Unexpected Surgical Complications Research Articles

Preoperative-postoperative immunotherapy as treatment of borderline resectable and oligoprogressive stage III B-D and IV melanoma

IntroductionPerioperative therapy has gained significant importance in patients with advanced melanoma. Currently, there is little data on the routine use of preoperative immunotherapy in metastatic melanoma outside clinical trials. This study aimed to evaluate the effectiveness of preoperative treatment in patients with borderline resectable stage III or IV melanoma as well as in oligoprogressing stage IV cases; the secondary aim is to describe the safety of surgery after immunotherapy. Materials and methodsSince 1/Jan/2016 seventeen patients were treated with curative intent neoadjuvant immunotherapy, surgery, and adjuvant immunotherapy, while nineteen patients were operated due to oligoprogression while treted with immunotherapy. Survival was analyzed using the Kaplan-Meier method and association between variables was tested using the chi-squared test. ResultsR0 resection was achieved in 76.5 % of cases after neoadjuvant immunotherapy. 24 % of patients achieved objective RECIST response and 35 % complete or major pathological response. At the median follow-up time of 51.4 months, 64.7 % of patients were free of PD after perioperative treatment, while 3-year RFS and OS rates were 68 % and 80.9 %, respectively. R0 resection was achieved in 73.7 % of oligo-progressing nodules. The median time to PD on immunotherapy after the first oligoprogression was 10.3 months. Immunotherapy did not result in any unexpected surgical complications. No patient died during preoperative treatment due to immunotherapy toxicity or disease progression. ConclusionsWe confirmed treatment safety and long-term disease control after perioperative immunotherapy. Patients with borderline resectable melanoma should be referred to reference centers using neoadjuvant immunotherapy.

Chapter 5 - Other median neuropathies

Median mononeuropathy is common, with carpal tunnel syndrome the most frequently encountered acquired mononeuropathy in clinical practice. However, other disorders of the median nerve and many known anatomical variants can lead to misdiagnosis and unexpected surgical complications if their presence is not correctly identified. A number of inherited and acquired disorders can affect the median nerve proximal to the wrist, alone or accompanied by other affected peripheral nerves. Recognizing other disorders that can masquerade as median mononeuropathies can avoid misdiagnosis and misguided management. This chapter explores median nerve anatomical variants, disorders, and lesions, emphasizing the need for careful examination and electrodiagnostic study in the localization of median neuropathy.

Phase Ib neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).

e16613 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0) and 1yr event free survival (EFS). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results: Between Nov 2020 and Feb 2023, 21 pts were enrolled with median age 75yrs, 81% male, 33% > cT2; 1 pt refused RC but was included in the ITT population. Treatment was stopped after 1 infusion of CG0070 in 1 pt due to treatment unrelated worsening of renal function. The overall rate of >grade 3 AEs was 12/20 (60%), and the vast majority were related to RC (83%). Immune related AEs were seen in 1 pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. Overall, 1 pt was unevaluable for efficacy, 2 pts progressed prior to RC, PaR was observed in 8/15 (53%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. On exploratory analysis, treatment response correlated with increased maturation of tertiary lymphoid structures and immunogenicity to bespoke tumor neoantigens. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 50%. Clinical trial information: NCT04610671 .

A Rare case of amyand’s hernia managed with laparoscopic repair

Amyand’s hernia is defined as when the appendix is trapped within an inguinal hernia. Although the incidence of Amyand’s hernia is rare, the appendix may become incarcerated within Amyand’s hernia and lead to further complications such as mechanical obstruction, strangulation, necrosis, perforation and catastrophic peritonitis. The aim of this paper is to provide insight into the diagnosis and treatment of Amyand’s hernia by describing the familiarization of the incarcerated appendixes within hernias in order to ensure potential successful surgical outcomes and avoid unexpected surgical complications.

Neoadjuvant atezolizumab plus docetaxel/oxaliplatin/capecitabine in non-metastatic gastric and gastroesophageal junction adenocarcinoma: The PANDA trial.

4059 Background: Immune checkpoint blockade improves clinical outcomes for patients with gastric and gastro-esophageal junction (GEJ) cancers, but its efficacy and impact on the tumor microenvironment in non-metastatic, resectable disease remains largely unknown. Peri-operative FLOT, the current standard-of-care, leads to pathologic complete responses (pCR) and major pathologic responses (MPR) in 16% and 37% of patients, respectively. An important open question is whether PDL-1 blockade monotherapy can prime the tumor microenvironment in a favorable manner, prior to combination with chemotherapy. Methods: We report results from the phase 2 PANDA trial (NCT03448835) of neoadjuvant atezolizumab (anti-PDL-1) plus docetaxel, oxaliplatin, and capecitabine (DOC) in patients with resectable gastric or GEJ adenocarcinoma. Patients received a single cycle of atezolizumab monotherapy, followed by 4 cycles of atezolizumab+DOC. Tumor tissue was collected at baseline, after atezolizumab monotherapy, the first atezolizumab+DOC, and at resection. The primary endpoints were safety and feasibility in 20 patients, and secondary endpoints included MPR (<10% viable tumor rest) and disease-free survival. Results: Twenty patients, of which 18 with mismatch repair (MMR) proficient and two with MMR-deficient tumors, were evaluable for safety and efficacy analyses. MPR was observed in 14/20 patients (70%; 95% CI 46–88%), including 9 pCR (45%; 95% CI 23-68%). Among patients with intestinal type adenocarcinoma, 12/15 (80%; 95% CI 52-96%) had an MPR, with 9/15 (60%; 95% CI 32-84%) pCR. Treatment was well tolerated, with two patients (10%) experiencing a grade 3 immune adverse event. At a median follow-up of 29 months (IQR 16-34), 15 patients (75%) were alive and disease-free. None of the patients with an MPR recurred. All patients underwent resections without treatment-related delays and no unexpected surgical complications were documented. Translational analyses, including baseline PDL-1 CPS score and whole exome sequencing (WES), plus CD8 T-cell infiltration and RNA sequencing at 4 timepoints will be presented at the meeting. Conclusions: Our data show that the addition of atezolizumab to neoadjuvant chemotherapy leads to promising pathologic responses in gastric/GEJ adenocarcinoma, which appears to be higher than in historical controls, with no recurrences in responders. These data should be validated in a large randomized controlled trial. Clinical trial information: NCT03448835.

Preliminary results from phase Ib/II neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).

4574 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results from a prespecified interim analysis following accrual of 15 patients is reported herein. Results: Between Nov 2020 and Jan 2022, 15 pts were enrolled with median age 75.5yrs, 73% male, 47% > cT2; 1 patient refused RC but was included in the ITT population. No DLTs were encountered. The overall rate of grade 3-4 AEs was 10/15 (75%), and the vast majority were related to RC (90%). Immune related AEs were seen in one pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. PaR was observed in 6/13 (46%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 54%. Clinical trial information: NCT04610671. [Table: see text]

Phase I/II trial of perioperative avelumab in combination with chemoradiation (CRT) in the treatment of stage II/III resectable esophageal and gastroesophageal junction (E/GEJ) cancer.

4034 Background: Neoadjuvant CRT followed by surgery is the standard of care for patients (pts) with stage II/III E/GEJ cancer, yet recurrence rates remain high. Immunotherapy has demonstrated activity in advanced E/GEJ cancer and was recently approved for adjuvant treatment of early stage disease. This trial evaluated the safety and efficacy of avelumab with perioperative CRT in resectable E/GEJ cancer. Methods: This is a two part phase I/II trial. Phase I was a safety run-in of 6 pts. Phase II planned to enroll an additional 18 pts in an expansion cohort. Pts with E/GEJ adenocarcinoma or squamous cell cancer received CRT (41.4 Gy in 23 fractions) with weekly carboplatin and paclitaxel. Three doses of avelumab (10 mg/kg IV, q14 days) were administered starting on day 29 of treatment, to coincide with the last chemotherapy dose. Surgery was performed 8-10 weeks after CRT completion. Pts received 6 doses of avelumab after resection (10 mg/kg IV, q14 days). The primary endpoint of the Phase 1 was safety and tolerability. The primary endpoint of the Phase II was pathologic complete response (pathCR) rate, assessing patients from the safety run in and expansion cohorts. Results: Between 6/2018 and 10/2021, 22 pts (20 males, median age 64) enrolled in the study. Enrollment was stopped after 16 patients in the expansion cohort due to accrual delays and changes in standard treatment. 19/22 patients (86%) had adenocarcinoma; 15/22 (68%) had lymph node positive disease at diagnosis. 19 pts underwent successful resection while on study. 3 pts went off study before resection due to grade 3 avelumab-related infusion reaction (1), patient preference (1), and non-adherence (1). There were no unexpected surgical complications. 4 pts (21%) had R1 resection with 3/4 having positive radial margin and 1/4 positive proximal margin. At resection, 5 pts (26%) had pathCR (3/16 adenocarcinomas, 2/3 squamous cell), 4 ypT1N0 disease, and 14/19 were ypN0. 42% had tumor regression score of 0 or 1. The combination of CRT and avelumab had an acceptable toxicity profile. No grade ≥3 immune-related AEs were observed. Immune-related hypothyroiditis was seen in 2 patients (grade 2). Three patients had grade 2 infusion-related reaction, but were able to continue with treatment. 21/22 pts had reversible grade ≥3 lymphopenia; 13/22 grade ≥ 3 wbc decrease; 6/22 grade 3 neutropenia. As of data cutoff on 2/1/2022, 1 patient remains on study treatment, 15 in follow up, 5 expired, 1 off study. Additional efficacy data is being collected. Correlative studies are ongoing. Conclusions: Perioperative CRT with avelumab is well tolerated with no unexpected toxicities. Neoadjuvant chemoradiation with immunotherapy is a promising approach for patients with E/GEJ tumors. Additional safety, efficacy and correlative analysis from this study will be presented at the meeting. Clinical trial information: NCT03490292.

Neoadjuvant nivolumab, ipilimumab, and celecoxib in MMR-proficient and MMR-deficient colon cancers: Final clinical analysis of the NICHE study.

3511 Background: The combination of PD-1 and CTLA4 blockade has changed the treatment landscape for several cancer types. Although this treatment is highly effective in metastatic mismatch-repair deficient (dMMR) colorectal cancers, metastatic MMR-proficient (pMMR) tumors do not respond. The NICHE study was the first neoadjuvant immunotherapy study in colon cancer (CC) to show impressive responses in 100% of dMMR ( n= 20) and 27% of pMMR ( n= 15) CC. In contrast, pathologic response to neoadjuvant chemotherapy using standard of care folfox is approximately 5% in dMMR tumors. Here we present the final efficacy data for the original NICHE study cohorts. Methods: Patients with non-metastatic, resectable dMMR or pMMR CC were treated with a single dose of ipilimumab 1mg/kg and two doses of nivolumab 3mg/kg and underwent surgery within 6 weeks. In addition, patients with pMMR tumors were randomized to receive celecoxib. The primary endpoints were safety and feasibility, and secondary endpoints included pathologic response rate and disease-free survival in 30 patients with dMMR and 30 with pMMR tumors. Pathologic response was defined as 50% or less viable tumor rest (VTR), and major pathologic response (MPR) as <10% VTR. Results: Thirty patients with pMMR and 32 with dMMR tumors were evaluable for the efficacy analyses. In the pMMR cohort, pathologic response was observed in 9/30 (30%, 95% CI 14-46%) patients, consisting of 7 MPR (including 3 pathologic complete responses {pCR}) and 2 partial responses. Four out of 9 pMMR responders had received celecoxib. Five patients received adjuvant chemotherapy. At a median follow-up of 25 months (IQR 12-35 months), 3 patients (all non-responders) in the pMMR group had disease recurrence. In the 32 patients with dMMR tumors, pathologic response was observed in 100% of patients, with 31/32 MPR (97%, 95% CI 91-100%) and one partial response. Pathologic complete response was observed in 22/32 (69%, 95% CI 53-85%) patients. None of the patients in the dMMR cohort had disease recurrence. Surgery was delayed in one patient with a pMMR tumor due to myositis. Grade 3 immune-related adverse events were observed in 12% of patients, consistent with our previous report on the primary endpoint. There were no grade 4 immune-related AEs nor unexpected surgical complications. Conclusions: These data confirm our previously published results of the NICHE study, with responses to neoadjuvant nivolumab plus ipilimumab in 30% of pMMR and 100% of dMMR CC in the completed original cohorts. Validation of the dMMR responses in a large group of dMMR patients is ongoing and has the potential to change current practice. Clinical trial information: NCT03026140.

Neoadjuvant sintilimab combined with chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC): Preliminary results from a phase II study.

e16008 Background: Although preoperative chemoradiotherapy is the standard of care for patients with resectable locally advanced esophageal cancer, prognosis still remains poor. Combining PD-1 blockade to chemotherapy has demonstrated significant clinical benefits in first line treatment of metastatic ESCC. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in metastatic ESCC. We aimed to assess the activity and safety profile of the combination of sintilimab with paclitaxel and cisplatin for neoadjuvant treatment of ESCC. Methods: In this ongoing, single-arm, phase II study, we recruited patients from the First Affiliated Hospital of Henan University of Technology in China with histopathologically diagnosed resectable ESCC who had clinical cT2-4/N1-3M0 (stage II-IVA). Patients were given 2 cycles of chemotherapy (nab-paclitaxel 260 mg/m2, d1 and cisplatin 75 mg/m2, d1-3) in combination with 2 cycles of sintilimab (200mg, iv, d1, q3w), followed by esophagectomy. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). Results: Between Nov 2020 and Dec 2021, 15 patients were enrolled and commenced treatment. A total of 11 patients (75%) completed neoadjuvant and radical resection, 4 patients refused surgery. Six patients (54.5%) achieved major pathologic response (MPR), including five (45.5%) with a pathologic complete response (pCR) in primary tumor. According to RECIST v1.1, 1 of 8 patients (12.5%) achieved partial response (CR), 4 of 8 patients (50%) achieved partial response, and 3 of 8 patients (37.5%) achieved stable disease (SD). The objective response rate (ORR) and disease control rate (DCR) for 8 patients were 62.5% and 100%, respectively. The most frequent treatment-related adverse events (TRAE) included leukopenia (60%), nausea (40%) and diarrhea (20%). The grade 3 or 4 TRAE were leukopenia (26.7%), neutropenia (20%) and pneumonia (6.7%). There was no surgical delays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of sintilimab and chemotherapy is a safe and efficacious treatment option for patients with resectable ESCC, and 45.5% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: ChiCTR2000040345.

Preoperative immunotherapy for head and neck cancers: state of art.

Programmed cell death 1 (PD-l)-targeting agents have been FDA-approved for treatment of recurrent/ metastatic head and neck squamous cell carcinoma (HNSCC). Clinical studies employing these agents preoperatively for HNSCC in the definitive setting are emerging and have important implications. Preclinical studies demonstrate enhanced effectiveness of preoperative PD-1 targeting compared with postoperative treatment. Nine HNSCC clinical studies evaluating preoperative treatment with PD-1-targeted pembrolizumab/nivolumab alone or in combination therapy were recently reported. These studies differed by preoperative treatment type and duration and reported no surgical delays, no unexpected surgical complications and grade 3-4 immune-related adverse events consistent with the employed immunotherapeutic agent(s). Rates of major pathologic response (MPR), reduced residual viable tumour to 10% or less, ranged from 2.9-31% across eight trials without neoadjuvant radiation therapy. Higher PD-1 ligand (PD-L1) expression, increased inflammatory gene expression and enhanced immune cell tumour infiltration in baseline biopsies were associated with pathologic tumour response (pTR) in some studies. Any degree of pTR was associated with improved survival/relapse outcomes in two studies. Emerging preoperative anti-PD-1 HNSCC clinical studies indicate that preoperative treatment does not impact surgical management. Defining predictive biomarkersand tumour pathologic response implications for patient survival are areas for further investigation.

Cervical radiculopathy and spinal cord indentation caused by vertebral artery loop

Cervical radiculopathy and spinal cord indentation caused by vertebral artery loop formation is a rare entity. We report here an 85-year-old woman had a four-year history of neck pain and left arm weakness. Radiologic evaluation showed vertebral artery loop formation compressing the adjacent nerve root and spinal cord. Accurate radiologic diagnosis of this condition is crucial to reduce unexpected surgical complications.

Phase II study of SHR1210 and trastuzumab in combination with CAPOX for neoadjuvant treatment of HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

296 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer. PANTHERA study had showed a significant tumor shrinkage for HER2 positive advanced gastric cancer treated with anti-PD-1 agent, transtuzumab and chemotherapy. SHR1210, a human IgG4 monoclonal antibody that binds to PD-1, has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the addition of SHR1210 and trastuzumab to CAPOX for neoadjuvant treatment of HER2-positive gastric or GEJ adenocarcinoma. Methods: In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable HER2-positive gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of transtuzumab (loading dose of 8mg/kg, with subsequent doses of 6 mg/kg, q3w) and CAPOX (oxaliplatin 130 mg/m2 day 1, capecitabine 1000 mg/ m2 bid po day 1-14, q3w) in combination with 3 cycles of SHR1210 (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of CAPOX. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). This trial is registered with ClinicalTrials.gov, number NCT03950271. Results: Between Jan 20, 2020, and Sept 15, 2021, 22 patients were enrolled and commenced treatment. Four patients had not completed neoadjuvant treatment. Twopatitents refused surgery. Sixteen patients who experienced D2 resection, 9 (56.3%) achieved MPR, including 5 (31.3%) with pCR (ypT0N0M0). The R0 rese-ction rate was 100%. The ORR was 77.3%. The main grade 3 or 4 treatment-related adverse events (TRAEs) included lymphocytopenia (22.7%), neutropenia(13.6%), thrombocytopenia (13.6%) and anaemia (5%). Most frequent grade 1 or 2 TRAEs were Nausea (68.2%), lymphocytopenia (63.6%), leukopenia (59.1%), Anaemia (59.1%), Thrombocytopenia (50%), Serum aspartate aminotransfe-rase increased (45.5%) and hypothyroidism (31.8%). There was no surgical del-ays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of SHR1210, transtuzumab and CAPOX is a safe and efficacious treatment option for patients with HER2-positive gastric or GEJ adenocarcinoma. More importantly, 31.3% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: NCT03950271.

442 COVID-19 And the Oral Surgery/Orthodontic Interface: Has A Delay in Treatment Complicated the Position of Unerupted And Ectopic Teeth Planned for Surgical Removal or Exposure?

Abstract Aim To evaluate whether there has been a change in clinical or radiographic position and the resultant occurrence of complications of unerupted and ectopic teeth due to delayed treatment during the COVID-19 pandemic Method Data was collected over a three-month period at the Royal United Hospital, Bath, Oral and Maxillofacial Surgery Department. This was via a questionnaire distributed to clinicians and prospectively completed for each surgical procedure planned for the removal or exposure of ectopic canines, premolars, and supernumerary teeth. Results A total of 20 surgical extractions or exposures were performed during the three-month period, with 33% (n = 6) having a marked difference between their expected and final position. Complications occurred in 66.6% (n = 4) of cases that demonstrated a discrepancy in location. These were an increased surgical time, increased removal of bone or a cancellation of intended treatment. This cancellation occurred as the tooth had erupted enough for non-surgical management. In cases where there was no discrepancy (n = 14), no complications were reported. Conclusions These findings suggest the delay in treatment caused by the COVID-19 pandemic has resulted in a clinically significant change in the position of ectopic teeth planned for surgical removal or exposure. Given these findings, it is crucial that clinicians be aware that radiographic investigations are diagnostic and recent. The threshold for repeat imaging in all cases which have been delayed should be low to avoid unexpected surgical complications arising from inaccuracy in tooth localisation.

Interim analysis for window of opportunity trial of single dose preoperative durvalumab (D) with or without tremelimumab (T) for operable head and neck squamous cell carcinoma (HNSCC).

e18043 Background: We aim to evaluate the efficacy and safety for single dose of preoperative D with or without T in patients with operable HNSCC with immune correlates. Methods: Patients with histologically confirmed, potentially resectable, stage II, III, and IVA HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma (HPV) infection status assessed by p16 expression. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered and followed 2 to 8 weeks later by surgical tumor resection with curative intent. Postoperative (chemo) radiation (PO-CRT) was planned based on standard guidelines, followed by maintenance with D every 4 weeks for one year. Pathology response was quantified as the proportion of the resection bed with viable tumor, tumor necrosis, fibrosis, and inflammation. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety and tolerability, disease-free survival, and immune dynamics incorporating multiple immunofluorescence and single cell transcriptomic analysis. A total 48 patients are planned to be enrolled. Results: As of Jan. 31, 2021, a total 36 patients were enrolled and received surgical resections with available data for pathologic response (D: 16 patients, D+T: 20 patients). Patient characteristics of both arms were well-balanced: hypopharynx/larynx/oral cavity as primary site (12.5%/12.5%/18.8%/56.3% in D, 20.0%/10.0%/10.0%/60.0% in D+T); HPV positivity (50.0% in D, 50.0% in D+T); cT1/T2/T3/T4 (6.3%/37.5%/31.3%/25.0% in D, 10.0%/25.0%/40.0%/25.0% in D+T); cN0/N1/N2/N3 (25.0%/18.8%/50.0%/6.3% in D, 30.0%/30.0%/40.0%/0% in D+T). Significant tumor shrinkage defined as more than 30% of size reduction was observed in 43.7% (7/16), including 2 patients with complete response in D and 20.0% (4/20) in D+T. During 128 days of median follow-ups, local recurrence was observed in 2 patients of D+T arm (5.6%). HPV positivity was numerically associated with favorable treatment response (average tumor shrinkage; -21.8% in p16-positive vs. -6.4% in p16-negative). Meaningful pathologic response was achieved in terms of tumor necrosis (average 10.3% in D, 5.5% in D+T), fibrosis (average 13.4% in D, 10.3% in D+T), and inflammation (average 15.0% in D, 5.8% in D+T), without significant differences according to HPV positivity. After preoperative D or D+T, serious adverse events and unexpected surgical complications did not occur. Conclusions: These early data suggested that preoperative D or D+T in patients with operable HNSCC was safe and feasible and had the potential to provide clinical benefits. The trial is ongoing and the updated outcomes with immune correlates including immunofluorescence and single cell transcriptomic analysis will be presented. Clinical trial information: NCT03737968.

Monocortical fixation for locking plate distal screws does not impair mechanical properties in open-wedge high tibial osteotomy

BackgroundThe neurovascular bundle containing the deep peroneal nerve has a potential risk of injury during open-wedge high tibial osteotomy (OWHTO), particularly due to drilling for bicortical fixation at distal screw holes. Therefore, monocortical fixation is recommended for distal fixation of a long locking plate as long as good stability is ensured. The purpose of this study was to analyse the biomechanical properties of monocortical fixation of distal locking screws for OWHTO.MethodsThree-dimensional models of bone and fixation materials simulating OWHTO were created using computed tomographic data of patients and material data of a T-shaped long locking plate and screws. Three of the four distal screws of the locking plate were chosen for a bicortical fixation or monocortical fixation procedure. In addition, loss of correction was assessed by measuring the medial proximal tibial angle (MPTA) in patients who underwent OWHTO with two bicortical and two monocortical distal fixation screws at 1 month and 1 year after surgery.ResultsNo significant differences in stress were observed in either the normal or osteoporotic bone model between the monocortical and bicortical fixation models, including in the area of the lateral hinge at the osteotomy site.Furthermore, there were no significant differences in MPTA between the early post-operative period and 1-year follow-up.ConclusionsThe monocortical fixation method for three distal screws of the locking plate did not worsen the mechanical properties of fixation for OWHTO using a long locking plate with four proximal and four distal screws. In actual surgery, the number of distal bicortical screws should be reduced based on the patient’s condition, taking into account the risk of lateral hinge fracture and unexpected surgical complications. Using at least two bicortical screws would be practical considering the various factors related to reduced fixing ability.

Phase II study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma.

216 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer, increasing 5-year overall survival from 23% with surgery alone to 45% with FLOT, Although FLOT has been recognized as the first choice for neoadjuvant chemotherapy in gastric or GEJ adenocarcinoma, its efficacy needs to be improved. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the combination of FLOT and sintilimab for neoadjuvant treatment of gastric or GEJ adenocarcinoma. Methods: In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 80 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2, 24-h infusion on day 1, q2w) in combination with 3 cycles of sintilimab (200mg, iv, d1, q3w), followed by D2 surgery and 4 postoperative cycles of FLOT. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and R0 resection rate and adverse events . Results: A total of 20 patients were enrolled in the study between Aug 10 2019 and Sep 15 2020. One patient refused surgery, one person's disease progressed. Two patients have not yet completed neoadjuvant treatment . 16 pts who experienced D2 resection, 10 (62.5%) achieved major pathologic response (MPR), including 3 (18.8%) with a pathologic complete response (pCR) in primary tumor. The R0 resection rate was up to 93.8%, The grade 3 or 4 treatment-related adverse events (TRAE) included lymphopenia(25%), anaemia (20%),fatigue (20%),leucopenia (15%), neutropenia (5%), diarrhea(5%), Alanine aminotransferase increased(5%),There was no surgical delays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of sintilimab and FOLT is a safe and efficacious treatment option for patients with gastric or GEJ adenocarcinoma, 18.8% pCR rate and 62.5%MPR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: NCT04341857.

The challenges of venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock.

Postcardiotomy cardiogenic shock describes the syndrome of refractory cardiac performance following cardiac surgery. The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for the management of postcardiotomy cardiogenic shock is controversial, and there are at least three scenarios where it may be necessary: first, pre-emptive postoperative VA-ECMO, where the decision for postoperative mechanical support is made prior to surgery, for example, in the context of poor pre-operative cardiac function; second, early yet unplanned post-cardiopulmonary bypass VA-ECMO following a long duration of cardiopulmonary bypass due to, for example, unexpected surgical complications; third, late rescue VA-ECMO following several attempts at weaning, either immediately following cardiopulmonary bypass or following transfer to the intensive care unit. The use of mechanical circulatory support for postcardiotomy cardiogenic shock is further complicated by the wide range of available devices, the availability of VA-ECMO in different centres, variations in experience and expertise as a function of local VA-ECMO workload, and regional variations in the diagnosis and management of postcardiotomy cardiogenic shock. Furthermore, survival appears to be low for such patients and it is not yet possible to predict who will survive. Many questions remain, however, such as those in relation to practices around patient selection, how best to study long-term outcomes, the ethics and efficacy of ECMO in such patients, and on all aspects of clinical decision-making. This review sets these clinical challenges in the context of the available evidence, including that from our centre.

Results from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy.

439 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) in MIBC improves survival which correlates with pathologic response (PaR) at radical cystectomy (RC). The combination of immunotherapy and NAC may improve PaR and outcomes in MIBC. We tested the efficacy and safety of nivolumab (N) with gemcitabine-cisplatin (GC) as neoadjuvant therapy for MIBC in our phase II trial (NCT03294304). Methods: Eligible pts with MIBC (cT2-T4a, N≤1, M0) who were candidates for RC were enrolled. Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1,D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 weeks. The primary endpoint was PaR (≤pT1,N0). Secondary objectives were safety of GC+N and PFS at 2 years. The correlative objectives based on pre-treatment biopsies were correlation of PaR with 1) WGS 2) molecular subtypes of BC; 3) PD-L1 expression; 4) baseline TILs, CD3, CD8 and CD56.. Evaluable pts. should have received at least 1 dose of N. PaR will be summarized by the PaR rate as estimated by the sample proportion with exact 95% confidence intervals. We specified a null PaR of 0.35 and an alternative hypothesis of 0.55; we will reject the null hypothesis if at least 20 of 41 pts. have a PaR. Results: Between Feb 2018 and June 2019, 41 pts. were enrolled (cT2N0 90%, cT3N0 7%, cT4N1 3%); 2 patients refused surgery but were included in ITT population. PaR was observed in 27/41 pts. (65.8%), including pts with N1 disease. The combination was safe with manageable toxicities and no deaths from treatment. Majority of AEs were from GC; the overall rates of grade 3-4 AEs was 20%, majority being neutropenia, thrombocytopenia and renal insufficiency. Immune related AEs were seen in 3 patients, 2 had "adenitis" which wasymptomatic,1 pt developed Guillian Barre Syndrome after surgery, which resolved with IVIG; and none of them required steroids. There was no delay in time to RC and no unexpected surgical complications from treatment. Patients are being followed for progression and survival. Correlative work is ongoing. Conclusions: Neoadjuvant N+GC is safe and effective in MIBC with significant pathologic downstaging rates and no added toxicities or delay to surgery. Clinical trial information: NCT03294304.

Safety of neoadjuvant chemoradiation (CRT) in combination with avelumab (A) in the treatment of resectable esophageal and gastroesophageal junction (E/GEJ) cancer.

4041 Background: Neoadjuvant CRT followed by surgery is the standard of care (SOC) for patients (pts) with stage II/III E/GEJ cancer. However, recurrence rates are high. Immunotherapy has demonstrated promising activity in advanced E/GEJ cancer. This trial evaluates safety and efficacy of perioperative A with CRT in resectable E/GEJ cancer. Methods: This is a 2-part phase I/II trial. Part 1 is a run-in phase with 6 pts for safety evaluation. Part 2 will enroll additional 18 pts in the expansion cohort. Pts with E/GEJ cancer of any histology receive CRT (41.4 Gy in 23 fractions) with carboplatin and paclitaxel as per SOC. Three doses of A (10 mg/kg, q14 days) are administered starting on day 29 of treatment, to coincide with the last chemotherapy dose. Surgery is performed ~8 weeks after CRT completion. Pts receive 6 doses of A after resection. Dose-limiting toxicity (DLT) evaluations are completed on the first post-operative clinic visit, 2-4 weeks post resection. Results: Between 6/2018 and 2/2019, 6 pts (all male, median age 62) enrolled in part 1: 6 adenocarcinoma (100%); 1 E, 3 Siewert 1, 2 Siewert 2; 1 cT2N0, 2 cT3N0, 3 cT3N1. All pts underwent successful resection with negative surgical margins. 1/6 pts had R1 resection due to tumor extension to inked adventitial surface without invasion of surrounding structures. There were no unexpected surgical complications. At resection, 2 pts had ypT0N0, 2 ypT1N0, 1 ypT2N0, and 1 ypT3N1 disease. Combination of CRT and A had an acceptable toxicity profile. No DLTs were seen in the first 5 pts, so expansion cohort is open to enrollment. No grade ≥3 immune-related AEs were observed. Immune-related hypothyroidism was seen in 1 patient (grade 2). 6/6 pts had reversible grade 3 or 4 lymphopenia; 1/6 had grade 3 neutropenia. Correlative studies are ongoing and will be presented at the meeting. Conclusions: Perioperative CRT with A is well tolerated with no unexpected toxicities. Additional safety and correlative data will be presented at the meeting. This study is actively enrolling pts to an expansion cohort at University of Wisconsin. Clinical trial information: NCT03490292.

Pre-duodenal Portal Vein and Its Rare Association With a Meckelʼs Diverticulum in a Pediatric Patient

A pre-duodenal portal vein (PDPV) is a congenital anomaly, that is rare in both pediatric and adult patients. PDPV results from persistence of a primitive vitelline vein, and rather than passing inferiorly and behind the pancreas, the portal vein crosses in front of the duodenum and pancreas. PDPV is usually found as an incidental finding during surgeries of the gastrointestinal tract but has been can cause an extrinsic compression of the duodenum leading to intestinal obstruction. PDPV association with such a complication is extremely rare. In fact, in a 25-year retrospective study in a single center, PDPV was found only in five neonates. In all of them, the PDPV was asymptomatic, and the duodenal obstruction was due to associated malformations, such as malrotation, duodenal atresia, duodenal web, or annular pancreas. Most of the cases of PDPV reported have been described in association with other congenital anomalies including heterotaxia, polysplenia syndrome, situs inversus, cardiac defects, malrotation, biliary or duodenal atresia, and annular pancreas. To our knowledge, out of the 100 pediatric and adult cases reported, an association with a Meckel's diverticulum has never been described. We hereby, report a 14-month old male with a history of heterotaxy syndrome, left atrial isomerism, severe gastroesophageal reflux disease, and failure to thrive with malrotation that was noted on an upper GI series. Surgical exploration revealed affixation of the midgut without volvulus without dilatation of the duodenum. A vascular structure crossing the duodenum anteriorly was noted, and identified, as a PDPV in association with a Meckel's diverticulum, which was removed. The PDPV was left in place, since no signs of duodenal obstruction or inflammation were noted. Although, an incidental finding, this anomaly is of great surgical importance as it can cause unexpected surgical complications from accidental injury to the portal vein. Therefore, knowledge of this anomaly is essential for avoiding injuries during laparotomy for surgical correction of gastrointestinal anomalies such as malrotation.