BACKGROUND:Our aim was to describe the clinical outcomes of surgical interventions performed for the management of colonoscopy-related perforations and to compare these outcomes with those of matched colorectal surgeries performed in elective and emergency settings.METHODS:We included patients with endoscopic colonic perforation who underwent surgical intervention from the 2014-2017 National Surgery Quality Improvement Program participant use data colorectal targeted procedure file. The primary outcome in this study was short term surgical morbidity and mortality. Patients (group 1) were matched with 1:2 ratio to control patients undergoing same surgical interventions for other indications on an elective (group 2) or emergency basis (group 3). Bivariate analysis was conducted to compare categorical variables between the three groups, and multivariate logistic regression was used to evaluate the association between the surgical indication and 30-day postoperative outcomes.RESULTS:A total of 590 patients were included. The average age of the patients was 66.5±13.6 with female gender predominance (381, 64.6%) The majority of patients underwent open colectomy (365, 61.9%) while the rest had suturing (140, 23.7%) and laparoscopic colectomy (85, 14.4%). Overall mortality occurred in 4.1% and no statistically significant difference in mortality was found between the three techniques (P=0.468). Composite morbidity occurred in 163 patients (27.6%). It was significantly lower in laparoscopic colectomy (14.1%) compared to 30.2% and 29.4% in open colectomy and suturing approaches (P=0.014). Patients undergoing colectomy for iatrogenic colonic perforation had less mortality, infection rates and sepsis, as well as bleeding episodes compared to those who had colectomy on an emergent basis. Outcomes were comparable between the former group and patients undergoing elective colectomy for other indications.CONCLUSIONS:Surgical management of colonoscopy related perforations is safe and effective with outcomes that are similar to that of patients undergoing elective colectomy.

Introduction: Cystic hydatidosis is a parasitic infection caused by the organism Echinococcus Granulosus that is well known to be endemic in the Mediterranean region, eastern Europe and South America and usually presents as hydatid disease of the liver but may affect other organs. The disease occurs when humans become the acci-dental host through ingestion of the eggs from contaminated food.Case presentation: We present a case of Hydatid disease presenting as hives refractory to medical therapy over 4 years duration which was revealed to be caused by para-rectal hydatid cysts. Patient received Albendazole for a duration of 2.5 months and then underwent laparoscopic resection of the para-rectal cysts.Clinical discussion: Pelvic Hydatidosis is a very rare condition accounting for 0.7 % of all cases reported. In most cases, it is coexistent with cysts present elsewhere in the body, namely the liver, which is the case in the pre-sented patient. Imaging is used as a modality to establish the diagnosis of cystic hydatidosis namely Ultrasound (US), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI). The incidental finding of the hydatid cysts in this patient demonstrated the efficiency of a CT scan as a tool for detection and subsequently diagnosis of the disease in the pelvis. Surgery is the treatment of choice for cysts with daughter vesicles that are not candidates for percutaneous drainage, large liver hydatid cysts of more than 10 cm in diameter, cysts with a risk of rupture in case of trauma, and extrahepatic disease such as the lung, bone, brain, kidneys or pelvis.Conclusion: This article reports the rare occurrence of para-rectal hydatid disease which is only described in few case reports in the literature and provides an overview on diagnosis, and management of the disease.

BACKGROUND:International medical graduates (IMGs) have been a critical part of the USA healthcare in the past 30 years, especially in small rural and poor counties. However, little to no publications are present on the distribution of these IMGs across general surgery residency programs.METHODS:All freely accessible information on current residents in accredited general surgery residency programs within the USA with at least a 5-year history was explored for IMGs in the current roster using the AMA residency and fellowship database in 2020. Demographic and geographic data were summarized.RESULTS:A total of 230 general surgery residency program were included. Programs were distributed among 46 (92%) states. Of a total 6304 categorical general surgery residents, 573 (9%) were IMGs. Florida (USA) had the highest total number of current IMG general surgery residents with 64. The highest percentage of current IMG residents was found in Maryland (USA) with 31%. IMGs obtained their medical degrees from 76 different countries worldwide. Grenada was the country with the highest origin of IMGs with 77 residents. Central/North America had the highest origin of IMGs with 217 (38%).CONCLUSIONS:IMGs make up a small portion of current general surgery residents in USA programs. Some states host more IMGs than others. Particular countries have contributed more IMGs than others. More research is needed to the challenges facing IMGs and come up with novel solutions for them.

BACKGROUND: The two approaches for performing cholecystectomy are open and laparoscopic ones. This study aims to characterize national trends of cholecystectomies in the United States (US) and determine differences by approach, age group, primary payer, teaching status and location of healthcare center. METHODS: Retrospective analysis of patients undergoing cholecystectomy was done using the US National Inpatient Sample from 1997 to 2011. Trends in open and laparoscopic cholecystectomy were analyzed, as well as comparison between age groups, primary payer, location and teaching status of hospitals operations were performed at. RESULTS: Around 6 million cholecystectomies performed from 1997 to 2011. The laparoscopic approach was significantly more common than the open (P<0.001). A significant decrease in open cholecystectomies is seen since 1997. Age group of 65-84 had significantly the most cases in the open approach (P<0.001), while in laparoscopic the 18-44 age group had the significantly highest amount (P<0.001). Medicare covered the most cases for open, while private insurance covered the most in the laparoscopic approach. Most cases were performed in urban, private non-profit, non-teaching hospitals in both groups. In the laparoscopic group the South had a significantly higher (P<0.001) number of cases compared to all other US regions. CONCLUSIONS: Cholecystectomies remained constant from 1997 to 2011. The number of open cholecystectomies decreased over time in favor of laparoscopic ones. More funding should be given to private non-teaching hospitals as they perform the majority of cholecystectomies nationwide. Better management of cholecystectomy risk factors is needed in the South.

BACKGROUND:Hepatopancreaticobiliary (HPB) diseases carry high morbidity despite efforts aimed at their reduction. An assessment of their trial characteristics is paramount to determine trial design adequacy and highlight areas for improvement. As such, the aim of this study is to assess HPB surgery trial characteristics, summarize logistic, financial, and practical reasons behind early discontinuation, and propose potential interventions to prevent this in the future.METHODS:All clinical trials investigating HPB surgery registered on ClinicalTrials.gov from October 1st, 2007 (inclusive), to April 20th, 2021 (inclusive), were examined. Trial characteristics were collected including, but not limited to, study phase, duration, patient enrollment size, location, and study design. Peer-reviewed publications associated with the selected trials were also assessed to determine outcome reporting.RESULTS:A total of 1776 clinical trials conducted in 43 countries were identified, the majority of which were conducted in the USA. Of these trials, 32% were reported as "completed" whereas 12% were "discontinued." The most common cause of trial discontinuation was low accrual, which was reported in 37% of terminated studies. These resulted in 413 published studies. Most trials had multiple assignment, randomized, or open-label designs. Treatment was the most common study objective (73%) with pharmacological therapy being the most commonly studied intervention.CONCLUSIONS:The main reasons for early discontinuation of clinical trials in HPB surgery are poor patient recruitment and inadequate funding. Improved trial design, recruitment strategies and increased funding are needed to prevent trial discontinuation and increase publication rates of HPB surgery clinical trials.

The aim of this study is to identify the optimal timing for cholecystectomy for acute cholecystitis. Patients undergoing cholecystectomy for acute cholecystitis from the National Surgery Quality Improvement Program database between 2014 and 2016 were included. The patients were divided into 4 groups, those who underwent surgery at days 0, 1, 2, or 3+ days. The primary outcome was short-term surgical morbidity and mortality. A total of 21,392 patients were included. After adjusting for confounders, compared to day 0 patients, those who underwent surgery at day 1 and day 2 had lower composite morbidity rate, while day 3+ patients had significantly higher bleeding and mortality rate. Subgroup analysis shows this trend to be more significant in the elderly and in diabetic patients who were delayed. Delay in cholecystectomy for over 72 h from admission is associated with statistically significant increase in bleeding and mortality.

Lesson Colonic lipomas are rare benign tumours that are usually asymptomatic. However, giant colonic lipomas tend to be symptomatic and can occasionally result in intussusception and intermittent colonic obstruction. As adult intussusception is an uncommon occurrence, the identification of the underlying aetiology is essential due to its high association with malignancy. Computed Tomography remains the tool of choice for the diagnosis of colonic lipomas. Surgical excision remains the mainstay treatment of giant symptomatic colonic lipomas. We hereby present the case of a 51-year-old male found to have a colonic lipoma causing recurrent intussusception. We discuss the approach, diagnostic tools and available treatment modalities for colonic lipomas. We also provide a brief literature review of intussusception in adults.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor that can affect multiple organs. Little is known about the pathophysiology, clinical course and management of this disease. The aim of this study is to determine survival rates and elucidate the role of various prognostic factors and therapeutic modalities as compared to surgery on patients with HEH. A retrospective analysis on patients diagnosed with HEH between 2004 and 2016 was performed utilizing the SEER database. Kaplan–Meier curves were constructed to determine overall and cancer-specific survival, and the log-rank test was used to compare between groups. To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed. A total of 353 patients with HEH (median age: 50.4 years) were identified. The most common surgery performed was liver resection (90.8%). One-year OS in the surgical group and non-surgical group was 86.6% and 61.0%, respectively, while 5-year OS was 75.2% and 37.4%, respectively. On multivariable analysis, surgery emerged as a favorable prognostic factor [HR (95%CI): 0.404 (0.215–0.758) p value = 0.005]. Age > 65 years [HR (95%CI): 2.548 (1.442–4.506) p value = 0.001] and tumor size > 10 cm [HR (95%CI): 2.401 (1.319–4.37) p value = 0.004] were shown to be poor survival prognostic factors. HEH is a rare disease that is poorly understood. Surgical intervention is associated with improved survival rates. Multicenter prospective collaborations are needed to improve our limited knowledge about this neoplasm and determine the optimal treatment strategy.

The Internet has become a central source of information on health-related issues. The aim of this study is to assess the quality and readability of online information present on the Whipple surgical procedure by applying recognized scoring tools. A search using the top three online search engines (Google, Bing and Yahoo) was conducted in July 2020. Websites were classified as academic, physician, commercial or unspecified. The quality of information was assessed using the JAMA and DISCERN assessment instruments and presence of a HONcode seal. Readability was assessed using the Flesch Reading Ease Score (FRES). A total of 34 unique sources were included in our study. The average JAMA and DISCERN scores of all websites were 2.22 ± 0.48 and 47.28 ± 1.17, respectively, with a median of 1.9 (range 0–4) and 47 (range 18–71), respectively. Website classification distribution was 38% academic, 18% commercial, 9% unspecified, and 1% from physician-based websites. Physician websites had the highest JAMA score with a mean of 3 ± 0.46. Unspecified websites had the highest DISCERN score with a mean of 54.60 ± 1.09. Only 3 websites had the HONcode seal. Physician websites had a significantly higher JAMA mean score than academic websites (p-value = 0.004). Readability was difficult and is on the level of university students. The results of this study show a poor quality of online information present on the Whipple surgery. Academic and physician websites need to improve the quality of their websites on the procedure. More HONcode-certified websites are needed as they are the best source for information on this operation.

The use robotics in surgery is gaining momentum. This approach holds substantial promise in pancreas surgery. Robotic surgery for pancreatic lesions and malignancies has become well accepted and is expanding to more and more center annually. The number of centers using robotics in pancreatic surgery is rapidly increasing. The most studied robotic pancreas surgeries are pancreaticoduodenectomy and distal pancreatectomy. Most studies are in their early phases, but they report that robotic pancreas surgery is safe feasible. Robotic pancreas surgery offers several advantages over open and laparoscopic techniques. Data regarding costs of robotics versus conventional techniques is still lacking. Robotic pancreas surgery is still in its early stages. It holds promise to become the new surgical standard for pancreatic resections in the future, however, more research is still needed to establish its safety, cost effectiveness and efficacy in providing the best outcomes.

Liver function tests (LFTs) use for common bile duct stone (CBDS) prediction in acute cholecystitis (AC) patients is challenging, especially in patients with chronic cholecystitis (CC) history.This study aims to describe characteristics of AC patients with CC history and assess LFTs' utility for CBDS prediction in these patients.A retrospective cohort study was conducted on adults with a diagnosis of AC and CC history included in the National Surgical Quality Improvement Program database from 2008 to 2016. Patients were categorized into CBDS- (without CBDS) and CBDS+ (with CBDS). Multivariate logistic regression was used to determine CBDS predictors.This study included 7458 patients, of which 40.2% were CBDS+. CBDS+ patients were more commonly females (64.4% vs 54.7%, P < .001). Mean levels of bilirubin (1.70 vs 0.90, P < .001), SGOT (105.9 vs 49.0, P < .001) and ALP (164.6 vs 103.8, P < .001) were significantly higher among CBDS+ patients.Significant positive predictors of CBDS were female gender, increased BMI, and abnormal bilirubin, ALP and SGOT. AC patients with CC history are more likely to have CBDS. Abnormal LFTs are significantly associated with CBDS in this patient population. Familiarity with these findings can help raise clinical suspicion of providers for earlier evaluation and management of CBDS.

BACKGROUND:Gastric cancer (GC) is the third most common cause of malignancy associated mortality globally. The cornerstone of curative treatment involves surgical gastrectomy. In this study, we explore clinical trials involving gastrectomy for GC, highlighting inadequacies and underlining promising surgical interventions and strategies.MATERIALS AND METHODS:On 1 May 2020, ClinicalTrials.gov was explored for interventional trials related to gastrectomy for GC, without adding limitations for location or date. All data pertaining to the trials were collected. Characteristics such as phase, duration, enrolment size, location, treatment allocation, masking and primary endpoint were analysed.RESULTS:One hundred thirty-eight clinical trials met the search criteria. Clinical trials were performed in only 14 countries; most of them occurring in China. Most trials (33%) were still in the recruiting phase. On average, the length of trials was 3.9 years. Most trials had parallel assignment, were randomised and masked. The primary endpoint which was mostly commonly studied was overall survival (33%). The most common intervention studied is laparoscopic gastrectomy in 43 (31%) trials.CONCLUSIONS:Our study exposed a small number of trials, publication rate, absence of geographic variety in clinical trials involving gastrectomy for GC. Adequate management of trial design can help decrease duration and increase validity of results. More trials comparing different surgical techniques are needed to update the surgical practice of gastrectomy for GC.

Background: The use of ACS-NSQIP has increased in pancreatic surgery (PS) research. The aim of this study is to critically appraise the methodological reporting of PS publications utilizing the ACS-NSQIP database. Study design: PubMed was queried for all PS studies employing the ACS-NSQIP database published between 2004 and 2021. Critical appraisal was performed using the JAMA-Surgery Checklist, STROBE Statement, and RECORD Statement. Results: A total of 86 studies were included. Median scores for number of fulfilled criteria for the JAMASurgery Checklist, STROBE Statement, and RECORD Statement were 6, 20, and 6 respectively. The most commonly unfulfilled criteria were those relating to discussion of missed data, compliance with IRB, unadjusted and adjusted outcomes, providing supplementary/raw information, and performing subgroup analyses. Conclusion: An overall satisfactory reporting of methodology is present among PS studies utilizing the ACS-NSQIP database. Areas for improved adherence include discussing missed data, providing supplementary information, and performing subgroup analysis. Due to the increasing role of large-scale databases, enhanced adherence to reporting guidelines may advance PS research.(c) 2021 Elsevier Inc. All rights reserved.

Abstract Locally advanced and borderline resectable pancreatic cancers are being increasingly recognized as a result of significant improvements in imaging modalities. The main tools used in diagnosis of these tumors include endoscopic ultrasound, computed tomography, magnetic resonance imaging, and diagnostic laparoscopy. The definition of what constitutes a locally advanced or borderline resectable tumor is still controversial to this day. Borderline resectable tumors have been treated with neoadjuvant therapy approaches that aim at reducing tumor size, thus improving the chances of an R0 resection. Both chemotherapy and radiotherapy (solo or in combination) have been used in this setting. The main chemotherapy agents that have shown to increase resectability and survival are FOLFORINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine–nab-paclitaxel. Surgery on these tumors remains a significantly challenging task for pancreatic surgeons. More studies are needed to determine the best agents to be used in the neoadjuvant and adjuvant settings, biologic markers for prognostic and operative predictions, and validation of previously published retrospective results.

BackgroundCurrent standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy.This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer.MethodsThe study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression.DiscussionRecent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC.Trial registrationTrial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (< 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.

Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here we examine the influence of pre-operative significant weight loss on venous thromboembolism (VTE) risk and determine whether pre-operative BMI and albumin could influence VTE outcomes in patients who have lost significant weight prior to surgery.Methods: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and identified 103,455 colorectal cancer patients undergoing major surgery from 2008 to 2012. Patients were assigned to one of two groups based on whether they lost significant weight preoperatively or not. Simple and stepwise multiple logistic regressions were used to evaluate the association between pre-operative unintended weight loss and 30-days postoperative outcomes. The association between weight loss and postoperative thrombosis was further assessed across several strata.Results: The overall prevalence of pre-operative significant weight loss was 6.8%. Significant weight loss prior to surgery was significantly and independently associated with a higher risk of VTE (adjusted OR 1.23, 95% CI 1.06-1.44), mortality (adjusted OR 1.55, 95% CI 1.35-1.78), composite morbidity (adjusted OR 1.52, 95% CI 1.42-1.62), bleeding (adjusted OR 1.78, 95% CI 1.67-1.91) and return to operation room (adjusted OR 1.29, 95% CI 1.16-1.42). The effect of pre-operative significant weight loss on thromboembolic outcome was evident across patients with a BMI <18.5 kg/m2, 18.5 < BMI < 24.99 and BMI >40kg/m2.Conclusions: Significant weight loss and BMI both need to be measured preoperatively to stratify patients who are at a higher risk of VTE.

e18060 Background: To evaluate the impact of timing and extent of cytoreduction on the survival of patients with EOC before (2002-2008) and after (2009-2018) the introduction of aggressive debulking. Methods: A retrospective review of 195 patients with Stages IIIC and IV EOC who underwent debulking between 2002-2018 (Group#1: G1:(2002-2008), and Group#2: G2:(2009-2018). Medical and surgical variables related to PFS and OS were analyzed. Results: Compared to patients in G1, more patients in G2 had neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) [56%(39/70 Vs. 76%(95/125) Vs), p = 0.003], had complete debulking (CD) [44%(31/71) Vs. 79%(103/131), P-value < 0.001]including [diaphragmatic resection [6%(4/72) Vs. 48%(63/131) p < 0.001], bowel ressection [15%(11/72) Vs. 37%(48/131), p = 0.001], peritnoectomy [11%(8/72) Vs. 62%(81/131) p < 0.001], and lymph node dissection [8%(6/72) Vs. 26%(34/131) p = 0.003] .More patients in G2 received Bevacizumab than in G1 [59%(38/65) Vs. 14%(4/29), p < 0.001]. More patients who had ACT and IDS had CD than optimal debulking (OD) than patients who had (PDS) (adjusted odds ratio (aOR) = 1.89, 95% CI: 0.98,3.6). After 2008, there was an increase in the number of patients with high tumor load and lower performance status who were referred for NACT and IDS. In patients with stage IIIC and IV, median PFS was longer in patients who had CD Vs. OD [in stage IIIC: 24 months, 95% CI: 21,27 Vs. 19 months, 95% CI: 17, 21, HR = 0.4, p = 0.006 respectively] [in stage IV: 18 months, 95% CI: 16,20 Vs. 14 months, 95% CI: 9,18, HR = 0.4, p = 0.1 respectively].Patients with stage IIIC who had PDS Vs. NACT and IDS had a non-statistically significant longer PFS [24 months, 95% CI; 20,27 Vs. 19 months, 95% CI: 17,21, HR = 0.8, p = 0.3]. Moreover, in stage IV, there was no difference in PFS in NACT and IDS Vs. PDS [16 months, 95% CI: 12,20 Vs. 17 months, 95% CI: 15,19 HR = 0.8, p = 0.7 respectively]. However, the timing and extent of the cytoreductive surgery did not significantly affect OS in both stages IIIC and IV. Conclusions: In Stage IIIC EOC, the extent but not timing of debulking surgery has the greatest impact on PFS. Longer follow-up is needed to assess the impact on OS.

Immunoscore is a validated prognostic tool in colon cancer that measures the densities of CD3 and CD8 positive T-lymphocytes at the tumor center and invasive margin. The aim of the present study was to evaluate the prognostic value of Immunoscore in the treatment of rectal cancer. Clinical (age, gender, clinical stage) and microscopic variables (Immunoscore, PD-L1 expression, tumor regression grade [TRG], apoptotic index, mitotic index, microvascular density assessed in normal and tumor tissue) were collected from patients diagnosed with locally advanced rectal cancer. Tissue samples were collected at diagnostic baseline biopsy, post-radiation and post mFOLFOX and avelumab with resection. Responders were defined as patients with > 95% pathological response on resection specimen. Trial registration number is NCT03503630. Fourteen patients were analyzed, 10 (71%) men and 4 (29%) women with a median age of 58 (34-73) years. Out of the 13 patients that underwent surgery, 7 were responders and 6 were non-responders. The optimal baseline Immunoscore cutoff in our population derived from the receiver operating characteristics (ROC) curve to distinguish between responders and non-responders was 61.8%. The mean Immunoscore in responders was 63.4% in comparison to 40.6% in non-responders. The mean Immunoscore also decreased post-radiation from 52.0% to 41.2%. Responders had higher CD8 positive cells in the invasive margin of tumor tissue post-radiation. In the normal tissue, radiation did not increase the CD3, CD4 or CD8 positive cells, while mFOLFOX and avelumab increased those counts (p< 0.05). In the tumor tissue, the mean CD8 positive cells in the invasive margin increased after mFOLFOX and avelumab and not radiation (p< 0.05). At diagnosis, all cases had negative PD-L1 expression in tumor cells. Post radiation, 2 cases switched to positive expression, which switched back to negative expression after mFOLFOX and avelumab. PD-L1 expression in the inflammatory environment increased in both normal and tumor tissues after radiation (p< 0.05); however, no difference between responders and non-responders was documented. There was a significant increase in the apoptotic index and microvascular density post-radiation (p< 0.05) in contrast to the mitotic index in both responders and non-responders (p< 0.05). A directly proportional correlation was found between the post-radiation Immunoscore and post-radiation apoptotic index in tumors (p< 0.05). However, no such correlation was found among Immunoscore, mitoses and microvascular density. Of note, microvascular density decreased after mFOLFOX and avelumab (p< 0.05). None of the patients involved in this cohort had microsatellite instability-high status. Despite the limited number of patients in our cohort, our customized Immunoscore showed that higher Immunoscore levels are associated with better tumor regression grade. This trial illustrated not only the tumor landscape evolution through radiation and mFOLFOX with avelumab treatment in locally advanced rectal cancer patients but also the predictors of response and progression in normal tissue in tumor vicinity.