Risk factors for recurrence of esophageal squamous cell carcinoma after pathological complete response to neoadjuvant therapy followed by esophagectomy.

BACKGROUND: Prognosis of patients who achieve pathological complete response (pCR) with neoadjuvant therapy (NAT) is better than that of non-pCR patients. Currently, there is no indication for adjuvant immune checkpoint inhibitor therapy after achieving pCR. However, recurrence risk after pCR is reportedly 10%-20% with a poor prognosis. Therefore, we investigated the preoperative risk factors for recurrence in patients with pCR. METHODS: We analyzed 56 patients with esophageal squamous cell carcinoma who underwent esophagectomy after neoadjuvant chemoradiotherapy (NACRT) or neoadjuvant chemotherapy (NAC) and were histologically diagnosed with pCR. Preoperative factors were compared between patients with and without recurrence to identify the risk factors. RESULTS: Forty-eight patients who achieved pCR received NACRT and 8 received NAC. Ten patients who experienced recurrence (17.9%) had undergone NACRT. The cN2 lesions were more frequent, and pre-NAT blood hemoglobin (Hb) was lower in the recurrence group. In addition, the pre-NAT cross-sectional area (CSA) product of the major and minor diameters of the primary tumor before NAT was significantly higher in recurrent cases (p = 0.041). Multivariate analysis, including the cTNM stage, pre-NAT Hb, and pre-NAT CSA, identified high pre-NAT CSA as the only risk factor for recurrence (odds ratio 11.6, 95% confidence interval 1.3-104.1, and p = 0.028). Cox regression analysis of recurrence-free and overall survival identified only high pre-NAT CSA as a prognostic factor. CONCLUSIONS: The recurrence risk is relatively high even in patients who achieve pCR after NAT. High pre-NAT CSA of the primary tumor is a risk factor for recurrence necessitating close surveillance.

Association between prognosis and lymph node status using 18F-fluorodeoxyglucose-positron emission tomography in esophageal squamous cell carcinoma treated with esophagectomy post-neoadjuvant chemotherapy.

BACKGROUND: There are few reports on the associations between lymph node (LN) status, determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy post-neoadjuvant chemotherapy (NCT). Additionally, details on the diagnostic performance of LN metastasis determination based on pathological examination versus FDG-PET have not been reported. In this study, we aimed to evaluate the associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis in patients with locally advanced ESCC who underwent esophagectomy post-NCT. METHODS: We reviewed the data of 124 consecutive patients with ESCC who underwent esophagectomy with R0 resection post-NCT between December 2008 and August 2022 and were evaluated pre- and post-NCT using FDG-PET. The associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis were assessed. RESULTS: Station-by-station analysis of PET-positive LNs pre- and post-NCT correlated significantly with pathological LN metastases (sensitivity, specificity, and accuracy pre- and post-NCT: 51.6%, 96.0%, and 92.1%; and 28.2%, 99.5%, and 93.1%, respectively; both p < 0.0001). Using univariate and multivariate analyses, LN status determined using PET post-NCT was a significant independent predictor of both recurrence-free survival and overall survival. CONCLUSION: The LN status assessed using FDG-PET post-NCT was significantly associated with the pathological LN status and prognosis in patients with ESCC who underwent esophagectomy post-NCT. Therefore, FDG-PET is a useful diagnostic tool for preoperatively predicting pathological LN metastasis and survival in these patients and could provide valuable information for selecting individualized treatment strategies.

Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

The treatment efficacy and prognosis of each treatment in early postoperative recurrence of esophageal squamous cell carcinoma.

PURPOSE: Various treatments are used for early postoperative recurrence of esophageal cancer, which has a poor prognosis. We evaluated the differences in outcomes and prognoses of each treatment modality between patients with early and late recurrence. METHODS: Early and late recurrence were defined as recurrence within and after six postoperative months, respectively. Of the 351 patients with esophageal squamous cell carcinoma who underwent R0 resection esophagectomy, 98 experienced postoperative recurrence (early recurrence, n = 41; late recurrence, n = 57). We evaluated the characteristics of patients with early and late recurrence and compared their treatment responses and prognoses. RESULTS: Regarding treatment responses for chemotherapy or immunotherapy, the objective response rate was not significantly different between the early- and late-recurrence groups. For chemoradiotherapy, the objective response rate was significantly lower in the early-recurrence group than in the late-recurrence group. The overall survival was significantly worse in the early-recurrence group than in the late-recurrence group. An analysis by treatment type showed that the early-recurrence group had significantly worse overall survival for chemoradiotherapy, surgery, and radiotherapy than the late-recurrence group. CONCLUSIONS: Patients with early recurrence had particularly poor prognoses with worse post recurrence treatment efficacy than those with late recurrence. The differences in the treatment efficacy and prognosis were particularly pronounced for local therapy.

Real-world management and outcomes of older patients with locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. METHODS: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. RESULTS: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10-11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10-3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717). CONCLUSIONS: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

BACKGROUND: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. RESULTS: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. CONCLUSION: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Evaluation of Neoadjuvant Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: It is occasionally difficult to diagnose cT3 or cT4b using imaging examinations for esophageal cancer. The optimal treatment strategy for borderline resectable esophageal squamous cell carcinoma (BR-ESCC) is unclear. METHODS: We included 131 patients with cT3 ESCC who received neoadjuvant chemoradiotherapy (NCRT) followed by surgery. The patients were classified as having definitive cT3 (D-cT3) or borderline resectable cT3 (BR-cT3), based on presence of undeniable adjacent organ invasion on pretreatment CT. Surgical outcomes and prognoses were compared among patients with D-cT3 and BR-cT3 tumors, and the risk factors for non-R0 resection were assessed. RESULTS: Ninety and 41 patients were classified as D-cT3 and BR-cT3, respectively. Although BR-cT3 had a significantly higher non-R0 resection rate than D-cT3 (D-cT3 3.7%; BR-cT3 14.6%), BR-cT3 was not correlated with shorter overall survival (OS) (D-cT3 5-year OS, 50.8%; BR-cT3 5-year OS 38.4%; p = 0.234). Conversely, non-R0 resection was significantly associated with poor OS (R0 resection 5-year OS 48.8%; non-R0 resection 5-year OS 22.2%; p = 0.031). Cox regression analysis of OS demonstrated that BR-cT3 was not a prognostic factor. In the analysis of risk factors for non-R0 resection, BR-cT3 (p = 0.027), suspected invasion of the trachea or bronchus (p = 0.046), and high SUVmax of the primary lesion after NCRT (p = 0.002) were risk factors. CONCLUSIONS: NCRT followed by surgery achieved a relatively high R0 resection rate and an almost equal overall survival rate for BR-cT3 compared with D-cT3 ESCC. Thus, NCRT followed by surgery is an effective treatment strategy for patients with BR-cT3 ESCC.

Blood biomarkers as predictors of pathological lymph node metastasis in clinical stage T1N0 esophageal squamous cell carcinoma.

Accurate preoperative evaluation of lymph node (LN) metastasis is important for determining the treatment strategy for superficial esophageal cancer. Blood biomarkers, such as the neutrophil-lymphocyte, platelet-lymphocyte, and lymphocyte-monocyte ratios (NLR, PLR, and LMR, respectively), have clinical applications as predictors of LN metastasis for different cancers. Here, we investigated the use of these ratios as predictors of pathological LN metastasis and prognosis in patients with clinical stage T1N0M0 esophageal squamous cell carcinoma (ESCC). Patients (n = 185) with cT1N0M0 ESCC who underwent esophagectomy with R0 resection between April 2003 and August 2021 were enrolled. We investigated the ability of pretreatment NLR, PLR, and LMR to predict pathological LN metastasis. The optimal cutoff values of NLR, PLR, and LMR to predict pathological LN metastasis were 2.1, 122, and 4.8, respectively. Univariate and multivariate analyses revealed that the primary tumor length, depth of invasion, and NLR were significant predictors of LN metastasis. Furthermore, similar to the 5-year overall survival, the 5-year relapse-free survival was significantly better in the low NLR group than in the high NLR group. The NLR was the most useful predictor of pathological LN metastasis. Patients diagnosed with clinical stage I ESCC and with a high NLR require adequate LN dissection and may be good candidates for preoperative adjuvant therapy.

Distribution of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma After Trimodal Therapy.

BACKGROUND: Although metastatic tumors in lymph nodes (LN) are potentially affected by neoadjuvant chemoradiotherapy (NCRT), the distribution of LN metastases of esophageal squamous cell carcinoma (ESCC) after trimodal therapy has never been sufficiently estimated. PATIENTS AND METHODS: We evaluated the distribution of LN metastases, relationships between LN metastases and radiation fields, risk factors for LN metastasis, and the influence of LN metastasis on the survival of 184 patients with ESCC who underwent NCRT followed by esophagectomy. RESULTS: Neoadjuvant chemoradiotherapy resulted in down-staged LN status in 74 (49.3%) patients. Pathological LN metastases were extensive in 177 LN stations in the cervical, mediastinal, and abdominal fields, and 162 (91.5%) metastases were located inside the radiation fields. Multivariate analysis showed that clinical N stage [N0 vs. 1/2/3: hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.22-5.92; p = 0.01] and clinical response of primary tumor (complete vs. noncomplete: HR, 2.93; 95% CI, 1.50-5.69; p = 0.002) were statistically significant for pathological LN metastasis. Recurrence-free and overall survivals were significantly stratified according to the number of pathological LN metastases, associations between clinical and pathological LN metastases, and presence or absence of pathological LN metastases outside radiation field. CONCLUSIONS: About 50% of patients who were clinically diagnosed with LN metastasis before treatment were downstaged by NCRT, and their prognoses were relatively good. However, LN metastases were extensive at the cervical, mediastinal, and abdominal areas, even within the radiation field. Thus, systematic and adequate lymphadenectomy is required for ESCC treated by NCRT.

Prediction of the tumor response and survival based on computed tomography in esophageal squamous cell carcinoma after trimodality therapy.

PURPOSE: Predicting the response to neoadjuvant chemoradiotherapy (NCRT) and the prognosis of esophageal squamous cell carcinoma (ESCC) is challenging. This study evaluated the potential of a preoperative computed tomography (CT) analysis for predicting the pathological response and survival of patients with ESCC who received trimodality therapy. METHODS: A total of 119 patients with cT3 or T4 ESCC who underwent surgery following NCRT between 2007 and 2019 were assessed. The CT-based parameters were measured with enhanced CT preoperatively, prior to and during treatment. Associations between these parameters and the pathologic response, as well as the prognosis, were examined. RESULTS: Pretreatment maximum CT value (p = 0.009), pretreatment mean CT value (p = 0.022), preoperative whole tumor volume (WTV, p = 0.003), preoperative largest cross section (LCS, p = 0.002), ΔLCS (pretreatment to preoperative, p = 0.004), ΔWTV (pretreatment to preoperative, p = 0.012), and Δmean CT value (pretreatment to preoperative, p = 0.012) of the primary lesion were significantly associated with a good pathological response. A Cox-regression analysis of recurrence-free survival (RFS) and overall survival (OS) showed that preoperative LCS was an independent CT-based predictor. RFS and OS were significantly higher at the optimal cut-off value of the preoperative LCS (p = 0.036 and p = 0.016, respectively). CONCLUSIONS: CT-based parameters are thus considered to be valuable predictors of the tumor response and survival after trimodality therapy for ESCC.

Predictions of Pathological Features and Recurrence Based on FDG-PET Findings of Esophageal Squamous Cell Carcinoma after Trimodal Therapy.

BACKGROUND: The degree of metabolic activity in tumor cells can be determined by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Associations between FDG uptake by primary tumors of locally advanced esophageal squamous cell carcinoma (ESCC) under trimodal therapy and the pathological features of such tumors have not been fully investigated. PATIENTS AND METHODS: We evaluated relationships between the maximal standardized uptake (SUVmax) in primary tumors on preoperative PET images and pathological features as well as cancer recurrence in 143 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. RESULTS: The post-SUVmax significantly differed after NCRT for ypT and ypN status, lymphatic invasion (LI), venous invasion (VI), and recurrence. Furthermore, the %ΔSUVmax (rate of decrease between before and after NCRT) for LI, VI, and recurrence significantly differed. Univariate and multivariate analyses selected post-SUVmax and %ΔSUVmax as independent preoperative predictors of recurrence-free survival [hazard ratio (HR) 1.46; 95% confidence interval (CI) 1.24-1.72 and HR 0.97; 95% CI 0.96-0.99, respectively; p < 0.001 for both]. Recurrence-free and overall survival were significantly stratified according to optimal SUVmax cutoffs for predicting recurrence (post- and %ΔSUVmax: 2.8 and 70, respectively). CONCLUSIONS: The post- and %ΔSUVmax of primary tumors were significantly associated with the pathological features and recurrence of ESCC under trimodal therapy. Therefore, FDG-PET can preoperatively predict the degree of aggressive tumor behavior in ESCC under trimodal therapy.

Clinical Significance of 18F-Fluorodeoxyglucose-Positron Emission Tomography-Positive Lymph Nodes to Outcomes of Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The clinical significance of lymph node (LN) status determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has not been investigated in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy). METHODS: This study reviewed 132 consecutive patients with ESCC who had been preoperatively evaluated using FDG-PET before and after NCRT to analyze associations among LN status according to PET findings, pathologic LN metastasis, and prognosis of ESCC after trimodal therapy. RESULTS: Lymph nodes that were PET-positive both before and after NCRT comprised significant predictive markers of pathologic LN metastasis in station-by-station analyses (sensitivity, specificity, and accuracy respectively 41.7%, 95.0%, and 92.7% before, and 12.0%, 99.4%, and 95.6% after NCRT; both p < 0.0001). The numbers of LNs evaluated using PET before and after NCRT were significantly associated with those of pathologic metastatic LNs. Uni- and multivariable analyses selected LN status determined by PET before NCRT as a significant independent predictor of both recurrence-free [LN-negative vs LN-positive: hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.02-3.23; p = 0.045] and overall survival (HR 2.62; 95% CI 1.29-5.30; p = 0.01). CONCLUSIONS: The status of LN determined by preoperative FDG-PET is significantly associated with pathologic LN status and the prognosis of ESCC with trimodal therapy. Thus, FDG-PET is a useful diagnostic tool for preoperative prediction of pathologic LN metastasis and survival among patients with ESCC.

Treatment Outcomes and Prognostic Factors After Recurrence of Esophageal Squamous Cell carcinoma.

BACKGROUND: The evaluation of treatment outcomes and detection of prognostic factors after recurrence are very important for tailoring optimal therapies for individual patients with recurrent esophageal cancer. METHODS: We reviewed 133 patients in whom esophageal squamous cell carcinoma (ESCC) recurred after curative surgery, and assessed recurrence patterns, treatment outcomes and prognostic factors. RESULTS: Recurrence in 57 (42.9%), 54 (40.6%) and 22 (16.5%) patients was locoregional, distant and combined, respectively. The median amounts of elapsed time until recurrence and median survival after recurrence for all patients were 9.1 and 8.3 months, respectively. Univariate and multivariate analyses selected time to recurrence (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.999; p = 0.04), recurrence location (locoregional vs. distant: HR, 1.63; 95% CI, 1.03-2.61; p = 0.04), number of organs with recurrence (1 vs. 3: HR, 3.49; 95% CI, 1.23-9.87; p = 0.02) and treatment after recurrence (best supportive care, [BSC] vs. chemotherapy [CT] or radiation therapy [RT]: HR, 0.37; 95% CI, 0.15-0.94; p = 0.04; BSC vs. CT and RT: HR, 0.50; 95% CI, 0.26-0.94; p = 0.03; BSC vs. surgery: HR, 0.47; 95% CI, 0.25-0.88; p = 0.02) as independent factors for survival after recurrence. Seventeen (12.8%) patients who had localized lymph node recurrence and lung oligometastasis and received multidisciplinary therapy after recurrence survived for >3 years thereafter. CONCLUSION: Despite the poor survival of patients with ESCC and early or distant recurrence or recurrence in ≥3 recurrent organs, appropriate multimodal therapies should be tailored for individual patients with recurrent ESCC.

Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy. METHODS: We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy. RESULTS: Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates for OS. CONCLUSIONS: Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.

Role of Postoperative C-Reactive Protein Levels in Predicting Prognosis After Surgical Treatment of Esophageal Cancer.

BACKGROUND: Elevated preoperative serum C-reactive protein (CRP) levels are reportedly associated with a poor prognosis for patients with various types of malignant tumors. However, the impact of postoperative CRP levels on the prognosis of patients with esophageal cancer remains unknown. The present study aims to clarify the prognostic significance of postoperative CRP levels on the survival of patients with esophageal cancer. METHODS: We reviewed the records of consecutive 202 patients with thoracic esophageal squamous cell carcinoma who underwent transthoracic esophagectomy. We measured serum CRP levels on postoperative days (PODs) 1, 2, 3, 5 and 7 and evaluated the relationships between postoperative CRP levels and survival. RESULTS: The findings of Cox regression analyses suggested that elevated CRP levels on POD 3, 5 and 7 were associated with poor recurrence-free survival (RFS). We divided CRP levels on POD 7 into three tertiles and found that RFS could be clearly stratified, being the poorest (p < 0.001) in the highest tertile (high CRP). The trend was similar even in patients with or without infectious complications and with or without advanced pathological stage. Multivariate analysis showed that pathologically advanced stage (Hazard ratio [HR], 5.14; 95% confidence interval [CI] 2.67-9.87; p < 0.001) and high CRP (HR, 2.27; 95% CI 1.3-3.96; p = 0.004) were independent predictors of RFS. CONCLUSION: Postoperative CRP levels could predict the prognosis of patients with esophageal cancer. We propose that the clinical course of postoperative CRP level should be carefully monitored as a predictor of survival.

Clinical Significance of FDG-PET to Predict Pathologic Tumor Invasion and Lymph Node Metastasis of Superficial Esophageal Squamous Cell Carcinoma.

PURPOSE: To determine the preoperative ability of [18F]-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to predict pathologic tumor invasion and lymph node status in cT1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed 40 consecutive patients diagnosed with cT1N0M0 ESCC between February 2006 and April 2011. All patients were treated by esophagectomy with two- or three-field lymphadenectomy without neoadjuvant therapy. We evaluated the relevance between clinical variables including maximum standardized uptake values (SUVmax) of the primary tumor on FDG-PET and pathologic tumor invasion and lymph node status using a logistic regression model. RESULTS: Tumors invaded the middle submucosal layer (SM2) and beyond in 21 (52.5 %) patients, and 6 (15 %) had lymph node metastases. The areas under receiver operating characteristic (ROC) curves for SUVmax of the primary tumor used to predict factors involved in tumor infiltration to SM2 or deeper and lymph node metastasis were 0.75 (p = 0.006) and 0.79 (p = 0.025), respectively. The optimal SUVmax cutoff was 2.7. The findings of univariate and multivariate analyses identified SUVmax as the only significant preoperative predictor associated with tumor infiltration into SM2 or beyond and lymph node metastasis. Furthermore, SUVmax ≥ 2.7 of the primary tumor on FDG-PET was associated with poor recurrence-free and disease-specific survival (p = 0.019 and p = 0.012, respectively). CONCLUSIONS: FDG-PET is helpful for diagnosing tumors that can infiltrate SM2 and beyond as well as occult lymph node metastasis of cT1N0M0 ESCC that are valuable indications in deciding therapeutic strategies for superficial ESCC.

Surgical Resection of Thoracic Esophageal Cancer with Interstitial Lung Disease: A Case Report.

Patients with esophageal cancer often have various comorbidities, and these sometimes limit treatment choices. We describe a patient with stage IA esophageal cancer accompanied by interstitial lung disease (ILD). Endoscopic resection and radiotherapy were not appropriate because of clinically diagnosed submucosal invasion and the patient was at high risk of ILD exacerbation. We therefore selected transhiatal esophagectomy without a thoracotomy considering the risk of postoperative respiratory complications, and administered methylprednisolone and sivelestat in the perioperative period for the reduction of surgical stress. To our knowledge, this is the first report of surgical treatment for esophageal cancer with ILD. The patient was discharged without postoperative complications. Transhiatal esophagectomy is an appropriate choice for patients with early-stage esophageal cancer without lymph node metastasis who are at high risk for postoperative respiratory complications. The appropriate selection of treatment is important for patients with esophageal cancer considering the risk of complications.

Emergency escape surgery for a gastro-bronchial fistula with respiratory failure that developed after esophagectomy.

A gastro-bronchial fistula (GBF) is a rare complication after esophageal reconstruction using a gastric tube, but it can cause severe pneumonia, and the surgical procedure is challenging. We herein describe a patient who was successfully managed using a two-stage operation for a GBF. Because the patient had life-threatening pneumonia and respiratory failure caused by the GBF, we first transected the duodenum, established a cervical esophagostomy and gastrostomy and placed a decompression catheter in the gastric tube without a thoracotomy. The patient recovered from pneumonia after the resolution of the salivary inflow and digestive juice reflux into the lungs through the GBF. Two months later, an esophageal bypass was achieved by reconstructing the esophagus using a long segment of pedicled jejunum. The patient was discharged 38 days thereafter. Appropriate treatment for GBF should be tailored to individual patients based on their current status and disease severity.