Histological prognosticators in neoadjuvant naive oesophageal cancer patients.

PURPOSE: Prognosis of oesophageal cancer is primarily based upon the TNM stage of the disease. However, even in those with similar TNM staging, survival can be varied. Additional histopathological factors including venous invasion (VI), lymphatic invasion (LI) and perineural invasion (PNI) have been identified as prognostic markers yet are not part of TNM classification. The aim of this study is to determine the prognostic importance of these factors and overall survival in patients with oesophageal or junctional cancer who underwent transthoracic oesophagectomy as the unimodality treatment. METHODS: Data from patients who underwent transthoracic oesophagectomy for adenocarcinoma without neoadjuvant treatment were reviewed. Patients were treated with radical resection, with a curative intent using a transthoracic Ivor Lewis or three staged McKeown approach. RESULTS: A total of 172 patients were included. Survival was poorer when VI, LI and PNI were present (p<0.001), with the estimated survival being significantly worse (p<0.001) when patients were stratified according to the number of factors present. Univariable analysis of factors revealed VI, LI and PNI were all associated with survival. Presence of LI was independently predictive of incorrect staging/upstaging in multivariable logistic regression analysis (OR 12.9 95% CI 3.6-46.6, p<0.001). CONCLUSION: Histological factors of VI, LI and PNI are markers of aggressive disease and may have a role in prognostication and decision-making prior to treatment. The presence of LI as an independent marker of upstaging could be a potential indication for the use of neoadjuvant treatment in patients with early clinical disease.

Significance of neoadjuvant downstaging in gastric adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy is established in the treatment of gastric adenocarcinoma. Histopathological regression may have important prognostic implications. There are little data comparing clinical outcomes of patients with gastric adenocarcinoma that received neoadjuvant treatment and those neoadjuvant naive. The aim of this study is to determine the impact of neoadjuvant chemotherapy upon prognosis of patients being treated for gastric adenocarcinoma. METHODS: Consecutive patients with gastric cancer from a single center between 2007 and 2017 were evaluated. Patients were treated with either a subtotal or total gastrectomy with D2 lymphadenectomy. Stage-by-stage comparison of the extent of pathological downstaging was conducted for patients who received neoadjuvant treatment (ypTNM) and those who did not (pTNM) using the TNM eighth edition. RESULTS: Overall, 384 patients underwent gastrectomy, 141 patients received neoadjuvant chemotherapy, and 86 patients (58.1%) were downstaged. Downstaged patients had improved overall survival compared to patients who did not respond to neoadjuvant chemotherapy (not reported vs 66 months, P < .001). Downstaging by >3 stages was the strongest independent predictor of overall survival (hazard ratio: 0.17; 95% confidence interval 0.062-0.44). Overall survival was significantly better among patients in the ypTNM groups when a stage-by-stage comparison was performed with the pTNM group. CONCLUSION: Pathological stage is a more accurate predictor of prognosis compared clinical stage with downstaged patients benefiting from lower recurrence rates and improved overall survival. Patients downstaged due to neoadjuvant chemotherapy may potentially have more favorable clinical outcomes compared to stage-matched patients who did not receive this.

Learning curves in minimally invasive esophagectomy: A systematic review and evaluation of benchmarking parameters.

BACKGROUND: Minimally invasive techniques are increasingly used in the treatment of esophageal cancer. The learning curve for minimally invasive esophagectomy is variable and can impact patient outcomes. The aim of this study was to review the current evidence on learning curves in minimally invasive esophagectomy and identify which parameters are used for benchmarking. METHODS: A search of the major reference databases (PubMed, Medline, Cochrane) was performed with no time limits up to February 2020. Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if an assessment of the learning curve was reported on, regardless of which (if any) statistical method was used. RESULTS: Twenty-nine studies comprising 3,741 patients were included. Twenty-two studies reported on a combination of thoracoscopic, hybrid, and total minimally invasive esophagectomy, 6 studies reported robotic-assisted minimally invasive esophagectomy alone, and 1 study evaluated both robotic-assisted minimally invasive esophagectomy and thoracoscopic esophagectomies. Operating time was the most frequently used parameter to determine learning curve progression (23/39 studies), with number of resected lymph nodes, morbidity, and blood loss also frequently used. Learning curves were found to plateau at 7 to 60 cases for thoracoscopic esophagectomy, 12 to 175 cases for total and thoracoscopic/hybrid esophagectomy, and 9 to 85 cases for robotic-assisted minimally invasive esophagectomy. CONCLUSION: Multiple parameters are employed to gauge minimally invasive esophagectomy learning curve progression. However, there are no validated or approved sets of outcomes. Further work is required to determine the optimum parameters that should be used to ensure best patient outcomes and required length of proctoring.

Does Cardiopulmonary Testing Help Predict Long-Term Survival After Esophagectomy?

BACKGROUND: Esophagectomy is associated with a high rate of morbidity and mortality. Preoperative cardiopulmonary fitness has been correlated with outcomes of major surgery. Variables derived from cardiopulmonary exercise testing (CPET) have been associated with postoperative outcomes. It is unclear whether preoperative cardiorespiratory fitness of patients undergoing esophagectomy is associated with long-term survival. This study aimed to evaluate whether any of the CPET variables routinely derived from patients with esophageal cancer may aid in predicting long-term survival after esophagectomy. METHODS: Patients undergoing CPET followed by trans-thoracic esophagectomy for esophageal cancer with curative intent between January 2013 and January 2017 from single high-volume center were retrospectively analyzed. The relationship between predictive co-variables, including CPET variables and survival, was studied with a Cox proportional hazard model. Receiver operation curve (ROC) analysis was performed to find cutoff values for CPET variables predictive of 3-year survival. RESULTS: The study analyzed 313 patients. The ventilatory equivalent for carbon dioxide (VE/VCO2) at the anerobic threshold was the only CPET variable independently predictive of long-term survival in the multivariable analysis (hazard ratio [HR], 1.049; 95% confidence interval [CI], 1.011-1.088; p = 0.011). Pathologic stages 3 and 4 disease was the other co-variable found to be independently predictive of survival. An ROC analysis of the VE/VCO2 failed to demonstrate a predictive cutoff value of 3-year survival (area under the curve, 0.564; 95% CI, 0.499-0.629; p = 0.056). CONCLUSIONS: A high VE/VCO2 before esophagectomy for malignant disease is an independent predictor of long-term survival and may be an important variable for clinicians to consider when counseling patients.

Evolution of gastrectomy for cancer over 30-years: Changes in presentation, management, and outcomes.

BACKGROUND: Gastric cancer has seen a considerable change in management, and outcomes for the past 30 years. Historically, the overall prognosis has been regarded as poor. However, the use of multimodal treatment, and integration of enhanced recovery pathways have improved short and long-term outcomes. The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for gastric cancers over 30 years. METHODS: Data from consecutive patients undergoing gastrectomy with curative intent for gastric adenocarcinoma between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies and outcomes were reviewed. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS: Between 1989 and 2018, 1,162 patients underwent gastrectomy with curative intent for cancer. Median age was 71 years (interquartile range, 63-76 years) and 763 (66%) were male. Patient presentation changed with epigastric discomfort now the most common presentation (67%). An improvement in overall complications from 54% to 35% (P = .006) and mortality from 8% to 1% (P < .001) was seen over the time period and overall survival improved from 28 months to 53 months (P < .001). CONCLUSION: Both short-term and long-term outcomes have significantly improved over the 30 years studied. The reasons for this are multifactorial and include the use of perioperative chemotherapy, the introduction of an enhanced recovery pathway, and improved preoperative assessment of patients through a multidisciplinary input.

Impact of Smoking Status on Perioperative Morbidity, Mortality, and Long-Term Survival Following Transthoracic Esophagectomy for Esophageal Cancer.

INTRODUCTION: Esophagectomy is a key component in the curative treatment of esophageal cancer. Little is understood about the impact of smoking status on perioperative morbidity and mortality and the long-term outcome of patients following esophagectomy. OBJECTIVE: This study aimed to evaluate morbidity and mortality according to smoking status in patients undergoing esophagectomy for esophageal cancer. METHODS: Consecutive patients undergoing two-stage transthoracic esophagectomy (TTE) for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between January 1997 and December 2016 at the Northern Oesophagogastric Unit were included from a prospectively maintained database. The main explanatory variable was smoking status, defined as current smoker, ex-smoker, and non-smoker. The primary outcome was overall survival (OS), while secondary outcomes included perioperative complications (overall, anastomotic leaks, and pulmonary complications) and survival (cancer-specific survival [CSS], recurrence-free survival [RFS]). RESULTS: During the study period, 1168 patients underwent esophagectomy for cancer. Of these, 24% (n = 282) were current smokers and only 30% (n = 356) had never smoked. The median OS of current smokers was significantly shorter than ex-smokers and non-smokers (median 36 vs. 42 vs. 48 months; p = 0.015). However, on adjusted analysis, there was no significant difference in long-term OS between smoking status in the entire cohort. The overall complication rates were significantly higher with current smokers compared with ex-smokers or non-smokers (73% vs. 66% vs. 62%; p = 0.018), and there were no significant differences in anastomotic leaks and pulmonary complications between the groups. On subgroup analysis by receipt of neoadjuvant therapy and tumor histology, smoking status did not impact long-term survival in adjusted multivariable analyses. CONCLUSION: Although smoking is associated with higher rates of short-term perioperative morbidity, it does not affect long-term OS, CSS, and RFS following esophagectomy for esophageal cancer. Therefore, implementation of perioperative pathways to optimize patients may help reduce the risk of complications.

The impact of age on patients undergoing transthoracic esophagectomy for cancer.

To compare long-term and short-term outcomes in patients <70 years old with those ≥ 70 years old, who underwent transthoracic esophagectomy for carcinoma. With an ageing population more patients, with increasing co-morbidities are being diagnosed with potentially curable esophageal cancer. Concerns exist regarding offering older patients esophagectomy, conversely undue prejudice may exists that may prevent surgery being offered. Consecutive patients from a single unit between January 2000 and July 2016 that underwent trans-thoracic esophagectomy with or without neoadjuvant treatment for carcinoma were included. Short-term outcomes including morbidity, mortality, length of stay and long-term survival were compared between those <70 and those ≥ 70. This study identified 992 patients who underwent esophagectomy during the study period, of which 302 (30%) ≥ 70 years old. Greater proportion ≥ 70 years old had SCC (squamous cell carcinoma) (23%) than <70 (18%) (p = 0.07). Patients ≥ 70 years old were noted to have higher ASA Grade 3 (34% vs 25%, p = 0.004) and were less likely to receive neoadjuvant treatment (64% vs 45% p<0.001). Length of stay was longer in ≥ 70 (14 vs 17 days p<0.001), and there were more complications (63% vs 75% p<0.001). In hospital mortality was higher in ≥ 70 (2% vs 5% p = 0.026). Overall survival was 50 months in <70 vs 36 months in ≥ 70 (p = <0.001). In <70s with adenocarcinoma, overall survival was 52 months vs 35 months in the ≥ 70 (p<0.001). No significant difference in survival in patients with SCC, 49 months in <70 vs 54 months in ≥ 70 (p = 0.711). Increased peri-operative morbidity and mortality combined with the reduction in the long term survival in the over 70s cohort should be addressed when counselling patients undergoing curative resection for oesophageal cancer.

Evolution of Esophagectomy for Cancer Over 30 Years: Changes in Presentation, Management and Outcomes.

BACKGROUND: Esophageal cancer has seen a considerable change in management and outcomes over the last 30 years. Historically, the overall prognosis has been regarded as poor; however, the use of multimodal treatment and the integration of enhanced recovery pathways have improved short- and long-term outcomes. OBJECTIVE: The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for esophageal cancer over 30 years from a single-center, high-volume unit in the UK. PATIENTS AND METHODS: Data from consecutive patients undergoing esophagectomy for cancer (adenocarcinoma or squamous cell carcinoma) between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies, and outcomes were evaluated. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS: Between 1989 and 2018, 1486 patients underwent esophagectomy for cancer. Median age was 65 years (interquartile range [IQR] 59-71) and 1105 (75%) patients were male. Adenocarcinoma constituted 1105 (75%) patients, and overall median survival was 29 months (IQR 15-68). Patient presentation changed, with epigastric discomfort now the most common presentation (70%). An improvement in mortality from 5 to 2% (p < 0.001) was seen over the time period, and overall survival improved from 22 to 56 months (p < 0.001); however, morbidity increased from 54 to 68% (p = 0.004). CONCLUSIONS: Long-term outcomes have significantly improved over the 30-year study period. In addition, mortality and length of stay have improved despite an increase in complications. The reasons for this are multifactorial and include the use of perioperative chemo(radio)therapy, the introduction of an enhanced recovery pathway, and improved patient selection.

Critical appraisal of the impact of surgical repair of type II-IV paraoesophageal hernia (POH) on pulmonary improvement: A systematic review and meta-analysis.

BACKGROUND: Paraoesophageal hernia (POH) comprising type II-IV hiatal hernia often presents with pulmonary symptoms such as shortness of breath. However, impact of surgical repair on improvement in pulmonary symptoms is unclear. OBJECTIVE: This systematic review and meta-analysis aimed at characterising impact of POH repair on patient reported improvement in pulmonary symptoms. METHODS: This systematic review identified studies reported pulmonary symptoms in patients with undergoing surgical repair for Type II-IV POH from 1st January 2001 to 1st December 2018. Primary outcome was improvement in pulmonary symptoms. Secondary outcomes were improvement in other patient-reported outcomes such as heartburn, regurgitation, chest pain, and dysphagia and intraoperative and postoperative outcomes. RESULTS: This systematic review identified 27 studies (n = 4428 patients) reporting assessment of pulmonary symptoms. However, only 21 studies (n = 2902 patients) reported preoperative and postoperative pulmonary symptoms and hence these were included in the final meta-analysis. There was significant improvement in pulmonary symptoms following POH repair (OR: 8.40, CI95%: 4.91-14.35, p < 0.001), with improvement in all types of POH. Rates of overall and major complications were 16% and 5%, respectively. Rates of conversion, 30-day mortality, reoperation and recurrence were 2%, 1% 4% and 12% respectively. CONCLUSION: This review demonstrates that POH repair is associated with improvement in pulmonary symptoms with acceptable low laparoscopic conversion rates, morbidity, mortality and recurrence rates.

Intra- and interobserver variability in skeletal muscle measurements using computed tomography images.

PURPOSE: The progressive loss of skeletal muscle and function (known as sarcopenia) has been shown to be associated with various adverse outcome measures. Sophisticated measurements of body composition are increasingly being incorporated into research studies to stratify patients into those with or without sarcopenia, monitor treatment effects, and predict complications. A typical approach is to select axial image(s) at the mid-lumbar level and use semi-automated software to identify and quantify the skeletal muscle area. This area is then used to estimate whole-body parameters. This approach is somewhat subjective, and in this study we investigate its reproducibility, both within and between observers. MATERIALS AND METHODS: Repeated muscle measurements were performed on a cohort of 29 patients by 3 radiologists, to examine their intra- and interobserver reproducibility. RESULTS AND DISCUSSION: Mean muscle area for the cohort was 156 cm2, with a wide range (98 - 261 cm2). There was good intraobserver agreement between measurements, with a mean absolute difference between repeated measurements on the same patient of 0.98 cm2, and a measurement variability of 2.92 cm2. Much of the variability was shown to be due to the choice of a different slice when performing the repeated measurement. Averaging two slices provided a small but non-significant improvement in comparison to the single slice approach. Interobserver results showed good agreement, though there was a small bias for one observer, who measured slightly larger volumes compared to the other two. We conclude that the approach described provides reproducible skeletal muscle area measurements, and offer three specific recommendations to minimise variability.

Trainee Involvement in Ivor Lewis Esophagectomy Does Not Negatively Impact Outcomes.

OBJECTIVE: The aim of the present study was to determine whether trainee involvement in esophageal cancer resection is associated with adverse patient outcomes. BACKGROUND: Operative experience for surgical trainees is under threat. A number of factors have been implicated in this leading to fewer hours for training. Esophagogastric cancer training is particularly vulnerable due to the publication of individual surgeon results and a perception that dual consultant operating improves patient outcomes. Resectional surgery is increasingly viewed as a subspeciality to be developed after completion of the normal training pathway. METHODS: Data from a prospectively maintained database of consecutive patients undergoing trans-thoracic esophagectomy for potentially curable carcinoma of the esophagus or gastroesophageal junction were reviewed. Patients were divided into 4 cohorts, according to whether a consultant or trainee was the primary surgeon in either the abdominal or thoracic phase. Outcomes including operative time, lymph node yield, blood loss, complications graded by Accordion score, and mortality were recorded. RESULTS: A total of 323 patients underwent esophagectomy during 4 years. The overall in-hospital mortality rate was 1.5%. At least 1 phase of the surgery was performed by a trainee in 75% of cases. There was no significant difference in baseline demographics of age, stage, neoadjuvant treatment, and histology between cohorts. There was no significant difference in blood loss (P = 0.8), lymph node yield (P = 0.26), length of stay (P = 0.24), mortality, and complication rate according to Accordion scores (P = 0.21) between cohorts. Chest operating time was a median 25 minutes shorter when performed by a consultant (P < 0.001). CONCLUSIONS: These findings demonstrate that patient outcomes are not compromised by supervised trainee involvement in transthoracic esophagectomy. Training is an essential role of all surgical units and training data should be more widely reported especially in areas of high-risk surgery.

Impact of Extent of Lymphadenectomy on Survival, Post Neoadjuvant Chemotherapy and Transthoracic Esophagectomy.

OBJECTIVE: The aim of this study was to evaluate the influence of lymph node yield and the location of nodes on prognosis in patients with distal esophageal or gastroesophageal junction adenocarcinoma who have received neoadjuvant chemotherapy followed by transthoracic esophagectomy. BACKGROUND: Debate continues regarding the extent of lymphadenectomy required when carrying out an esophagectomy. Lymph node yield has been used as a surrogate for extent of lymphadenectomy. Node location must, however, be reviewed to determine the true extent of lymphadenectomy. METHODS: Data from consecutive patients with potentially curable adenocarcinoma of the lower esophagus or gastroesophageal junction were reviewed. Patients were treated with neoadjuvant chemotherapy, transthoracic esophagectomy, and 2-field lymphadenectomy. Outcomes according to lymph node yield were determined. Projected prognosis of carrying out less radical lymphadenectomies was calculated according to 3 groups: group 1-exclusion of proximal thoracic nodes, group 2-a minimal abdominal lymphadenectomy, and group 3-a minimal abdominal and thoracic lymphadenectomy. RESULTS: Three hundred five patients were included. Median cancer-related survival was 37.7 months (confidence interval 29-46 mo). Absolute lymph node retrieval was not related to survival (P = 0.520). An estimated additional 4 (2-6) cancer-related deaths were projected if group 1 nodes were omitted, 2 (1-4) additional deaths if group 2 nodes were omitted, and 9 (6-12) extra deaths if group 3 nodes were omitted. A minimal lymphadenectomy (groups 1, 2, and 3) was projected to lead to a 23% reduction in survival in patients with N1 or N2. CONCLUSIONS: The present study demonstrates high lymph node yields are possible after transthoracic esophagectomy with en bloc 2-field lymphadenectomy in patients post neoadjuvant chemotherapy. This allows excellent postoperative staging. Furthermore, the extent of lymphadenectomy must be correlated with node location, which may have important implications in patients who have a less extensive lymphadenectomy.

Educating surgical patients to reduce the risk of venous thromboembolism: an audit of an effective strategy.

OBJECTIVES: Venous thromboembolism (VTE) causes approximately 25,000 deaths each year from hospital-acquired thrombosis in the UK. Patient understanding of risk factors and preventive measures is important in preventing VTE. This audit was designed to assess surgical patient awareness and understanding of VTE risk factors and prophylaxis. DESIGN: A questionnaire was designed to assess preoperative patient understanding of components of the National Institute for Health and Clinical Excellence (NICE) guidelines. Leaflets were designed to address gaps in understanding and junior doctors were given guidance on patient education. A second group of patients completed the same questionnaire after introduction of the education system. SETTING: Worthing Hospital, UK. PARTICIPANTS: One hundred and twenty-one patients due to undergo major general surgery. Seventy-one participants completed the questionnaire prior to implementation of the education system, and 50 after. MAIN OUTCOME MEASURES: Improvement in patient awareness of VTE, its risk factors and its preventative measures (in response to the education system). RESULTS: Following the introduction of a targeted VTE education system, there was a significant improvement in the awareness of VTE to 90% (P < 0.01), its signs to 80% (P < 0.01), and its preventative measures to 84% (P < 0.01). CONCLUSIONS: Patient education is of paramount importance in reducing the risks of VTE perioperatively. A simple method of introducing patient education at pre-assessment clinic and as part of their discharge planning, for major elective surgery, is an effective system in improving patient understanding of VTE, its risk factors and the importance of prophylaxis. It may also increase compliance.