bluuebunny/crossref_metadata_2025 huggingface dataset:
632 SUTURED VERSUS MESH-AUGMENTED HIATUS HERNIA REPAIR: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Petric Josipa , Bright Tim , Liu David , Wee Melissa , Watson David
Published: September 2021

Repair of large hiatus hernias is increasingly being performed. However, there is no consensus for the optimal technique for hiatal closure between sutured versus mesh-augmented (absorbable or non-absorbable) repair. This meta-analysis systematically reviewed published randomized control trials (RCTs) comparing sutured versus mesh-augmented hiatus hernia (HH) repair. Our primary endpoint was HH recurrence at short- and long-term follow-up. Secondary endpoints were: surgical complications, operative times, dysphagia and quality of life.

Methods

A systematic review of Medline, Scopus (which encompassed Embase), Cochrane Central Register of Controlled Trials, Web of Science and PubMed was performed to identify relevant studies comparing mesh-augmented versus sutured HH repair. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals.

Results

Seven RCTs were found which compared mesh-augmented (non-absorbable mesh: n = 296; absorbable mesh: n = 92) with sutured repair (n = 347). There were no significant differences for short-term hernia recurrence (defined as 6–12 months, 10.1% mesh versus 15.5% sutured, P = 0.22), long-term hernia recurrence (defined as 3–5 years, 30.7% mesh vs 31.3% sutured, P = 0.69), functional outcomes and patient satisfaction. The only statistically significant difference was that the mesh repair required a longer operation time (P = 0.05, OR 2.33, 95% CI 0.03–24.69).

Conclusion

Mesh repair for hiatus hernia does not offer any advantage over sutured hiatal closure. As both techniques deliver good and comparable clinical outcomes, a suture only technique is still an appropriate approach.
651 A META-ANALYSIS OF SURVIVAL AFTER NEOADJUVANT CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY IN RESECTABLE LOCALLY ADVANCED ESOPHAGEAL CANCERS BASED ON HISTOLOGIC SUBTYPES
Authors: Waratchanont Rawat , Leelapatanadit Jirat , Asanprakit Wichitra , Kaewkangsadan Viriya , Sattaporn Sukchai
Published: September 2021

Neoadjuvant treatments provided survival benefits over surgery alone in resectable locally advanced esophageal and esophagogastric junction (EGJ) cancer patients. Both neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) are shown to be effective treatments. However, the direct comparison between two methods based on histologic subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC) is still limited. This study examined the hypothesis that nCRT could provide the better overall survival (OS) than nCT.

Methods

A comprehensive search of studies comparing nCRT and nCT in patients with esophageal and EGJ cancer based on histologic subtypes was conducted. A meta-analysis of randomized (8 articles) and non-randomized (15 articles) studies was performed using odds ratio (OR) and 95% confidence intervals (CI95%). The OS was the main objective, whereas the secondary objective were complete pathological response (pCR) rate, curative resection (R0) rate, locoregional progression free-survival (L-PFS) rate, postoperative complications and mortality.

Results

Twenty three articles included 1,671 SCC and 9,285 AC patients. Neither 3- nor 5-year OS was found to be different. However, SCC patients receiving nCRT showed the better 3-year OS (OR 1.67, CI95% 1.17–2.40, p = 0.005). Both pCR and R0 rates were superior in nCRT group (OR 3.30, CI95% 2.46–4.44 and 2.46, CI95% 1.66–3.65, p < 0.00001, respectively). The better 3-year L-PFS was observed in nCRT group (OR 1.47, CI95% 1.17–1.85, p = 0.008), but 5-year L-PFS was comparable. The 30-day mortality was comparable, while 90-day mortality was higher in nCRT group (OR 1.32, CI95% 1.01–1.72, p = 0.04).

Conclusion

The nCRT provided the better overall survival especially in SCC patients and also increased locoregional control. Meanwhile, postoperative complications and mortality were higher after nCRT. Due to clinical heterogeneity, the multidisciplinary team management for each patient is required before treatment.
667 PEGYLATED RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING FACTOR IN DEFINITIVE CHEMORADIOTHERAPY OF ESOPHAGEAL CANCER: PRELIMINARY RESULTS
Authors: Zhu Hongcheng , Zhu Huijun , Ai Dashan , Chen Yun , Liu Qi , Zhao Kuaile
Published: September 2021

To compare the efficiency and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), on the risk of neutropenia in patients with esophageal squamous cell carcinoma (ESCC) of definitive chemoradiotherapy (dCRT).

Methods

ESCC patients receiving dCRT in our hospital were adopted in this study. Patients in the PEG-rhG-CSF group were treated with preventive PEG-rhG-CSF 6 mg subcutaneously at 24–48 h after completion of chemotherapy of each cycle, while the control group was not. The usage of rhG-CSF was permitted when the absolute neutrophil count (ANC) ≤2 × 109/L, or white blood cell count (WBC) ≤3 × 109/L.

Results

A total of 34 ESCC patients were in the PEG-rhG-CSF group and 41 were in the control group. Improved chemotherapy cycle completion and radiation dose completion were identified in the PEG-rhG-CSF group (P < 0.001). Leukocyte recovery and neutrophil recovery, (P < 0.001). PEG-rhG-CSF reduced incidence of neutropenia, and time to ANC recovery in different chemotherapy cycles, with (Cycle 1–2, P < 0.001 ~ P = 0.02) or without RT (Cycle 3–4, P = 0.04 ~ P = 0.8799). Antibiotics utilization rates were significantly higher in the PEG-rhG-CSF group during concurrent chemotherapy with RT, but not during consolidative CRT (Cycle 3 and Cycle 4: P > 0.05).

Conclusion

PEG-rhG-CSF prescribed as prophylaxis reduces acute toxicities by concurrent CRT and contributes to completion of dCRT regime in locally advanced ESCC therapeutics. The significance was not observed in chemotherapy alone without RT in the current findings.
668 USEFULNESS OF PRONE-POSITION COMPUTED TOMOGRAPHY AS PREOPERATIVE SIMULATION OF THORACOSCOPIC ESOPHAGECTOMY FOR THORACIC ESOPHAGEAL CANCER
Authors: Higuchi Tadashi , Koyanagi Kazuo , Ninomiya Yamato , Yatabe Kentaro , Yamamoto Miho , Tajima Kohei , Ozawa Soji
Published: September 2021

The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer.

Methods

A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed.

Results

A significant correlation of the magnitude of change in VE (distance between ventral aspect of vertebral body and the midpoint of esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, VE showed a negative correlation with the thoracic operation time (p = 0.01) and blood loss during the thoracic procedure (p = 0.01). Multivariate analysis identified a magnitude of change in VE □9 mm as an independent risk factor for postoperative pneumonia.

Conclusion

This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE.
675 FUNDOPLICATION VERSUS ORAL PROTON PUMP INHIBITORS FOR GASTROESOPHAGEAL REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS
Authors: Tristão Luca Schiliró , Tustumi Francisco , Tavares Guilherme , Datrino Letícia Nogueira , Serafim Maria Carolina Andrade , Orlandini Marina Feliciano , Santos Clara Lucato , Bernardo Wanderley Marques
Published: September 2021

Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few is reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies.

Methods

This systematic review was guided by PRISMA statement. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. The inclusion criteria were (I) patients with GERD; (II) Randomized clinical trials, comparing oral intake PPI with FPT; (III) relevant outcomes for this review. The exclusion criteria were (I) reviews, case reports, editorials and letters (II) transoral or endoscopic FPT (III) studies with no full text. No restrictions were set for language or period. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool.

Results

Ten RCT were included. Meta-analysis showed that heartburn (RD = −0.19; 95% CI = −0.29, −0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). There was no significant difference between groups in the percentage of time with pH less than 4 in 24 hours, sustained remission and Gastrointestinal Symptom Rating Scale. Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching.

Conclusion

FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT, such as those with severe erosive esophagitis, severe respiratory symptoms, low adherence to continuous drug treatment and patients with non-acid reflux, to ensure better results.
684 MODERATELY DIFFERENTIATED ESOPHAGEAL SQUAMOUS CELL CARCINOMA HAS A POOR PROGNOSIS AFTER NEOADJUVANT CHEMORADIOTHERAPY
Authors: Leng Xue-feng , Mao Tianqin , Yan Jiaxin , Leng Xuefeng , Han Yongtao
Published: September 2021

Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT.

Methods

All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status.

Results

Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P < 0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall’s tau-b = 0.857, P < 0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P < 0.05).

Conclusion

Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.
70 IMPACT OF LYMPH NODE YIELD ON SURVIVAL IN PATIENTS UNDERGOING NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY SURGERY FOR LOCALLY ADVANCED ESOPHAGEAL CANCER
Authors: Guo Xufeng
Published: September 2021

A survival benefit of neoadjuvant chemoradiotherapy (nCRT) added to surgery has been demonstrated and therefore is regarded as standard of care for patients with locally advanced esophageal cancer in many countries. It remains unclear whether it is necessary to perform extended lymphadenectomy for patients with esophageal squamous cell carcinoma (ESCC) after nCRT. This study aimed to evaluate the impact of lymph node yield (LNY) on survival in ESCC patients undergoing nCRT plus esophagectomy.

Methods

Patients receiving R0 resection for locally advanced ESCC were included from the prospective randomized NEOCRTEC5010 trial [surgery (S) alone vs nCRT plus S]. With Cox proportional hazard regression models, the association between survival and LNY as a categorical variable (<20 vs ≥20 nodes) was analyzed in the nCRT group as well as the pCR subgroup.

Results

Compared with the S group, the nCRT group achieved a better 5-year OS (65.9% vs 55.8%; P = 0.010). Less LNY [20 (IQR 15–27) vs 26 (IQR 19–35); P < 0.001] and positive nodes [0 (IQR 0–1) vs 1 (IQR 0–2.5); P < 0.001] were harvested in nCRT group compared to S group. The number of LNY was significantly associated with OS [HR, 0.363; 95% CI, 0.208–0.635; P < 0.001] and DFS (HR, 0.423; 95% CI, 0.249–0.719; P = 0.001) for patients in nCRT group. Furthermore, an increased LNY was not associated with worse postoperative complications.

Conclusion

The benefit of a higher lymph node yield on overall and disease-free survival is identified for the patients with ESCC who received nCRT followed by esophagectomy. Therefore, an extended lymphadenectomy should be the standard of care after nCRT.
703 SARCOPENIA OBESITY AND MYOSTEATOSIS ARE RISK FACTORS FOR COMPLICATIONS FOLLOWING RESECTION OF OESOPHAGOGASTRIC CANCERS
Authors: Siddaiah-subramanya Manjunath , Kamarajah Sivesh , Halle-Smith Jame , Ghoneim Abdulrahman , Sinha Yashashwi
Published: September 2021

Oesophagogastric cancer resection carries a morbidity, as high as 60%. Better patient selection, not only with regards to clinical stage but also with fitness reduces morbidity and improves outcome. Assessment of sarcopenia (SMI) and incremental shuttle walk test (ISWT) are two such tools to evaluate patients’ fitness. We investigate the influence of these two tools in predicting post-operative outcomes following Oesophagogastric resection.

Methods

All patients who underwent Oesophagogastric cancer resection between 2017–2019 and consented to participate in ISWT were included and outcomes evaluated retrospectively. Patient demographics, comorbidity profile and distance walked in ISWT were collected from the hospital cancer database. SMI was calculated on the pre-operative staging CT at the level of L3. Outcomes assessed included overall complications, major complications (Clavien-Dindo III-V) and 30-day mortality.

Results

Sixty-seven patients (median age = 67) met the inclusion criteria with majority receiving neoadjuvant chemotherapy (79%). Overall complication rate was 69% including 34% major complications. There was no difference in overall and major complication between patients with ISWT distance of >350 and < 350 m. Sarcopenia was diagnosed in 58% of the patients. Adjusted analyses showed female patients (OR: 9.31, CI95%: 1.49–94.15, p = 0.030), myosteatosis (OR: 7.52, CI95%: 1.64–48.62, p = 0.017), and sarcopenic obesity (OR: 6.16, CI95%: 3.28–36.59, p = 0.021) to be independent predictors of overall complications. Correlation plot shows no interaction between SMI and ISWT scores. Conclusion: The study shows that ISWT does not predict post-operative mortality and morbidity following Oesophagogastric cancer resection. Sarcopenia is associated with higher overall complication rates. SMI and ISWT score do not correlate in predicting post-operative outcomes. We recommend that assessment of sarcopenia to be used routinely as a pre-operative assessment tool for prediction of outcomes in patients undergoing Oesophagogastric cancer resection.
711 POST-REFLUX SWALLOW-INDUCED PERISTALTIC WAVE IS IMPAIRED IN LARYNGOPHARYNGEAL AND GASTRO-OESOPHAGEAL REFLUX DISEASE
Authors: Park Jin-soo , Van der Wall Hans , Falk Gregory
Published: September 2021

Laryngopharyngeal reflux (LPR) and gastro-oesophageal reflux disease (GORD) result from the reflux of gastric contents. The post-reflux swallow-induced peristaltic wave (PSPW) induces chemical clearance following reflux events. PSPW index is a novel parameter that has been validated in GORD, but not in LPR. This study aimed to assess the efficacy of chemical clearance by assessing PSPW indices in patients with LPR and GORD.

Methods

Reviewers blindly analysed off-therapy impedance-pH tracings from 187 patients divided into LPR (n = 105) or GORD (n = 82) by predominant symptom profile. Conventional impedance-pH measures and PSPW indices were analysed for the two groups.

Results

Mean PSPW index in the LPR group was higher than in the GORD group (39.7% (±17.7%) vs. 20.6% (±13.4%); p < 0.001). Abnormally low PSPW index (<61%) was seen in 85 (81%) of the LPR group, and 80 (97.6%) of the GORD group (p < 0.001). Area under the ROC curve for PSPW index to diagnose LPR was 0.828 (95% CI: 0.767–0.889; p < 0.001). The LPR group had a lower AET (1.5% vs. 8.1%; p < 0.001) and fewer distal reflux episodes (46.5 (±24.5) vs. 64.4 (±39); p < 0.001).

Conclusion

PSPW was impaired in patients with LPR as well as oesophageal GORD, indicating an abnormality of chemical clearance following a reflux episode in both groups. PSPW index was more severely impaired in gastro-oesophageal reflux disease (GORD). The present study shows PSPW index is useful in aiding in the diagnosis of both LPR and GORD.
72 PHASE II ADJUVANT CANCER-SPECIFIC VACCINE THERAPY FOR ESOPHAGEAL CANCER PATIENTS CURATIVELY RESECTED AFTER PREOPERATIVE THERAPY WITH PATHOLOGICALLY POSITIVE NODES
Authors: Yasuda Takushi , Nishiki Kohei , Hiraki Yoko , Kato Hiroaki , Iwama Mitsuru , Shiraishi Osamu , Yasuda Atsushi , Shinkai Masayuki , Kimura Yutaka , Sukegawa Yasushi , Chiba Yasutaka , Imano Motohiro , Takeda Kazuyoshi , Satou Takao , Shiozaki Hitoshi , Nakamura Yusuke
Published: September 2021

Esophageal squamous cell carcinoma (ESCC) patients with pathologically positive nodes have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. To elucidate the efficacy of adjuvant vaccine monotherapy using three HLA-A*24-restricted tumor-specific peptide antigens for ESCC, up-regulated lung cancer 10, cell division cycle associated 1 and KH domain-containing protein overexpressed in cancer 1, we conducted an exploratory prospective phase II clinical trial (UMIN000003557).

Methods

Patients with ESCC who underwent curative resection after preoperative therapy and were found pathologically positive lymph node metastasis were enrolled from December 2009 to September 2014 and allocated into the control and vaccine groups (CG and VG) based on the HLA-A*2402 positive or negative. One mg each of three epitope peptides mixed with 1 mL of Montanide ISA 51 VG was administered the first 10weekly injections followed by 10 additional biweekly injections to VG. No other adjuvant therapy was given until recurrence occurred. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was esophageal cancer-specific survival (ECSS).

Results

Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs. 45.3%, p = 0.205 (one-sided)), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs. 32.4%, p = 0.045 (one-sided)) probably due to the better clinical responses in patients of the VG to the post-recurrence therapy and this difference was more prominent in patients with CD8+ and programmed death-ligand 1 double negative tumor (68.0% vs. 17.7%, p = 0.010 (two-sided)).

Conclusion

Our results suggested that the cancer peptide vaccine suppressed the postoperative recurrence, enhanced the post-recurrence therapy and improved the survival of ESCC patients, particularly in the cases without CD8 infiltration and PD-L1 expression. A phase III randomized controlled study has been conducted in response to these results, and the results are waiting to be published.
734 PL11.06 PROGNOSTIC FACTORS FOR MORTALITY IN PATIENTS WITH ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY FOR CANCER (TENTACLE—ESOPHAGUS STUDY)
Authors: Ubels Sander , Verstegen Moniek , Bouwense Stefan , Hannink Gerjon , Klarenbeek Bastiaan , Siersema Peter , Workum Frans , Rosman Camiel ,   on behalf of the TENTACLE - Esophagus Collaborative group
Published: September 2021

Anastomotic leakage (AL) is a common and potentially life-threatening complication after esophagectomy. In patients with AL it is largely unknown which patient parameters and leakage characteristics are associated with leak severity and mortality. We aimed to identify prognostic factors for mortality in patients with anastomotic leakage after esophagectomy.

Methods

The TENTACLE—Esophagus study is an international retrospective cohort study, in which 1451 patients with AL after esophagectomy between 2011 and 2019 were included in 71 centers from 20 countries. Potential prognostic factors were selected from literature and a hypothetical association with mortality. Confounders of (individual) prognostic factors were identified using a directed acyclic graph approach to minimize bias. Primary outcome was 90-day mortality. Logistic regression analysis was performed to estimate crude and adjusted odds ratios (AOR) and 95% confidence intervals (95%CI). The study protocol is accessible at www.tentaclestudy.com.

Results

Overall 90-day mortality rate was 11.6%. Leakage characteristics with the largest prognostic effect on mortality were gastric conduit ischemia/necrosis (AOR 2.23, 95%CI 1.43-3.49), defect circumference ≥ 25% (AOR 2.10, 95%CI 1.32-3.36) and intrathoracic fluid collections (drained AOR 1.98, 95%CI 1.05-3.75; undrained AOR 2.43, 95%CI 1.57-3.75). Patient parameters with the largest prognostic effect were ASA-score ≥ 3 (AOR 4.18, 95%CI 1.67-10.51), ECOG-score ≥ 2 (AOR 2.83, 95%CI 1.56-5.14) and respiratory failure (AOR 3.89, 95%CI 2.67-5.66), hemodynamic failure (AOR 3.09, 95%CI 1.96-4.88) or renal failure (AOR 4.08, 95%CI 2.20-7.59) at time of AL diagnosis.

Conclusion

Defect circumference, intrathoracic fluid collections, gastric conduit condition and several patient parameters were identified as prognostic factors for mortality in patients with AL. Adjusting for these prognostic factors may reduce confounding bias in future studies assessing efficacy of AL treatments. The identified prognostic factors contribute to the understanding of the severity of anastomotic leakage after esophagectomy and may be used to recognize the severity of an anastomotic leak in individual patients.
756 LONG-TERM OUTCOME AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ENTIRE CIRCUMFERENTIAL CT1AN0M0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Inaba Atsushi , Kadota Tomohiro , Nishihara Keiichiro , Sato Daiki , Nakajo Keiichiro , Yukami Hiroki , Mishima Saori , Sawada Kentaro , Kotani Daisuke , Fujiwara Hisashi , Nakamura Masaki , Hojo Hidehiro , Yoda Yusuke , Kojima Takashi , Fujita Takeo , Yano Tomonori
Published: September 2021

Endoscopic submucosal dissection (ESD) is the standard treatment for cT1a esophageal squamous cell carcinoma (ESCC), however its indication for the entire circumferential lesions is still controversial because of the risk of severe stricture after ESD. Therefore, several treatment options are performed based on physicians’ choice, however, each clinical course is unclear. This study aimed to clarify the long-term outcome after ESD for patients with entire circumferential cT1aN0M0 ESCC, comparing with esophagectomy or chemoradiotherapy.

Methods

Patients with entire circumferential cT1aN0M0 SESCC treated with ESD, chemoradiotherapy, or esophagectomy as the initial treatment between January 2010 and December 2016 in our institution were included. Patients who had a history of any malignancy at cStage II-IV within 5 years were excluded. The 5-year overall survival (OS), 5-year disease-free survival (DFS), stricture rate, refractory stricture rate (defined as requiring >6 dilations), curative resection (defined as pT1a without lymphovascular invasion and negative for vertical margin in the pathological evaluation) rate of ESD, and complete response rate of chemoradiotherapy were evaluated for each treatment.

Results

Of the 48 eligible patients, 25/13/10 patients were performed ESD/chemoradiotherapy/esophagectomy as an initial treatment. Curative resections rate of ESD was 72%, and additional esophagectomy and chemoradiotherapy were performed in three and one patients with non-curative resection. Complete response rate of chemoradiotherapy was 100%, however, 4 patients had recurrence thereafter. No recurrences occurred after esophagectomy in all patients treated with esophagectomy. During median follow-up of 83 months, stricture and refractory stricture rate was 80/44% after ESD, 0/0% after chemoradiotherapy, and 20/10% after esophagectomy. The 5-year OS/DFS was 91/87% after ESD, 92/59% after chemoradiotherapy, and 90/90% after esophagectomy.

Conclusion

While some patients required additional treatments due to non-curative resection, the long-term survival after ESD for circumferential cT1aN0M0 ESCC was similar as those after chemoradiotherapy or esophagectomy. In contrast, the stricture and refractory stricture rate after ESD was higher than others. Further investigation in a large cohort is necessary to clarify the indication criteria of ESD for patients with the lesion.
761 PATIENT PREFERENCES FOR ACTIVE SURVEILLANCE VERSUS STANDARD SURGERY AFTER NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL CANCER TREATMENT
Authors: Hermus Merel , Wilk Berend , Collee Gerlise , Chang Rebecca , Noordman Bo , Dekker Jan Willem , Esser Stijn , Nieuwenhuijzen Grard , Luyer Misha , Rosman Camiel , Klarenbeek Bastiaan , Coene Peter-Paul , Harst Erwin , Wijnhoven Bas , Busschbach Jan , Lanschot Jan , Lagarde Sjoerd , Kranenburg Leonieke
Published: September 2021

The need for standard surgical resection in esophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) is subject of debate. Possibly, active surveillance (AS) is an option for patients with a clinically complete response (cCR), in whom no vital tumor cells are detected after nCRT. In a large Dutch multicenter randomized trial (SANO trial), standard surgery is compared to AS in patients with a cCR. Within this trial, we performed a side-study on patient treatment preferences.

Methods

Esophageal cancer patients, who declined participation in the SANO-trial due to a strong treatment preference for either AS or surgery were included. In-depth interviews were held on patient’s motives for their treatment choice. First, personal motives were addressed in an open manner, and later specific topics were addressed: earlier experiences with illness and health care, future health expectations, emotional motives, religious or spiritual believes and values in life. Data was recorded, transcribed verbatim and qualitatively analyzed according to the grounded theory principles. In addition, questionnaires on health literacy, coping, anxiety and decision regret were administered at two time points.

Results

Forty patients participated: twenty preferred AS and twenty standard surgery. The central principle for all patients is striving for safety while dealing with the threat of cancer. However, patients express different coping strategies in dealing with this threat. Patients preferring AS rely on trusting their bodies and good outcomes, while questioning the need for surgery. Patients preferring surgery try to minimize insecurity by eliminating the source of the cancer, while arguing that chances for undergoing surgery are high anyway. Interestingly, for either treatment option comparable arguments were used, with the most striking one of wishing ‘not to become a patient’.

Conclusion

Patients’ preferences in the treatment of esophageal cancer are determined by the way they cope with the threat of cancer. Since the arguments given for either AS or standard surgery can be comparable or even similar, the need for healthcare professionals to discuss what truly matters to their patients is of high importance. Subsequently, attuning to the personal needs of esophageal cancer patients will benefit the decision making process on future treatment.
780 ISOLATED BRAIN METASTASIS OF ESOPHAGEAL CARCINOMA AFTER MINIMALLY INVASIVE ESOPHAGECTOMY MIGHT NOT HAVE A DISMAL PROGNOSIS
Authors: Stuart S , Kuypers T , Martijnse I , Heisterkamp J , Matthijsen R
Published: September 2021

After esophagectomy for esophageal carcinoma, 2–13% of patients develop brain metastases (BM) which are associated with a poor prognosis. Further investigation into treatment and prognosis is beneficial given the scarce publications and varying outcomes.

Methods

Case files of all 339 patients who underwent esophagectomy in a single high-volume centre between January 2015 and December 2020 were retrospectively reviewed, all procedures were minimally invasive esophagectomies (MIE). Patients with BM and isolated brain metastases (iBM) were identified and a Kaplan–Meier analysis was performed.

Results

15 out of 339 patients (4,4%) undergoing MIE developed BM of which 9 (60,0%) were iBM. Most patients were diagnosed with squamous cell carcinoma (55,6%), localised in the middle third of the esophagus (66,7%) and had a pathologic complete response (66,7%). Treatment consisted of gamma knife (GK) radiosurgery (44,4%), surgical resection (22,2%), GK and surgical resection (11,1%) and best supportive care (22,2%). Median time to diagnose iBM was 8,4 months (95% CI 0,0–17,2) and survival after recurrence was 14,3 months (95% CI 0,0–45.9). 2 patients (22,2%) remain disease-free after at least 2 years of follow-up.

Conclusion

iBM after esophagectomy for esophageal carcinoma is rare, but when encountered should be treated with a curative intent in selected cases. More research should be conducted on the benefits of screening for iBM after esophagectomy, especially in patients diagnosed with a squamous cell carcinoma in the middle third of the esophagus with a pathological complete response.
782 PATTERNS OF FAILURE AND ADEQUACY OF CLINICAL TARGET VOLUME (CTV) MARGINS IN PATIENTS TREATED WITH DEFINITIVE CHEMO-RADIATION IN ESOPHAGEAL CANCER
Authors: Tahmeed Tahseena , Tibdewal Anil , Ghosh-Laskar Sarbani , Mummudi Naveen , Noronha Vanita , Prabhash Kumar , Agarwal Jai Prakash
Published: September 2021

Esophageal cancer is a locally aggressive malignancy with dismal overall survival (OS) rates. Approximately 50–60% of patients fail loco-regionally after definitive chemoradiation (CTRT). There is a lack of consensus regarding clinical target volume (CTV) margins. Improved diagnostic investigations and patterns of failure (POF) data, suggested scope of reduced CTV margins. In this retrospective study, we evaluated the POF (defined as first site of failure) and the adequacy of CTV margins.

Methods

All patients treated with CTRT between Jan 2013 to Dec 2017 were included. CTV margin was given as 3–5 cm cranio-caudal and 1–1.5 cm radial from gross tumor volume (GTV). Patients were treated either with combined technique (anterior–posterior followed by conformal) or with volumetric arc radiotherapy to a dose of 60-63Gy in 30–35 fractions. PET-CT/CT thorax and upper GI-endoscopy were performed at regular intervals. Loco-regional failure (LRF) was defined as recurrence at local site or regional nodes respectively and classified as infield, marginal and out-field. CT was co-registered with planning CT to document these failures.

Results

158 patients were eligible. Twenty-one patients were excluded as they either progressed or did not attend the first follow-up. Median age was 57 years, >90% had squamous histology, and most common subsite was upper third. Median follow-up was 45.8 months, 53 patients (41.7%) had progression. Local recurrence (LR) was seen in 37 (69.8%), followed by regional in 25 (47.1%) and distant in 21 patients (39.6%). All LR were within the GTV. Of regional failures, 50% were within GTV and 50% were outside the radiotherapy portals. This suggest that 3 cm cranio-caudal CTV margin was adequate.

Conclusion

Our study demonstrated that loco-regional recurrence was the most common pattern of failure after definitive CTRT. As majority of loco-regional failures were within the GTV, hence, 3 cm cranio-caudal CTV margins appear to be adequate enough for control of microscopic disease. Further prospective studies are needed to validate the use of 3 cm CTV margins in definitive CTRT for esophageal cancer.
784 TRANSHIATAL HERNIA: AN UNDERDIAGNOSED BUT OVER-TREATED COMPLICATION AFTER MINIMALLY INVASIVE ESOPHAGECTOMY
Authors: Kuypers Toon , Stuart Sanne , Martijnse Ingrid , Heisterkamp Joos , Matthijsen Robert
Published: September 2021

Postoperative transhiatal hernia is a possible life-threatening complication following esophagectomy. The incidence and indications to treat remain open to debate with apparently an increase after minimally invasive esophagectomy (MIE). The aim of this study is to analyze a large series of patients after MIE in a single high-volume center with a transhiatal herniation after minimally invasive esophagectomy (THAMIE) and obtain new insights in this pathology.

Methods

We included all patients who underwent a MIE (Ivor Lewis and McKeown procedure) in our hospital between 2015 and 2020. Retrospective analysis of demographic, clinical and surgical data was performed. Outcomes of measure were incidence, initial clinical presentation, treatment of choice, postoperative complications and symptoms, herniation recurrence.

Results

In 341 MIE 25 (7.3%) patients were diagnosed with a THAMIE postoperatively. 4 patients (16.0%) were asymptomatic at the time of presentation. 5 patients (20%) were treated conservatively because of recurrent carcinoma. 20 patients received a laparoscopic reduction of the transhiatal hernia and cruraplasty (19 non-absorbable sutures, 1 mesh) regardless whether they were symptomatic or not. 25.0%(5/20) of the patients were operated in emergency settings and 5.0% (1/20) was converted to a laparotomy. Postoperatively 6 of the 18 symptomatic patients (33.3%) experienced no relief of symptoms and 40.0% (8/20) of the THAMIE recurred. 35% had serious postoperative complications (clavien-dindo IIIa or more) and mortality was 0.0%.

Conclusion

The incidence of 7.33% found in our data suggests that THAMIE is a common complication after MIE. We almost exclusively (95.0%) treated patients in a laparoscopic way. Due to the high percentage of morbidity (35.0% ≥ CD IIIa), recurrence (40.0%) and patients with unrelieved symptoms(33.3%) we recommend a conservative treatment for the asymptomatic patients, and further analysis of predictive symptoms associated with a THAMIE to evolve to a shared decision making algorithm for elective symptomatic patients.
793 PATIENTS’ PREFERENCES FOR ACTIVE SURVEILLANCE OR STANDARD ESOPHAGECTOMY AFTER NEOADJUVANT CHEMORADIOTHERAPY: A DISCRETE CHOICE EXPERIMENT IN PATIENTS AFTER STANDARD ESOPHAGECTOMY
Authors: Van Der Wilk Berend , Spronk Inge , Noordman Bo J , Eyck Ben M , Haagsma Juanita , Coene Peter-Paul L O , Harst Erwin , Heisterkamp Joos , Lagarde Sjoerd M , Wijnhoven Bas P L , Lanschot J Jan B
Published: September 2021

Active surveillance after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal cancer is currently topic of investigation. In a discrete choice experiment, patients’ preferences can be quantified by asking patients to state their preference over hypothetical treatment alternatives. The aim of the present study was to assess patients’ preferences for either active surveillance or standard esophagectomy in patients who underwent neoadjuvant chemoradiotherapy followed by surgery without signs of recurrence.

Methods

A discrete choice experiment was performed in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by standard esophagectomy at least one year earlier. Patients completed a questionnaire consisting of eighteen choice sets considering active surveillance or standard esophagectomy. Treatment alternatives were characterized by attributes with varying attribute levels hypothesized to influence treatment choice: five-year survival, short-term and long-term health related quality of life (HRQOL), annual number of diagnostics required and the risk that esophagectomy is still necessary later in time. The importance of attributes and willingness to trade-off 5-year survival for other attributes were assessed using panel latent class model.

Results

A total of 107 patients were consecutively included, of whom 100 (93%) responded between August 2018 and October 2020. Regardless of the attribute levels, 28 patients preferred active surveillance and 28 patients preferred standard esophagectomy. When considering both treatments, five-year survival and long-term HRQOL were considered most important attributes. Patients were willing to trade-off 5.4% five-year overall survival to obtain a better long-term HRQOL.

Conclusion

At least one year after neoadjuvant chemoradiotherapy and esophagectomy, over a quarter of patients would choose not to undergo standard esophagectomy again, regardless of the attribute levels. Patients were willing to trade-off five-year survival chance in order to achieve an HRQOL which was much better than their own situation. When considering both treatments, five-year survival and long-term HRQOL were the most important determinants in the choice for treatment.
801 EXOSOMES CONTAINING LUNG SELF-ANTIGENS COLLAGEN-V AND Kα1-TUBULIN ARE PREVALENT IN PATIENTS WITH SYMPTOMATIC GASTROESOPHAGEAL REFLUX: RESULTS FROM A PILOT STUDY
Authors: Razia Deepika , Ravichandran Ranjithkumar , Bansal Sandhya , Fournier Sarah , Baboli Komeil , Bremner Ross M , Mohanakumar Thalachallour , Mittal Sumeet K
Published: September 2021

Gastroesophageal reflux disease (GERD) has been associated with aspiration-induced pulmonary injury; however, good clinical or laboratory markers are not available. Increased serum levels of exosomes containing normally sequestered primary lung self-antigens (collagen-V, Kα1-tubulin) have been associated with lung injury in the lung transplant population. The aim of this pilot study was to assess the prevalence of exosomes containing collagen-V and/or Kα1-tubulin in patients with severe GERD.

Methods

After IRB approval, the institutional biobank database was queried to identify non-lung transplant patients who underwent primary anti-reflux surgery (ARS) from 2019 to 2020. Serum samples were retrieved from the repository. Exosome pellets were isolated using the Invitrogen® kit using the manufacturer’s protocol. The size of exosomes in the pellet was confirmed using NanoSight. Western blot of the exosomes was used to isolate and quantify collagen-V and Kα1-tubulin, using CD-9 as the standard. A ratio > 1 was considered abnormal.

Results

Ten patients (6 females) with a median (IQR) age of 53 (42, 63) years were included in this study. All patients had symptomatic GERD as an indication for ARS. Five patients (50%) had exosomes containing abnormal levels of collagen-V and/or Kα1-tubulin (Figure 1). There was a mean 2.9- and 8.2-fold increase in collagen-V and Kα1-tubulin, respectively.

Conclusion

Humoral factors associated with lung injury are highly prevalent in patients undergoing elective ARS for GERD. This suggests that detection of exosomes containing lung self-antigens collagen-V and Kα1-tubulin could be useful as a biomarker of GERD-induced lung injury.
804 THE PATTERN OF CT RECURRENCE FOLLOWING RESECTION OF ESOPHAGEAL CARCINOMA
Authors: Chowdhury Sheuli , Wong Lye-Yeng , DeSouza Melissa L , Dewey Elizabeth N , Hunter John G , Wood Stephanie G
Published: September 2021

While esophagectomy is the mainstay of multimodal treatment of esophageal cancer, the risk of recurrence is high. In spite of this, no formal recommendations exist on frequency or duration of computed tomography (CT) imaging for surveillance. The goal of this study was to determine the pattern of cancer recurrence following esophagectomy to develop an optimal surveillance program.

Methods

We performed a retrospective review of a single-institution esophageal disease registry, evaluating patients who underwent esophagectomy for esophageal cancer between 2000–2019. The surveillance protocol is CT in 3-month intervals for one year, 6-month intervals in year 2, then annually until the fifth year. Rates of recurrence were compared by stage, tumor factors, and chemoradiation status using chi-square tests. Monthly rates of recurrence and overall survival were assessed using Kaplan–Meier. Risk ratios for recurrence were evaluated with multivariate Cox regression accounting for age, gender, cancer type, stage, chemoradiation therapy, and tumor grade.

Results

Of the 368 included, 88% had Adenocarcinoma, 85% male, 96% Caucasian, 85% received chemotherapy, and 82% received radiation. 24% had pathologic complete response (pCR). The recurrence rate was 33%. 46% had clinical symptoms at time of recurrence, and 58% were diagnosed by routine surveillance CT. 21% of pCR had recurrence. 85% of recurrences occurred within 5 years, 72% within 3 years, and 56% within 2 years of surgery. Most frequent recurrence was lung (22%), followed by multi-site (21%), and regional lymph node (17%). There were notable differences in time to recurrence by site of recurrence (Figure 1) (p = 0.03).

Conclusion

In our population, 33% of patients had recurrence of esophageal cancer following surgical resection, with highest risk of recurrence within the first 3 postoperative years. These findings favor more frequent surveillance during this period, followed by annual surveillance until 5 years.
807 ASSOCIATION OF BOLUS TRANSIT TIME ON BARIUM ESOPHAGOGRAM WITH ESOPHAGEAL PERISTALSIS
Authors: Razia Deepika , Trahan Amy , Giulini Luca , Baboli Komeil M , Mittal Sumeet K
Published: September 2021

The threshold criteria for diagnosing ineffective esophageal motility (IEM) has changed over the years and is based on the proportion of failed and weak peristalses. Bolus transit time (BTT) on barium esophagogram (BE) can intuitively be the ‘gold standard' for assessing the effectiveness of esophageal peristalsis. The aim of this study was to associate upright and prone BTT with esophageal peristalsis and dysphagia in patients with normal lower esophageal sphincter (LES) parameters.

Methods

Patients with normal LES on high-resolution manometry (HRM) who also had a standard-protocol BE from 2017 to 2020 were included. Patients with previous foregut surgery, hiatal hernia, jackhammer esophagus, distal esophageal spasm, fragmented peristalsis, and those with < or > 10 single swallows on HRM were excluded. Based on the number of normal swallows (DCI >450 mmHg.s.cm), the patients were divided into 11 groups (10 normal to 0 normal). Upright and prone BTT were measured on BE. Fractional polynomial and logistic regression analysis were used to study association (along with rate of change) between BTT, dysphagia, and peristalsis.

Results

In total, 146 patients met the inclusion criteria. Prone BTT increased in tandem with a decrease in the number of normal peristalses (p < 0.001), but no difference was noted in upright BTT (p = 0.317). Two deflection points were noted on the association between peristalsis and prone BTT at 50%, 40 seconds and 30%, 80 seconds on the y and x-axes, respectively, after which declining peristaltic function was independent of prone BTT. Patients with prone BTT >40 seconds had nearly 6-fold higher odds of having zero normal peristalses (p = 0.002). Increasing prone BTT was associated with increasing dysphagia (p < 0.05).

Conclusion

Prone, but not upright BTT, correlates with the proportion of normal esophageal peristalses and dysphagia. The phenotype of abnormal swallows (failed, weak) appears to have minimal impact on BTT. The current perspective of manometric classification may need to be adjusted to use the proportion of normal peristalses as a criterion.
814 SMAD4 AS A POTENTIAL GATEKEEPER FOR GENOMIC INSTABILITY AND MTOR-MEDIATED TUMORIGENESIS IN ESOPHAGEAL ADENOCARCINOMA
Authors: Milne Julia , Gotovac Jovana , Fujihara Kenji , Simpson Kaylene , Duong Cuong , Phillips Wayne , Clemons Nicholas
Published: September 2021

Extensive genomic analysis of patient samples has identified genes whose mutation or loss map malignant progression from Barrett’s metaplasia, through low- (CDKN2A) and high-grade dysplasia (TP53), to invasive adenocarcinoma (SMAD4). Interestingly, loss of SMAD4 has been found to occur exclusively in the invasive disease stage, but the reason for this is unknown. This work aimed to characterise the role of SMAD4 in esophageal adenocarcinoma (EAC) tumorigenesis and identify novel therapeutic targets for SMAD4-deficient EAC.

Methods

We developed a novel in vivo tumorigenesis model that demonstrates progression of dysplastic Barrett’s esophagus (BE) to invasive EAC upon knockout of SMAD4. We conducted parallel genome-wide CRISPR-Cas9 knockout screens, both in vitro and in vivo, on a background of either wildtype-SMAD4 or SMAD4-knockout dysplastic BE cells to identify co-operative drivers of tumorigenesis in vivo, as well as synthetic lethal interactions to identify potential therapeutic targets in SMAD4-deficient EAC. Functional validation of hits was performed using cell-based assays and drugs targeting candidate molecular targets.

Results

We identified a synthetic lethal relationship between SMAD4-deficiency and cell cycle checkpoint inhibition, suggesting a role for SMAD4 in maintaining genomic stability and a potential novel therapeutic avenue for SMAD4-deficient EAC. A concurrent in vivo CRISPR-Cas9 tumorigenesis screen produced tumors 4-fold faster than loss of SMAD4 alone and identified regulators of mTOR signalling and SMAD4 as co-operative drivers of tumorigenesis in EAC. Interestingly, these tumorigenic cells exhibited an inherent dependency on specific translation mechanisms downstream of mTOR. Meanwhile, wildtype-SMAD4 BE cells failed to thrive in vivo with mTOR modifications alone, indicating a true co-operative effect at play with SMAD4 loss.

Conclusion

This study uncovered a potential gatekeeping role of SMAD4 in maintaining genomic stability and inhibiting mTOR-mediated EAC tumorigenesis. In sum, loss of SMAD4 was found to increase genomic instability, thereby rendering EAC cells sensitive to cell cycle checkpoint impediment, whilst simultaneously co-operating with modulated mTOR signalling to promote tumorigenesis in EAC xenograft models.