Incidence and management of esophageal cancer recurrence to regional lymph nodes after curative esophagectomy.

Up to 50% of patients treated with curative esophagectomy for esophageal cancer will develop recurrence, contributing to the dismal survival associated with this disease. Regional recurrence may represent disease that is not yet widely metastatic and may therefore be amenable to more-aggressive treatment. We sought to assess all patients treated with curative esophagectomy for esophageal cancer who developed regional recurrence. We retrospectively identified all patients who underwent esophagectomy for esophageal adenocarcinoma and esophageal squamous cell carcinoma at a single institution from January 2000 to August 2019. In total, 1626 patients were included in the study cohort. As of June 2022, 595 patients had disease recurrence, which was distant or systemic in 435 patients (27%), regional in 125 (7.7%) and local in 35 (2.2%). On multivariable analysis, neoadjuvant chemoradiation with a total radiation dose <45 Gy (hazard ratio [HR], 3.5 [95% CI, 1.7-7.3]; P = .001), pathologic node-positive disease (HR, 1.9 [95% CI, 1.3-3.0]; P = .003) and lymphovascular invasion (HR, 1.6 [95% CI, 1.0-2.5]; P = .049) were predictors of isolated nodal recurrence, whereas increasing age (HR, 0.97 [95% CI, 0.96-0.99]; P = .001) and increasing number of excised lymph nodes (HR, 0.98 [95% CI, 0.95-1.00]; P = .021) were independently associated with decreased risk of regional recurrence. Patients treated with a combination of local and systemic therapies had better survival outcomes than patients treated with systemic therapy alone (P < .001). In patients with recurrence of esophageal cancer limited to regional lymph nodes, salvage treatment may be possible. Higher radiation doses and more-extensive lymphadenectomy may reduce the risk of regional recurrence.

Distinct Differences in Gastroesophageal Junction and Gastric Adenocarcinoma in 2194 Patients: In Memory of Rebecca A. Carr, February 24, 1988-January 19, 2021.

OBJECTIVE: We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences. SUMMARY BACKGROUND DATA: GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinico-pathological and oncological differences between the 2 have not been fully evaluated. METHODS: We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared. RESULTS: In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC ( P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer ( P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001). CONCLUSIONS: GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies.

Induction FOLFOX and PET-Directed Chemoradiation for Locally Advanced Esophageal Adenocarcinoma.

OBJECTIVE: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. SUMMARY OF BACKGROUND DATA: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. METHODS: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression. RESULTS: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. CONCLUSIONS: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma.

OBJECTIVE: Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis. METHODS: All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors. RESULTS: Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)-was associated with increased risk of recurrence. CONCLUSIONS: One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Early implementation of a perioperative nutrition support pathway for patients undergoing esophagectomy for esophageal cancer.

BACKGROUND: Unintentional weight loss and malnutrition are associated with poorer prognosis in patients with cancer. Risk of cancer-associated malnutrition is highest among patients with esophageal cancer (EC) and has been repeatedly shown to be an independent risk factor for worse survival in these patients. Implementation of nutrition protocols may reduce postoperative weight loss and enhance recovery in these patients. METHODS: We retrospectively identified all patients who underwent Ivor Lewis esophagectomy for EC from January 2015 to August 2019 from a prospectively collected institutional database. Patients who underwent surgery after the implementation of this protocol (September 2017-August 2019) were compared with patients who underwent resection before protocol implementation (January 2015-July 2017). Patients undergoing surgery during the month of protocol initiation were excluded. RESULTS: Of the 404 patients included in our study, 217 were in the preprotocol group, and 187 were in the postprotocol group. Compared with the preprotocol group, there were significant reductions in length of hospital stay (p < 0.001), time to diet initiation (p < 0.001), time to feeding tube removal (p = 0.012), and postoperative weight loss (p = 0.002) in the postprotocol group. There was no significant difference in the incidence of postoperative complications, 30-day readmission, or mortality rates between groups. CONCLUSIONS: Results of the present study suggest a standardized perioperative nutrition protocol may prevent unintentional weight loss and improve postoperative outcomes in patients with EC undergoing resection.

Treatment of Anastomotic Recurrence After Esophagectomy.

BACKGROUND: Isolated local recurrence after curative esophagectomy for esophageal cancer is a rare event. Although it is potentially curable, management can be challenging. METHODS: We retrospectively reviewed all patients undergoing esophagectomy for esophageal adenocarcinoma (EAC) from 2000 to 2019. Date of recurrence was defined as the date at which the initial abnormal surveillance study result or symptomatic presentation led to further workup and subsequent pathologic diagnosis of recurrence. Overall survival after recurrence was estimated using Kaplan-Meier methods and compared between treatment groups using the log-rank test. RESULTS: Of the 1370 patients with EAC who underwent esophagectomy in our cohort, 531 (39%) developed recurrence of their disease. The 5-year cumulative incidence of recurrence was 2.7% (95% CI, 2.0%-3.6%) for local, 6.3% (95% CI, 5.2%-7.8%) for regional, and 22.0% (95% CI, 20.0%-24.4%) for distant recurrences. On univariable and multivariable competing-risk regression analysis, advanced pT stage, signet ring histology, and serious complication were independently associated with local recurrence. Patients with local recurrence treated with definitive therapy had a median survival after recurrence of 19.1 months (95% CI, 11.4-33.2 months) compared with 10.6 months (95% CI, 8.5-14.2 months) for chemotherapy or radiotherapy alone and 1.73 months (95% CI, 0.23-15.6 months) for no treatment (P < .001). CONCLUSIONS: Isolated local recurrence occurred in only 3% of patients. Advanced T stage, signet cell histology, and serious complication were risk factors for recurrence. Although complex surgical resection is required, in very select cases, more aggressive treatment may be warranted.

Primary lung cancer in women after previous breast cancer.

BACKGROUND: Breast cancer is the most common malignancy among women in the USA. Improved survival has resulted in increasing incidence of second primary malignancies, of which lung cancer is the most common. The United States Preventive Services Task Force (USPSTF) guidelines for lung-cancer screening do not include previous malignancy as a high-risk feature requiring evaluation. The aim of this study was to compare women undergoing resection for lung cancer with and without a history of breast cancer and to assess whether there were differences in stage at diagnosis, survival and eligibility for lung-cancer screening between the two groups. METHODS: Women who underwent lung-cancer resection between 2000 and 2017 were identified. Demographic, clinicopathological, treatment and outcomes data were compared between patients with a history of breast cancer (BC-Lung) and patients without a history of breast cancer (P-Lung) before lung cancer. RESULTS: Of 2192 patients included, 331 (15.1 per cent) were in the BC-Lung group. The most common method of lung-cancer diagnosis in the BC-Lung group was breast-cancer surveillance or work-up imaging. Patients in the BC-Lung group had an earlier stage of lung cancer at the time of diagnosis. Five-year overall survival was not statistically significantly different between groups (73.3 per cent for both). Overall, 58.4 per cent of patients (1281 patients) had a history of smoking, and 33.3 per cent (731 patients) met the current criteria for lung-cancer screening. CONCLUSION: Differences in stage at diagnosis of lung cancer and treatment selection were observed between patients with and without a history of breast cancer. Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer. The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast-cancer history, did not meet the current USPSTF criteria for lung-cancer screening.

Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse.

Magnetic resonance spectroscopy (MRS) studies in alcohol use disorder (AUD) typically report lower levels of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in several brain regions. Metabolite levels, however, are labile and can be affected by several competing factors, some related to drinking variables.. This in vivo MRS study included 20 recently sober (19.6±12.6 days) individuals with AUD and 15 controls. MRS was performed in single voxels placed in frontal white matter and thalamic regions using Constant-Time Point Resolved Spectroscopy (CT-PRESS) for absolute quantification of NAA, Cho, total creatine (tCr), and glutamate (Glu). A trend toward a thalamic NAA deficit in the total AUD group compared with controls was attributable to the subgroup of alcoholics who relapsed 3 or so months after scanning. In the total AUD group, frontal and thalamic NAA and Cho levels were lower with more recent drinking; frontal and thalamic Cho levels were also lower in AUD individuals with past stimulant abuse. Thalamic Cho levels were higher in binge-drinking AUD individuals and in those with longer length of alcohol dependence. MRS-visible metabolite peaks appear to be modulated by variables related to drinking behaviors, suggesting a sensitivity of MRS in tracking and predicting the dynamic course of alcoholism.

Association of synovial inflammation and inflammatory mediators with glenohumeral rotator cuff pathology.

HYPOTHESIS: We hypothesized that patients with full-thickness rotator cuff tears would have greater synovial inflammation compared with those without rotator cuff tear pathology, with gene expression relating to histologic findings. METHODS: Synovial sampling was performed in 19 patients with full-thickness rotator cuff tears (RTC group) and in 11 patients without rotator cuff pathology (control group). Cryosections were stained and examined under light microscopy and confocal fluorescent microscopy for anti-cluster CD45 (common leukocyte antigen), anti-CD31 (endothelial), and anti-CD68 (macrophage) cell surface markers. A grading system was used to quantitate synovitis under light microscopy, and digital image analysis was used to quantify the immunofluorescence staining area. Quantitative polymerase chain reaction was performed for validated inflammatory markers. Data were analyzed with analysis of covariance, Mann-Whitney U, and Spearman rank order testing, with significance set at α = .05. RESULTS: The synovitis score was significantly increased in the RTC group compared with controls. Immunofluorescence demonstrated significantly increased staining for CD31, CD45, and CD68 in the RTC vs control group. CD45+/68- cells were found perivascularly, with CD45+/68+ cells toward the joint lining edge of the synovium. Levels of matrix metalloproteinase-3 (MMP-3) and interleukin-6 were significantly increased in the RTC group, with a positive correlation between the synovitis score and MMP-3 expression. CONCLUSIONS: Patients with full-thickness rotator cuff tears have greater levels of synovial inflammation, angiogenesis, and MMP-3 upregulation compared with controls. Gene expression of MMP-3 correlates with the degree of synovitis.