Pathologic stage of ypT0N+ rectal cancers following neo-adjuvant treatment: clinical interpretation of an orphan status.

Approximately 20% of locally advanced rectal cancers treated with neoadjuvant therapy achieve a pathologic complete response, but approximately 10% of them present residual nodal metastases (ypT0N+). We aimed this research to compare the survival rates of ypT0/ypTisN+ and stage 3a rectal cancer patients. A large multicenter study recently investigated ypT0/ypTis rectal cancers treated between 2005 and 2015 in Italy and Spain. ypT0/ypTisN+ were selected and compared with stage 3a rectal cancers treated at the same institutions with upfront surgery (ySICO group). Additionally, the SEER database was searched for patients with stage 3a rectal cancers treated with surgery in the same years. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were analyzed using Kaplan-Meier curves and random survival forest analysis (RSF). The ySICO study population consisted of 19 ypT0/2ypTisN+ (mean follow-up 41.8 months) and 72 Stage 3a patients (mean follow-up 56.9 months). These subgroups were comparable, but stage 3a patients were treated more frequently with adjuvant therapy (90.5% vs 61.9%, p 0.0001). No significant differences were reported between the ySICO subgroups for the OS, DFS, and DSS curves. When the 1213 SEER patients were added to Stage 3a, the RFS model failed to differentiate OS between groups that presented identical survival. Root analysis showed that adjuvant therapy was the only variable differentiating OS and DSS in the ySICO population. These findings suggest that ypT0/ypTisN+ and stage 3a rectal cancers could be ranked together based on their similar outcomes and pathologic assessment, and they stress the importance of adjuvant therapy in patients presenting with residual nodal metastases.

Time interval between neoadjuvant radio-chemotherapy and surgery in rectal cancer: is the long interval correct for all patients?

BACKGROUND: Optimal time between neoadjuvant radio-chemotherapy period and surgery remains controversial in patients with rectal cancer: an increasing number of studies show results in favor of a long interval. METHODS: We conducted a retrospective analysis of the cases of low-middle rectal adenocarcinoma undergoing neoadjuvant RT-CT and surgery: the primary endpoint was the complete pathological response rate and the secondary endpoint the rate of complications. We analyzed cases from 1/01/2003 to 31/12/2018 divided in two periods: from 2003 to 2010 (23 pts) and from 2011 to 2018 (23 pts). The two periods were characterized by two different surgical teams which use different time intervals (≤ vs. >8 weeks). RESULTS: The pCR rate is 21.7% in both groups; as regards the complications, the difference between the two groups is in grade IIIb: 8.7% in the first group and 17.4% in the second group (P=0.66). CONCLUSIONS: Although our study is based on a small number of patients, it shows the same rate of pCR with respect to two different time intervals; this suggests the need for studies based on the division of patients into subgroups and the evaluation of different time intervals in order to reach the best oncological outcomes.

Better survival of patients with oligo- compared with polymetastatic cancers: a systematic review and meta-analysis of 173 studies.

Background: The modern concept of oligometastatic (OM) state has been initially developed to describe patients with a low burden of disease and with a potential for cure with local ablative treatments. We systematically assessed the risk of death and relapse of oligometastatic (OM) cancers compared to cancers with more diffuse metastatic spread, through a meta-analysis of published data.  Methods: PubMed, the Cochrane Library, and EMBASE were searched for studies reporting prognosis of patients with OM solid tumors. Risk of death and relapse were extracted and pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI).  The primary outcome of the study refers to overall mortality in OM vs. polymetastatic (PM) patients.  Results. Mortality and relapse associated with OM state in patients with cancer were evaluated among 104,234 participants (n=173 studies). Progression-free survival was better in patients with OM disease (hazard ratio [HR] = 0.62, 95% CI 0.57-0.68; P <.001; n=69 studies). Also, OM cancers were associated with a better overall survival (OS) (HR = 0.65, 95% CI 0.62-0.68; P<.01; n=161 studies). In colorectal (CRC), breast, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) the reduction in the risk of death for OM patients were 35, 38, 30 and 42%, respectively. Biliary tract and cervical cancer do not significantly better in OM stage likely for paucity of data. Conclusions. Patients with OM cancers have a significantly better prognosis than those with more widespread stage IV tumors. In OM cancer patients a personalized approach should be pursued.

Definition and assessment of frailty in older patients: the surgical, anaesthesiological and oncological perspective.

The number of oncology, surgery and anaesthesia procedures in older patients has greatly increased in recent years due to ageing populations. Older patients are typically characterised by physical changes such as comorbidities, decline in physiological activities and cognitive impairment. All these factors, together with polypharmacological therapies, may substantially impact perioperative outcome, quality of recovery and, more in general, quality of life. A comprehensive multidisciplinary approach to perioperative care is thus needed. The assessment of frailty has a central role in the pre-operative evaluation of older patients and, with a multidisciplinary approach. The best surgical procedures and oncologic therapies can be accurately discussed in the pre- and post-operative periods. All clinicians involved in this scenario should be proactive in multidisciplinary care to achieve better outcomes.

Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-analysis of Treatment Outcomes.

BACKGROUND: The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in locally advanced rectal cancer could increase pathological downstaging and act on occult micrometastatic disease, leading ultimately to a better outcome. A systematic review was carried out of the existing literature on the treatment outcomes of total neoadjuvant therapy (TNT) on locally advanced rectal cancer. TNT was defined as chemotherapy using cycles of induction and/or consolidation in conjunction with standard chemoradiotherapy prior to surgery. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was performed according to the PRISMA statement up until January 2019. The primary endpoints were complete pathologic response (pCR), disease-free survival, and overall survival rates. RESULTS: A total of 28 studies (3 retrospective and 25 prospective for a total of 3579 patients) were included in the final analysis (n = 2688 treated with TNT and n = 891 with neoadjuvant chemoradiotherapy therapy). The pooled pCR rate was 22.4% (95% CI 19.4%-25.7%) in all patients treated with TNT (n = 27 studies with data available). In n = 10 comparative studies with data available, TNT was found to increase the odds of pCR by 39% (1.40, 95% CI 1.08-1.81, P = 0.01). CONCLUSIONS: The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate. Given that the comparative analysis was derived from few randomized publications, large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT.

Microsatellite Instability and Survival in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: About 15-20% of colorectal cancers (CRCs) have deficiency in a mismatch repair (MMR) protein. MMR has a high level of microsatellite instability (MSI-H). We have conducted this review and meta-analysis to determine the prognostic role of MSI-H status in stage II CRC. MATERIALS AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, and SCOPUS for studies reporting data on overall survival (OS) and disease-free or relapse-free survival (DFS or RFS) for MSI-H compared to microsatellite stable (MSS) CRC. RESULTS: A total of 39 studies were analysed, including 12,110 patients. MSI-H status was associated with a significantly reduced risk of death (HR=0.64, 95%CI=0.52-0.8, p<0.01) and relapse (HR=0.59, 95%CI=0.45-0.77, p<0.01) in stage II CRC. CONCLUSION: MSI-H represents an important prognostic determinant in stage II CRC and may be considered when estimating the risk of recurrence in stage II CRC.

Risk of second primary tumors in GIST survivors: A systematic review and meta-analysis.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in the gastrointestinal tract. Second primary tumors (SPTs) have been reported frequently, either synchronously or during follow-up, in patients diagnosed with GISTs. METHODS: We carried out an electronic search of PubMed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library seeking articles investigating the incidence of SPTs in patients with concomitant GIST. All studies were evaluated for heterogeneity before meta-analysis and for publication bias. Pooled incidence rate was estimated using fixed- and random-effects models. Subsite of SPTs was also investigated. RESULTS: A total of 32 studies met the inclusion criteria, for a total of 19,627 patients with a diagnosis of GIST. The pooled prevalence of SPTs was 20%, with 14% and 3% being synchronous and metachronous tumors, respectively. We found a risk for several specific cancer sites, in particular gastrointestinal (5%) and genitourinary tract cancers (3%). The most frequently associated malignancies were: colorectal (17%), prostate (14%), gastric (9%), esophageal (5.5%), lung (5.4%), hepato-biliopancreatic (4.7%), breast (4.6%), lymphoma (4.4%), kidney (4.35%), and sarcomas (3.3%). Regression analyses revealed a significant positive association for all SPTs with follow-up and Miettinen risk. CONCLUSIONS: Our results indicate that 20% of patients with GIST experienced a SPT, primarily synchronously with a diagnosis of GIST. In particular, we observed an excess of incident gastrointestinal tumors. These findings have important implications for both pathologists, who should perform extensive molecular analysis of surgical non-GIST specimens in resected patients, and for oncologists, who should continue to follow up GIST patients.

Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis.

(1) Background: The optimal timing of adjuvant chemotherapy (CT) in gastrointestinal malignancies is still a matter of debate. For colorectal cancer, it is recommended to start post-operative treatment within eight weeks. The objective of this study was to assess the clinical effects of starting adjuvant CT within or after 6-8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2) Methods: MEDLINE, EMBASE, and the Cochrane Library were searched in December 2018. Publications comparing the outcomes of patients treated with adjuvant CT administered before (early) or after (delayed) 6-8 weeks post-surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS). (3) Results: Out of 8752 publications identified, 34 comparative studies assessing a total of 141,853 patients were included. Meta-analysis indicated a statistically significant increased risk of death with delayed CT (>6-8 weeks post-surgery) in colorectal cancer (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.21-1.33; p <0.001). Similarly, for gastric cancer, delaying adjuvant CT was associated with inferior overall survival (HR = 1.2, 95% CI 1.04-1.38; p = 0.01). Conversely, the benefit of earlier CT was not evident in pancreatic cancer (HR = 1, 95% CI 1-1.01; p = 0.37). Conclusions: Starting adjuvant CT within 6-8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer.

Quality of Life and Gastrointestinal Symptoms Following Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy: a Systematic Review.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are the most common bariatric operations performed worldwide. Quality of life (QoL) is a crucial outcome metric. An electronic systematic search using PubMed, EMBASE, and Web of Science of studies comparing QoL after LSG and LRYGB was performed. QoL after both LSG and LRYGB considerably improves regardless the type of surgery. The QoL has a slight downward trend from the second to the fifth year postoperatively, but it remains higher than the baseline. LSG patients are more likely to suffer from gastroesophageal symptoms (GES). GES represent the only significant difference between the two procedures. A routine screening with gastroscopy and 24 h pH metry to help tailor the most appropriate surgical approach is advised.

Number of lymph nodes assessed has no prognostic impact in node-negative rectal cancers after neoadjuvant therapy. Results of the "Italian Society of Surgical Oncology (S.I.C.O.) Colorectal Cancer Network" (SICO-CCN) multicentre collaborative study.

INTRODUCTION: We retrospectively investigated the impact of number or complete absence of nodes retrieved on survival of patients with rectal cancer (RC) treated with neoadjuvant radiation-therapy (NAT). METHODS: All patients with RC treated with NAT followed by curative surgery from 2000 to 2014 in 14 Italian referral Centres for Colorectal Surgery were enrolled. Information about number of nodes harvested, node ratio, type of radiation therapy schedule and tumour stage were recorded. Impact of number or complete absence of nodes retrieved on overall survival (OS) and on cumulative incidence of death for disease (CIDD) was assessed and factors influencing node yield were investigated. RESULTS: In total, 1407 patients were included. Mean number of nodes retrieved was 12.9, while no lymph nodes were found in only 32 patients (2%, ypNnull). Definite nodal stage was ypN0 in 1001 patients (71%) and ypN+ in 372 patients (27%). In multivariable analysis ypNnull patients showed worse OS and CIDD compared to both ypN0 and ypN+. In ypN0 patients, number of nodes assessed, stratified in 4 groups (<5, 5-10, 11-15 and > 15), did not significantly influence OS and CIDD. Long-course radiation schedule and early T stages negatively affected node assessment. CONCLUSION: Complete absence of nodes assessed was associated with worse prognosis compared to node-negative and node-positive patients. In node-negative patients number of nodes was not associated to OS and CIDD. Based on data from this large population of irradiated RC, number of nodes assessed has no prognostic impact in node-negative patients.

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy.

Prognostic value of diffuse versus intestinal histotype in patients with gastric cancer: a systematic review and meta-analysis.

BACKGROUND: There are two distinct types of gastric carcinoma (GC), intestinal, more frequently sporadic and linked to environmental factors, and diffuse (undifferentiated) that is highly metastatic and characterized by rapid disease progression and a poor prognosis. However, there are many conflicting data in the literature concerning the association between histology and prognosis in GC. This meta-analysis was performed to provide demonstration if histology according to Lauren classification is associated with different prognosis in patients with GC. METHODS: We searched PubMed, the Cochrane Library, SCOPUS, Web of Science, CINAHL, and EMBASE for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival (OS) were evaluated. RESULTS: A total of 73 published studies including 61,468 patients with GC were included in this meta-analysis. Our analysis indicates that GC patients with diffuse-type histology have a worst prognosis than those with intestinal subgroup in all studies (HR 1.23; 95% CI, 1.17-1.29; P<0.0001), in both loco-regional confined (HR 1.21; 95% CI, 1.12-1.30; P<0.0001) and advanced disease (HR 1.25; 95% CI, 1.046-1.50; P=0.014), in Asiatic (HR 1.2; 95% CI, 1.14-1.27; P<0.0001) and Western patients (HR 1.3; 95% CI, 1.19-1.41; P<0.0001), and in those not exposed (HR 1.15; 95% CI, 1.07-1.24; P<0.0001) or exposed (HR 1.27; 95% CI, 1.17-1.37; P<0.0001) to (neo)adjuvant therapy. CONCLUSIONS: Our results indicated that histology might be a useful prognostic marker for both early and advanced GC patients, with intestinal-type associated with a better outcome. This information could be used for stratification purpose in future clinical trials.

Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis.

IMPORTANCE: Primary tumor location is emerging as an important prognostic factor owing to distinct biological features. However, the side of origin of colon cancer (CC) still does not represent a prognostic parameter when deciding for adjuvant or palliative chemotherapy. OBJECTIVE: To determine the prognostic role of left vs right-sidedness of primary tumor location in patients with CC. DATA SOURCES: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, LILACS, CINAHL, and SCOPUS for prospective or retrospective studies reporting data on overall survival for left-sided colon cancer (LCC) compared with right-sided colon cancer (RCC). STUDY SELECTION: Studies were selected if: (1) side of CC was reported among variables entered into survival analysis, (2) survival information was available (overall survival [OS] was reported in the article as hazard ratio (HR) according to multivariate analysis, (3) articles were published in the English language. DATA EXTRACTION AND SYNTHESIS: Data were pooled using HRs for OS of LCC vs RCC according to fixed or random-effects models. Subgroup analysis and multivariate random-effects model meta-regression was also implemented adjusting for stage distribution, sample size, race, year of publication, type and quality of studies, and adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. In this analysis, all HRs with 95% CIs were pooled to obtain prognostic information on the location of the primary tumor (left vs right location site of CC) independent of other common clinicopathological covariates. RESULTS: An analysis was made from the 66 studies conducted. It included 1 437 846 patients with a median follow-up of 65 months. Left sided primary tumor location was associated with a significantly reduced risk of death (HR, 0.82; 95% CI, 0.79-0.84; P < .001) and this was independent of stage, race, adjuvant chemotherapy, year of study, number of participants, and quality of included studies. CONCLUSIONS AND RELEVANCE: Based on these results, CC side should be acknowledged as a criterion for establishing prognosis in all stages of disease. It should be considered when deciding treatment intensity in metastatic settings, and should represent a stratification factor for future adjuvant studies.

3D vs 2D laparoscopic systems: Development of a performance quantitative validation model.

BACKGROUND: The new technology ensures 3D laparoscopic vision by adding depth to the traditional two dimensions. This realistic vision gives the surgeon the feeling of operating in real space. Hospital of Treviglio-Caravaggio isn't an university or scientific institution; in 2014 a new 3D laparoscopic technology was acquired therefore it led to evaluation of the of the appropriateness in term of patient outcome and safety. The project aims at achieving the development of a quantitative validation model that would ensure low cost and a reliable measure of the performance of 3D technology versus 2D mode. In addition, it aims at demonstrating how new technologies, such as open source hardware and software and 3D printing, could help research with no significant cost increase. For these reasons, in order to define criteria of appropriateness in the use of 3D technologies, it was decided to perform a study to technically validate the use of the best technology in terms of effectiveness, efficiency and safety in the use of a system between laparoscopic vision in 3D and the traditional 2D. METHODS: 30 surgeons were enrolled in order to perform an exercise through the use of laparoscopic forceps inside a trainer. The exercise consisted of having surgeons with different level of seniority, grouped by type of specialization (eg. surgery, urology, gynecology), exercising videolaparoscopy with two technologies (2D and 3D) through the use of a anthropometric phantom. The target assigned to the surgeon was that to pass "needle and thread" without touching the metal part in the shortest time possible. The rings selected for the exercise had each a coefficient of difficulty determined by depth, diameter, angle from the positioning and from the point of view. RESULTS: The analysis of the data collected from the above exercise has mathematically confirmed that the 3D technique ensures a learning curve lower in novice and greater accuracy in the performance of the task with respect to 2D.