Importance of long-term surveillance after curative esophagectomy for esophageal squamous cell carcinoma

Summary Background The long-term outcomes after esophagectomy for esophageal cancer remain uncertain and the optimal surveillance strategy after curative surgery remains controversial. Methods In this study, the clinicopathological characteristics of patients who underwent curative thoracic esophagectomy between 1991 and 2015 at Toranomon Hospital were retrospectively analyzed and reviewed until December 2020. We evaluated the accumulated data regarding the pattern and rates of recurrence and second malignancy. Results A total of 1054 patients were eligible for inclusion in the study. Of these, 97% were followed up for 5 years, and the outcomes after 25 years could be determined in 65.5%. Recurrence was diagnosed in 318 patients (30.2%), and the most common pattern was lymph node metastasis (n = 168, 52.8%). Recurrence was diagnosed within 1 year in 174 patients (54.7%) and within 3 years in 289 (90.9%). Second malignancy possibly occurred through the entire study period after esophagectomy even in early-stage cancer, keeping 2%–5% of the incidental risk. There was no significant difference in the prognosis between 3-year survivors with and without a second malignancy. Conclusions Most recurrences after resection of esophageal cancer occurred within 3 years regardless of disease stage. However, these patients have an ongoing risk of developing a second malignancy after esophagectomy. Further consideration is required regarding the efficacy of long-term surveillance.

The Combination of Inflammation and Nutrition Factors Reinforces the Prognostic Prediction for Stage III Colorectal Cancer Patients After Curative Resection

Purpose Inflammation and nutritional status are known to be associated with the prognosis of several malignancies. Herein, we attempted to develop inflammation–nutrition scores and predict the prognosis of stage III colorectal cancer (CRC). Methods This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and the Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dL albumin level, >450 monocyte counts, and <1.65 × 105 platelet counts, which were associated with disease-free survival (DFS). Using KPS, DFS and overall survival (OS) were validated in VS. Results The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. Conclusion KPS serves as a new model for the prognosis of patients with stage III CRC.

Advances in lung cancer diagnosis and treatment - a review

Lung cancer is the second and third most common cancer in Iceland for females and males, respectively. Although the incidence is declining, lung cancer still has the highest mortality of all cancers in Iceland. Symptoms of lung cancer can be specific and localized to the lungs, but more commonly they are unspecific and result in significant diagnostic delay. Therefore, majority of lung cancer patients are diagnosed with non-localized disease. In recent years, major developments have been made in the diagnosis and treatment of lung cancer. Positive emission scanning (PET) and both transbroncial (EBUS) or transesophageal ultrasound (EUS) biopsy techniques have resulted in improved mediastinal staging of the disease and minimal invasive video-assisted thoracic surgery (VATS) has lowered postoperative complications and shortened hospital stay. Technical developments in radiotherapy have benefitted those patients who are not candidates for curative surgery. Finally, and most importantly, recent advances in targeted chemotherapeutics and development of immunomodulating agents have made individual tailoring of treatment possible. Recent screening-trials with low-dose computed tomography show promising results in lowering mortality. This evidence-based review focuses on the most important developments in the diagnosis and treatment of lung cancer, and includes Icelandic studies in the field.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Particularities of Surgical Treatment for the Neuropathic Diabetic Foot

Diabetic neuropathy is one of the chronic complications of diabetes and along with other complications causes a pathology called diabetic foot. The present study analyzed a group of 164 patients admitted to the surgery department of the Clinical Hospital “Doctor Ioan Cantacuzino” Bucharest, between September and December 2019. The results of the study highlight the potential for contamination of neuropathic lesions and the need for curative surgery, most conservative. The conclusion of the analysis emphasizes that the imbalance of the underlying disease changes, in a negative sense, the prognosis of any complication of it.

Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1)

PURPOSE Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC). METHODS In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed. RESULTS Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months v 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months v 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002). CONCLUSION HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.

P-OGC36 Staging Laparoscopy in Oesophago-gastric cancers; A highly selective approach and its impact on patient outcome during COVID 19

Background Staging laparoscopy is performed in all Oesophago-gastric cancer patients suitable for radical treatment with tumour staged ≥T2 prior to neoadjuvant chemotherapy. In response to COVID 19 pandemic, on 25th March 2020, the joint statement issued by the Royal College of Surgeons and AUGIS advised all laparoscopic procedures should be avoided due to the risk of virus transmission associated with aerosol-generating procedures. In accordance with the guidance, a more selective approach on who underwent a staging laparoscopy was followed. This audit explores its impact on patient outcome comparing data from pre COVID period with the COVID period. Methods Retrospective and prospective data was collected for 24months on all OG cancer patients from 25th March2019 to 24th March2021. ‘Pre COVID’ period was defined as 25th March 2019 to 24th March 2020 and ‘COVID’ period was defined as 25th March 2020 to 24th March 2021. All patients with Oesophago-gastric cancer with MDT cancer staged ≥T2, suitable for neoadjuvant chemotherapy were included. Patients with tumour staged &lt;T2 and or diagnosed with squamous cell carcinoma involving upper or middle third of oesophagus were excluded. Fishers Exact model using SPSS V24 was used to identify any statistically significant differences between the 2 groups. Results Pre-COVID Period: 80patients underwent staging laparoscopy. Of these, 9patients(11.6%) with tumour staged as ≥T3 were declined curative surgery due to advanced disease(n = 2), metastatic disease(n = 3) or both(n = 4). In total, 40patients underwent curative surgery and there were 0 open/close laparotomies. COVID Period: Of the 79patients suitable for staging laparoscopy, only 7patients(8.7%) underwent laparoscopy. Of these, 3patients(3.8%) with tumour staged as ≥T3 were declined curative surgery due to advanced disease(n = 2) and metastatic disease(n = 1). In total, 33patients underwent curative surgery and only 1patient had an open/close laparotomy due to a liver metastases. No statistically significant difference was found p = 0.0913 Conclusions Staging laparoscopy is a useful tool for accurate staging of Oesophago-gastric cancers. It helps avoid unnecessary open and close laparotomy due to advanced disease and also allows us to assess patient fitness to major surgery. During the pandemic, the number of staging laparoscopies performed declined significantly but with no statistically significant difference to patient outcome. Thus we conclude, the COVID 19 pandemic has enabled us to have a selective approach to performing staging laparoscopy in Oesophago-gastric patients with advanced disease staged ≥T3 only.

P-OGC30 High volume oesophagogastric resection in a small private hospital during COVID 19, April 2020- April 2021

Background Like other hospitals at the peak of the pandemic, our institution had limited elective critical care capacity. This study summarises the outcomes of patients undergoing oesophagogastric (OG) resection at our institution, treated as the result of the emergency national contract between the NHS and the independent sector hospitals. Methods Patients undergoing OG resection at our institution between April 2020 and April 2021 were included. Patients were managed through the multidisciplinary team and were treated according to standard ERAS pathways, involving critical care input. National OG Cancer Audit (NOGCA) metrics were collected and compared to pre-COVID data. Results 81 patients underwent oesophagogastric resection in the private sector (60 oesophagectomies). Median length of stay was 9 days (9 pre-COVID). This included 21 patients who were repatriated to our main centre for ongoing management. 30-day mortality was 3.7% (1.8% pre-COVID), 90-day mortality 6.7% (4.2% pre-COVID). This included one patient who contracted COVID following discharge. 9 patients suffered an anastomotic leak, equating to a leak rate of 11% (7% pre-COVID). 22 resections were performed at our main centre (110-140 OG resection pre-COVID) Conclusions It is likely the private institution in this study represented one of the busiest oesophagogastric centres in the UK during COVID-19. A large cohort of patients underwent potentially curative surgery as a result of the emergency contract, who would have otherwise been placed on prolonged or palliative chemotherapy. 30 and 90-day mortality and anastomotic leak rates were higher than pre-pandemic levels, reinforcing the value of centralised tertiary OG resection services.

P-OGC09 Evaluating the Availability of Services for Cancer Patients Following Surgical Resection of Esophago-Gastric Tumours

Background Upper gastrointestinal (UGI) cancers account for 11% of cancers in the UK, with oesophago-gastric cancers having the highest incidence rate in males. Since publication of the NHS Cancer Plan in 2001, mortality rates of oesophago-gastric cancer patients following curative surgery have been decreasing, causing an increased demand for services, particularly during follow-up post-operatively. Current guidelines recommend that patients are treated by specialised multi-disciplinary teams, involving both cancer nurse specialists and dieticians. However, the integration of these workers into patient care is still ongoing in UGI, with no national recommendations for trusts on the minimum requirements needed to run adequate services. Methods This was a retrospective observational study from October 2020 to April 2021. Cancer nurse specialists from all cancer trusts in England and Wales carrying out surgical resection of oesophago-gastric tumours were identified and contacted to complete a survey. The survey was divided into 4 main themes: the organisational setup of the trust, the follow-up of patients, the dietetic input and post-operative symptoms and survivorship. Results A total of 12 trusts out of 38 returned a completed survey. Differences were observed in the number of CNSs and UGI dieticians available across trusts. 50% of responders felt that the number of CNSs at their trust was not adequate to run efficient services for patients. In 42% of cases, the CNS was solely responsible for long-term follow-up of patients, up to 5-years in the majority of trusts. 11 trusts routinely follow-up patients with a dietician, integrated into MDT clinics. 75% of trusts had an associated patient group that could provide additional support to patients. Conclusions Differences in the availabilities of services and staff for oesophago-gastric cancer patients are present across trusts in England, which can lead to inequalities in patient care. Further longitudinal studies are needed to evaluate the impact of these differences on patient surgical outcomes and mortality.

P-OGC54 Economic cost utility analysis of stage directed oesophageal adenocarcinoma treatment

Background Oesophageal Cancer (OC) treatment levies substantial financial burden on Health Services and Best Supportive Care (BSC) outcomes are poor. Potentially Curative Surgery with or without Chemotherapy is offered to patients with locally advanced disease and this study aimed to examine treatment costs related to life-years gained in patients having potentially curative treatment (oesophagectomy) and those receiving Best Supportive Care (BSC). Methods Consecutive 179 patients diagnosed with potentially curative adenocarcinoma of the oesophagus between 2010 and 2017 were classified according to treatment modality by intention to treat (surgery vs. neoadjuvant/adjuvant chemotherapy). Cost calculations for one-year’s treatment from referral were made according to network diagnostic, staging, and treatment algorithms. Primary outcome was Overall Survival (OS). Results OC median survival after BSC is reported to be 3 months costing £4391 compared with Oesophagectomy median survival (all stages) of 44 months costing an average of £26,652 for one year’s treatment: BSC cost per QALY £92,448 compared with £12,207.20 for potentially curative surgery. Cost incurred for stage I OC was £25,153.09, stage II £26,795.17, stage III £28,781.81, and stage IV £28,592.64. Based on these values, the cost per Quality Adjusted Life Year (QALY) for stage I OC was - £8,361, II - £12,319, III - £21,998 IV - £35,011. Conclusions Potentially curative treatment that included oesophagectomy improved OS fifteen-fold compared with BSC and was cost effective at national thresholds of readiness to pay per QALY.