Resection Of Gastroesophageal Cancer Research Articles

33 CRISCO-UGIS: COMPOSITE RISK SCORE TO PREDICT POST-OPERATIVE COMPLICATIONS FOR UPPER GASTROINTESTINAL CANCER SURGERY

Abstract Gastroesophagectomy for cancer is associated with high risk of morbidity and mortality. Careful patient selection for surgery is essential for optimizing outcomes. The purpose of this study was to develop a reliable composite risk calculator to inform pre-operative decision-making using readily available patient and tumour characteristics. Methods Patients undergoing curative-intent resection for gastroesophageal cancer from January 2010 to December 2018 were identified from a prospectively collected database. Data were verified and collected from patients’ medical records. Multiple logistic regression modeling identified pre-operative variables associated with significantly elevated risk of moderate to severe post-operative complications (Clavien-Dindo score ≥ 2) within 30 days of surgery and a nomogram was developed to form the composite risk score (CRiSCo-UGIS). Internal model validation was performed. Results Among 520 patients, independent pre-operative risk factors for complications were: female sex, age-adjusted Charlson comorbidity index ≥5, albumin <35 g/L, proximal tumour location (esophagus and gastroesophageal junction) and reduced performance status (Eastern Cooperative Oncology Group performance status 2–3) (Table 1). CRiSCo-UGIS had a good model fit (Hosmer-Lemeshow p = 0.47, area under receiver operating characteristic curve = 0.69). The overall observed-to-expected ratio was 1.0 [95% confidence interval 0.9–1.1]. Patients were divided into low (0), moderate (1–2) and high (≥3 points) risk categories. The observed risk of complications was: 42% in low-risk, 53% in moderate-risk and 80% in high-risk. Conclusion CRiSCo-UGIS can reliably predict post-operative complications for gastroesophageal cancer resection based on readily available pre-operative characteristics. This composite score can be used to guide patient selection for surgery and enhance informed consent discussions.

Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastroesophageal cancer.

4069 Background: A microscopically positive (R1) resection margin following resection for gastroesophageal (GE) cancer has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. Methods: A retrospective analysis was performed for patients (pts) with GE cancer treated at the Princess Margaret Cancer Centre from 2006-2016. Electronic medical records of all pts with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. Results: We identified 78 GE cancer pts with an R1 resection. 11% had neoadjuvant chemotherapy, 14% chemoradiation (CRT), 75% surgery alone. 28% had involvement of the proximal margin, 13% distal, 56% radial, 3% had multiple positive margins. By the American Joint Committee on Cancer 7th edition classification, 88% had a pT3-4 tumour, 66% pN2-3 nodal involvement, 64% grade 3, 68% with lymphovascular invasion. 3% were pathological stage I, 21% stage II and 74% stage III. Adjuvant therapy was given in 46% of R1 pts (24% CRT, 18% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS for all pts was 12.6 months (95% CI 10.3-17.2). Site of first recurrence was 71% distant, 16% locoregional, 13% mixed. Median OS was 29.3 months (95% CI 22.9-50) for all pts. The 5 year survival rate was 23% (95% CI 12%-43%). There was no significant difference in RFS (log-rank test p = 0.63, adjusted p = 0.14) or OS (log-rank test p = 0.68, adjusted p = 0.65) regardless of adjuvant therapy. Conclusions: Most pts with positive margins after resection for GE cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one pt had reresection. The main failure pattern was distant recurrence, suggesting that pts being considered for adjuvant RT should be carefully selected. Further studies are required to determine factors to select pts with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.

Transhiatal versus Left Transthoracic Esophagectomy for Gastroesophageal Junction Cancer; The Impact of Surgical Approach on Postoperative Complications.

BACKGROUND Esophagectomy is the mainstay of treatment for esophageal cancer. Although different surgical approaches have been described, choosing the most appropriate technique is still on debate. We compared the complications of transhiatal esophagectomy (THE) versus left transthoracic esophagectomy (LTE) among a group of Iranian patients with gastroesophageal junction cancer. METHODS This was a retrospective study between 2011 and 2013 on 40 patients with gastroesophageal cancer. 23 patients underwent THE and the others underwent LTE. 30-day postoperative mortality, complications, duration of hospital stay, and number of dissected lymph nodes were studied. RESULTS 37.5% of the patients had squamous cell carcinoma. No mortality was seen. Totally, 10 patients suffered from complications. Cardiac and pulmonary complications occurred in eight and six patients, respectively. No patients suffered from vocal cord injuries and anastomotic leakage. The mean duration of postoperative hospital stay was 11.82 ± 3.8 days, and the mean number of dissected lymph nodes was 8.2 ± 3.9. No significant difference was seen between the two groups (p > 0.05). CONCLUSION Choosing between the approaches for resection of gastroesophageal cancer may not impact the complications and mortality rates. We propose that LTE approach could be used safely in comparison with THE, and that selecting between THE and LTE may be based on the surgeon’s preference and experience.

Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastroesophageal cancer.

164 Background: A microscopically positive (R1) resection margin following resection for gastroesophageal (GE) cancer has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. Methods: A retrospective analysis was performed for patients (pts) with GE cancer treated at the Princess Margaret Cancer Centre from 2006-2016. Electronic medical records of all pts with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. Results: We identified 78 GE cancer pts with an R1 resection. 11% had neoadjuvant chemotherapy, 14% chemoradiation (CRT), 75% surgery alone. 28% had involvement of the proximal margin, 13% distal, 56% radial, 3% had multiple positive margins. By the American Joint Committee on Cancer 7th edition classification, 88% had a pT3-4 tumour, 66% pN2-3 nodal involvement, 64% grade 3, 68% with lymphovascular invasion. 3% were pathological stage I, 21% stage II and 74% stage III. Adjuvant therapy was given in 46% of R1 pts (24% CRT, 18% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS for all pts was 12.6 months (95% CI 10.3-17.2). Site of first recurrence was 71% distant, 16% locoregional, 13% mixed. Median OS was 29.3 months (95% CI 22.9-50) for all pts. The 5 year survival rate was 23% (95% CI 12%-43%). There was no significant difference in RFS (log-rank test p= 0.63, adjusted p= 0.14) or OS (log-rank test p= 0.68, adjusted p= 0.65) regardless of adjuvant therapy. Conclusions: Most pts with positive margins after resection for GE cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one pt had reresection. The main failure pattern was distant recurrence, suggesting that pts being considered for adjuvant RT should be carefully selected. Further studies are required to determine factors to select pts with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.

Endoscopic or Surgical Resection for Gastro-Esophageal Cancer.

Early gastro-esophageal cancer is staged as m1 to m3 depending on the infiltration of the anatomical layers of the mucosa or, analogously, as sm1 to sm3 depending on the depth of infiltration into the submucosa. The risk of lymph node metastases is low in mucosal carcinoma but increases with the depth of infiltration into the submucosa. This review is based on pertinent publications retrieved by a selective search in MEDLINE, PubMed, the Cochrane Library, and the International Standard Randomised Controlled Trial Number (ISRCTN) registry. New technologies such as narrow-band imaging have improved the endo- scopic diagnosis and staging of early gastro-esophageal cancer. The development of endoscopic submucosal dissection has led to a higher R0 resection rate, a lower risk of recurrence, and an increase in the number of endoscopic resections that are performed with curative intent. In squamous-cell carcinoma of the esophagus, surgical oncological esophagectomy is indicated if the cancer infiltrates into the third mucosal layer (T1a, m3) or deeper. In esophageal adenocarcinoma, the prevalence of lymph node metastases is low if the cancer is restricted to the mucosa and in- creases only when the submucosa is infiltrated. In the current German S3 guideline, endoscopic resection is recommended for intramucosal adenocarcinoma as long as there are no further histopathological risk factors. Lymph node metastasis in gastric carcinoma begins in the deep mucosal infiltration stage (m3). If certain special con- ditions ("extended criteria") are met, carcinoma expanding into the first submucosal layer (sm1) can be removed endoscopically. All further stages must be treated with total or subtotal gastrectomy with systematic D2 lymphadenectomy. Borderline cases between endoscopic and surgical resection of early carcinoma of the esophagus or stomach must be managed with an interdisciplinary treatment algorithm. If there is a risk of lymph node metastasis, surgical oncological resection is indicated. Such resections of gastroesophageal cancer in the locally advanced stage should always be part of a multimodal treatment approach.

Does lymph node ratio affect prognosis in gastroesophageal cancer?

BackgroundIncreasing evidence suggests that the ratio of number of nodes harboring metastatic cancer to the total number of lymph nodes examined (lymph node ratio, LNR) may affect survival after esophagogastric resection for cancer. We analyzed the impact of LNR in overall survival in patients undergoing esophagogastric resection for cancer. MethodsPatients who underwent gastroesophageal resection for cancer (1998 to 2008) were categorized into 4 groups according to their LNR: 113 patients had negative nodes (N0), 86 LNR less than .3, 40 LNR .31 to .6, and 47 LNR greater than .6. Study endpoint was overall median survival. ResultsHigher LNR was associated (P < .001) with more advanced stage and adverse pathologic features (eg, grading, venous/perineural invasion). Multivariate analysis demonstrated that LNR is an independent predictor of survival. ConclusionIn our experience, LNR correlates with adverse pathologic features and is a negative prognostic factor in patients undergoing radical resection for gastroesophageal cancer.

Intrathoracic anastomotic leakage after gastroesophageal cancer resection is associated with increased risk of recurrence

ObjectiveIntrathoracic anastomotic leakage after intended curative resection for cancer in the esophagus or gastroesophageal junction has a negative impact on long-term survival. The aim of this study was to investigate whether an anastomotic leakage was associated with an increased recurrence rate. MethodsThis nationwide study included consecutively collected data on patients undergoing curative surgical resection with intrathoracic anastomosis, alive 8 weeks postoperatively, between 2003 and 2011. Patients with incomplete resection, or metastatic disease intraoperatively, were excluded. Only biopsy-proven recurrences were accepted. ResultsIn total, 1085 patients were included. The frequency of anastomotic leakage was 8.6%. The median follow-up time was 29 months (interquartile range [IQR]: 13-58 months). Overall, 369 (34%) patients had disease recurrence, of which 346 patients died of recurrent gastroesophageal carcinoma. Twenty-three patients were alive with recurrence at the censoring date. In the study period, 333 patients died without signs of recurrent disease.The overall median time to recurrence was 66 weeks (IQR: 38-109 weeks). Distant metastases were found in 267 (25%), and local disease recurrence in 102 (9%) patients. Overall, 5-year disease-free survival in patients with leakage was 27%, versus 39% in those without leakage (P = .017). Anastomotic leakage was independently associated with higher risk of recurrence (hazard ratio [HR] = 1.63; 95% confidence interval [CI]: 1.17-2.29, P = .004) and all-cause mortality (HR = 1.57; 95% CI: 1.23-2.05, P < .0001). ConclusionsIntrathoracic anastomotic leakage increased the risk of recurrence in patients who underwent curative gastroesophageal cancer resection.

Neutrophil to Lymphocyte Ratio Predicts Biologic Behavior in Patients Undergoing Curative Resection for Gastroesophageal Cancer

cancer, steroid use, and recent surgery were significantly more common among emergent patients; postoperative outcomes including superficial surgical site infection (2.7% vs 1.3%), pneumonia (6.4% vs 2.0%), reintubation (4.3% vs 1.7%), extended ventilation (8.7% vs 1.8%), UTI (5% vs 1.6%), stroke (0.7% vs 0.06%), cardiac arrest (1.7% vs 0.3%), MI (2.7% vs 0.5%), transfusion (8.7% vs 1.6%), DVT (2.7% vs 0.8%), sepsis (5.4% vs 1.4%), septic shock (2.7% vs 0.6%) were more common, and LOS was longer (10.4 vs 4.2 days) for emergent patients (all p<0.05). In univariate analysis, emergent patients demonstrated increased odds of 30-day mortality (OR 6.3, p<0.001); however, on adjusted analysis, emergent surgery was no longer independently associated with mortality (OR 1.6, p1⁄40.352). Only poor functional status, steroid use and ASA class 3 remained independently associated with mortality.

Intrathoracic Anastomotic Leakage after Gastroesophageal Cancer Resection Is Associated with Reduced Long‐term Survival

Most likely because of low statistical power, no previous studies have shown any significant association between long-term survival and anastomotic leakage in patients who have undergone gastroesophageal cancer resection. The present study included, prospectively and consecutively, nationwide collected patients who underwent gastroesophageal cancer resection between 2003 and 2011 in Denmark. The operation was carried out as an Ivor Lewis procedure. Only patients with intrathoracic anastomosis were included in the analysis. From 2003 to 2011, 1,296 patients underwent gastroesophageal resection, and 128 (9.9 %) of these experienced anastomotic leakage. The overall 5-year survival rates in patients with and without anastomotic leakage were 20 and 35 % (P < 0.0001), respectively. After exclusion of 4 weeks mortality, the 5-year survival rate in patients with leakage was 22 % compared to 36 % in patients without anastomotic leakage (P < 0.001). After exclusion of 8 weeks mortality, the 5-year survival rate was 23 % in patients with leakage and 36 % in those without (P = 0.009). The corresponding median time of survival was 74 versus 128, 87 versus 138, and 95 versus 138 weeks, respectively. The overall hazard ratios of death after anastomotic leakage, unadjusted, and after adjusting for potentially confounding factors, were 1.59 (1.27-1.99) and 1.45 (1.14-1.84). The unadjusted and adjusted odds ratios after exclusion of 4 weeks mortality were 1.51 (1.19-1.90) and 1.41 (1.10-1.81). After exclusion of 8 weeks mortality the odds ratios were 1.38 (1.08-1.77) and 1.32 (1.02-1.71). This nationwide study confirms that patients experiencing anastomotic leakage after gastroesophageal cancer resection have a significantly lower long-term survival, even following full recovery after the leakage.

Sa1983 Anastomotic Leakage After Gastro-Esophageal Cancer Resection Is Associated With Lower Long-Time Survival. A Danish National Database Study

Sa1983 Anastomotic Leakage After Gastro-Esophageal Cancer Resection Is Associated With Lower Long-Time Survival. A Danish National Database Study

Improving Outcomes After Gastroesophageal Cancer Resection

Extended lymphadenectomy in gastroesphageal cancer leads to improved long-term survival without compromising postoperative outcomes in Western patients to attain the standard achieved in Japanese centers. Cohort study comparing postoperative outcomes and long-term survival with data from the National Cancer Center (NCC) of Tokyo, Japan. Outcomes were also compared with data from the UK National Oesophago-Gastric Cancer Audit (NOGCA) and a representative cohort from southeast England. Prospectively collected data were independently audited. University medical center. From 2003 to 2010, 100 patients underwent gastrectomy and 109 underwent esophagectomy. Postoperative mortality and morbidity and long-term overall survival. Lymph node count was used as a measure for the extent of lymphadenectomy. One death occurred after esophagectomy and none after gastrectomy. Anastomotic leak rate was approximately 2% in both cohorts. Kaplan-Meier estimates of 5-year overall survival after gastrectomy and esophagectomy were 58.4% and 47.8%, respectively. Postoperative mortality and technical complications for gastric and esophageal cancer resections were similar to NCC rates (P = .20). Stage for stage 5-year survival rates in patients with esophageal cancer and stages II and III gastric cancer were similar to outcomes in the NCC. The 5-year survival for patients with gastric cancer was worse for those with stage I (P < .001) and better for those with stage IV (P < .001) disease compared with NCC rates. Postoperative outcomes and long-term survival were significantly better than those reported by the NOGCA and the data from the southeast of England (P < .05). This study demonstrates that postoperative outcomes and long-term survival after gastroesophageal cancer resection can be improved in Western patients to the highest standard achieved in Japan.

Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after gastroesophageal cancer surgery

This study assessed the diagnostic accuracy of C-reactive protein (CRP) after gastroesophageal cancer resection for postoperative inflammatory complications (PIC). The clinical data and CRP values of patients operated on for gastroesophageal cancer surgery between 1997 and 2009 were retrospectively analyzed. The results of this study were compared with published data using a meta-analytic approach for diagnostic outcomes. Of 210 patients included in the study, 59 developed PIC (28.1 %; 95 % CI: 22.5-34.5 %). On the postoperative day (POD) 4 and 7, CRP had the best diagnostic accuracy for PIC (AUC 0.77; 95 % CI, 0.64-0.91, AUC 0.81; 95 % CI, 0.71-0.91). Using a cut-off value of 141 mg/L (95 % CI, 131-278 mg/L) for CRP on POD 4, the sensitivity was 0.78 (95 % CI, 0.55-0.91), the specificity was 0.70 (95 % CI, 0.53-0.83) and the NPV was 0.89 (95 % CI, 0.77-0.95). The in-hospital mortality rate was 3.3 % (95 % CI, 1.5-6.9 %). In a diagnostic meta-analysis that included two additional studies, CRP had a significant predictive value after POD 3. There is limited evidence for the diagnostic accuracy of CRP levels for PIC after gastroesophageal cancer surgery. CRP levels on POD 4 might be useful to rule out PIC, but its diagnostic accuracy is moderate at best. For clinical routine use CRP levels are clearly not sufficient to predict PIC and have to be interpreted in the context of the whole clinical picture.

Interrelationships between Tumor Proliferative Activity, Leucocyte and Macrophage Infiltration, Systemic Inflammatory Response, and Survival in Patients Selected for Potentially Curative Resection for Gastroesophageal Cancer

A number of accepted criteria, including pathological tumor, node, metastasis system stage, lymph node metastasis, and tumor differentiation, predict survival in patients undergoing surgery for gastroesophageal cancer. We examined the interrelationships between standard clinicopathological factors, systemic and local inflammatory responses, tumor proliferative activity, and survival. The interrelationships between the systemic inflammatory response (Glasgow prognostic score, mGPS), standard clinicopathological factors, local inflammatory response (Klintrup criteria, macrophage infiltration), and tumor proliferative activity (Ki-67) were examined by immunohistochemistry in 100 patients (44 esophageal [19 squamous, 25 adenocarcinoma], 19 junctional, and 37 gastric cancers) selected for potentially curative resection. The minimum follow-up was 59months. On multivariate survival analysis, lymph node ratio (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11-2.40, P<0.05), tumor differentiation (HR 2.63, 95% CI 1.45-4.77, P=0.001), mGPS (HR 3.91, 95% CI 1.96-8.11, P<0.001), Klintrup score (HR 3.47, 95% CI 1.14-10.55, P<0.05), and Ki-67 (HR 0.67, 95% CI 0.47-0.96, P<0.05) were independently associated with cancer-specific survival. A higher lymph node ratio was associated with poor tumor differentiation (P<0.05), low-grade Klintrup criteria (P<0.005), and low tumor proliferative activity (P<0.05). Tumor proliferation rate and local and systemic inflammatory responses are important predictors of survival, albeit in a heterogeneous cohort of patients including esophageal, junctional, and gastric cancers. These scores may be combined with accepted tumor-based factors to improve prediction of outcome.

Endoscopic mucosal resection for gastroesophageal cancer in a U.K. population. Long-term follow-up of a consecutive series

Endoscopic mucosal resection (EMR) of early gastric and esophageal tumors is effective and avoids the morbidity and mortality of surgery. We report the long-term results of a consecutive series of 93 endoscopic resections, during a 7-year period, in a U.K. population. Eighty-eight patients with 93 lesions were included. EMR was performed for 64 and 29 malignant and benign lesions, respectively. Patients with malignant disease were subgrouped into "high risk" or "low risk" for recurrence. Of the 35 lesions in the low-risk group, local control was achieved in 31; 29 after 1 EMR session. Two had residual invasive carcinoma, one had treatment ceased due to pancreatic cancer, and one patient did not attend follow-up. Of the 29 lesions in the high-risk group, local control was achieved in 15; 13 after 1 EMR session. Median follow-up was 53 months. Cancer specific survival for the 45 invasive cancers (T1m and T1sm) was 93%; three patients died from their disease. This study has shown for the first time in a U.K. population that EMR is effective in controlling disease in patients with local high grade dysplasia (HGD) and early invasive carcinoma, with no mortality and low morbidity.

A laterally rotating surgical device attached to the operating table.

A laterally rotating surgical device that can be attached to conventional operating tables is described. The position of the patient can be safely and rapidly changed from a supine to a right or left lateral position of 60 degrees. This device is beneficial for performing operations using a thoracoabdominal approach such as is used in cases of resection of gastroesophageal cancer.