Induction Therapy Followed by Surgery for Unresectable Thymic Epithelial Tumours

Background and ObjectivesThe treatment of unresectable thymic epithelial tumours (TETs) remains controversial. Here, we present the efficacy and safety of induction therapy followed by surgery for unresectable TET.MethodsEighty-one patients with unresectable TETs treated with induction therapy followed by surgery were selected from a retrospective review of consecutive TETs from January 2005 to January 2021. Clinicopathological data were analyzed to assess tumour responses, resectability, adverse events, progression-free survival (PFS) and overall survival (OS).ResultsInduction therapy produced a major tumour response rate of 69.1%, a tumour response grade (TRG) 1-3 rate of 84.0% and an R0 resection rate of 74.1%. The most common toxic effects were all-grade neutropenia (35.8%) and anaemia (34.6%). The 10-year OS and PFS rates were 45.7% and 35.2%. Multivariate analysis showed that ypTNM stage, ypMasaoka stage, complete resection, and TRG were significant independent prognostic factors. Exploratory research revealed that different induction modalities and downstaging of T, N, M, TNM, or Masaoka classifications did not significantly alter the pooled hazard ratio for survival.ConclusionsInduction therapy followed by surgery is well tolerated in patients with unresectable TETs, with encouraging R0 resection rates. Multimodality management provides good control of tumors for unresectable TET patients.

Effectiveness of S-O Clip-Assisted Colorectal Endoscopic Submucosal Dissection

This study aimed to assess the utility of the S-O clip during colorectal endoscopic submucosal dissection (ESD). We conducted a retrospective study on 185 patients who underwent colorectal ESD from January 2015 to January 2020. The patients were divided into two groups: before and after the introduction of the S-O clip. Forty-two patients underwent conventional ESD (CO group) and 29 patients underwent ESD using the S-O clip (SO group). We compared the surgery duration, dissection speed, en bloc resection rate, and complication rate between both groups. Compared with the CO group, the SO group had a significantly shorter surgery duration (70.7 ± 37.9 min vs. 51.2 ± 18.6 min; p = 0.017), a significantly higher dissection speed (15.1 ± 9.0 min vs. 26.3 ± 13.8 min; p < 0.001), a significantly higher en bloc resection rate (80.9% vs. 98.8%; p ≤ 0.001), and a significantly lower perforation rate (4.3% vs. 1.3%). In the right colon, the surgery duration was significantly shorter and the dissection speed was significantly higher in the SO group than in the CO group. Moreover, the rate of en bloc resection improved significantly in the right colon. S-O clip-assisted ESD reduces the procedure time and improves the treatment effects, especially in the right colon.

Compared the effectiveness and safety of different methods of colorectal endoscopic submucosal dissection: a systematic review and network meta-analysis

Background: Traditional endoscopic submucosal dissection (ESD) has developed different methods, such as pocket method(P-ESD), traction-assisted method(T-ESD) and Hybrid method(H-ESD). In this meta-analysis, the benefits and drawbacks of different ESD methods were discussed and ranked. Study design: Studies comparing different methods of colorectal ESD were searched by PubMed, Embase, and Cochrane Library databases. The study was conducted for five endpoints: en bloc resection rate, R0 resection rate, operation time, dissection speed, and adverse events rate. Pairwise and network meta-analyses were performed through Rev Man 5.4 and Stata 16.0. The quality of all included studies was assessed using the Cochrane Risk of Bias Tool and Newcastle-Ottawa Scale. Results: Twenty-six studies met the inclusion criteria, including 7 RCTs and 19 non-RCTs, with a total of 3002 patients. The pooled analysis showed that the en bloc resection rate of H-ESD was significantly lower than C-ESD, P-ESD and T-ESD [RR=0.28, 95%CI (0.12, 0.65); RR = 0.11, 95% CI (0.03, 0.44); RR = 8.28, 95% CI (2.50, 27.42)]. Compared with C-ESD, the operation time of H-ESD and T-ESD was significantly shorter [MD=-21.83, 95%CI (-34.76, -8.90); MD=-23.8, 95%CI (-32.55, -15.06)]. Meanwhile, the operation time of T-ESD was also significantly shorter than P-ESD [MD=-18.74, 95%CI (-31.93, -5.54)]. The dissection speed of T-ESD was significantly faster than C-ESD [MD=6.26, 95%CI (2.29, 10.23)]. Conclusion: P-ESD and T-ESD are probably the two best methods of colorectal ESD at present. The advantages of P-ESD are high en bloc resection rate and low incidence of adverse events. The advantages of T-ESD are rapid dissection and short operation time.

Endoscopic Submucosal Dissection (ESD) skills transfer to clinical practice after hands-on workshops: an international survey

Background Endoscopic submucosal dissection (ESD) is a complex procedure, requiring enhanced technical skills. Translation into clinical practice of ESD training programs has not been documented. Our aim was to assess ESD training pathways of endoscopists participating in dedicated workshops and its clinical impact on ESD outcomes. Methods Participants of live porcine models ESD workshops, from 2013 to 2019, were included. They were invited to complete a survey focusing in human ESD performance after training, prior skills/competencies, complete learning pathway and clinical outcomes. Results From 118 invited participants, 40 (34%) completed the questionnaire. Nineteen (47%) endoscopists performed human ESD after the workshop, predominantly male (89%). At the beginning of human ESD, endoscopists had a mean of 7,7 (SD 4,1) years of endoscopic experience and were all performing endoscopic mucosal resection (EMR) and emergency endoscopy. Before ESD practice, 100% trained with live animal models and 68% with ex vivo models. The majority started clinical ESD in the lower third of the stomach or rectum (90%), with lesions ≤30mm (89%). Each endoscopist performed a median of 19 (IQR 8-32) cumulative ESDs, over a mean of 3,9 (SD 2,0) years. Total en bloc resection rate was 92%, R0 resection rate 88%, curative resection rate 86%, whereas adverse events remained <10%. Endoscopists with >10 human ESD procedures achieve clinical competence thresholds. Conclusions Participants of ESD workshops are adequately skilled prior to clinical ESD, complying with recommendations for training and properly implementing the technique. Transfer to clinical practice, of prior ESD skills obtained in hands-on training courses was documented. Structured training programs achieve clinical outcomes exceeding established standards, namely in the very initial clinical phase.

Ligation-assisted endoscopic mucosal resection has high complete resection rate in rectal carcinoid tumor

Aim We aimed to compare the outcomes of different therapeutic modalities in rectal carcinoid tumors. Method We retrospectively collected 145 patients with rectal carcinoid tumors which were pathologically diagnosed from 2005/01/01 to 2016/12/31. We compared tumor size, complete resection rate and recurrent rate between different therapeutic modalities. Then, prospectively compared the treatment outcomes of 28 patients treated with ligation assisted endoscopic mucosal resection (LEMR) and 25 patients treated with endoscopic mucosal resection with cap (EMRC). Result The mean size of tumors was 6.5 mm (1–25 mm), and the mean follow-up duration was 26 months (6–118 months). The therapeutic modalities included ligation-assisted endoscopic mucosal resection (LEMR) (25 tumors, 17%), endoscopic mucosal resection (EMR) (31 tumors, 21%), snare polypectomy (30 tumors, 21%), biopsy forceps removal (46 tumors, 32%) and surgical resection (13 tumors, 11%), including 6 tumors treated with transanal endoscopic microsurgery (TEM) method. In view of pathologically complete resection rate, LEMR was highest (100%), followed by surgical resection (85%). However, EMR only had 42% pathologically complete resection rate. Besides, LEMR and surgical resection had no local recurrence and significantly higher clinically complete resection rate, compared to other treatments. For the further prospective study, complete resection was noted in 28 (100%) patients in LEMR group and 13 (52%) patients in EMRC group. Conclusion In the treatment of rectal carcinoid tumors, LEMR is safe and effective compared with traditional endoscopic treatments.

P-P42 Neo-adjuvant Chemoradiation for Borderline Resectable Pancreatic Adenocarcinoma: A UK Tertiary Surgical Oncology Centre Series

Background Pancreatic ductal adenocarcinoma (PDAC) is associated with a historically poor long-term survival of 5-10%, despite surgical resection. Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is reported as potentially resectable disease with a degree of vascular involvement, increasing the risk of a positive surgical margin. This cohort of patients have the worst survival despite curative resection and adjuvant chemotherapy. Emerging evidence suggests that neo-adjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease free survival (DFS) and overall survival (OS) in our patients, who had undergone NCR for BR-PDAC at our institution. Methods Data was collected retrospectively for all patients undergoing NCR for BR-PDAC between Jan 2010 to Mar 2020 for this study. Surgical management was ratified by clinical assessment and cross-sectional imaging in a pancreatic multidisciplinary team meeting (MDM). Patients underwent NCR by a number of standardised regimens. Patients with proven regressive or stable disease on imaging underwent a pancreatic resection. All BR-PDAC patients underwent resection in the form of classical Whipple’s or pylorus preserving pancreaticoduodenectomy (PPPD) depending on intra-operative findings. Patient morbidity, R0 resection rate, histological parameters, DFS and OS were evaluated. Results 29 patients were included in the study (16 men and 13 women), with a median age of 65 years (range, 46-74 years). 17 patients received FOLFIRINOX and 12 patients received gemcitabine (GEM) based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45-56Gy). 75% had an R0 resection, with a greater proportion in the FOLFIRINOX group. Whole cohort median DFS was 35 months, survival was superior in the FOLFIRINOX group (42 months). Median OS was 30 months for the whole group, with a greater median OS in the FOLFIRINOX versus the GEM cohort (42 versus 29 months). Conclusions We present a single centre retrospective study utilising NCR for BR-PDAC, we reiterate the strong association of an R0 resection with superior patient overall survival following surgery in this cohort. We show that in patients with BR-PDAC, NCR results in superior R0 resection rates with an associated increase in patient survival. Our results show that survival advantage is greatest in BR-PDAC patients who received neo-adjuvant FOLFIRINOX. Our findings affirm the advantage of NCR prior to surgery, particularly FOLFIRINOX based treatment, in this cohort of patients.

Neoadjuvant camrelizumab plus chemotherapy in treating locally advanced esophageal squamous cell carcinoma patients: a pilot study

Background Camrelizumab (a PD-1 inhibitor) has been used as a potential therapy in unresectable advanced esophageal squamous cell carcinoma (ESCC) along with adjuvant treatment in locally advanced ESCC, exhibiting an acceptable efficacy and safety profile. This pilot study was designed to further investigate the clinical value and tolerance of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC. Methods A total of 16 patients with locally advanced ESCC were recruited. Patients received 2 cycles of neoadjuvant therapy including 2 doses of camrelizumab concurrent with 2 cycles of paclitaxel plus carboplatin followed by surgery 4 weeks afterward. Then, the treatment response after neoadjuvant therapy, R0 resection rate, tumor regression grade (TRG), and pathological complete remission (pCR) rate were measured. Besides, adverse events were documented. At last, progression-free survival (PFS) and overall survival (OS) were assessed. Results Generally, objective remission rate (ORR) was 81.3% whereas disease control rate (DCR) was 100% after neoadjuvant therapy. Concerning TRG grade, 31.3, 37.5, 18.8, and 12.5% patients reached TRG0, TRG1, TRG2, and TRG3, respectively. Then, pCR rate and R0 resection rate were 31.3 and 93.8%, respectively. Besides, mean PFS and OS were 18.3 months (95%CI: (16.2–20.5) months) and 19.2 months (95%CI: (17.7–20.7) months), respectively, with a 1-year PFS of 83% and OS of 90.9%. Adverse events included white blood cell decrease (37.5%), neutrophil decrease (31.3%), reactive cutaneous capillary endothelial proliferation (37.5%), and nausea or vomiting (25.0%), which were relatively mild and manageable. Conclusion Neoadjuvant camrelizumab plus chemotherapy exhibits good efficacy and acceptable tolerance in patients with locally advanced ESCC.

Long-Term Efficacy of Neoadjuvant Concurrent Chemoradiotherapy for Potentially Resectable Advanced Siewert Type II and III Adenocarcinomas of the Esophagogastric Junction

BackgroundReports have shown that neoadjuvant concurrent chemoradiotherapy (nCRT) increases the R0 resection rate for patients with Siewert type II or III adenocarcinoma of the gastroesophageal junction (AEG). However, the long-term efficacy of nCRT for AEG patients remains unclear. In this multicenter study, we investigated the long-term results of AEG patients treated with nCRT.MethodsA total of 149 patients with potentially resectable advanced AEG (T3/4, Nany, M0) were randomly divided into two groups: the nCRT-treated group (treated group) (n = 76) and the surgery group (control group) (n = 73). The primary endpoint was disease-free survival (DFS), and the secondary outcome indexes included the R0 resection rate, HER-2 expression, tumor regression grade (TRG), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events.ResultsIn the treated group, the overall therapeutic efficacy rate was 40.8%, and the pathological complete response (pCR) rate was 16.9%. The rates of patients who underwent R0 resection in the treated and control groups were 97.0% and 87.7%, respectively (p &lt; 0.05). The toxic effects were mainly graded 1–2 in the treated group. The median DFS times in the treated and control groups were 33 and 27 months, respectively (p = 0.08), whereas the median OS times were 39 and 30 months, respectively (p = 0.01). The median DFS times of patients with positive and negative HER-2 expression in the treated group were 13 and 43 months, respectively (p = 0.01), and the median OS times were 27 and 41 months, respectively (p = 0.01).ConclusionSurgery after nCRT improved the efficacy of treatment for AEG patients and thus provided a better prognosis.Clinical Trial RegistrationThe trial is registered with ClinicalTrials.gov (number NCT01962246).

Improving the management of early colorectal cancers (eCRC) by using quantitative markers to predict lymph node involvement and thus the need for major resection of pT1 cancers

BackgroundSince implementing the NHS bowel cancer screening programme, the rate of early colorectal cancer (eCRC; pT1) has increased threefold to 17%, but how these lesions should be managed is currently unclear.AimTo improve risk stratification of eCRC by developing reproducible quantitative markers to build a multivariate model to predict lymph node metastasis (LNM).MethodsOur retrospective cohort of 207 symptomatic pT1 eCRC was assessed for quantitative markers. Associations between categorical data and LNM were performed using χ2 test and Fisher’s exact test. Multivariable modelling was performed using logistic regression. Youden’s rule gave the cut-point for LNM.ResultsAll significant parameters in the univariate analysis were included in a multivariate model; tumour stroma (95% CI 2.3 to 41.0; p=0.002), area of submucosal invasion (95% CI 2.1 to 284.6; p=0.011), poor tumour differentiation (95% CI 2.0 to 358.3; p=0.003) and lymphatic invasion (95% CI 1.3 to 192.6; p=0.028) were predictive of LNM. Youden’s rule gave a cut-off of p>5%, capturing 18/19 LNM (94.7%) cases and leading to a resection recommendation for 34% of cases. The model that only included quantitative factors were also significant, capturing 17/19 LNM cases (90%) and leading to resection rate of 35% of cases (72/206).ConclusionsIn this study, we were able to reduce the potential resection rate of pT1 with the multivariate qualitative and/or quantitative model to 34% or 35% while detecting 95% or 90% of all LNM cases, respectively. While these findings need to be validated, this model could lead to a reduction of the major resection rate in eCRC.