Abstract Introduction There is increasing evidence to suggest that cancer-associated inflammation is associated with poorer long-term outcomes. Various markers have been studied over the past decade in an attempt to improve selection of patients for surgery. This meta-analysis explored the association between the neutrophil-lymphocyte ratio and prognosis following curative-intent surgery for solid tumours. Methods Studies were identified from US National Library of Medicine (Medline) and the Exerpta Medica database (EBASE) performed in March 2013. A systematic review and meta-analysis were performed to generate combined hazard ratios for overall survival (OS) and disease-free survival (DFS). Results Forty-nine studies containing 14282 patients were included. Elevated NLR was associated with poorer overall survival [HR: 1.92, 95% CI (1.64–2.24)] ( p < 0.001) and disease-free survival [HR: 1.99, 95% CI (1.80–2.20)] ( p < 0.001). Significant heterogeneity was found with an I2 of 77% and 97% for OS and DFS respectively. Subgroup analyses demonstrated that gastro-intestinal malignancies; mainly gastric [HR: 1.97, 95% CI (1.41–2.76)], colorectal [HR: 1.65, 95% CI (1.21–2.26)] and oesophageal [HR: 1.48, 95% CI (0.91–2.42)] cancers were predictive of OS (I2 = 54.3%). A separate analysis for studies using an NLR cutoff of 5 demonstrated significantly poorer outcomes [HR: 2.18, 95% CI (1.74–2.73)] ( p = 0.002) with less heterogeneity ( I2 = 58%). Conclusion Elevated NLR correlates with poorer prognosis. It potentially represents a simple, robust and reliable measure that may be useful in identifying high-risk groups who could benefit from adjuvant therapy.
Abstract Minimally invasive surgery represents one of the main evolutions of surgical techniques aimed at providing a greater benefit to the patient. However, minimally invasive surgery increases the operative difficulty since the depth perception is usually dramatically reduced, the field of view is limited and the sense of touch is transmitted by an instrument. However, these drawbacks can currently be reduced by computer technology guiding the surgical gesture. Indeed, from a patient’s medical image (US, CT or MRI), Augmented Reality (AR) can increase the surgeon’s intra-operative vision by providing a virtual transparency of the patient. AR is based on two main processes: the 3D visualization of the anatomical or pathological structures appearing in the medical image, and the registration of this visualization on the real patient. 3D visualization can be performed directly from the medical image without the need for a pre-processing step thanks to volume rendering. But better results are obtained with surface rendering after organ and pathology delineations and 3D modelling. Registration can be performed interactively or automatically. Several interactive systems have been developed and applied to humans, demonstrating the benefit of AR in surgical oncology. It also shows the current limited interactivity due to soft organ movements and interaction between surgeon instruments and organs. If the current automatic AR systems show the feasibility of such system, it is still relying on specific and expensive equipment which is not available in clinical routine. Moreover, they are not robust enough due to the high complexity of developing a real-time registration taking organ deformation and human movement into account. However, the latest results of automatic AR systems are extremely encouraging and show that it will become a standard requirement for future computer-assisted surgical oncology. In this article, we will explain the concept of AR and its principles. Then, we will review the existing interactive and automatic AR systems in digestive surgical oncology, highlighting their benefits and limitations. Finally, we will discuss the future evolutions and the issues that still have to be tackled so that this technology can be seamlessly integrated in the operating room.
Abstract Primary liver cancer is the sixth most common cancer overall and the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma accounts for up to 90% of all primary hepatic malignancies and represents a major international health problem. While surgical resection and transplantation are the cornerstone of therapy in early-stage hepatocellular carcinoma, locoregional therapy and sorafenib are beneficial in those with more advanced disease or those who are not surgical candidates. At times, the integration of both surgical and locoregional therapy may be necessary. Hence, hepatocellular carcinoma requires a multidisciplinary approach to determine the most appropriate treatment as well as the timing of various treatments for optimal outcomes.
Abstract Introduction Colorectal carcinoma can present with acute intestinal obstruction in 7%–30% of cases, especially if tumor is located at or distal to the splenic flexure. In these cases, emergency surgical decompression becomes mandatory as the traditional treatment option. It involves defunctioning stoma with or without primary resection of obstructing tumor. An alternative to surgery is endoluminal decompression. The aim of this review is to assess the effectiveness of colonic stents, used as a bridge to surgery, in the management of malignant left colonic and rectal obstruction. Methods We considered only randomized trials which compared stent vs surgery for intestinal obstruction from left sided colorectal cancer (as a bridge to surgery) irrespective of their size. No language or publication status restrictions were imposed. A systematic search was conducted in Medline, Cochrane Central Register of Controlled Trials and the Science Citation Index (from inception to December 2011) Results We identified 3109 citations through our electronic search and 3 through other sources. Initial screening of the titles and abstracts resulted in the exclusion of 3104 citations. A further 5 citations were excluded after detailed screening of full articles. Three published studies were included in this systematic review. A total of 197 patients were included in our analysis, 97 of them had colorectal stent vs 100 who had emergency surgery. Clinical success has been defined in different manners. In included trials the clinical success rate was significantly higher in the emergency surgery group (99%) compared with the stent group (52.5%) ( p < 0.00001). There was no difference in the overall complication rate in the stent group (48.5%) vs emergency surgery group (51%) ( p = 0.86). There was no difference in 30-days postoperative mortality ( p = 0.97). The overall survival was analyzed in none trial. When used as a bridge to surgery, colorectal stents provide some advantages: the primary anastomosis rate was significantly higher in the stent group (64.9%) vs emergency surgery group (55%) ( p = 0.003); the overall stoma rate was significantly lower in the stent group (45.3%) compared with the emergency surgery group (62%) ( p = 0.02). There were no significant differences between the two groups as to permanent stoma rate (46.7% in stent group vs 51.8% in surgical group, p = 0.56), anastomotic leakage rate (9% in stent group vs 3.7% in surgical group, p = 0.35) and intra-abdominal abscess rate (5.1% in stent group vs 4.9% in surgical group, p = 0.97). Conclusion Although colonic stenting appears to be an effective treatment of malignant large bowel obstruction, the clinical success resulted significantly higher in the emergency surgery group without any advantages in terms of overall complication rate and 30-days postoperative mortality. On the other hand, the colonic stenting as a bridge to surgery provides surgical advantages, as higher primary anastomosis rate and a lower overall stoma rate, without increasing the risk of anastomotic leak or intra-abdominal abscess. However, these results should be interpreted with caution because few studies reported data on these outcomes. Due to the small and variable sample size of the included trials, further RCTs are needed including a larger number of patients and evaluating long term results (overall survival and quality of life) and cost-effectiveness analysis.
Abstract Background Recent reviews suggest that enhancing fitness and functional capacity prior to surgery can accelerate post-surgery recovery and reduce mortality. However, the effect of pre-surgical exercise interventions in cancer patients is not fully explained. The aim of this paper is to systematically review the available literature regarding pre-surgery exercise training interventions in cancer patients and examine their effects on physiological outcomes as well as quality of life (QOL) and length of hospital stay. Methods Relevant studies were identified through a search on MEDLINE, PreMEDLINE, AMED, MEDLINE Daily Update, CINAHL and SPORTDiscus. All randomized controlled trials (RCTs) and non-RCTs that had some form of physical exercise undertaken prior to surgery were included. Descriptive characteristics such as participant characteristics, study design, types of cancer, length of study, and primary outcomes were extracted. Methodological rigour was assessed using a modified Delphi List. Due to the heterogeneity and the dearth of pre-surgical studies, we were limited to a systematic review rather than a meta-analysis. Results Eighteen studies were included consisting of a total of 966 participants. Lung cancer studies were the predominant group represented. Most of the studies prescribed an aerobic intervention programs done prior to surgery. Mode, frequency, duration, and intensity of exercise intervention varied across the different cancer groups. The majority of studies showed preliminary positive change in clinical outcomes with significant improvements in the rate of incontinence, functional walking capacity and cardiorespiratory fitness. Conclusion Pre-surgical exercise may benefit cancer patients through positive effects on function and physical capacity. Surgical oncologists may consider pre-surgical exercise interventions as a potential adjuvant therapy to improve patients' outcomes.
Abstract Background Surgery remains the best curative option for appropriately selected patients with lung cancer. Evidence suggests that improving cardiovascular fitness and functional capacity can accelerate post-surgery recovery and reduce mortality. However, the effect of exercise intervention for patients surgically treated for Non-Small Cell Lung Cancer [NCSLC] has not been fully examined. Purpose This review examines the literature regarding exercise intervention for patients who are surgically treated for NSCLC focussing on three key areas: methodological quality, intervention design (e.g. duration, frequency, type) and outcomes measured. Methods A search of Medline, EMBASE, CINAHL and PsychINFO was undertaken. Randomised Controlled Trials [RCTs] and non-RCTs including exercise training pre or post lung cancer resection were included. Descriptive characteristics were extracted and methodological quality assessed using Downs and Black appraisal checklist. Results Twenty studies (eight RCT's) were included: nine pre-surgical, nine post-surgical and two pre to post-surgical. The quality of evidence is questionable with many limitations (e.g. small samples, inadequate allocation concealment and a lack of clear reporting on timing, adverse events and follow-up). Regarding design of exercise intervention and outcomes measured, there was much variation between studies producing a disparate set of data. An optimal programme is still to be determined; however, suggestions are made relating to type of exercise (i.e. mixing aerobic, resistance and breathing exercises). Preliminary work from this review suggests that exercise intervention compared with usual care both pre and post-surgery is associated with improved cardiopulmonary exercise capacity, increased muscle strength and reduced fatigue, post-operative complications and hospital length of stay. Results concerning pulmonary function, quality of life, and blood gas analysis were variable and inconsistent. Conclusion In order to implement exercise intervention appropriate for patients surgically treated for NCSLC, more high quality randomised controlled trials are required and more work concerning feasibility, acceptability and effectiveness of specific interventions on outcomes is warranted.
Abstract Background Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospective biomarkers for metachronous liver metastasis would be invaluable in evaluating patients' clinical outcomes and developing personal treatment therapy. Methods Here we investigated the role of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in predicting liver metastasis for early stage CRC. To accomplish this goal, a multi-center retrospective study was performed which included three stages: exploration stage (43 patients), identification stage (162 patients) and validation stage (38 patients). TBL1XR1 expression was evaluated using immunohistochemical staining and RT-qPCR. The prognostic significance of TBL1XR1 in both stage IV CRC patients and early stage CRC patients were evaluated by Kaplan-Meier survival analysis and multivariate analysis, respectively. Results For stage IV CRC patients, TBL1XR1 expression was correlated with the number of liver metastases (P = 0.036), and high levels of TBL1XR1 in liver metastases indicated poor overall survival (P = 0.028). Moreover, high expressions of TBL1XR1 can serve as a predictor for liver metastasis in early stage CRC patients (P = 0.003). Conclusions TBL1XR1 is a promising biomarker for predicting liver metastasis in early stage CRC patients.
Abstract Although gallbladder cancer (GBC) is the most common malignancy of the biliary tract, its relatively low incidence and confounding symptomatology result in advanced disease at the time presentation, contributing to the poor prognosis and decreased survival associated with this disease. It is therefore increasingly important to understand its pathogenesis and risk factors to allow for the earliest possible diagnosis. To date, gallbladder cancer is poorly understood compared to other malignancies, and is still most commonly discovered incidentally after cholecystectomy. Moreover, while much is known about biliary neoplasms as a whole, understanding the clinical and molecular nuances of GBC as a separate disease process will prove a cornerstone in the development of early intervention, potential screening and overall more effective treatment strategies. The present work reviews the most current understanding of the pathogenesis, diagnosis, staging and natural history of GBC, with additional focus on surgical treatment. Further, review of current adjuvant therapies for unresectable and advanced disease as well as prognostic factors provide fertile ground for the development of future studies which will hopefully improve treatment outcomes and affect overall survival for this highly morbid, poorly understood malignancy.
Abstract The concept of the tumor microenvironment, developed from Paget’s “seed and soil” theory is made up of the cancer cells, the stromal tissue, and the extracellular matrix. In this mini-review, each of the components of this dynamic network will be examined. We will show that there are a multitude of complex interactions and a host of molecules involved in tumorogenesis and metastasis. We will further illustrate this notion with examples from the tumor microenvironment of breast cancer. Lastly, we conclude with thoughts about how this will influence the surgical field with examples of therapeutic agents already in use that target aspects of this microenvironment.
Abstract Introduction Survivin a multifunctional protein that controls cell division, inhibition of apoptosis and promotion of angiogenesis. It is expressed in most human neoplasm, but is absent in normal and differentiated tissues. The purpose of this article is to overview the expression of survivin, effect of its expression in response to treatment, correlation with other markers and newer advancement in targeting survivin. Methods A detailed search of Medline was carried out using the following search strategy: “((survivin) OR ((apoptosis) AND (inhibitor OR inhibitors))) AND ((breast) AND (neoplasm OR neoplasms OR tumor OR tumor OR cancer OR carcinoma))”. Abstract of all articles thus identified were reviewed to identify the relevant studies, full articles of studies thus identified were then obtained and reviewed. All relevant data was extracted and tabulated. Results Survivin expression by Immunohistochemistry was identified in 65.3% (55.2–90.0%) of the breast cancer patients among the identified studies while survivin mRNA by RT-PCR was identified in 93.6% (90–97%). Survivin expression has been reported to be associated with over expression of HER 2, vascular endothelial growth factor (VEGF), urokinase plasminogen activator (uPA)/PAI-1. Conclusion Survivin is over expressed in majority of breast cancers. The over expression of survivin is found to correlate with HER 2 and EGFR expression. Survivin expression has been found to confer resistance to chemotherapy and radiation. Targeting survivin in experimental models improves survival. More studies are needed on the role of survivin in multi drug resistance (MDR) in the presence of Pgp/uPA/PAI-1 and the impact of survivin over expression in triple negative breast cancer.
LncRNA ZEB1 Antisense 1 (ZEB1-AS1) has been suggested to be an oncogenic role in human hepatocellular carcinoma, osteosarcoma, glioma and esophageal carcinoma progression. However, the clinical significance and biological function of ZEB1-AS1 in gastric cancer is poorly understood. Levels of ZEB1-AS1 expression in gastric cancer tissues and cell lines were detected by qRT-PCR. Loss-of-function and gain-of-function studies were conducted to explore the biological function of ZEB1-AS1 in gastric cancer cells migration, invasion and EMT process. Rescued-function studies were performed to explore the association between ZEB1-AS1 and ZEB1 in gastric cancer cells migration, invasion and EMT process. ZEB1-AS1 was overexpressed in gastric cancer tissues and cell lines, and correlated with malignant status and prognosis in gastric cancer patients. ZEB1-AS1 regulated gastric cancer cells migration, invasion and EMT process. ZEB1-AS1 positively regulated ZEB1 expression in gastric cancer cells, and had a strongly positive correlation with ZEB1 expression in gastric cancer tissues. Rescued-function studies showed ZEB1 was critical for ZEB1-AS1 induced gastric cancer cells migration, invasion and EMT process. ZEB1-AS1 served as oncogenic roles in the regulation of gastric cancer cells migration, invasion and EMT process through modulating ZEB1.
Abstract Background Hepatocellular carcinoma (HCC) often recurs after curative hepatectomy; and early recurrence after hepatectomy (ERAH) is associated with poor prognosis. This study aimed to clarify risk factors and disease patterns for ERAH. Methods We retrospectively analyzed clinicopathological factors of 232 patients who underwent initial curative hepatectomies for HCC between April 2000 and March 2013, and examined associated risk factors and early recurrence patterns by liver function status (as indicated by indocyanine green retention rate at 15 min [ICGR15]). Results Patients who experienced recurrence within 6 months after hepatectomy (i.e., ERAH) had significantly shorter survival than those with longer disease-free intervals ( P < 0.001). In multivariate analysis, microvascular invasion (mVI; P = 0.034) and ICGR15 ≥ 16% ( P = 0.010) were independent risk factors for ERAH. In the ICGR1<16% subgroup, positive L3-AFP ( P = 0.04), tumor size ≥5 cm ( P = 0.011), surgical margin = 0 ( P = 0.0103), mVI ( P = 0.034), and extrahepatic recurrence were significant predictors of ERAH; in the ICGR15 ≥ 16%, subgroup, multiple tumors ( P = 0.046) were identified as a risk factor for ERAH; however, this group did not experience much extrahepatic recurrence. Conclusions ERAH was associated with mVI and ICGR15 ≥ 16%. Recurrence patterns and risk factors vary by liver function status, which should be considered in forming management strategies for early recurrence of HCC after curative hepatectomy.
Abstract Objective This study aims to answer the superiority of comparing laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) in the treatment early gastric cancer (EGC). Material and methods A comprehensive search up to May 31, 2014 was conducted on PubMed, Web of science, and the Cochrane Library. All eligible studies comparing LADG versus ODG were included. Data synthesis and statistical analysis were performed using RevMan 5.2 software. Results Seven randomized controlled trials (RCTs) totaling 390 patients (195 LADG and 195 ODG) were analyzed. Compared to ODG, LADG showed longer operative time (WMD = 79.60; 95%CI = 59.86 to 99.35; P < 0.00001), but was associated with less blood loss (WMD = −108.11; 95%CI = −145.97 to −70.26; P < 0.00001), fewer administered analgesics (WMD = −1.70; 95%CI = − 2.19 to −1.22; P < 0.00001), fewer number of harvested lymph node (WMD = −2.77; 95%CI = −4.38 to −1.16; P = 0.0007), lower incidence of postoperative complications (OR = 0.26; 95%CI = 0.13 to 0.54; P = 0.0003), shorter postoperative hospital stay (WMD = −1.0; 95% CI = −1.83 to −0.16; P = 0.02) and earlier passage of flatus (WMD = −0.62; 95% CI = −0.96 to −0.27; P = 0.0005). Conclusion This meta-analysis demonstrated that LADG significantly reduced blood loss, decreased the frequency of analgesic administration, faster recovery, a shorter hospital stay and fewer postoperative complications compared with ODG, though at the price of longer operative times and the number of harvested lymph nodes lesser as compared to ODG.
Abstract Background Approximately one-third of patients with localized osteosarcoma at presentation relapse as well as about three-fourths of the patients with metastases at diagnosis, about 90% of relapses are lung metastases. The role of lung metastasectomy remains to be determined. Patients and methods: Three hundred and twenty three patients, 88 with resectable lung metastases at diagnosis and 235 with localized disease at presentation who relapsed with lung metastases were treated. Results A total of 498 lung surgeries and 607 thoracotomies were performed. The 5 year overall survival was 37%. Final outcome was significantly related to presence or absence of metastasis, time of first relapse and presence of local recurrences. According to stage of the disease, the rate of a 5 year event-free survival (EFS) was 36% for patients with localized disease who later relapsed and 9% for patients with resectable lung metastases at presentation ( p < 0.0001). However, there were no differences in EFS between patients who underwent two or three thoracotomies and patients who had four or five thoracotomies (7.5 vs 18.7%, p = 0.29). Conclusions In patients with recurrent resectable pulmonary metastases from high grade osteosarcoma treated with adjuvant or neoadjuvant chemotherapy, thoracotomy should always be considered regardless the number of previous lung relapses and the number of secondary pulmonary lesions.
Abstract Background The purpose of this retrospective study was to assess the 5-year survival outcomes of cervical cancer patients who underwent an, open radical hysterectomy (ORH), robotic-assisted radical hysterectomy (RRH) or laparoscopic radical hysterectomy (LRH) for the treatment of their disease. Method We conducted a review of all cervical cancer patients who were managed with an ORH, RRH or LRH. Result Forty-nine patients were treated with LRH, 58 were managed via RRH and 39 patients underwent an ORH. The LRH (1.78 h) patients had a significantly shorter operative duration than the RRH (2.88 h) and ORH (2.39 h) subjects (p < 0.001). Blood loss was the highest in the ORH (475 cc) group (RRH = 207 cc and LRH = 312 cc) (P < 0.001). Moreover, the ORH (5.04 days) patients had a significantly longer hospital stay than the LRH (2.95 days) and RRH (2.50 day) subjects (P < 0.001). Kaplan–Meier survival analysis revealed a progression free survival (PFS) rate of 84.6% for the ORH group, 89.8% for the LRH group and 89.7% for the RRH patients (P = 0.271) at 60 months; overall survival was 92.3% for the ORH group, 95.9% for the LRH group and 96.6% for the RRH patients (P = 0.80). Conclusion The results from this study suggest that, irrespective of operative approach, patients who underwent a radical hysterectomy for early stage cervical cancer attained similar 5-year disease free and overall survival outcomes.
Advances in molecular biology have enabled identification of tumor biomarkers that allow for individualized risk assessment for patients with cancer. Molecular predictors of clinical outcome can help inform discussion regarding the role of adjuvant chemotherapy in patients with resected colon cancer, such as those with stage II colon cancer in which the benefit of adjuvant therapy is controversial or those with stage III colon cancer who may have a lower risk of recurrence and less absolute benefit from oxaliplatin therapy. This article summarizes the data surrounding the development, validation, and clinical and economic utility of the Oncotype DX colon cancer assay, a multigene expression assay validated to independently predict recurrence risk in patients with stage II and III colon cancer beyond traditional factors.
Abstract Objective The aim of this narrative review is to update the current knowledge on the treatment of recurrent cervical cancer based on a literature review. Material and methods A web based search in Medline and CancerLit databases has been carried out on recurrent cervical cancer management and treatment. All relevant information has been collected and analyzed, prioritizing randomized clinical trials. Results Cervical cancer still represents a significant problem for public health with an annual incidence of about half a million new cases worldwide. Percentages of pelvic recurrences fluctuate from 10% to 74% depending on different risk factors. Accordingly to the literature, it is suggested that chemoradiation treatment (containing cisplatin and/or taxanes) could represent the treatment of choice for locoregional recurrences of cervical cancer after radical surgery. Pelvic exenteration is usually indicated for selected cases of central recurrence of cervical cancer after primary or adjuvant radiation and chemotherapy with bladder and/or rectum infiltration neither extended to the pelvic side walls nor showing any signs of extrapelvic spread of disease. Laterally extended endopelvic resection (LEER) for the treatment of those patients with a locally advanced disease or with a recurrence affecting the pelvic wall has been described. Conclusions The treatment of recurrences of cervical carcinoma consists of surgery, and of radiation and chemotherapy, or the combination of different modalities taking into consideration the type of primary therapy, the site of recurrence, the disease-free interval, the patient symptoms, performance status, and the degree to which any given treatment might be beneficial.
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio. We retrospectively examined tumor PD-L1 expression in 508 surgically resected primary NSCLC cases by immunohistochemical analysis (cut-off value: 1%). The association of PD-L1 expression with preoperative systemic inflammatory markers was assessed by univariate and multivariate analyses. We generated a PD-L1 association score (A-score) from serum CRP level (cut-off value: 0.3 mg/dl) and smoking status to predict PD-L1 expression. Among the total 508 patients, 188 (37.0%) patients were positive for PD-L1 expression at the 1% cut-off value and 90 (17.5%) had elevated serum CRP level. Multivariate logistic regression revealed that PD-L1 positivity was significantly associated with advanced stage, the presence of vascular invasion and high serum CRP level ( = .0336, .0106 and 0.0018, respectively). Though not significant, smoking history tended to be associated with PD-L1 protein expression ( = .0717). There was no correlation with other inflammatory markers. Smoking history with elevated CRP level (A-score: 2) was strongly associated with PD-L1 protein expression (odds ratio: 5.18, < .0001), while it was inversely associated with mutation (odds ratio: 0.11, < .0001). Our results indicate that among all systemic inflammatory markers examined, serum CRP seems to predict PD-L1 expression in patients with NSCLC however the clinical applicability is limited given the obtained area under the receiver operating characteristic curve values.
Abstract In the US, the total projected cancer incidence will increase by 45% yearly from 2010 to 2030. The majority of these neoplasms will affect the elderly. The National Institute on Aging has characterised the aging of our society as a “silver tsunami”. Thus, the management of cancer in the older aged person represents a priority for health care delivery in the immediate future. Aging, age-related changes, frailty, prolongation of active life expectancy, prevention of Adverse Drugs Reactions (ADRs), Comprehensive Geriatric Assessment (CGA), and individualised treatment in the future will become the most widely used concepts in the management of cancer patients.
Abstract Squamous cell carcinoma (SCC) of the vulva is the fourth most common gynecological cancer, usually staged with the TNM or FIGO systems. Since 2009, FIGO staging has taken the extranodal extension (ENE) of lymph node metastases into account. ENE is defined as the spread of a lymph node metastasis into surrounding soft tissue. Although the TNM and FIGO systems acknowledge the importance of ENE in SCC, no comprehensive studies have analyzed the prognostic impact of this parameter. We therefore queried the PubMed and SCOPUS databases from their inception up until 04/01/2015, adopting no language restrictions: all prospective studies reporting on prognostic parameters in patients with vulvar SCC, and comparing participants with and without ENE were eligible for our analysis. Data were summarized using risk ratios (RR) for the number of deaths/recurrences and hazard ratios (HR) for the time-dependent risk related to ENE positivity, adjusting for potential confounders. Among 859 hits, 13 studies were found eligible and were included in our meta-analysis. Compared with ENE-negative (ENE-) cases, the ENE-positive (ENE+) patients had significantly higher rates of all-cause mortality (6 studies: RR = 3.18; 95%CI: 2.02–5.00, p < 0.0001, I2 = 56%), cancer-specific mortality (3 studies: RR = 2.03; 95%CI: 1.12–3.69, p = 0.02, I2 = 80%), and recurrence (4 studies: RR = 2.69, 95%CI: 1.61–3.76, p < 0.0001, I2 = 57%). Using HRs after adjusting for potential confounders, ENE + carried a significantly higher risk of all-cause mortality (6 studies: HR = 3.08, 95%CI: 1.73–5.48, p < 0.0001, I2 = 66%), and recurrence (5 studies: HR = 3.93, 95%CI: 2.33–6.62, p < 0.0001, I2 = 28%). Our meta-analysis clarifies the prognostic significance of ENE in vulvar SCC, also pointing to its implications for gross sampling, histology and oncological staging.