Efficacy and Safety of Salvage-line Nivolumab Monotherapy for Advanced Esophageal Squamous Cell Carcinoma: Comparison of 240 mg Versus 480 mg Doses.

BACKGROUND: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. METHODS: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. RESULTS: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. CONCLUSIONS: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.

Association between preoperative serum zinc level and prognosis in patients with advanced esophageal cancer in the neoadjuvant treatment era.

Background: Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear. Methods: This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients' outcomes. Results: The patients were divided into a low Zn group (<64 µg/dL) and a high Zn group (≤64 µg/dL) according to the mean preoperative serum Zn level. Low Zn had significantly worse overall survival (OS) (2-year OS rate: 76.2% vs. 83.3% in low vs. high Zn; p = 0.044). A low Zn in pathological non-responders (Grade ≤ 1a) was significantly associated with a shorter 2-year recurrence-free survival (RFS) rate (39.6% vs. 64.1% in low vs. high Zn; p = 0.032). The multivariate analysis identified low BMI and Zn level among preoperative nutritional status indices as an independent risk factor for worse RFS in non-responders. Compared with responders, pathological non-responders comprised significantly more males and a performance status of ≥1, and there was no difference in Zn level according to pathological response. Conclusion: A preoperative low Zn level had a negative impact on early recurrence in esophageal cancer patients who underwent neoadjuvant chemotherapy. This suggests the need to administer Zn supplementation to patients with esophageal cancer who have preoperative Zn deficiency.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of esophageal squamous cell carcinoma after neoadjuvant triplet chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy followed by esophagectomy is the standard treatment for resectable advanced esophageal squamous cell carcinoma (ESCC) in Japan. Triplet chemotherapy is the standard neoadjuvant regimen. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) are well-known prognostic factors for esophageal cancer. However, their usefulness in patients with resectable advanced disease undergoing esophagectomy after neoadjuvant triplet chemotherapy is unknown. METHOD: We examined 144 ESCC patients who underwent neoadjuvant triplet chemotherapy followed by esophagectomy between January 2015 and December 2020 to investigate the relationship between inflammatory markers and recurrence-free survival (RFS). Optimal marker cutoff values for RFS were determined using receiver operating characteristic curve analysis. Patients were divided into high and low NLR groups (NLR cutoff, 3.0). RESULTS: NLR was high in 61 patients and low in 83. Univariate analyses demonstrated that low NLR was significantly associated with worse RFS (p = 0.049). Multivariate analyses demonstrated that high NLR was an independent predictor of RFS (odds ratio, 1.911; 95% confidence interval, 1.098-3.327; p = 0.022). RFS significantly differed between the low and high NLR groups. RFS did not significantly differ between the patients when stratified according to the other inflammatory markers. CONCLUSION: Preoperative NLR is an easily obtained and useful predictor of RFS in patients with resectable advanced ESCC treated with neoadjuvant triplet chemotherapy followed by esophagectomy.

Neoadjuvant Chemotherapy Improves Feasibility of Larynx Preservation and Prognosis in Resectable Locally Advanced Cervical Esophageal Cancer.

BACKGROUND: The optimal strategy for cervical advanced esophageal cancer remains controversial in terms of oncologic outcome as well as vocal and swallowing function. Recently, in East Asian countries, neoadjuvant chemotherapy (NAC) has been a standard strategy for advanced esophageal cancer. METHODS: This study included 37 patients who underwent NAC, and 33 patients who underwent definitive chemoradiation therapy (dCRT) as larynx-preserving treatment for locally advanced cervical esophageal cancer from 2016 to 2021. This study retrospectively investigated outcomes, with comparison between NAC and dCRT for locally advanced cervical esophageal cancer. RESULTS: Larynx preservation was successful for all the patients with NAC and dCRT. After NAC, the rate of complete or partial response was 78.4%, and 30 patients underwent larynx-preserving surgery. On the other hand, after dCRT, the complete response rate was 71.9%, and 4 patients underwent larynx-preserving salvage surgery. Overall survival (OS) and progression free survival were similar between the two groups. However, for the patients with resectable cervical esophageal cancer (cT1/2/3), the 2-year OS rate was significantly higher with NAC (79.9%) than with dCRT (56.8%) (P = 0.022), and the multivariate analyses identified only NAC and cN0, one of the two as a significantly independent factor associated with a better OS (NAC: P = 0.041; cN0, 1: P = 0.036). CONCLUSION: The study showed that NAC as larynx-preserving surgery for resectable cervical esophageal cancer preserved function and had a better prognosis than dCRT. The authors suggest that NAC may be standard strategy for larynx preservation in patients with resectable cervical esophageal cancer.

Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

BACKGROUND: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. METHODS: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. RESULTS: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. CONCLUSION: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND: Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population. METHODS: Patients with histologically confirmed resectable EGJ-AC who received preoperative DCF (docetaxel 70 mg/m2 and cisplatin 70 mg/m2 on day 1 and continuous infusion of 5-fluorouracil 750 mg/m2/day on days 1-5 every 3 weeks with a maximum of three cycles) between January 2015 and April 2020 were retrospectively evaluated. We assessed the rates of completion of ≥ 2 courses of DCF and R0 resection, histopathological response, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Thirty-two patients were included. Median follow-up was 28.7 (range, 5.2-70.8) months and median age was 63 (range, 42-80) years. Twenty-one patients (66%) had a performance status of 0. The proportions of clinical stage IIA/IIB/III/IVA/IVB disease were 3%/0%/44%/44%/9%, respectively. The treatment completion rate was 84%. A histopathological response of grade 1a/1b/2/3 was obtained in 58%/26%/13%/3% of cases. Median PFS was 40.7 months (95% confidence interval 11.8-NA). Median OS was not reached (80.8% at 3 years). Grade ≥ 3 adverse events were observed in 63% of cases (neutropenia, 44%; febrile neutropenia, 13%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative DCF for resectable EGJ-AC was well tolerated and has promising efficacy.

Preoperative physical activity is associated with prognosis in patients with esophageal cancer undergoing thoracoscopic-laparoscopic esophagectomy after neoadjuvant chemotherapy.

OBJECTIVE: This study examined the association between a single preoperative physiotherapy session during neoadjuvant chemotherapy and physical function and that between preoperative physical activity and prognosis. METHODS: In this retrospective, single-center, observational study, we evaluated data from 234 patients scheduled for neoadjuvant chemotherapy and thoracoscopic-laparoscopic esophagectomy who underwent a single preoperative physiotherapy session. The five-repetition sit-to-stand test was performed before and after neoadjuvant chemotherapy. After neoadjuvant chemotherapy, patients were classified into high- and low-physical activity groups based on preoperative physical activity. To examine the association between preoperative physiotherapy and changes in physical function, a multivariate regression analysis was performed. The Cox proportional hazards model was used to investigate the association between preoperative physical activity and overall survival. RESULTS: The median percentage change in the five-repetition sit-to-stand test score was - 3.36%. In the multivariate regression analysis, the regression coefficient of the constant term was - 23.93 (95% confidence interval - 45.31 to - 2.56; P = 0.028). Low physical activity was significantly associated with overall survival after adjustment for confounding factors (P = 0.040). CONCLUSIONS: This study demonstrated that a single preoperative physiotherapy session during neoadjuvant chemotherapy improves physical function, and preoperative physical activity is significantly associated with prognosis.

Significance of Surgery for Resectable M1 Lymph Node Metastases Without Organ Metastasis in Esophageal Carcinoma in the Era of Neoadjuvant Treatment.

BACKGROUND: M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma. PATIENTS AND METHODS: This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis. RESULTS: Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status. CONCLUSION: The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Non-curative resection for surgical T4b esophageal cancer: esophagectomy or non-esophagectomy?

BACKGROUND: Recently, with the development of multidisciplinary treatment, the treatment outcomes of esophageal cancer (EC) have improved. However, despite advances in diagnostic imaging modalities, preoperative diagnosis of T4 EC is still difficult, and the prognosis of T4 EC remains very poor. In addition, the prognosis of surgical T4b EC (sT4b EC) after surgery remains unclear. In this study, we retrospectively reviewed sT4b EC. METHODS: We evaluated the clinical course of sT4b EC and compared palliative esophagectomy with R2 resection (PE group) with other procedures without esophagectomy (NE group) (e.g., only esophagostomy) for sT4b EC. RESULTS: Forty-seven patients with thoracic EC underwent R2 resection at our institution between January 2009 and December 2020. Thirty-four patients were in the PE group, and 13 patients were in the NE group. The 2-year overall survival rate was 0% in the PE group and 20.2% in the NE group (p = 0.882). There was one case of long-term survival in the NE group that underwent surgery followed by definitive chemoradiation. Postoperative complications (Clavien-Dindo grade ≥ 3) were observed in 25 patients (73.5%) in the PE group and in three patients (23.1%) in the NE group (p = 0.031). The median time to the initiation of postoperative treatment was 68.1 days in the PE group and 18.6 days in the NE group (p = 0191). CONCLUSIONS: If EC is diagnosed as sT4b, palliative esophagectomy should be avoided because of the high complication rate and the lack of long-term survival.

Oncologic significance of lymphovascular invasion in patients with superficial esophageal squamous cell carcinoma reaching the muscularis mucosae or with slight invasion of the submucosa.

BACKGROUND: The clinicopathological features and the distribution of lymph node metastasis in patients with T1a-MM and T1b-SM1 superficial esophageal squamous cell carcinoma remain unclear; therefore, the optimal treatment strategy is still controversial. METHODS: One hundred and ninety-one patients who had undergone a thoracic esophagectomy with 3-field lymphadenectomy and who were pathologically confirmed to have thoracic superficial esophageal squamous cell carcinoma that had reached the T1a-MM or T1b-SM1 stage were retrospectively reviewed. Risk factors of lymph node metastasis, the distribution of lymph node metastasis, and long-term outcomes were evaluated. RESULTS: A multivariate analysis revealed that lymphovascular invasion was the only independent risk factor of lymph node metastasis (odds ratio: 6.410, P < .001). Patients with primary tumors in the middle thoracic region had lymph node metastasis in all 3 fields, whereas patients with primary tumors in the upper or lower thoracic region did not have distant lymph node metastasis. The frequencies of neck (P = .045) and abdominal (P < .001) lymph node metastasis were significantly higher in lymphovascular invasion-positive patients than those in lymphovascular invasion-negative patients in all cohort. MM/lymphovascular invasion-positive patients with middle thoracic tumors had lymph node metastasis spread from the neck to the abdomen. SM1/lymphovascular invasion-negative patients with middle thoracic tumors did not have lymph node metastasis in the abdominal region. The SM1/pN+ group had a significantly poorer overall survival and relapse-free survival than the other groups. CONCLUSION: The present study revealed that lymphovascular invasion was associated with not only the frequency of lymph node metastasis, but also the distribution of lymph node metastasis. It also suggested that superficial esophageal squamous cell carcinoma patients with T1b-SM1 and lymph node metastasis had a significantly poorer outcome than those with T1a-MM and lymph node metastasis.

The evaluation of the association between preoperative sarcopenia and postoperative pneumonia and factors for preoperative sarcopenia in patients undergoing thoracoscopic-laparoscopic esophagectomy for esophageal cancer.

PURPOSE: This study identified the relationship between postoperative pneumonia and preoperative sarcopenia as well as the factors for preoperative sarcopenia in patients with esophageal cancer. METHODS: In this retrospective, single-center, observational study, we evaluated the data of 274 patients who were scheduled for thoracoscopic-laparoscopic esophagectomy. Sarcopenia was defined using the skeletal muscle index, handgrip strength, and gait speed. The physical activity and nutritional status were evaluated. A multivariate logistic regression analysis was performed to confirm the association between sarcopenia and postoperative pneumonia and identify sarcopenia-related factors. A Spearman's correlation analysis was used to identify the relationship between physical activity and nutritional status. RESULTS: Age, male sex, sarcopenia, and postoperative recurrent laryngeal nerve palsy were significantly associated with postoperative pneumonia. Age, male sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. There was a significant correlation between physical activity and nutritional status. CONCLUSIONS: Preoperative sarcopenia was confirmed to be a predictor of postoperative pneumonia. Furthermore, age, sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. Physical activity and nutritional status are closely associated with each other in patients with esophageal cancer. A multidisciplinary approach to preoperative sarcopenia, taking exercise and nutrition into account, is recommended.

Evaluating the efficacy of post-operative chemotherapy after curative resection of stage IV gastric cancer with synchronous oligo metastasis: a multicenter retrospective study.

BACKGROUND: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis. METHODS: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery. RESULTS: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05). CONCLUSIONS: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival.

Perioperative Decrease in Tongue Pressure is an Intervenable Predictor of Aspiration After Esophagectomy.

Despite the increasing use of minimally invasive esophagectomies, aspiration pneumonia remains the most serious complication. This study clarified the association between perioperative tongue pressure and postoperative aspiration after thoracoscopic-laparoscopic esophagectomy in patients with esophageal cancer. This retrospective, single-center, observational study evaluated data of 216 patients scheduled for thoracoscopic-laparoscopic esophagectomy. Tongue pressure was measured before the procedure and on postoperative day 6; perioperative changes were assessed. Patients were divided into non-aspiration and aspiration groups according to penetration-aspiration scale scores. Hierarchical and stratified logistic regression analyses were performed to identify factors associated with aspiration. Receiver operating characteristic curves were used to assess the cut-off value of perioperative changes in tongue pressure for aspiration. Perioperative changes in tongue pressure (odds ratio 0.92; 95% confidence interval 0.88-0.96, P < 0.001), age (odds ratio 1.07; 95% confidence interval 1.01-1.13, P = 0.013), and postoperative recurrent laryngeal nerve palsy (odds ratio 3.04; 95% confidence interval 1.15-8.03, P = 0.025) were significantly associated with aspiration. The cut-off value of perioperative changes in tongue pressure for postoperative aspiration was - 6.58%. In addition, decreases in tongue pressure were associated with aspiration regardless of recurrent laryngeal nerve palsy and age. The perioperative decrease in tongue pressure, higher age, and postoperative recurrent laryngeal nerve palsy were significant factors strongly associated with aspiration in the acute phase post-esophagectomy. Decreased tongue pressure is the only intervenable predictor of aspiration. Rehabilitation for preventing decreases in tongue pressure may reduce the risk of aspiration.

Significance of lymphovascular invasion in esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by esophagectomy.

BACKGROUND: Lymphovascular invasion (LVI) was previously reported to be an independent factor associated with survival in locally advanced esophageal squamous cell carcinoma (LAESCC) patients receiving neoadjuvant chemotherapy (NAC); however, the detailed clinicopathological significance of LVI remains unclear. This study evaluated the prognostic impact of LVI in patients with LAESCC after NAC with cisplatin and 5-fluorouracil (CF) or docetaxel, cisplatin and 5-fluorouracil (DCF) followed by surgery and in LAESCC patients with recurrence after NAC and surgery. METHODS: 438 patients with thoracic LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were assessed using a propensity score matched analysis, and their long-term outcomes were retrospectively reviewed. RESULTS: In matched cohort, a multivariate analysis of relapse-free survival (RFS) in the NAC-CF group suggested that ypN (≥ 1, HR = 3.715, p = 0.004) and LVI (positive, HR = 3.366, p = 0.012) were independent factors associated with RFS; in the NAC-DCF group, ypN (≥ 1, HR = 4.829, p < 0.001) was the only independent factor associated with RFS. Comparisons of overall survival (OS) between the ypN + /LVI + group and other groups among patients with recurrence in each NAC regimen showed significant differences in both of NAC groups (p < 0.001, respectively). The ypN + /LVI + group had a significantly poor OS in both an oligometastatic recurrence (OMR) group (p < 0.001) and a non-OMR group (p < 0.001). CONCLUSIONS: The present study suggested that the independent factor associated with prognosis of patients with LAESCC after NAC and surgery may differ according to the NAC regimen, and the presence of both ypN and LVI was a prognostic factor for patients with recurrence, including those with OMR. These results might be helpful when deciding on an additional treatment strategy for LAESCC patients.

Safety and short-term efficacy of preoperative FOLFOX therapy in patients with resectable esophageal squamous cell carcinoma who are ineligible for cisplatin.

BACKGROUND: The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (LAESCC) in Japan is docetaxel, cisplatin (CDDP), and 5-fluorouracil. However, patients with renal or cardiac dysfunction and elderly patients are ineligible for a CDDP-containing regimen because of toxicities. Oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) therapy has less renal toxicity than CDDP-containing regimens and does not require hydration. However, there are limited data on preoperative FOLFOX therapy in these patients. METHODS: This retrospective study analyzed patients with resectable LAESCC who were aged ≥ 75 years or had renal or cardiac dysfunction and received preoperative FOLFOX between 2019 and 2021. FOLFOX was administered every 2 weeks for 3 or 4 cycles and was followed by surgery. Adverse events associated with chemotherapy, the complete resection (R0) rate, relative dose intensity (RDI), and histopathological response were evaluated. RESULTS: Thirty-five patients were eligible. Median age was 77 (range 65-89) years; 68.6% were aged ≥ 75 years, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction. The RDI was 70.2% and 87.1% for bolus and continuous intravenous 5-fluorouracil, respectively and 85.2% for oxaliplatin. The most common grade ≥ 3 adverse events were neutropenia (60.0%) and leucopenia (28.6%). Two patients (5.7%) had febrile neutropenia and grade 3 pneumonia. Thirty-one patients underwent surgery. The R0 resection rate was 87.1%, and there was no histopathological evidence of residual tumor in 16.1%. There were no treatment-related deaths. CONCLUSIONS: Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ineligible for CDDP-containing treatment.

Impact of pre-diabetes, well-controlled diabetes, and poorly controlled diabetes on anastomotic leakage after esophagectomy for esophageal cancer: a two-center retrospective cohort study of 1901 patients.

BACKGROUND: Diabetes is known to be associated with anastomotic leakage (AL) after esophagectomy. However, it is unknown whether well-controlled diabetes is also associated with AL. METHODS: We conducted a two-center retrospective cohort database study of patients who underwent oncological esophagectomy (2011-2019). Patients were divided into four groups: normoglycemia, pre-diabetes, well-controlled diabetes (hemoglobin A1c [HbA1c] < 7.0%), and poorly controlled diabetes (HbA1c ≥ 7.0%). The occurrence of AL and length of stay were compared between groups using multivariable analyses. The relationship between categorical HbA1c levels and AL was also investigated in patients stratified by diabetes medication before admission. RESULTS: Among 1901 patients, 1114 (58.6%) had normoglycemia, 480 (25.2%) had pre-diabetes, 180 (9.5%) had well-controlled diabetes, and 127 (6.7%) had poorly controlled diabetes. AL occurred in 279 (14.7%) patients. Compared with normoglycemia, AL was significantly associated with both well-controlled diabetes (odds ratio 1.83, 95% confidence interval [CI] 1.22-2.74) and poorly controlled diabetes (odds ratio 1.95, 95% CI 1.23-3.09), but not with pre-diabetes. Preoperative HbA1c levels showed a J-shaped association with AL in patients without diabetes medication, but no association in patients with diabetes medication. Compared with normoglycemia, only poorly controlled diabetes was significantly associated with longer hospital stay after surgery, especially in patients with operative morbidity (unstandardized coefficient 14.9 days, 95% CI 5.6-24.1). CONCLUSIONS: Diabetes was associated with AL after esophagectomy even in well-controlled patients, but pre-diabetes was not associated with AL. Operative morbidity, including AL, in poorly controlled diabetes resulted in prolonged hospital stays compared with normoglycemia.

Surveillance Strategy after Curative Resection for Oesophageal Squamous Cell Cancer Using the Hazard Function.

BACKGROUND: The optimal surveillance period and frequency after curative resection for oesophageal squamous cell carcinoma (OSCC) remain unclear, and current guidelines are mainly based on traditional Kaplan-Meier analyses of cumulative incidence rather than risk analysis. The aim of this study was to determine a suitable follow-up surveillance program following oesophagectomy for OSCC using the hazard function. METHODS: A total of 1187 patients who underwent curative resection for OSCC between 2000 and 2014 were retrospectively analyzed. The changes in the estimated hazard rates (HRs) of recurrence over time were analyzed according to tumour-node-metastasis stage. RESULTS: Four hundred seventy-eight (40.2%) patients experienced recurrence during the follow-up period (median, 116.5 months). The risk of recurrence peaked at 9.2 months after treatment (HR = 0.0219) and then decreased to half the peak value at 24 months post-surgery. The HRs for Stage I and II patients were low (< 0.007) post-treatment. The HR for Stage III patients peaked at 9.9 months (HR = 0.031) and the hazard curve declined to a plateau at 30 months. Furthermore, the HR peaked at 10.8 months (HR = 0.052) in Stage IV patients and then gradually declined from 50 months. CONCLUSIONS: According to tumour-node-metastasis stage, changes in the HRs of postoperative recurrence in OSCC varied significantly. Intensive surveillance should be undertaken for 3 years in Stage III patients and for 4 years in Stage IV patients, followed by annual screening. For Stage I OSCC patients, a reduction in the surveillance intensity could be taken into consideration.

Clinicopathological Features of Early-Stage Esophageal Carcinosarcoma.

Esophageal carcinosarcoma (EC) is a rare malignant tumor, accounting for 0.5-2.8% of esophageal cancers. Most are advanced cancers that are detected as polypoid lesions and are treated with multidisciplinary therapy with a focus on surgery. However, endoscopic findings, pathological findings, and long-term outcomes of early-stage EC are often unclear because there are very few reported cases. This paper reports three cases of EC confined to the mucosal layer. The macroscopic type of all tumors was polypoid lesion with a slightly depressed lesion. All cases were clinically diagnosed as invasive cancer before treatment. Pathological diagnosis of tumor depth showed that one case had invaded the lamina propria mucosae, and two cases had invaded the muscularis mucosae (MM). One case of diagnosed MM had lymphoid invasion and lymph node metastasis to the upper mediastinum. After 1 year, although adjuvant treatment had been administered, there was lymph node recurrence in the left upper clavicle, and thus chemoradiation therapy was performed. Two other cases survived without recurrence. Early-stage EC is characterized by polypoid lesions with a slightly depressed lesion, and it is challenging to predict the histology on biopsy. Furthermore, it is difficult to determine the depth of invasion in the MM and submucosal layer in squamous cell carcinoma by endoscopy alone, and hence depth diagnosis by multiple modalities should be considered.

Clinical significance of sarcopenic dysphagia for patients with esophageal cancer undergoing esophagectomy: A review.

The relationships among esophagectomy for esophageal cancer, dysphagia, and sarcopenia are still unclear. We considered appropriate interventions for patients with resectable esophageal cancer for the purpose of reducing postoperative dysphagia and aspiration pneumonia. Dysphagia in patients with esophageal cancer is caused by patient characteristics, such as pathophysiology and age, or complications after esophagectomy. Recently, sarcopenic dysphagia, defined as dysphagia associated with whole-body sarcopenia, has attracted attention in various fields, and a large proportion of patients with esophageal cancer are expected to have sarcopenic dysphagia. Our systematic review and meta-analysis suggested that preoperative sarcopenia in patients with esophageal cancer is related to pulmonary complications after esophagectomy, and some reports also suggested that sarcopenia in swallowing-related muscles, such as the geniohyoid muscle and tongue, might be associated with postoperative pneumonia or dysphagia after esophagectomy. However, clinical studies on sarcopenic dysphagia in patients with esophageal cancer have been limited. To prevent sarcopenic dysphagia after esophagectomy, perioperative interventions involving not only swallowing rehabilitation, but also physical exercise and nutritional support are important. Moreover, several reports have suggested that the chin-down maneuver might be effective for preventing aspiration after an esophagectomy. To inhibit the progression of sarcopenic dysphagia after esophagectomy, evaluations and interventions by multidisciplinary staff are likely to be necessary.