Prognostic value of soluble P-selectin levels in colorectal cancer

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC

Systemic Treatment of Patients With Gastrointestinal Cancers During the COVID-19 Outbreak: COVID-19-adapted Recommendations of the National Cancer Institute of Milan

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak poses a major challenge in the treatment decision-making of patients with cancer, who may be at higher risk of developing a severe and deadly SARS-CoV-2 infection compared with the general population. The health care emergency is forcing the reshaping of the daily assessment between risks and benefits expected from the administration of immune-suppressive and potentially toxic treatments. To guide our clinical decisions at the National Cancer Institute of Milan (Lombardy region, the epicenter of the outbreak in Italy), we formulated Coronavirus-adapted institutional recommendations for the systemic treatment of patients with gastrointestinal cancers. Here, we describe how our daily clinical practice has changed due to the pandemic outbreak, with the aim of providing useful suggestions for physicians that are facing the same challenges worldwide

Systemic Treatment of Patients With Gastrointestinal Cancers During the COVID-19 Outbreak : COVID-19-adapted Recommendations of the National Cancer Institute of Milan

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak poses a major challenge in the treatment decision-making of patients with cancer, who may be at higher risk of developing a severe and deadly SARS-CoV-2 infection compared with the general population. The health care emergency is forcing the reshaping of the daily assessment between risks and benefits expected from the administration of immune-suppressive and potentially toxic treatments. To guide our clinical decisions at the National Cancer Institute of Milan (Lombardy region, the epicenter of the outbreak in Italy), we formulated Coronavirus-adapted institutional recommendations for the systemic treatment of patients with gastrointestinal cancers. Here, we describe how our daily clinical practice has changed due to the pandemic outbreak, with the aim of providing useful suggestions for physicians that are facing the same challenges worldwide

Cross-cultural adaptation of the locally recurrent rectal cancer – Quality of life questionnaire

Aim: The Locally Recurrent Rectal Cancer – Quality of Life (LRRC-QoL) questionnaire was developed as a disease specific measure of health-related quality of life (HrQoL) in locally recurrent rectal cancer (LRRC), it has previously been validated for use in the UK and Australia. The aim of this study was to translate and cross-culturally adapt the LRRC-QoL to enable its use on an international platform. Materials and methods: Cross-cultural adaptation of the LRRC-QoL was undertaken through a process of 1) Translatability Assessment (TA), 2) forward-backward translation, and 3) pre-testing interviews to establish content validity and conceptual equivalence across all versions. The QQ-10 measure was used to assess face validity and acceptability. The LRRC-QoL was translated into 13 languages: Danish, Dutch, French, Hindi, Italian, Mandarin, Marathi, Portuguese, Russian, Spanish, Swedish, Telugu, and Urdu. Results: In total, 67 patients and 6 clinicians were recruited to pre-testing interviews across 12 countries: Brazil, Canada, Denmark, France, India, Italy, the Netherlands, New Zealand, Pakistan, Singapore, Spain, and Sweden. TA was also undertaken in the USA and Ireland, and translations were prepared in Russian, Marathi, and Telugu. The LRRC-QoL was found to demonstrate conceptual equivalence and content validity across all versions. Mean QQ-10 Value score 76.80 (SD 13.88) and mean Burden score 20.22 (SD 23.03), confirming face validity and acceptability in this international cohort. Conclusion: The LRRC-QoL has now undergone cross-cultural adaptation to enable its use in 10 languages and 16 countries. Its psychometric properties will be further examined through external validation in an international cohort.</p

Cross-cultural adaptation of the locally recurrent rectal cancer – Quality of life questionnaire

Aim: The Locally Recurrent Rectal Cancer - Quality of Life (LRRC-QoL) questionnaire was developed as a disease specific measure of health-related quality of life (HrQoL) in locally recurrent rectal cancer (LRRC), it has previously been validated for use in the UK and Australia. The aim of this study was to translate and cross-culturally adapt the LRRC-QoL to enable its use on an international platform. Materials and methods: Cross-cultural adaptation of the LRRC-QoL was undertaken through a process of 1) Translatability Assessment (TA), 2) forward-backward translation, and 3) pre-testing interviews to establish content validity and conceptual equivalence across all versions. The QQ-10 measure was used to assess face validity and acceptability. The LRRC-QoL was translated into 13 languages: Danish, Dutch, French, Hindi, Italian, Mandarin, Marathi, Portuguese, Russian, Spanish, Swedish, Telugu, and Urdu. Results: In total, 67 patients and 6 clinicians were recruited to pre-testing interviews across 12 countries: Brazil, Canada, Denmark, France, India, Italy, the Netherlands, New Zealand, Pakistan, Singapore, Spain, and Sweden. TA was also undertaken in the USA and Ireland, and translations were prepared in Russian, Marathi, and Telugu. The LRRC-QoL was found to demonstrate conceptual equivalence and content validity across all versions. Mean QQ-10 Value score 76.80 (SD 13.88) and mean Burden score 20.22 (SD 23.03), confirming face validity and acceptability in this international cohort. Conclusion: The LRRC-QoL has now undergone cross-cultural adaptation to enable its use in 10 languages and 16 countries. Its psychometric properties will be further examined through external validation in an international cohort

Contemporary results from the PelvEx collaborative: improvements in surgical outcomes for locally advanced and recurrent rectal cancer

Aim: The PelvEx Collaborative collates global data on outcomes following exenterative surgery for locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study is to report contemporary data from within the collaborative and benchmark it against previous PelvEx publications. Method: Anonymized data from 45 units that performed pelvic exenteration for LARC or LRRC between 2017 and 2021 were reviewed. The primary endpoints were surgical outcomes, including resection margin status, radicality of surgery, rates of reconstruction and associated morbidity and/or mortality. Results: Of 2186 patients who underwent an exenteration for either LARC or LRRC, 1386 (63.4%) had LARC and 800 (36.6%) had LRRC. The proportion of males to females was 1232:954. Median age was 62 years (interquartile range 52-71 years) compared with a median age of 63 in both historical LARC and LRRC cohorts. Compared with the original reported PelvEx data (2004-2014), there has been an increase in negative margin (R0) rates from 79.8% to 84.8% and from 55.4% to 71.7% in the LARC and LRRC cohorts, respectively. Bone resection and flap reconstruction rates have increased accordingly in both cohorts (8.2%-19.6% and 22.6%-32% for LARC and 20.3%-41.9% and 17.4%-32.1% in LRRC, respectively). Despite this, major morbidity has not increased. Conclusion: In the modern era, patients undergoing pelvic exenteration for advanced rectal cancer are undergoing more radical surgery and are more likely to achieve a negative resection margin (R0) with no increase in major morbidity

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: Study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8Gy in radiotherapy-naive patients, and 15 × 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P &lt; 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease