Thoracic Esophageal Cancer Research Articles

Gastro-tracheal fistula following esophageal cancer surgery through the retrosternal route: a case report

BackgroundGastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment.Case presentationA 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital.ConclusionsA gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment.

Perioperative gum-chewing training prevents a decrease in tongue pressure after esophagectomy in thoracic esophageal cancer patients: a nonrandomized trial

Tongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 °C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy.

Robot-assisted minimally invasive esophagectomy for esophageal cancer in the left lateral decubitus position.

The use of robot-assisted minimally invasive esophagectomy (RAMIE) in the prone position for esophageal cancer has been currently increasing worldwide. In future, as surgical-assisted robots become more widespread, it is estimated that only two methods of transthoracic approach will remain: RAMIE and open thoracotomy for thoracic esophageal cancer. RAMIE in the left lateral decubitus position (RAMIE-LLDP) has the same field of view as open thoracotomy, is safe in emergency situations, and provides education on open thoracotomy. Between September 2020 and April 2024, RAMIE-LLDP was performed in 64 consecutive patients with esophageal cancer. RAMIE-LLDP was performed with the operating table rotated and tilted 45° to the ventral side under artificial pneumothorax. The hand-control setting of the surgical-assist robot system was reversed left to right when the Patient Cart was rolled from the same direction as the RAMIE in the prone position. The mean total surgery and console times during the thoracic procedure were 254-min overall and 225min in the last 24 cases and 195-min overall and 178-min in the last 24 cases, respectively. The mean amount of blood loss was 203.4g overall and 28.3g in the last 24 cases. Postoperative recurrent laryngeal nerve palsy with Clavien-Dindo classification (CD) was ≥ 2 in six patients (9.4%). Postoperative pneumonia with CD ≥ 2 was observed in 11 patients (17.2%). Conversion to open thoracotomy was observed in three patients (4.7%). In all three patients, an immediate conversion to thoracotomy without patients' position change was actually possible and no serious complications were noted. No mortality occurred within 30days postoperatively. RAMIE-LLDP which facilitates emergency thoracotomy has perioperative results comparable to those of conventional thoracoscopic esophagectomy and is educational for open surgery. RAMIE-LLDP is the safest and most optimal surgery for esophageal cancer.

Effect of replanning boost radiotherapy plan in locally advanced unresectable middle to lower thoracic esophageal cancer

Thoracic bulky esophageal cancer shrinks during radiotherapy, changing the location and shape of the surrounding heart and lungs. The current study aimed to explore how replanning by volumetric-modulated arc radiotherapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) influences the target coverage and dose to organs at risk in locally advanced unresectable middle to lower thoracic esophageal cancer. We retrospectively collected CT simulation images of initial and boost radiotherapy plans for locally advanced unresectable thoracic esophageal cancer in 17 consecutive patients. First, we created boost plans of 20 Gy using 3DCRT and VMAT on the initially acquired CT images. Second, we replicated the process on CT images acquired after 20–40 Gy of radiotherapy. We then compared non-replanned boost radiotherapy plans with replanned boost plans. Replanned radiotherapy delivered more conformal doses to the target and reduced heart and lung doses. VMAT reduced more irradiated mean doses to the heart than 3DCRT in the case of replanning (1.7 and 1.1 Gy, p < 0.001). Replanning to accommodate tumor shrinkage during radiotherapy effectively lowers the irradiated doses to the heart and lungs in patients with locally advanced unresectable middle to lower thoracic esophageal cancer, especially those treated with VMAT.

Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study

BackgroundCervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose.MethodWe retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50–55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55–63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS).ResultsThe median OS was 33.0 months (95% CI: 29.401–36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05).ConclusionHD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn’t improve survival but enhances ORR.

Inspiratory Muscle Training Before Esophagectomy Increases Diaphragmatic Excursion: A Randomized Controlled Trial.

Inspiratory muscle training (IMT) has preventive effects against postoperative pulmonary complications (PPCs) after upper abdominal surgery. However, its impact on diaphragmatic function has not been evaluated. This study investigated the effect of preoperative IMT on diaphragmatic excursion (DE) and prevention of PPCs for patients with esophageal cancer. This study was an unblinded, parallel, randomized controlled trial. Patients with thoracic or abdominal esophageal cancer scheduled for esophagectomy were randomized into the incentive spirometry (IS) or IMT group. During preoperative neoadjuvant chemotherapy, IS or IMT intervention was performed. The inspiratory resistance of the IMT group was consistently set at 50% maximal inspiratory pressure. The primary outcome was the amount of change in DE evaluated with ultrasonography, and the secondary outcome was the incidence of Clavien-Dindo grade II or higher PPCs. This study recruited 42 patients. Among these patients 21 were randomized into the IS or IMT group, and 2 patients dropped out from the study. Finally, 40 patients were included in this analysis. The DE of the IMT group increased significantly after the intervention. The IMT group had significantly larger DE changes than the IS group. Of the 39 patients analyzed for postoperative outcome, 5 experienced gradeII PPCs. The IMT group had a lower incidence of PPCs than the IS group. Patients with thoracic and abdominal esophageal cancer scheduled for surgery who had preoperative IMT have increased DE, which may have an important role in prevention of PPCs.

Robot-assisted cervical esophagectomy with simultaneous transhiatal abdominal procedure for thoracic esophageal carcinoma

BackgroundMinimally invasive robot-assisted cervical esophagectomy has been sporadically reported as a novel thoracic esophagectomy technique for patients with thoracic esophageal carcinoma. Most reports indicate that the abdominal component of robot-assisted cervical esophagectomy is performed sequentially after the cervical phase. However, if the cervical and abdominal phases are performed simultaneously using a nerve integrity monitoring system with no administration of muscle relaxants, there are two major advantages: a reduced risk of recurrent nerve palsy and a shorter operative time. We herein report our experience performing novel robot-assisted transcervical esophagectomy with a simultaneous transhiatal abdominal approach using a nerve integrity monitoring system.MethodsThirty cases of robot-assisted cervical esophagectomy performed from 2023 to April 2024 were reviewed. The operative and short-term surgical outcomes of this procedure were compared with those of robot-assisted cervical esophagectomy using a sequential abdominal approach, and the feasibility and efficacy of the simultaneous procedure were analyzed.ResultsAll patients successfully underwent robot-assisted cervical esophagectomy with no intraoperative adverse events. There were no differences in the patients’ demographic or operative data between the two groups. There was no difference in the mean operation time for the cervical procedure (p = 0.23). However, there was a significant difference in the total time for the whole procedure (sequential group: 453.8 ± 26.8 min, simultaneous group: 291.2 ± 36.1 min; p < 0.01). There were no differences in postoperative surgical complications between the groups. There was also no difference in the total number of surgically harvested mediastinal lymph nodes (p = 0.33).ConclusionsRobot-assisted transcervical esophagectomy, a new technique for thoracic esophageal cancer, was safe and feasible under intraoperative management using nerve integrity monitoring without muscle relaxants. This procedure facilitates intraoperative monitoring of recurrent laryngeal nerve activity, significantly shortening the total operative time.

256. PROGNOSIS AND RISK FACTORS FOR SUPRACLAVICULAR LYMPH NODE METASTASIS IN PATIENTS WITH MIDDLE AND LOWER THORACIC ESOPHAGEAL CANCER

Abstract Background Whether supraclavicular lymph node metastases (#104 LNM) in patients with thoracic esophageal cancer are classified as distant or regional metastases differs between Western countries and East Asia. Therefore, in Japan, 3FL is a standard procedure, but in Western countries, 3FL may be rarely practiced. We aimed to determine the frequency and prognosis of #104 LNM compared with other regional LN stations and to identify risk factors for #104 LNM in patients with advanced thoracic esophageal cancer to investigate value of treatment of #104 LNM. Methods The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy radically from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography positive LNs. The effectiveness of LN dissection was assessed using an efficacy index (EI) that we calculated by multiplying the rate of metastasis (%) to each LN station by the 5-year overall survival (OS) rate of each patient and then dividing by 100. In order to clarify the indication for 3FL, risk factors for #104 LNM were determined by multivariable logistic regression. Results Among of 567 patients, 66 (11.6%) had #104 LNM. #104 LNM occurred in 31.7%, 10.7%, and 5.6% of patients with upper, middle, and lower thoracic lesions respectively. All patients had squamous cell carcinoma. Neoadjuvant chemotherapy was administered to 71% of patients, and chemo-radiation to 11%. The 5-year OS was 45.8%. The EI for #104 LNs (5.3) was like that for #101 LNs. Risk factors were age &amp;lt;65 years, upper lesion, clinical stage N2–3, and #101/106rec LNM. When assessing only middle and lower lesions, the 5-year OS of patients was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs, with similar risk factors to overall population. Conclusions The EI of patients with #104 LNM was similar to that of patients with other regional LNM such as #101 and #8/9/11 LNs, Therefore, patients with #104LNM were worth treated LN dissection. However, we recommend 3FL exclusively for patients with #104 LNM or those at high risk of metastasis due to the overall metastatic rate not being high.

342. BILATERAL THORACOSCOPIC APPROACH FOR ADVANCED ESOPHAGEAL CANCER COMPLICATED WITH DOUBLE AORTIC ARCH (DAA)

Abstract Background Double aortic arch (DAA) is a relatively rare vascular malformation that causes few problems in adults. However, the presence of DAA makes esophageal cancer surgery difficult, especially during upper mediastinal dissection. Here we report a bilateral thoracoscopic surgical technique in a patient with highly advanced esophageal cancer complicated with DAA. Case 73-year-old male, cT3N4M0 stage III (UICC-TNM 7th) mid-thoracic esophageal cancer with DAA was diagnosed. After two courses of neoadjuvant chemotherapy, surgical treatment was planned. To develop a surgical strategy for esophagectomy for this complex malformation, we created a 3D printer model of the case. The results suggested that a bilateral thoracoscopic approach in the prone position was the ideal approach for upper mediastinal dissection. As expected, it was difficult to dissect the upper mediastinum using only a right-sided approach, especially on the esophagus oral side behind the right aortic arch (RAA), where dissection from the right side was impossible. By adding a left lateral approach, the oral side of the esophagus was pulled in from the left aortic arch (LAA) and was easily dissected. The operation was successful and the postoperative course was uneventful. In this presentation, we will demonstrate the technique of bilateral approach for advanced esophageal cancer complicated with DAA. Discussion The surgical strategy for patients with thoracic esophageal cancer and a coexisting complex vascular anomaly known as a double aortic arch (DAA) is a highlight. Typically, surgical approaches have been limited to either left or right thoracic access. However, through preoperative simulation using 3D printing, a bilateral approach was deemed safe and effective for these cases. The 3D printer models provided invaluable insights into the anatomical relationships of blood vessels, trachea, and heart, allowing for precise planning and execution of the surgery. Challenges such as the proximity of the descending aorta to the trachea and the optimal approach angle were successfully addressed through simulation, enhancing surgical outcomes. Furthermore, the bilateral thoracoscopic approach demonstrated potential benefits in preserving delicate structures like the recurrent laryngeal nerve. This innovative use of 3D printing technology in preoperative planning represents a significant advancement in the field of gastrointestinal surgery, offering improved safety and precision for patients with complex anatomical variations like DAA. Conclusions 3D printer is useful for simulating thoracoscopic esophagectomy with macrovascular malformations. Bilateral approach is appropriate for surgery of esophageal cancer complicated with DAA and a 3D printer is a useful tool for simulating esophageal surgery.

264. SIGNIFICANCE AND USEFULNESS OF PLASMA SUBSTANCE P CONCENTRATION IN PREDICTING HIGH-RISK PATIENTS FOR ASPIRATION AFTER ESOPHAGEAL CANCER SURGERY

Abstract Background The greatest challenge in postoperative complications of esophageal cancer is the prevention of pulmonary complications, especially aspiration pneumonia. Although the introduction of minimally invasive surgery and intervention in breathing and swallowing rehabilitation can improve the motor function of breathing and swallowing, we reported the possibility that a decline in the swallowing reflex may play a significant role in esophageal cancer patients, many of whom are elderly. In fact, about 80% of esophageal cancer patients in Japan are over 60 years old, and 53% of them have asymptomatic cerebral infarction, about half of which are reported to be found near the basal ganglia, which control the swallowing reflex. The swallowing reflex is controlled by the secretion of substance P, synthesized in the cervical sympathetic ganglia, into the pharynx and trachea upon stimulation of dopamine synthesized in the basal ganglia. Methods To test the hypothesis that patients with preoperative subclinical cerebral infarction are more likely to develop aspiration postoperatively due to decreased substance P secretion. To compare the association between the presence or absence of cerebral infarction near the basal ganglia and serum substance P levels and the development of postoperative aspiration or aspiration pneumonia due to videoendoscopy and video fluorography in patients with thoracic esophageal cancer scheduled for video-assisted esophagectomy by preoperative brain MRI imaging and blood sampling. Results We report the results of an interim analysis of 54 cases in which the measurement of substance P was completed. Male: 39 cases, female: 15 cases. Mean age: 69.3 (49-82) years. Tumor location: Ut/Mt/Lt=13/25/14. MRI showed infarction in or near the basal ganglia in only 2 cases. Median preoperative blood substance P concentration: 48.2 pg/ml. Eleven one patients had postoperative aspiration. Preoperative substance P levels ≥48.2 pg/ml were defined as the High group, and those below 48.2 pg/ml were defined as the Low group. Postoperative aspiration was observed in 2/27 (7.4%) patients in the High group, while 9/26 (34.6%) patients in the Low group, which was significantly higher (p=0.015). Conclusion In fact, subclinical cerebral infarction was much less common than reported and was not useful as a predictor of postoperative aspiration. On the other hand, patients with low preoperative blood substance P levels had a very high risk of developing aspiration postoperatively due to impaired swallowing reflexes, suggesting that preoperative blood substance P levels may be useful in assessing postoperative aspiration risk in patients with thoracic esophageal cancer.

251. THE COMPARISON OF UNIPORTAL VERSUS MULTIPORTAL VIDEO-ASSISTED THORACIC SURGERY FOR ESOPHAGEAL CANCER: A PROPENSITY-WEIGHTED ANALYSIS

Abstract Background Uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, however, there are few studies on uniportal VATS for esophagectomy. Methods Data from patients with clinical stage T1–3/N0/M0 thoracic esophageal cancer who underwent surgery between January 2017 and December 2020 were retrospectively collected and retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to assess the outcomes. Results Overall, 55 patients who underwent uniportal, and 212 patients who underwent multiportal, VATS were identified. Surgery-related postoperative complications (Clavien-Dindo grades 1–2) occurred less frequently after uniportal than multiportal VATS in both crude and IPTW models (10.1% versus 28.8%, respectively; P = 0.018). The median postoperative length of stay was 9 (9–10) days in the uniportal VATS and 10 (9–14) days in the multiportal VATS group (P = 0.006 after IPTW). Upon IPTW analysis, in uniportal and multiportal VATS groups, the rates of pneumonia (grades 1-2) were 7.3% and 23.2% (P = 0.037). The visual analog scale (VAS) was administered on postoperative first 7 days and were significantly lower in the uniportal VATS group (P &amp;lt; 0.001). No surgical mortality was observed in the uniportal VATS group, and the survival benefit between the two groups was comparable before (P = 0.320) and after IPTW (P = 0.824). Conclusion Uniportal VATS for esophagectomy resulted in a lower rate of postoperative complications with less postoperative pain, and is practical for treating patients with esophageal cancer.

539. ASSOCIATION BETWEEN WAITING PERIOD FOR RADICAL SURGERY AND POSTOPERATIVE RELAPSE IN CLINICAL STAGE I ESOPHAGEAL CANCER

Abstract Background Esophagectomy with locolegional lymphanedectomy based on potential lymph node metastatic risk is the current standard treatment for clinical Stage I thoracic esophageal cancer. Local excision by endoscopic submucosal dissection (ESD) is the standard treatment for clinical Stage 0, however surgery is considered as an additional treatment for pathological T1b cases due to potential metastatic risk. Cases of additional resection after ESD are those pathologically demonstrated to have a high risk of metastasis based on tumor depth and vascular invasion, etc. Compared to cases of surgery for clinical Stage I, many of these cases have a high risk of metastasis, and therefore a poor prognosis is generally expected. Addionally, the prolonged waiting time between initial diagnosis and radical surgery due to ESD may be a factor in poor prognosis, but there is currently no consensus on the risk. Therefore, we conducted a study to clarify the effect of waiting period before surgery (WP) on the risk of recurrence in clinical Stage I esophageal cancer surgery. Methods We retrospectively evaluated the association between WP and 3-year postoperative recurrence-free survival (3y-RFS) in 65 patients who underwent primary esophagectomy and gastric tube reconstruction for clinical Stage I esophageal cancer and 22 patients who underwent additional resection after ESD at our hospital. Results The WP of 87 patients was 2.12 ± 1.43 months (mean± SD), and 13 patients had postoperative recurrence (3y-RFS 85.1%). A 2-arm comparison of short or long WP with a cutoff value of 2.83 months (mean+0.5 SD) showed no clear association with 3y-RFS (100% vs 81.4%, p=0.071). A strong correlation was shown between WP and ESD (r=0.647, p&amp;lt;0.01). WP was 1.69±1.20 months (mean± SD) in 65 patients who underwent surgery as initial treatment, and 12 patients had postoperative recurrence (3y-RFS 81.5%). A 2-arm comparison of short or long WP with a cutoff value of 2.29 months (mean+0.5 SD) suggested an association with 3y-RFS (85.7% vs 55.6%, p=0.018). Conclusion Although this is a single-center, retrospective study of a small number of cases and only a univariate study due to the small number of events, it suggests that a longer waiting period before surgery may be a risk factor for postoperative recurrence.

785. MANAGEMENT OF ESOPHAGEAL CANCER WITH CONCURRENT CERVICAL NODE METASTASIS: A NATIONWIDE POPULATION-BASED COHORT STUDY

Abstract Background In the Netherlands, the standard treatment of locally advanced, resectable esophageal cancer without metastasis is neoadjuvant chemoradiotherapy followed by esophagectomy. There is a small subset of patients that present with concurrent cervical lymph node metastasis (LNM). Historically this was seen as distant metastasis and surgical intervention has usually not been an option for these patients. The contemporary TNM classification now categorizes these lymph node stations as locoregional disease. Our current study aims to describe current treatment paradigms in the Netherlands for patients presenting with esophageal cancer and concurrent cervical LNM. Methods This population-based cohort study utilized data from the Netherlands Cancer Registry (NCR), encompassing patients with locally advanced thoracic esophageal or gastroesophageal junction cancer and concurrent cervical lymph node metastasis. Treatment modalities were categorized into five options: neoadjuvant therapy followed by surgery (Neo + S), definitive chemoradiotherapy (dCRT), chemotherapy with or without radiotherapy &amp;lt; 30 Gray (CT), radiotherapy (RT), and best supportive care (BSC). Overall survival (OS) was assessed using the Kaplan-Meier method and compared via the log-rank test. Hazard rates were computed using Cox proportional hazards regression, with adjustment for confounding achieved through inverse probability of treatment weighting (IPTW). Results Between 2015 and 2021, a cohort of 412 patients was identified from the NCR database. Median survival durations were observed as follows: 24.2 months for Neo + S, 18.0 months for dCRT, 14.5 months for CT, 7.0 months for RT, and 3.2 months for BSC (Figure). A comparison between the Neo + S group and dCRT demonstrated a significant improvement in survival (p=0.02). Further subdivision of the surgical group into neoadjuvant CRT or chemotherapy did not reveal a significant difference in survival (p=0.6). Utilizing IPTW to adjust for confounding factors, Neo + S maintained its survival advantage. Conclusion The retrospective cohort findings suggest that neoadjuvant therapy followed by surgery may represent the optimal approach for managing esophageal cancer patients with cervical LNMs Yet, it's vital to recognize the influence of confounding by indication, which statistical adjustments may not entirely rectify. Furthermore, immortal time bias notably skews results favorably toward surgery. Nevertheless, the results emphasize the importance of considering surgery as a viable option for these patients. These limitations underscore the critical need for a prospective study, prompting the launch of the NODE-II trial.

205. MINIMALLY INVASIVE IVOR LEWIS ESOPHAGECTOMY WITH TOTAL MEDIASTINAL LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL CANCER: SHORT- AND LONG-TERM OUTCOMES IN 139 PATIENTS

Abstract Background The McKeown approach is a standard surgery for thoracic esophageal cancer in Japan, as lymph node dissection of upper mediastinum and neck is mandatory. The thoracoscopic approach allows access to the lymph node chain along the laryngeal nerves from the chest and led us to introduce minimally invasive Ivor Lewis esophagectomy (MIILE) with radical lymphadenectomy for middle and lower esophageal cancer. Although circular-stapled anastomosis is popular in MIILE, the frequency of anastomotic complications has been reported to be high. We introduced MIILE with linear-stapled anastomosis in 2010. Methods To evaluate the short- and long-term outcomes of MIILE with radial lymphadenectomy and linear stapled anastomosis, we performed a retrospective cohort study of 139 consecutive patients. The endpoints included overall complications, anastomotic leak rate, nutritional status at 12 months after MIILE, and 5-year overall survival, and disease-free survival. Surgical Procedure After laparoscopic gastric tube construction, thoracoscopic or robotic esophagectomy with total mediastinal lymphadenectomy was done in the prone position. ICG angiography was used to assess gastric tube viability and sacrifice the ischemic portion in recent cases. Esophago-gastric anastomosis was performed using a linear stapler. The opening was closed with interrupted sutures and covered with the omentum to secure the anastomosis. Results There was 122 male and 17 female patients with median age of 69 years. Preoperative diagnosis was stage I/II/III/IV in 44/46/37/12 patients. Pathology results were SCC in 108 cases. Tumor location was middle/lower/EGJ in 58/64/17 patients. Preoperative chemotherapy or CRT was administered in 77 patients. Median thoracic surgery time was 297 minutes and blood loss was 53 mL. Median hospital stay was 17 days. The short-term complication rate of grade IIIa or higher was 8.7%. Anastomotic leak occurred in 8 patients (5.8%), three of whom required intervention. No leakage occurred after introduction of intraoperative ICG angiography. 90-day mortality was 0.7%. With a median follow-up of 41 months, 5-year overall survival rate was 68.3% and disease-free survival rates was 56.7%. For the 65 SCC patients with clinical stage II/III disease, 5-year OS rate was 58.7%. During follow-up period, 2 patients (1.4%) required balloon dilatation due to anastomotic stenosis. At 12 months after MIILE, the mean weight loss was 11.6% and the mean albumin level was 3.9. Discussion Compared to benchmark complication rates reported by the international Esophagectomy Complication Consensus Group (ECCG), the overall complication rate (47% vs. 59%) was not significantly lower, but the anastomotic leak rate was significantly lower (5.8 vs. 11.4%). Overall survival, disease-free survival, and nutritional outcomes were similar to those reported in Japanese clinical trials. Conclusions MIILE with linear-stapled anastomosis is a safe procedure with a low rate of serious complications. Survival and nutritional outcomes were excellent. It may be recommended as a standard procedure for lower and middle esophageal cancer. https://www.dropbox.com/scl/fi/z6zyllnmie9qh3zhz2wd5/Okabe_ISDE.wmv?rlkey=4mig28fv5z2vhaui31tbk0mr9&amp;dl=0

575. PATHOLOGIC RESPONSE AND RESIDUAL LYMPH NODE PATTERNS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS UNDERGOING NEOADJUVANT IMMUNOCHEMOTHERAPY COMPARED TO NEOADJUVANT CHEMORADIOTHERAPY

Abstract Background Concurrent chemoradiotherapy is the cornerstone treatment for locally advanced esophageal cancer. Immunochemotherapy, established as the standard treatment for advanced esophageal cancer, concurrently exhibits excellent short-term efficacy in the neoadjuvant stage. Combining concurrent chemoradiotherapy with immunochemotherapy may enhance control over primary tumor and metastatic lymph nodes, potentially improving patients’ outcomes and survival. Therefore, comparing the pros and cons of these two treatment modalities in controlling primary lesions and lymph node metastasis is crucial for guiding clinical treatment. Methods Our study enrolled a total of 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant immunochemotherapy (NICT) and 151 ESCC patients who underwent neoadjuvant chemoradiotherapy (NCRT) between January 2019 and March 2022. We documented baseline patient characteristics, including clinical TNM stage, tumor location, and clinical metastatic lymph nodes, as well as pathologic outcomes such as pathological stage, pathologic complete response (pCR), tumor regression grade (TRG), and pathological metastatic lymph nodes. To balance baseline patient characteristics, we employed inverse probability of treatment weighting (IPTW) to adjust for confounding in different neoadjuvant treatment groups. Results After balancing baseline characteristics, there was no statistically significant difference in pathologic outcomes, including pCR rate, major pathologic response rate, TRG, yp-TNM stage, and R0 resection rate between NCRT and NICT. However, patients with clinical N2-3 stage (OR 2.66; 95% CI 1.05 to 6.79) or lower thoracic esophageal tumors (OR 2.31; 95% CI 1.05 to 5.04) had a higher chance of achieving pCR after NICT compared to NCRT. For patients undergoing NICT, the ypN0 rates for clinically N0 patients were 100.0% (5/5), while only 65.0% (13/20) of clinical N0 patients achieved ypN0 in the NCRT group. Even after adjusting for differences in clinical stage, tumor location, and baseline lymph node metastasis rates in various locations, the NICT group still demonstrated a lower rate of abdominal lymph node metastasis during surgery (p=0.030). Conclusion In comparison to concurrent chemoradiotherapy, immunochemotherapy exhibits comparable overall disease control for primary lesions and lymph node metastasis. Notably, patients with clinical N2-3 and lower thoracic esophageal cancer may derive greater benefits from NICT. The potential of immunochemotherapy in enhancing the effectiveness of chemoradiotherapy is evident in its ability to improve the control of occult metastatic lymph nodes and reduce abdominal lymph node metastasis.

538. COMPARISON OF EARLY POSTOPERATIVE OUTCOMES OF CERVICAL ANASTOMOSIS TO HIGH INTRATHORACIC ANASTOMOSIS AMONG PATIENTS WITH UPPER THORACIC ESOPHAGEAL CANCER

Abstract Background For upper thoracic esophageal cancer, esophagectomy combined with cervical esophagogastrostomy (cervical anastomosis, CA) and three-field lymph node dissection (3FLND) has been proposed as the standard surgical approach. However, while CA provides sufficient length of proximal resection margins, it is associated with a higher incidence of postoperative complications such as anastomotic leaks, recurrent laryngeal nerve (RLN) injury, and increased mortality. As an alternative, high-intrathoracic esophagogastric anastomosis (high-ITA) with 3FLND has been performed. We aimed to evaluate the benefits and limitations of high-ITA compared to conventional CA in terms of early postoperative outcomes. Methods A total of 232 patients, who underwent curative esophagogastrostomy with 3FLND and either of high-intrathoracic anastomosis (high-ITA) or cervical anastomosis (CA) for upper thoracic esophageal cancer a tertiary hospital from January 2010 to December 2021. Collected data from medical records were analyzed retrospectively regarding morbidity and mortality rates. The primary end point was recurrence. Anastomotic leak, RLN palsy, hospital stay, and 90-day mortality and in-hospital mortality were evaluated using Chi-squared test, Fisher’s exact test, and T-test. The risk of mortality and recurrence were analyzed using Cox-proportional hazard regression with a median follow-up of 39.1(IQR 17.8, 80.2) months. Results Among the fifty patients with high-ITA and 182 patients with CA, the high-ITA group reported fewer anastomotic leaks (6.0% vs. 19.8%, p=0.02) and a shorter hospital stay (median 12days vs. 15 days, p&amp;lt;0.001). No significant difference was observed in RLN palsy (6.0% vs. 13.7%, p=0.22) and the 90-day or in-hospital mortality rate (2.0% vs. 2.2%, p=1.0). The number of lymph nodes dissected (LND) was similar between the groups (47.4(±15.4) vs. 52.7(±18.3), p=0.06), and there was no difference in the risk of mortality and recurrence according to the high-ITA method (HR 0.9, 95% CI 0.6-1.6; HR 1.0, 95% CI 0.6-1.7) after adjustment for age, sex, and stage. Conclusion In the esophagogastrostomy with three-field lymph node dissection, performing high-intrathoracic anastomosis may reduce the incidence of anastomotic leaks and shorten the hospital stay without adversely affecting overall survival.

289. OUTCOME OF CONVERSION SURGERY FOR ESOPHAGEAL CANCER WITH SYNCHRONOUS ABDOMINAL PARAAORTIC LYMPH NODE METASTASIS

Abstract Background and Purpose Stage IVb esophageal cancer with distant metastasis has a poor prognosis with a 5-year survival rate of approximately 10%. Among distant metastases, the treatment strategy for esophageal cancer with metastasis to the #16 para-aortic lymph node has not been defined, and the significance of surgical resection is not clear. Methods Using the database of Osaka University and related institutions, we selected 41 cases of thoracic esophageal cancer with simultaneous #16 metastasis that underwent surgical resection between 2005 and 2021, and examined treatment outcomes. Results Patient background was median age 64 (43-76) years, gender M/F = 32/9, and primary site of occupancy Ut/Mt/Lt = 1/17/23. Tumor progression was cT factor T1/T2/T3/T4 =0/6/25/10, cN factor N0/N1/N2/N3 =0/13/19/9. Chemotherapy was administered as initial therapy in 38 patients, and CRT was administered in 3. Primary esophageal resection was performed in all 41 patients, and metastases were resected in 36 patients (88%). 38 patients (93%) were eligible for R0 resection. Pathologically, pT0-2/T3-4=22(54%)/19(46%), pN0/1/2-3 8(20%)/6(15%)/27(66%), and pN2 or higher were common. The 3-/5-year survival rate for all patients was 22.8%/19.0%. In all cases, pN0-1 had significantly better survival than pN2-3 (p=0.0252). Conclusion Conversion surgery for esophageal cancer with simultaneous #16 metastasis had a relatively good outcome, suggesting that the pN factor may be a prognostic factor.

416. SUCCESSFUL TREATMENT OF ESOPHAGO-MEDIASTINAL FISTULA DUE TO ESOPHAGEAL CANCER WITH IMMUNE CHEMOPOINT INHIBITOR FOLLOWED BY ROBOTIC RADICAL ESOPHAGECTOMY

Abstract Background Esophagomediastinal fistula caused by intrathoracic esophageal cancer perforation poses significant challenges in treatment. We present a case of such a patient successfully treated by achieving complete resolution through surgical resection following chemotherapy with 5-FU, cisplatin, and pembrolizumab. Methods Clinical and surgical findings of the patient were reviewed through chart analysis. A 46-year-old male presented to the emergency room with fever and cough. Computed tomography (CT) indicated esophageal-mediastinal fistula due to mid-thoracic esophageal cancer and perforation. Endoscopic examination revealed a 5cm circumferential mass 20cm from the upper incisors, along with perforation. Biopsy confirmed poorly differentiated squamous cell carcinoma, with a PD-L1 CPS score of 80. The patient received multidisciplinary treatment involving chemotherapy followed by planned surgical intervention. Results First of all, the patient underwent peroral endoscopic gastrostomy for dietary intake. After 3-weeks interval three cycles of 5-FU (800mg/BSA, Day1-5), cisplatin (80mg/BSA, Day1), and pembrolizumab (200mg, Day1), complete resolution of the abscess cavity and significant reduction in esophageal cancer lesions were observed. Robotic transthoracic esophagectomy and Mckeown operation were performed, achieving complete resection of the esophagus including the primary lesion. Pathological examination revealed complete remission of the primary lesion and absence of metastatic nodes among the 51 dissected lymph nodes. After subsequent additional three cycles of anticancer-immunotherapy combined therapy were done, no signs of recurrence were found on CT scan performed 3 months post-surgery. Conclusion We report a case of successful treatment of a patient with thoracic esophageal cancer complicated by difficult-to-treat esophago-mediastinal fistula, managed effectively with concurrent chemotherapy and surgical intervention.

746. ESOPHAGECTOMY, WITH CHOLECYSTECTOMY HAS A HIGH INCIDENCE OF REFLUX ESOPHAGITIS AND GASTRIC TUBE ULCER

Abstract The surgical methods for thoracic esophageal cancer was subtotal esophagectomy, with gastric pull up via retrosternal route, and cervical anastomosis. However, some cases were complicated by acute cholecystitis in the early postoperative period, and cholecystectomy was performed intraoperatively to prevent postoperative cholecystitis in some cases. The disruption of normal anti-reflux mechanisms including the lower esophageal sphincter, angle of His, and diaphragmatic muscle and the denervation of the vagus nerve are generally thought to be the main factors that interfere with gastric motor function. Furthermore, the pressure difference between thoracic (negative) and abdominal cavity (positive) is another factor that promotes reflux across the anastomosis. Due to these factors, postoperative reflux esophagitis is frequently experienced. Furthermore, after cholecystectomy, due to loss of gallbladder reservoir function after cholecystectomy and decrease in antroduodenal motility, bile is not excreted by food intermittently but continuously, resulting in duodenogastric reflux. We investigated postoperative reflux esophagitis and gastric tube ulcers in cases with and without intraoperative cholecystectomy for the past three years. We investigated cholecystectomy with esophagectomy (n=65) and non-cholecystectomy with esophagectomy (n=101) in 166 cases of radical surgery for esophageal cancer in which 2-3 regions had been dissected in the past 3 years. As shown in Fig. 1, there are no differences in location, TNM, gender, and PPI administration .reflux esophagitis of the cervical esophagus is A:0 B:2 (3%), C:5 (8%), D:3 (5%) for chole(+), A:2 (2%), B:2 (2%), C:2 (2%), and D:2 (2%) for chole(-). Gastritis was Chole(+) superficial gastritis 14 (21%), metaplasia 4 (6%), chole(-) superficial gastritis 25 (25%), metaplasia 3 (2%). However, gastric tube ulcers occurred in 5 cases (7%) of Chole(+) and 1 case of perforation, while only 1 case (1%) of gastric tube ulcers occurred in Chole(-).. (Conclusion) Esophagectomy, gastric pull up with cholecystectomy has a high incidence of reflux esophagitis in the neck and can also cause ulcers in the gastric tube. Therefore, care should be taken in postoperative follow-up.

Prognostic impact of shift to low visceral fat mass after neoadjuvant chemotherapy in patients with esophageal cancer.

Based on the JCOG1109 trial, it is suggested that the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) could potentially become a standard neoadjuvant chemotherapy regimen, alongside the conventional 5-fluorouracil and cisplatin (CF) therapy, for esophageal cancer. However, there are few reports on the impact of body composition changes associated with neoadjuvant chemotherapy on prognosis. Our study aimed to explore the effect of different neoadjuvant chemotherapy regimens on body composition during treatment and the impacts of body composition changes on their prognosis. This is a retrospective study of 215 patients with advanced thoracic esophageal cancer who had surgery after neoadjuvant chemotherapy from 2013 to 2019. Computed tomography scans were performed before and after neoadjuvant chemotherapy to assess body composition. Skeletal muscle mass index (SMI) was calculated by dividing total skeletal muscle mass at the 3rd lumbar level by the square of height, while visceral and subcutaneous fat masses were measured at the level of umbilicus. Patients in the lowest 25% of both sexes were classified into the low visceral fat and low subcutaneous fat groups, respectively. Of the patients enrolled, 178 were male and 37 were female. Among them, 91 had clinical Stage II disease, and 124 had clinical Stage III disease. Additionally, 146 patients received neoadjuvant chemotherapy CF, and 69 received neoadjuvant chemotherapy DCF. Comparing the DCF and CF groups, the DCF group consisted of significantly younger patients (p < .01), a higher proportion of males (p = .03), and a greater number of clinical Stage III cases (p < .01). However, although percent change in SMI and visceral fat mass was not significantly different between two regimens, percent change in subcutaneous fat mass was significant in the DCF group. The major prognostic factors for patients undergoing surgery after neoadjuvant chemotherapy for thoracic esophageal cancer were clinical Stage III, transition to low visceral fat, and response rating (SD/PD), while the specific neoadjuvant chemotherapy regimen did not significantly influence the outcomes. This study suggests that prevention of the shift to low visceral fat throughout the neoadjuvant chemotherapy process should improve patient outcomes.