Background
The Charlson Comorbidity Index (CCI), an indicator that objectively quantifies comorbidities, reduces nutritional status; however, the impact of the CCI on the postoperative nutrition ...indexes of patients with esophageal cancer remains unclear.
Methods
In total, 336 patients with esophageal cancer who underwent surgery between January 2011 and April 2017 were included in this study. We investigated the relationship between the CCI and postoperative nutrition indexes.
Results
Patients were divided into two groups: CCI ≤1 (low CCI group) and CCI ≥2 (high CCI group). A high CCI was significantly associated with shortened overall survival (OS; 3-year OS rate of 77.9% in the low CCI group versus 59.7% in the high CCI group;
p =
0.008). Nutritional indexes, such as the Prognostic Nutritional Index (PNI), at 1 month after esophagectomy were significantly lower in the high CCI group than in the low CCI group (
p =
0.031); however, the PNI at 6 months after surgery was similar between the high and low CCI groups. Multivariate analysis identified high CCI as an independent risk factor associated with PNI <45 in esophageal cancer patients at 1 month after esophagectomy (
p =
0.047).
Conclusion
This study showed that CCI ≥2 was significantly associated with poor PNI at 1 month after surgery for esophageal cancer, indicating that it is necessary to administer effective nutritional interventions for patients with postoperative malnutrition, especially those with multiple comorbidities.
Here, we assess the ability of metabolic tumor volume (MTV) as measured by F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) to evaluate neoadjuvant chemotherapy ...response for patients with locally advanced esophageal cancer (EC).
Optimal methods to evaluate treatment response for EC patients have not yet been established. Although previous studies have reported the value of standardized uptake value (SUV), the accuracy of predicting histological response or long-term survival in EC is limited.
In all, 102 EC patients without distant metastasis who underwent F-FDG PET/CT both before and after the preoperative chemotherapy series were analyzed.
The median primary tumor MTV values before and after preoperative chemotherapy were 22.55 (range 0.4-183.1) and 2.75 (0-52.9), respectively, and the median MVT reduction rate was 86.5%. We found the most significant difference in survival between PET responders and nonresponders with a cut-off value of 60% MTV reduction, using a 10% stepwise cut-off analysis 2-year progression-free survival (PFS): 79.2 vs 44.4%; hazard ratio (HR) 3.397; P < 0.0001). With this cut-off value, histological response (P = 0.0091), tumor location (P = 0.0102), pT (P = 0.0011), and pN (P = 0.0110) were significantly associated with PET response. Univariate analysis of PFS indicated a correlation between PFS and tumor size, cT, decrease of primary lesion by CT, SUVmax reduction rate, MTV reduction rate, pT, pN, and pM. Multivariate analysis further identified pM (HR 3.063; P = 0.0279) and MTV reduction rate (HR 2.471; P = 0.0263) to be independent prognostic predictors, but not decrease of primary lesion by CT or SUVmax reduction rate.
MTV change is clinically useful in predicting both long-term survival and histological response to preoperative chemotherapy in EC patients, after determining the optimal cut-off value based on survival analysis.
To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance.
NAC is a standard treatment for locally advanced ...esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown.
One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin-eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis.
Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types.
After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis.
To evaluate pathological response to NAC in metastatic LNs, and assess its clinical prognostic significance in patients with EC.
The pathological response to preoperative treatment is commonly ...evaluated in the PT. However, LN metastases strongly correlate with systemic micro-metastases. Thus, pathological evaluation of LN response could more accurately predict prognosis in EC patients undergoing NAC before surgery.
We enrolled 371 consecutive patients who underwent triplet NAC followed by surgery for EC between January 2010 and December 2016. Pathological LN regression grade was defined by the proportion of viable tumor area within the whole tumor bed area for all metastatic LNs: grade I, >50%; II, 10%-50%; III, <10%; and IV, 0%. We analyzed the correlation of grade with clinico-pathological parameters.
Among 319 patients with clinically positive LNs, pathological LN regression grades were I/II/III/IV in 115/51/58/95 patients, and 191 patients (59.9%) showed discordance between the PT and LN pathological regression grades. LN regression grade significantly correlated with cN positive number, ypTNM, lymphovascular invasion, and clinical/pathological PT response. Multivariate analysis for recurrence-free survival revealed that LN regression grade hazard ratio (HR) = 2.25, P < 0.001, ypT (HR = 1.65, P = 0.005), and ypT (HR = 1.62, P = 0.004) were independent prognostic factors, but not pathological PT regression grade (P = 0.67).
Compared to PT response, pathological LN response better predicted long-term survival in EC patients who received NAC plus curative surgery.
Background
The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection.
Methods
In this six-institution, matched-cohort study, ...2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns.
Results
Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (
p
= 0.0078), 41.0% (
p
= 0.0297), and 55.3% (
p
= 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (
p
= 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (
p
= 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (
p
= 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (
p
= 0.0183).
Conclusions
Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.
Background
Sarcopenia was previously linked to clinical outcomes for several cancer types, including esophageal cancer (EC), but most studies only measured the quantity of skeletal muscle mass. We ...aim to assess the clinical significance of evaluating the quantity and quality of skeletal muscle in patients with EC who underwent neoadjuvant chemotherapy (NAC) followed by esophagectomy.
Methods
We included 333 consecutive patients with EC who underwent NAC followed by esophagectomy. The psoas muscle index (PMI) and intracellular muscle adipose tissue content (IMAC) were measured by computed tomography. We defined low PMI combined with high IMAC as severe sarcopenia, and assessed its impact on clinical outcomes.
Results
Thirty-seven patients (11.1%) had severe sarcopenia. Compared with patients without severe sarcopenia, those with severe sarcopenia showed a significantly worse NAC response rate (54.1% vs 74.7%;
P
= 0.008), worse pathological response rate (24.3% vs 40.2%,
P
= 0.061), higher morbidity rate (67.6% vs 38.5%;
P
= 0.001), particularly for pneumonia (32.4% vs 14.9%
P
= 0.007) and expectoration disorder (37.8% vs 13.5%
P
< 0.001), and unfavorable survival (3-year overall survival rate: 54.1% vs 66.6%
P
= 0.027). Multivariable analysis of overall survival showed that severe sarcopenia (HR 1.68,
P
= 0.025) and cT (HR 1.52,
P
= 0.032) were independent prognostic factors of poor outcome.
Conclusions
PMI combined with IMAC represents a new criterion for sarcopenia that might be useful for predicting NAC response, postoperative complications, and long-term survival in patients with EC undergoing multidisciplinary treatments.
The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating ...locally advanced ESCC in a multi-institutional, randomised, Phase II trial.
We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m
, cisplatin 70 mg/m
i.v. on day 1, fluorouracil 700 mg/m
continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis.
Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517).
Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC.
University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).
Objective
To compare short-term outcomes between two- vs. three courses of neoadjuvant chemotherapy (NAC) to clarify the optimal treatment for esophageal squamous cell cancer (ESCC) in a multicenter, ...randomized, phase II trial.
Background
An optimal number of NAC cycles remains to be established for locally advanced ESCC.
Methods
Patients with locally advanced ESCC were randomly assigned to either two (
N
= 91) or three (
N
= 89) courses of DCF (70 mg/m
2
intravenous docetaxel and 70 mg/m
2
intravenous cisplatin on day 1, and a continuous 700 mg/m
2
fluorouracil infusion for 5 days) every 3 weeks followed by surgery. We compared the two groups for perioperative parameters, adverse events, and the response to NAC.
Results
The two- and three-course groups showed similar completion rates and overall NAC dose reductions. Although the two-course group showed significantly lower overall grades 3–4 leukopenia and anemia compared to the three-course group, the two groups had similar overall toxicity rates. Postoperative complications were not significantly different between the two groups, except arrhythmia (13 vs
.
0%,
P
= 0.0007). Only two postoperative in-hospital deaths occurred in the three-course group, due to sepsis following severe pneumonia. Compared to the two-course group, the three-course group was associated with a significantly better clinical response (42.9 vs. 65.2%,
P
= 0.0027) and a relatively higher rate of pathological complete response (9.1 vs. 15.3%,
P
= 0.212).
Conclusion
Both two- and three-course DCF regimens in the NAC setting seemed to be equally feasible in locally advanced ESCC patients. Additional DCF courses led to a better NAC response without increasing the incidence of adverse events or postoperative morbidity.
Clinical Trial Registration
University Hospital Medical Information Network Clinical Trials Registry of Japan (Identification Number UMIN 000015788).
Background
Definitive chemoradiation therapy or chemotherapy alone is generally recommended for patients with unresectable cT4b esophageal cancer. However, conversion surgery has emerged as a ...therapeutic option when downstaging is achieved by induction therapy.
Methods
We studied 169 patients with cT4 esophageal cancer who underwent induction therapy. Survival and prognostic factors were examined.
Results
Of 169 patients, 25 who achieved a clinical complete response (cCR) underwent surveillance, 72 patients underwent conversion surgery, while another 72 patients whose tumors were regarded as unresectable after induction therapy did not undergo surgery. Among 169 patients, the 3- and 5-year survival rates were 31.0% and 25.9%, respectively. Sixty-four patients who underwent curative resection showed better survival comparable with survival of 25 patients who achieved cCR (3- and 5-year survival; 56.8% and 48.6% versus 64.0% and 52.0%, respectively). However, the survival of eight patients who underwent noncurative resection was as dismal as that of patients who did not undergo conversion surgery. Multivariate analysis in 169 patients identified female sex and achieving cCR or R0 resection as independent prognostic factors. Multivariate analysis in 72 patients who underwent conversion surgery identified sex, lymph node status, and R0 resection as independent prognostic factors in patients with cT4b esophageal cancer.
Conclusions
The present study showed that conversion surgery after induction therapy can be a potentially curative treatment option for select patients with cT4b esophageal cancer. An important issue for further research is to establish a method for more accurately diagnosing tumor resectability after induction therapy for cT4b esophageal cancer.
Summary Background and aims The clinical value of synbiotics in patients receiving neoadjuvant chemotherapy currently remains unclear. The aim of this study was to investigate the effects of ...synbiotics in esophageal cancer patients receiving neoadjuvant chemotherapy on the intestinal microbiota and the adverse events of chemotherapy. Methods Sixty-one patients with advanced esophageal cancer who were scheduled to receive neoadjuvant chemotherapy were randomly allocated to 2 groups. One group received synbiotics during chemotherapy (n = 30), while the other group did not (n = 31). The fecal microbiota and organic acid concentrations were analyzed. The primary endpoint was the incidence of chemotherapy-related adverse events. Results The numbers of beneficial and harmful bacteria were significantly larger and smaller, respectively, in the synbiotics group than in the control group on day 10 of chemotherapy. The concentrations of acetic acid and propionic acid were significantly higher in the synbiotics group on day 10 of chemotherapy. The frequencies of severe lymphopenia and diarrhea were significantly less in the synbiotics group than in the control group (P = 0.033, 0.035, respectively). Furthermore, febrile neutropenia occurred less in the synbiotics group (10/30 in the synbiotics group vs 19/31 in the control group, P = 0.029). Conclusions Synbiotics during neoadjuvant chemotherapy in esophageal cancer patients reduced the occurrence of adverse events of chemotherapy through adjustments to the intestinal microbiota. (University Hospital Medical Information Network ( http://www.umin.ac.jp ), registration number UMIN000006875).
