect to the survival benefit of a primary tumor resection in patients with stage IV CRC, recent studies demonstrated a 31% reduction in mortality with surgical resection of the primary tumor and an increase in survival in elderly patients with stage IV CRC [10, 11]. Consistent with previous studies, our retrospective study showed that patients who underwent a primary tumor resection followed by chemotherapy had a significantly longer survival time than patients who received first-line chemotherapy (17.2 vs. 13.6 months, P = 0.002) [12]. On the basis of the current limited results, a primary tumor resection is potentially associated with survival benefits in elderly patients with stage IV CRC. However, primary-tumor-related complications are a major concern. The rates of complication in patients with an unresected primary tumor have been reported to range from 11.0% to 30% [2, 13, 14]. This study analyzed retrospectively the survival outcomes and the prognostic factors in elderly patients with stage IVB CRC. The current study showed that the patients in the resection group had significantly longer median survival times compared to the patients in the nonresection group (12.43 months vs. 3.58 months, P < 0.001). In addition, male gender, higher level of carcinoembryonic antigen, higher aspartate aminotransferase level, and nonresection of the primary tumor were independent poor prognostic factors on the multivariate analysis. However, the relatively short follow-up time and the small sample size are major drawbacks to interpreting the survival benefits and the prognostic factors clearly [15]. A large-scale, randomized study is needed to clearly establish the true benefits primary tumor resection for stage IVB CRC. In conclusion, the appropriate role of a surgical resection for treating stage IVB CRC, including its prognostic impact on tumor-related symptom control, its survival benefits and its impact on quality of life, remains to be fully evaluated.