Hepatic Artery Anomalies in Pancreaticoduodenectomy: Outcomes from a High-Volume Center.

INTRODUCTION: Hepatic artery anomalies (HAA) may have an impact on surgical and oncological outcomes of patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at our institution between July 2015 and January 2020 were retrospectively reviewed and classified into two groups: group 1, with presence of HAA, and group 2, with no HAA. A weighted logistic regression model was employed to assess the association between HAA and postoperative complications, and to assess the association between HAA and R status in patients with pancreatic cancer. RESULTS: 502 patients were considered for analysis, with 75 (15%) of them in group 1. They had either an accessory (n = 28, 40.8%) or replaced (n = 26, 36.6%) right hepatic artery. Most patients underwent surgery for a malignancy (n = 451; 90%); among them, vascular resection was performed in 69 cases (15%). The presence of a HAA was reported at preoperative imaging only in 4 cases (5%) and the aberrant vessel was preserved in 72% of patients. At weighted multivariable logistic regression analysis, HAA were not associated to higher odds of morbidity (odds ratio [OR]: 0.753, 95% confidence interval [CI]: 0.543-1.043) nor to R1 status in case of pancreatic cancer (OR: 1.583, 95% CI: 0.979-2.561). CONCLUSION: At our institution, the presence of HAA does not have an impact on postoperative outcomes or affects oncological clearance after PD. Hospitals', surgeons', volume and systematic review of preoperative imaging are all factors that help reduce possible adverse events.

IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients - a cohort study.

BACKGROUND: Studies evaluating sex differences in colorectal cancer (CRC) tumor microenvironment are limited, and no previous study has focused on rectal cancer patients' constitutive immune surveillance mechanisms. The authors aimed to assess gender-related differences in the immune microenvironment of rectal cancer patients. METHODS: A systematic review and meta-analysis were conducted up to 31 May 2021, including studies focusing on gender-related differences in the CRC tumor microenvironment. Data on the mutational profile of rectal cancer were extracted from the Cancer Genome Atlas (TCGA). A subanalysis of the two IMMUNOREACT trials (NCT04915326 and NCT04917263) was performed, aiming to detect gender-related differences in the immune microenvironment of the healthy mucosa in patients with early (IMMUNOREACT 1 cohort) and locally advanced rectal cancer following neoadjuvant therapy (IMMUNOREACT 2 cohort). In the retrospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 442 patients (177 female and 265 male), while in the retrospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), we enrolled 264 patients (80 female and 184 male). In the prospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 72 patients (26 female and 46 male), while in the prospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), the authors enrolled 105 patients (42 female and 63 male). RESULTS: Seven studies reported PD-L1 expression in the CRC microenvironment, but no significant difference could be identified between the sexes. In the TGCA series, mutations of SYNE1 and RYR2 were significantly more frequent in male patients with rectal cancer. In the IMMUNOREACT 1 cohort, male patients had a higher expression of epithelial cells expressing HLA class I, while female patients had a higher number of activated CD4+Th1 cells. Female patients in the IMMUNOREACT 2 cohort showed a higher infiltration of epithelial cells expressing CD86 and activated cytotoxic T cells (P=0.01). CONCLUSIONS: Male patients have more frequent oncogene mutations associated with a lower expression of T-cell activation genes. In the healthy mucosa of female patients, more Th1 cells and cytotoxic T cells suggest a potentially better immune response to the tumor. Sex should be considered when defining the treatment strategy for rectal cancer patients or designing prognostic scores.

Rectal Sparing Approaches after Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-Analysis Comparing Local Excision and Watch and Wait.

Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31-2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75-3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20-3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37-1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.

Limits of Clinical Restaging in Detecting Responders After Neoadjuvant Therapies for Rectal Cancer.

BACKGROUND: Accurate clinical restaging is required to select patients who respond to neoadjuvant chemoradiotherapy for locally advanced rectal cancer and who may benefit from an organ preservation strategy. OBJECTIVE: The purpose of this study was to review our experience with the clinical restaging of rectal cancer after neoadjuvant therapy to assess its accuracy in detecting major and pathological complete response to treatment. DESIGN: This was a retrospective cohort study. SETTING: This study was conducted at 2 high-volume Italian centers for Colorectal Surgery. PATIENTS: Data were included from all consecutive patients who underwent neoadjuvant therapy and surgery for locally advanced rectal cancer from January 2012 to July 2020. Criteria to define clinical response were no palpable mass, a superficial ulcer <2 cm (major response), or no mucosal abnormality (complete response) at endoscopy and no metastatic nodes at MRI. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, positive predictive values, and negative predictive values of clinical restaging in detecting pathological complete response (ypT0) or major pathological response (ypT0-1) after neoadjuvant therapy. RESULTS: A total of 333 patients were included; 81 (24.3%) had a complete response whereas 115 (34.5%) had a pathological major response. Accuracy for clinical complete response was 80.8% and for major clinical response was 72.9%. Sensitivity was low for both clinical complete response (37.5%) in detecting ypT0 and clinical major response (59.3%) in detecting ypT0-1. Positive predictive value was 68.2% for ypT0 and 60.4% for ypT0-1. LIMITATIONS: The main limitation of the study its retrospective nature. CONCLUSION: Accuracy of actual clinical criteria to define pathological complete response or pathological major response is poor. Failure to achieve good sensitivity and precision is a major limiting factor in the clinical setting. Current clinical assessments need to be revised to account for indications for rectal preservation after neoadjuvant chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/C63 . LMITES DE LA REESTADIFICACIN CLNICA EN LA DETECCIN DE RESPONDEDORES DESPUS DE TERAPIAS NEOADYUVANTES PARA EL CNCER DE RECTO: ANTECEDENTES:Se requiere una nueva reestadificación clínica precisa para seleccionar pacientes que respondan a la quimiorradioterapia neoadyuvante para el cáncer de recto localmente avanzado y que puedan beneficiarse de una estrategia de preservación de órganos.OBJETIVO:El propósito de este estudio fue revisar nuestra experiencia con la reestadificación clínica del cáncer de recto después de la terapia neoadyuvante para evaluar su precisión en la detección de una respuesta patológica importante y completa al tratamiento.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Este estudio se realizó en dos centros italianos de alto volumen para cirugía colorrectal.PACIENTES:Incluimos datos de todos los pacientes consecutivos que se sometieron a terapia neoadyuvante y cirugía por cáncer de recto localmente avanzado desde enero de 2012 hasta julio de 2020. Los criterios para definir la respuesta clínica fueron ausencia de masa palpable, úlcera superficial <2 cm (respuesta mayor) o ausencia de anomalías en la mucosa. (respuesta completa) en la endoscopia, y sin ganglios metastásicos en la resonancia magnética.PRINCIPALES MEDIDAS DE RESULTADO:Exploramos la sensibilidad, la especificidad, los valores predictivos positivos y negativos de la reestadificación clínica para detectar una respuesta patológica completa (ypT0) o mayor (ypT0-1) después de la terapia neoadyuvante.RESULTADOS:Se incluyeron 333 pacientes; 81 (24,3%) tuvieron una respuesta completa mientras que 115 (34,5%) tuvieron una respuesta patológica mayor. La precisión de la respuesta clínica completa y la respuesta clínica importante fue del 80,8 % y el 72,9 %, respectivamente. La sensibilidad fue baja tanto para la respuesta clínica completa (37,5 %) en la detección de ypT0 como para la respuesta clínica mayor (59,3 %) en la detección de ypT0-1. El valor predictivo positivo fue del 68,2 % para ypT0 y del 60,4 % para ypT0-1.LIMITACIONES:Nuestro estudio tiene como principal limitación su carácter retrospectivo.CONCLUSIÓNES:La precisión de los criterios clínicos reales para definir una respuesta patológica completa o mayor es pobre. El hecho de no lograr una buena sensibilidad y precisión es un factor limitante importante en el entorno clínico. La indicación para la preservación rectal después de la quimiorradioterapia neoadyuvante necesita una mejora de la evaluación clínica actual. Consulte Video Resumen en http://links.lww.com/DCR/C63 . (Traducción-Dr. Mauricio Santamaria ).

COVID-19 free pathways decrease postoperative complications in patients undergoing elective colorectal surgery.

Background: To reduce the exposition risk to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in surgical patients more prone to develop serious forms of Coronavirus disease 2019, a reorganization that previewed the creation "COVID-19-free" hospitals or units was pursued. The aim of this study was to quantify the effect of clear pathways to reduce the risk of SARS-Cov-2 transmission, on postoperative complications. Methods: Data of all consecutive patients undergoing surgical procedure for colorectal diseases, between November 2019 and July 2020 in two Italian referral centers, were retrospectively analyzed. Patients were divided into two groups: the ones underwent surgical procedures during the period before the pandemic from November 2019 to March 2020 (Group 1) (before-COVID), and those who underwent surgical procedure from April to July 2020 during the pandemic (Group 2) (during-COVID pandemic). Results: Overall, 264 patients were collected, 168 (63.4%) in Group 1 and 96 (36.4%) Group 2. Preoperative characteristics were similar between groups; during the pandemic there was a higher proportion of patients who underwent surgical procedures for malignancy compared with the period before the pandemic (92.7% vs 72%; p = 0.001). Patients in Group 2 had a lower rate of postoperative general complications (21.9% vs 34.5%; p = 0.03) and a lower rate of surgical complications (14.6% vs 25%; p = 0.05). No difference in term of medical complications, infections, and intraoperative complications were found. Minimally invasive approach (OR 0.46; 95% CI 0.04-0.83; p = 0.01) and isolation of patients (OR, 0.18; 95% CI, 0.04-0.83; p = 0.03) were independently associated with lower risk of postoperative complications. Conclusion: In this cohort study COVID-19-free pathways were significantly associated with low rate of postoperative morbidity in patients undergoing colorectal elective surgery.

Contrast-Enhanced CT Texture Analysis in Colon Cancer: Correlation with Genetic Markers.

Background: The purpose of the study was to determine whether contrast-enhanced CT texture features relate to, and can predict, the presence of specific genetic mutations involved in CRC carcinogenesis. Materials and methods: This retrospective study analyzed the pre-operative CT in the venous phase of patients with CRC, who underwent testing for mutations in the KRAS, NRAS, BRAF, and MSI genes. Using a specific software based on CT images of each patient, for each slice including the tumor a region of interest was manually drawn along the margin, obtaining the volume of interest. A total of 56 texture parameters were extracted that were compared between the wild-type gene group and the mutated gene group. A p-value of <0.05 was considered statistically significant. Results: The study included 47 patients with stage III-IV CRC. Statistically significant differences between the MSS group and the MSI group were found in four parameters: GLRLM RLNU (area under the curve (AUC) 0.72, sensitivity (SE) 77.8%, specificity (SP) 65.8%), GLZLM SZHGE (AUC 0.79, SE 88.9%, SP 65.8%), GLZLM GLNU (AUC 0.74, SE 88.9%, SP 60.5%), and GLZLM ZLNU (AUC 0.77, SE 88.9%, SP 65.8%). Conclusions: The findings support the potential role of the CT texture analysis in detecting MSI in CRC based on pre-treatment CT scans.

Very Early Recurrence After Curative-Intent Surgery for Gastric Adenocarcinoma.

BACKGROUND: Recurrence after curative-intent surgery can occur in more than 50% of gastric cancer (GC) patients. We sought to identify predictors of very early recurrence (VER) among GC patients who underwent curative-intent surgery. METHODS: A multi-institutional database of GC patients undergoing curative-intent surgery between 2000 and 2020 at 8 major institutions was queried. VER was defined as local or distant tumor recurrence within 6 months from surgery. Univariable Cox proportional hazard models were used to evaluate the predictive value of clinical-pathological features on VER. A regularized Cox regression model was employed to build a predictive model of VER and recurrence within 12 months. The discriminant ability of the Cox regularized models was evaluated by reporting a ROC curve together with the calibration plot, considering 200 runs. RESULTS: Among 1133 patients, 65 (16.0%) patients experienced a VER. Preoperative symptoms (HR 1.198), comorbidities (HR 1.289), tumor grade (HR 1.043), LNR (HR 4.339) and T stage (HR 1.639) were associated with an increased likelihood of VER. Model performance was very good at predicting VER at 6 months (AUC of 0.722) and 12 months (AUC 0.733). Two nomograms to predict 6-month and 12-month VER were built based on the predictive model. A higher nomogram score was associated with worse prognosis. There was good prediction between observed and estimated VER with minimal evidence of overfitting and good performance on internal bootstrapping validation. CONCLUSION: One in 6 patients experienced VER following curative-intent surgery for GC. Nomograms to predict risk of VER performed well on internal validation, and stratified patients into distinct prognostic groups relative to 6- and 12-months recurrence.

Early Barriers to Career Progression of Women in Surgery and Solutions to Improve Them: A Systematic Scoping Review.

OBJECTIVE: This study aims to summarize the evidence concerning the barriers that exist to the career progression of women in surgery and to provide potential solutions to overcome these obstacles. BACKGROUND: Visible and invisible impediments can hinder female doctors' pursuit of a surgical career, from choosing a surgical specialty to training opportunities and all the way through career progression. METHODS: Database search of original studies about barriers for female surgeons during choice of surgical career, residency, and career progression. A query including possible solutions such as mentorship and network was included. RESULTS: Of 4618 total articles; 4497 were excluded as duplicates, having incorrect study focus, or not being original studies; leaving 120 studies meeting the inclusion criteria. Of the articles included, 22 (18%) focused on factors affecting the pursuit of a surgical career, such as surgical work hours and limited time for outside interests, 55 (46%) analyzed the main barriers that exist during surgical residency and fellowship training, such as discrimination and sexual harassment, 27 (23%) focused on barriers to career advancement, heavy workloads, ineffective mentorship, unclear expectations for advancement, inequality in pay or work-home conflicts. Among studies reporting on possible solutions, 8 (6.5%) articles reported on the role of effective mentorship to support career advancement and to provide moral support and 8 (6.5%) on the emerging role of social media for networking. Our analysis showed how different impediments hinder surgical career progression for women, with notable consequences on burnout and attrition. CONCLUSIONS: Identification and recognition of obstacles to career progression is the first step to addressing the gender gap in surgery. Active strategies should be improved to promote a culture of diversity and to create equal opportunity for women in surgery, while implementing structured mentoring programs and investing on an adequate communication on social media to engage the future generations.

Dynamic Prediction of Survival After Curative Resection of Intrahepatic Cholangiocarcinoma: A Landmarking-Based Analysis.

BACKGROUND: The current study aimed to develop a dynamic prognostic model for patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) using landmark analysis. METHODS: Patients who underwent curative-intent surgery for ICC from 1999 to 2017 were selected from a multi-institutional international database. A landmark analysis to undertake dynamic overall survival (OS) prediction was performed. A multivariate Cox proportional hazard model was applied to measure the interaction of selected variables with time. The performance of the model was internally cross-validated via bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index. Accuracy was evaluated with calibration plots. RESULTS: Variables retained in the multivariable Cox regression OS model included age, tumor size, margin status, morphologic type, histologic grade, T and N category, and tumor recurrence. The effect of several variables on OS changed over time. Results were provided as a survival plot and the predicted probability of OS at the desired time in the future. For example, a 65-year-old patient with an intraductal, T1, grade 3 or 4 ICC measuring 3 cm who underwent an R0 resection had a calculated estimated 3-year OS of 76%. The OS estimate increased if the patient had already survived 1 year (79%). The discrimination ability of the final model was very good (C-index: 0.80). CONCLUSION: The long-term outcome for patients undergoing curative-intent surgery for ICC should be adjusted based on follow-up time and intervening events. The model in this study showed excellent discriminative ability and performed well in the validation process.

The impact of anastomotic leak on long-term oncological outcomes after low anterior resection for mid-low rectal cancer: extended follow-up of a randomised controlled trial.

PURPOSE: The impact of anastomotic leaks (AL) on oncological outcomes after low anterior resection for mid-low rectal cancer is still debated. The aim of this study was to evaluate overall survival (OS), disease-free survival (DFS), and local and distant recurrence in patients with AL following low anterior resection. METHODS: This is an extension of a multicentre RCT (NCT01110798). Kaplan-Meier method and the log-rank test were used to estimate and compare the 3-, 5-, and 10-year OS and DFS, and local and distant recurrence in patients with and without AL. Predictors of OS and DFS were evaluated using the Cox regression analysis as secondary aim. RESULTS: Follow-up was available for 311 patients. Of them, 252 (81.0%) underwent neoadjuvant chemoradiotherapy and 138 (44.3%) adjuvant therapy. AL occurred in 63 (20.3%) patients. At a mean follow-up of 69.5 ± 31.9 months, 23 (7.4%) patients experienced local recurrence and 49 (15.8%) distant recurrence. The 3-, 5-, and 10-year OS and DFS were 89.2%, 85.3%, and 70.2%; and 80.7%, 75.1%, and 63.5% in patients with AL, and 88.9%, 79.8% and 72.3%; and 83.7, 74.2 and 62.8%, respectively in patients without (p = 0.89 and p = 0.84, respectively). At multivariable analysis, AL was not an independent predictor of OS (HR 0.65, 95%CI 0.34-1.28) and DFS (HR 0.70, 95%CI 0.39-1.25), whereas positive circumferential resection margins and pathological stage impaired both. CONCLUSIONS: In the context of modern multimodal rectal cancer treatment, AL does not affect long-term OS, DFS, and local and distant recurrence in patients with mid-low rectal cancer.

Management of Desmoid Tumors.

The management of desmoid tumors (DT) is shifting toward conservative and patient-tailored strategies. Active surveillance is currently considered the first line of treatment for most DT patients, according to international guidelines. When active treatment is required, several systemic and local treatments are considered. The choice of the first-line systemic therapy and the management of recurrence still represent a therapeutic challenge, for which well-defined and shared guidelines are lacking. Such issues represent the next challenge for The Desmoid Tumor Working Group.

18F-FDG-PET/MRI texture analysis in rectal cancer after neoadjuvant chemoradiotherapy.

OBJECTIVE: Reliable markers to predict the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are lacking. We aimed to assess the ability of 18F-FDG PET/MRI to predict response to nCRT among patients undergoing curative-intent surgery. METHODS: Patients with histological-confirmed LARC who underwent curative-intent surgery following nCRT and restaging with 18F-FDG PET/MRI were included. Statistical correlation between radiomic features extracted in PET, apparent diffusion coefficient (ADC) and T2w images and patients' histopathologic response to chemoradiotherapy using a multivariable logistic regression model ROC-analysis. RESULTS: Overall, 50 patients were included in the study. A pathological complete response was achieved in 28.0% of patients. Considering second-order textural features, nine parameters showed a statistically significant difference between the two groups in ADC images, six parameters in PET images and four parameters in T2w images. Combining all the features selected for the three techniques in the same multivariate ROC curve analysis, we obtained an area under ROC curve of 0.863 (95% CI, 0.760-0.966), showing a sensitivity, specificity and accuracy at the Youden's index of 100% (14/14), 64% (23/36) and 74% (37/50), respectively. CONCLUSION: PET/MRI texture analysis seems to represent a valuable tool in the identification of rectal cancer patients with a complete pathological response to nCRT.

Women surgeons: How can we shape the future of new leaders? A celebration of the past with a glimpse of the future.

BACKGROUND: Sporadic women involvement in surgery has been recorded since ancient times. Nevertheless, the presence of women in surgical disciplines has been marginal until the last 2 decades, with several barriers still existing worldwide. The aim of the study was to explore the history of women in surgery, with a main focus in North America from until the foundation women surgical societies. METHODS: Database search of studies about the history of women in surgery. RESULTS: The 19th century registered an increased presence of women in medicine; during the 20th century, pioneer women surgeons opened the way to a more consistent involvement of women in surgical specialties. In the last 20 years, increased awareness of barriers limiting women progression in surgical career led to the development of women's surgical societies, with the aim to share common experiences and find solutions to common issues. CONCLUSION: The history of women in surgery has been paved with challenges: during the last centuries, several barriers limited the inclusion of women in surgical fields, from training to leadership positions. Nevertheless, some pioneers actually broke the rules imposed by a male-dominated field and opened the way to a more diverse and equal future for women surgeons. Nowadays, the existence of women's surgical societies in different countries and their interconnection represents a way to support women surgeons at different stages of their career.