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PurposeTo arrange multidisciplinary treatment for esophageal cancer, a simple and accurate predictive marker for prognosis is required. The current multicenter prospective study aims to validate the prognostic significance of fibrinogen and albumin score (FA score) for esophageal cancer patients.Patients and MethodsPatients who were planned to undergo surgical resection for esophageal cancer at four participating institutions were enrolled in this study. Patient background, clinicopathological factors, and blood concentration of plasma fibrinogen and albumin were collected. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2; those with only one of these abnormalities were allocated a score of 1; and those with neither of these abnormalities were allocated a score of 0. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as a primary endpoint.ResultsFrom four participating institutions, 133 patients were registered for the current analysis. The distribution of FA score of 0/1/2 was 84 (63%)/34 (26%)/15 (11%), respectively. In the analysis of primary endpoint, the preoperative FA score significantly classified RFS (FA score 1/2: HR 2.546, p = 0.013/6.989, p < 0.001) and OS (FA score 1/2: HR 2.756, p = 0.010/6.970, p < 0.001). We further evaluated the prognostic significance of FA score under stratification by pStage. As a result, with increasing FA score, RFS and OS were significantly worse in both pStage 0–I and II–IV groups.ConclusionsThe prognostic impact of preoperative FA score was confirmed for esophageal cancer patients in the current multicenter prospective trial. FA score can be considered to predict postoperative survival and rearrange the treatment strategy before esophagectomy.

BackgroundAlthough radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed.Patients and MethodsWe conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated.ResultsAmong all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002–1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374.ConclusionsNLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.

Background Recent advances in endoscopic examinations have resulted in the detection of a larger number of early esophageal cancers; however, there have been many cases with clinically negative but pathologically positive lymph node metastasis (LNM). In this study, we aimed to evaluate the discrepancy between the clinical and pathological diagnoses of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer, and assess LNM size in these patients to clarify the presence of LNM that cannot be detected with current modalities. Methods This study included 50 patients who underwent surgery for cT1a-MM/cT1b N0M0 thoracic esophageal squamous cell carcinoma between January 2012 and November 2016 at our institution. The maximum size of involved LNs and metastatic nests were measured, and the distribution of LNM was investigated. Results Of the 50 patients, 13 (26%) had LNM on pathological examination. Lymphatic invasion was significantly more frequent in the LNM-positive group than in the LNM-negative group ( p  = 0.005). The median sizes of 28 involved LNs and metastatic nests were 3 and 1.6 mm, respectively. Of these LNs, 20 (71%) were classified as micrometastases (≤ 2 mm). The involved nodes were distributed across three fields. Conclusions There was a discrepancy between the clinical and final pathological findings of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer. The detection of involved nodes with current modalities in these patients was difficult because of the small size of LNM. Therefore, continued strong consideration for extended LN dissection is necessary in these patients to ensure appropriate diagnosis and treatment.

Perioperative and surgical management of gastric cancer have been changing as pivotal phase II trials and landmark phase III trials offer new insights to the existing knowledge. The results of many landmark trials have been published or presented in the past year, many of which have changed or will change current clinical practice. For example, FLOT4 has completely changed the regimen of perioperative chemotherapy in Europe. Furthermore, evidence for minimally invasive surgery for clinical Stage I was firmly established by KLASS‐01 and JCOG0912 for distal gastrectomy and CLASS‐02, KLASS‐03, and JCOG1401 for total gastrectomy. Moreover, promising results were provided by CLASS‐01 and KLASS‐02 for locally advanced gastric cancer. For adjuvant chemotherapy, JACCRO GC‐07 (START‐2) has provided a new doublet regimen for pathological Stage III, which is often refractory to chemotherapy. Conversely, JCOG0501 poses a significant challenge for advanced tumors, such as large type 3 and scirrhous (type 4) tumors. In this review, we briefly review recent updates and discuss future perspectives of gastric cancer treatment. The article reviewed updates in the management of gastric cancer surgery by covering most pivotal recent trials and studies, and then discusses future perspectives of gastric cancer treatment.

PurposePostoperative sarcopenia following esophagectomy for esophageal cancer has become a severe problem due to the increasing number of elderly patients undergoing surgery. This study aimed to clarify the relationship between early postoperative skeletal muscle change and cancer prognosis, and propose effective interventions to prevent sarcopenia.MethodsThis study retrospectively analyzed 152 patients who underwent esophagectomy for esophageal cancer. Total psoas muscle area (TPA) was measured before surgery as baseline and on postoperative day 7 (± 2). The effect of early postoperative skeletal muscle loss on 5-year survival was investigated. Moreover, 5-year survival in patients with postoperative complications and a high inflammatory status, which were previously reported as poor prognostic factors of esophageal cancer, was also investigated.ResultsAmong the 152 patients, 52 (34.2%) showed a decrease in TPA, while 100 (65.8%) maintained their TPA. The TPA decreasing group exhibited poor 5-year overall survival (OS) (p = 0.003) and 5-year recurrence-free survival (RFS) (p < 0.001). The TPA decreasing group also showed a poor 5-year OS in patients who developed severe postoperative complications (p = 0.015). Multivariate analyses showed that decreased TPA was found to be independently associated with OS (p = 0.017) as well as RFS (p = 0.002).ConclusionsOur findings suggested a relationship between decreased TPA within 1 week after esophagectomy and long-term prognosis among patients with esophageal cancer. If TPA can be maintained, the prognosis was better even in cases with serious complications.

BackgroundThe tumor, node, metastasis staging system of the Union for International Cancer Control (UICC) has been used worldwide for esophageal cancer, and, in Japan, the Japan Esophageal Society Japanese Classification of Esophageal Cancer (JES) has also been used; however, there is a big difference between the two classifications with regard to node staging. We hypothesized that these two node staging systems may lead to different outcome predictions in terms of tumor location.MethodsThis study enrolled 409 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2005 and December 2017. We included those who underwent R0 or R1 resection or esophagectomy with additional organ excision, and excluded those who underwent salvage surgery. Thereafter, we investigated how the number or spread of metastatic lymph nodes affected the prognosis.ResultsFor all 409 patients, the 5-year overall survival rate was 64.1% and the 5-year recurrence-free survival rate was 58.4%. The concordance indices were 0.756 for UICC 8th edition pathological node staging and 0.732 for JES 11th edition pathological node staging (p = 0.06). Based on tumor location, the difference in the concordance indices between these two classifications was greatest for lower thoracic esophageal tumors (p = 0.02).ConclusionsFor all patients, the UICC 8th edition node staging system tended to reflect survival more precisely than that of the JES 11th edition. For lower thoracic esophageal tumors in particular, the former node staging system could be more useful.

Background Esophageal cancer has a poor prognosis because of its rapid progression and early and extensive lymph node metastasis. Simple, objective indicators for predicting long-term outcomes are needed to select optimal perioperative treatment and appropriate follow-up for patients with esophageal cancer. The aim of this study is to investigate the relationship between the lymphocyte-to-C-reactive protein ratio (LCR) and the survival of patients with esophageal cancer, by performing time-dependent receiver operating characteristic (ROC) curve analysis. The results were compared to those of traditional inflammation-based markers. Methods This study enrolled 495 patients who underwent thoracic esophagectomy for esophageal cancer as the primary treatment between 2000 and 2019 in our department. We investigated the predictability of the LCR for oncological outcomes compared to that of other traditional inflammatory markers. Results The 3-year overall survival (OS) and recurrence-free survival (RFS) were 72.6% and 57.5%, respectively. Low LCR was significantly associated with higher cancer stage, included depth of invasion ( p  < 0.001), lymph node metastasis ( p  < 0.001) and cStage ( p  < 0.001). The LCR had the highest AUC value (0.675) for predicting OS compared to the other examined inflammatory markers. In multivariate analysis, the LCR (optimal cutoff threshold = 19,000) was identified as a significant predictor of death (hazard ratio, 2.24; 95% confidence interval [CI], 1.61–3.12; p  < 0.001) and recurrence (hazard ratio, 1.97; 95%CI, 1.48–2.63; p  < 0.001). Conclusion The LCR is novel indicator for oncological outcomes for patients with esophageal cancer and may assist to facilitate personalized multidisciplinary treatments.

Background Esophagectomy for esophageal cancer is one of the most invasive operative procedures. Surgical stress induces the release of proinflammatory cytokines, and overproduction induces a systemic inflammatory response syndrome, which may lead to acute lung injury and multiple organ dysfunction syndrome. In addition, surgical stress may cause immunosuppression, which may affect not only perioperative mortality but also long-term survival. Methods Between 2006 and 2013, levels of perioperative serum cytokines were evaluated in 90 patients who underwent esophagectomy for esophageal carcinoma. The serum interleukin (IL)-6, IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assays. We reviewed and assessed medical records, including cytokine profiles, and determined the factors affecting postoperative serum cytokine levels. Results These cytokine levels peaked on postoperative day 1 and decreased gradually. Of the clinicopathologic factors, a thoracoscopic approach was a significant factor in attenuating IL-6 and IL-8 levels on postoperative day 1 in multivariate analysis, and a longer operative time was a significant factor in increasing these levels. During postoperative days 3–7, the thoracoscopic approach and early enteral nutrition were significant factors in attenuating serum cytokine changes in multivariate analysis, and postoperative infectious complications were significant factors in increasing these levels. Conclusions The thoracoscopic approach and early enteral nutrition could attenuate the cytokine change after esophagectomy, and a longer operative time and postoperative infectious complication could increase it. We should undertake strategies to minimize the surgical stress to reduce potential short-term and long-term consequences for patients.

Background The correlation between postoperative systemic inflammation and cancer survival needs to be elucidated. This study evaluated postoperative inflammation using the peak concentration of postoperative serum C-reactive protein (CRP) levels and duration of CRP elevation, then investigated its correlation with prognosis. Methods The study retrospectively reviewed 216 consecutive patients who underwent curative transthoracic esophagectomy at the authors’ institution between 2004 and 2012. The postoperative serum CRP levels in 215 patients were analyzed during 14 days after esophagectomy. The patients’ characteristics, surgical procedures, postoperative complications, and survival were investigated. To evaluate postoperative inflammatory status objectively using CRP, patients with a delayed CRP level peak and persistent CRP elevation were classified as having an intense postoperative inflammatory response (IIR). Results The distributions of postoperative pathologic stages 0, 1, 2, 3, and 4 were respectively 5, 70, 58, 66, and 16. Regarding postoperative complications, pneumonia was diagnosed in 42 patients (20 %), anastomotic leakage in 32 patients (15 %), and superficial surgical-site infection in 21 patients (10 %). A delayed CRP level peak was observed in 88 patients (41 %) and persistent CRP elevation in 49 patients (23 %). Overall, 31 patients (14 %) were classified as having IIR. In the survival analysis, the patients with IIR showed a significantly shorter overall survival. In the multivariate analysis, using histology, neoadjuvant treatment, field of lymph node dissection, pathologic stage, and IIR as covariates, IIR was seen as a significantly independent predictive factor for overall survival (hazard ratio 2.019; P  = 0.019). Conclusions In this study, IIR was significantly correlated with postoperative survival. Therefore, the oncologic benefit of reducing postoperative inflammation in esophageal cancer needs to be investigated.

Background Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory long-term prognosis. Moreover, CRT can lead to esophageal fistula, perforation, and strictures. Therefore, strong induction chemotherapeutic treatments are necessary to reduce the tumor volume for subsequent radical esophagectomy. This study aimed to determine the oncological utility of docetaxel plus cisplatin and 5-fluorouracil (DCF) and the technical feasibility of subsequent esophagectomy for locally advanced esophageal cancer. Methods Eighty-seven patients with clinical borderline unresectable T3 and T4 esophageal squamous cell carcinoma without distant metastases were included in this study. There were 44 patients in primary DCF group and 43 patients in definitive CRT group, and perioperative and long-term oncological outcomes were compared between the two groups. Results Twenty-two patients (50%) achieved R0 resection in the DCF group. Albeit not significant, the rate of curative treatment was higher in the DCF group than the definitive CRT group ( p  = 0.099). The overall survival (OS) and progression-free survival (PFS) were better with DCF than with definitive CRT (median OS, 29 vs. 17 months, p  = 0.206; median PFS, 10 vs. 6 months, p  = 0.020). Specifically, the OS of patients with a Charlson score of less than 3 among the DCF-treated patients tended to be better than those among the definitive CRT-treated patients. Conclusion DCF and subsequent esophagectomy achieved R0 resection in 50% of the patients and was associated with better long-term oncological outcomes in patients with initially unresectable esophageal cancer if their systemic status is acceptable.