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.

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.

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.

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.

Predictive Ability of the Five-time Chair Stand Test for Postoperative Pneumonia after Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: The revised sarcopenia guidelines proposed handgrip strength (HGS) and five-time chair stand test (5-CST) as the primary parameters of muscle function. HGS and 5-CST are associated with pulmonary function among community-dwelling people, although few reports have described an association between these parameters and surgical outcomes in carcinomas. We examined the predictive ability of 5-CST for postoperative pneumonia after minimally invasive esophagectomy (MIE) compared with that of HGS. METHODS: This retrospective, single-center, observational study evaluated 222 male patients who underwent MIE for esophageal cancer between February 2018 and October 2020. Sarcopenia parameters included 5-CST, HGS, and skeletal muscle index. Postoperative pneumonia predictors were determined by using multivariate logistic regression analysis. We assessed the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to analyze the predictive ability of 5-CST and HGS. RESULTS: MIE was performed for squamous cell carcinoma (n = 179), adenocarcinoma (n = 38), and other cancers (n = 5). Forty-nine (22.1%) patients developed postoperative pneumonia. Multivariate logistic regression showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.10; p = 0.027), 5-CST (OR, 1.19; 95% CI 1.00-1.40; p = 0.046), and recurrent laryngeal nerve palsy (RLNP) (OR, 3.37; 95% CI 1.60-7.10; p = 0.001) significantly predicted postoperative pneumonia. Category-free NRI and IDI showed that adding 5-CST in the prediction model with age and RLNP resulted in significantly greater reclassification and discrimination abilities than did HGS. CONCLUSIONS: The 5-CST significantly predicted postoperative pneumonia after MIE. NRI and IDI analyses suggested that 5-CST had significantly better predictive ability for postoperative pneumonia than did HGS.

Handgrip strength predicts early postoperative dysphagia after thoracoscopic-laparoscopic esophagectomy in male patients with esophageal cancer.

BACKGROUND: Dysphagia after esophagectomy, especially in the early postoperative period, remains a severe complication. The association between sarcopenia and dysphagia has received attention in geriatric non-cancer populations. This study aimed to determine the associations between sarcopenia parameters and early postoperative dysphagia after esophagectomy. METHODS: This retrospective observational study included 201 consecutive male patients undergoing thoracoscopic-laparoscopic esophagectomy (TLE) for esophageal cancer between October 2018 and December 2020. We used three sarcopenia parameters: handgrip strength (HGS), skeletal muscle index, and gait speed. Postoperative swallowing function was assessed by videofluoroscopy using the penetration-aspiration scale (PAS; range 1-8). Logistic regression analyses were used to predict factors associated with postoperative aspiration (PAS 6-8). Furthermore, we compared values in patients with symptomatic aspiration (PAS 6-7) and with silent aspiration (PAS 8). RESULTS: Aspiration occurred in 38 of 201 patients (18.9%). On multivariate analysis, significant predictors of aspiration included age [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.05-1.17; p < 0.001], low HGS (OR 3.05; 95% CI 1.06-8.78; p = 0.039), upper third esophageal cancer (OR 2.79; 95% CI 1.03-7.54; p = 0.044) and recurrent laryngeal nerve palsy (OR 2.98; 95% CI 1.26-7.06; p = 0.013). Furthermore, among patients with aspiration (PAS 6-8), low HGS was significantly associated with silent aspiration (OR 6.43; 95% CI 1.06-39.00; p = 0.043). CONCLUSIONS: Low HGS was significantly associated with early postoperative aspiration and impairment of airway protective reflexes after TLE.

Preoperative predictors of extended resection in patients with complicated acute appendicitis undergoing surgery.

Background : Appendectomy can be challenging and occasionally converted to extensive resection for complicated appendicitis. However, optimal treatment strategies can be developed using preoperative risk assessment. Thus, we aimed to investigate the preoperative predictors of extensive resection in complicated appendicitis patients undergoing surgery. Materials and methods : In total, 173 complicated appendicitis patients undergoing surgery between 2014 and 2019 were classified into the appendectomy (n = 153) or extensive resection (n = 20) groups. Clinicopathological factors and surgical outcomes were compared between groups. Results : Extensive resection was performed in 20 of 173 complicated appendicitis patients (11.5%). The rates of having defects in the wall structure at the appendix root on computed tomography images were significantly higher, and the duration from onset to surgery was significantly longer in the extensive resection group. Significant differences were found in operative duration, blood loss and postoperative hospitalization, but none in the incidence of postoperative complications between groups. Multivariate analyses showed that defects in the wall structure at the appendix root and five days or longer from onset were identified as independent predictors of extensive resection. Conclusions : Defects in the wall structure at the appendix root and five days or longer from onset predict extensive resection performance in complicated appendicitis patients. J. Med. Invest. 68 : 334-341, August, 2021.

Serum C-reactive protein level on first postoperative day can predict occurrence of postoperative pancreatic fistula after laparoscopic gastrectomy.

Purpose : Postoperative pancreatic fistula (POPF) is a serious complication after gastrectomy for gastric cancer. The purpose of this study is to identify the risk factor of POPF and evaluate C-reactive protein on postoperative day 1 (POD1) as the predictor for POPF after laparoscopic gastrectomy (LG). Methods : Between May 2013 and September 2016, 226 patients who underwent LG for gastric cancer were investigated. Patients were divided into 2 groups; POPF group (n = 17) and control group (n = 209). Clinicopathological factors were compared between 2 groups. Results : In POPF group, there are more male patients (p = 0.003) compared with control group. Preoperative factors, such as age, BMI, and prevalence of previous operation and comorbidity showed no significant difference between 2 groups. Regarding tumor factors and perioperative data such as blood loss and operative time, there were also no significant difference between 2 groups. POPF group showed longer postoperative hospital stay, and higher serum CRP level on POD1 (p < 0.0001). Multivariate analysis revealed that high CRP level on POD1 ( ≥ 3mg/dl) was independent risk factor of POPF. Conclusions : High serum CRP level on POD1 can predict the occurrence of POPF. J. Med. Invest. 66 : 285-288, August, 2019.