Association Between Cross-Stapling Technique in Mechanical Colorectal Anastomosis and Short-term Outcomes.

BACKGROUND: The double-stapled technique is the most common method of colorectal anastomosis in minimally invasive surgery. Several modifications to the conventional technique have been described to reduce the intersection between the stapled lines, as the resulting lateral dog-ears are considered possible risk factors for anastomotic leakage. OBJECTIVE: This study aimed to analyze the outcomes of patients receiving conventional versus modified stapled colorectal anastomosis after minimally invasive surgery. DATA SOURCES: A systematic review of the published literature was undertaken. PubMed/MEDLINE, Web of Science, and Embase databases were screened up to July 2023. STUDY SELECTION: Relevant articles were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles reporting on the outcomes of patients with modified stapled colorectal reconstruction compared with the conventional method of double-stapled anastomosis were included. INTERVENTIONS: Conventional double-stapling colorectal anastomosis and modified techniques with reduced intersection between the stapled lines were compared. MAIN OUTCOME MEASURES: The rate of anastomotic leak was the primary end point of interest. Perioperative details including postoperative morbidity were also appraised. RESULTS: There were 2537 patients from 12 studies included for data extraction, with no significant differences in age, BMI, or proportion of high ASA score between patients who had conventional versus modified techniques of reconstructions. The risk of anastomotic leak was 62% lower for the modified procedure than for the conventional procedure (OR = 0.38 [95% CI, 0.26-0.56]). The incidences of overall postoperative morbidity (OR = 0.57 [95% CI, 0.45-0.73]) and major morbidity (OR = 0.48 [95% CI, 0.32-0.72]) following modified stapled anastomosis were significantly lower than following conventional double-stapled anastomosis. LIMITATIONS: The retrospective nature of most included studies is a main limitation, essentially because of the lack of randomization and the risk of selection and detection bias. CONCLUSIONS: The available evidence supports the modification of the conventional double-stapled technique with the elimination of 1 of both dog-ears as it is associated with a lower incidence of anastomotic-related morbidity.

Prediction of Metachronous Peritoneal Metastases After Radical Surgery for Colon Cancer: A Scoring System Obtained from an International Multicenter Cohort.

BACKGROUND: Since novel strategies for prevention and treatment of metachronous peritoneal metastases (mPM) are under study, it appears crucial to identify their risk factors. Our aim is to establish the incidence of mPM after surgery for colon cancer (CC) and to build a statistical model to predict the risk of recurrence. PATIENTS AND METHODS: Retrospective analysis of consecutive pT3-4 CC operated at five referral centers (2014-2018). Patients who developed mPM were compared with patients who were PM-free at follow-up. A scoring system was built on the basis of a logistic regression model. RESULTS: Of the 1423 included patients, 74 (5.2%) developed mPM. Patients in the PM group presented higher preoperative carcinoembryonic antigen (CEA) [median (IQR): 4.5 (2.5-13.0) vs. 2.7 (1.5-5.9), P = 0.001] and CA 19-9 [median (IQR): 17.7 (12.0-37.0) vs. 10.8 (5.0-21.0), P = 0.001], advanced disease (pT4a 42.6% vs. 13.5%; pT4b 16.2% vs. 3.2%; P < 0.001), and negative pathological characteristics. Multivariate logistic regression identified CA 19-9, pT stage, pN stage, extent of lymphadenectomy, and lymphovascular invasion as significant predictors, and individual risk scores were calculated for each patient. The risk of recurrence increased remarkably with score values, and the model demonstrated a high negative predictive value (98.8%) and accuracy (83.9%) for scores below five. CONCLUSIONS: Besides confirming incidence and risk factors for mPM, our study developed a useful clinical tool for prediction of mPM risk. After external validation, this scoring system may guide personalized decision-making for patients with locally advanced CC.

Sarcobesity Index Predicts Poor Disease-Specific Survival After Resection for Colorectal Cancer.

INTRODUCTION: Sarcobesity (SO) is traditionally defined as the association between low muscle mass and obesity and has been reported to worsen prognosis after curative resection for colorectal cancer (CRC). This study aimed to propose a new definition of SO based on computed tomography measurements of the skeletal muscle area (SMA) and visceral adipose tissue (VAT) and to assess its implications on long-term survival after curative resection for stage I-III CRC. METHODS: We retrospectively analyzed 506 patients with stage I-III CRC who underwent surgery between January 2010 and December 2019. Preoperative computed tomography images were analyzed and the sarcobesity index (SI) was calculated for each patient as the VAT/SMA ratio. The optimal cutoff value for predicting survival was determined using time-dependent receiver operating characteristic analysis. Overall survival and disease-specific survival (DSS) were compared between SO (SI > 1.25) and non-SO (SI ≤ 1.25) patients. The rates and modes of recurrence were also compared between the two groups. RESULTS: Three hundred (59.3%) patients were identified to be sarcobese. No differences in short-term outcomes and administration of adjuvant chemotherapy were found, except for a longer length of stay in patients with SO. In a univariable analysis, SO was associated with a worse 5-y overall survival and DSS, considering the whole population and stages II and III separately. A multivariable analysis confirmed SO to be an independent risk factor for DSS (hazard ratio 2.29; 95% confidence interval 1.13-4.62, P = 0.02). Although the overall recurrence rate did not differ between the groups, a significantly higher rate of recurrence at multiple sites was observed in patients with SO (P = 0.01). CONCLUSIONS: The SI, defined as per the VAT/SMA ratio, seems to be a reliable tool for identifying patients with worse DSS after potentially curative surgery for stage I-III CRC.

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.

Laparoscopic versus open surgery for left flexure colon cancer: A propensity score matched analysis from an international cohort.

AIM: Surgical treatment of splenic flexure cancer (SFC) still presents some debated issues, including the role of laparoscopic surgery. The literature is based on small single-centre series, while randomized controlled studies comparing open and laparoscopic treatment for colon cancer exclude SFC. This study aimed to determine the role of laparoscopic surgery in the treatment of SFC, comparing short- and long-term outcomes with open surgery. METHOD: This was an international multicentre retrospective cohort study that analysed patients from 10 tertiary referral centres. From a cohort of 641 cases, 484 patients with Stage I-III SFC submitted to elective surgery with curative intent were selected. After 1:1 propensity score matching, 130 patients in the laparoscopic group (LapGroup) were compared with 130 patients in the open surgery group (OpenGroup). RESULTS: After propensity score matching, the two groups were comparable for demographic and clinical parameters. OpenGroup presented a higher incidence of overall (P = 0.02) and surgery-related complications (P = 0.05) but a similar rate of severe complications (P = 0.75). Length of stay was notably shorter in the LapGroup (P = 0.001). Overall (P = 0.793) as well as cancer-specific survival (P = 0.63) did not differ between the two groups. CONCLUSIONS: Elective laparoscopic surgery for Stage I-III SFC is feasible and associated with improved short-term postoperative outcomes compared to open surgery. Moreover, laparoscopic surgery appears to provide excellent long-term cancer outcomes.

High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy.

INTRODUCTION: Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF). METHODS: Drain fluid TGF-ß, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF. RESULTS: The study population consisted of 66 patients. POPF and Clavien-Dindo ≥3 morbidity rates were 12.1% and 9.1%, respectively. Patients developing POPF presented significantly higher values of POD1 serum amylase level (477 vs. 54 UI/L, p < 0.001), drain fluid amylase (7,500 vs. 127 UI/L, p < 0.001), TGFß (94 vs. 40 pg/g, p = 0.045), and EGF (17 vs. 13, p = 0.015). There were no differences in terms of IGF-1 and IL-6 values. CONCLUSION: Assessing the local inflammatory response after pancreatoduodenectomy could represent a promising field of research since both TGFß and EGF seem to be associated with the occurrence of POPF.

Laparoscopic surgery does not reduce the need for red blood cell transfusion after resection for colorectal tumour: a propensity score match study on 728 patients.

BACKGROUND: Patients with colorectal tumour often present with anaemia, and up to 60% will receive red blood cells (RBC) transfusion. Some evidence suggests a correlation between RBC transfusion and worse outcomes. Since laparoscopy minimizes intraoperative blood loss, we retrospectively investigated its role in reducing haemoglobin (Hb) drop and requirements for postoperative RBC transfusions. METHODS: Patients were identified from consecutive cases undergone elective surgery for non-metastatic colorectal tumour between 2005 and 2019. Laparoscopic cases were matched 1:1 with open controls through propensity score matching (PSM). The main outcome measures were postoperative Hb drop and requirement for RBC. The secondary aim was evaluation of risk factors for postoperative RBC transfusions. RESULTS: After application of PSM, 364 patients treated by laparoscopy were matched with 364 patients undergone open surgery. The two groups presented similar clinical and pathological characteristics, as well as comparable postoperative outcomes. 56 patients in the open group and 47 in the laparoscopic group required postoperative RBC (P = 0.395). No difference was observed in terms of mean number of RBC units (P = 0.608) or Hb drop (P = 0.129). Logistic regression analysis identified preoperative anaemia and occurrence of postoperative complications as relevant risk factors for postoperative RBC transfusion, while surgical approach did not prove statistically significant. CONCLUSION: Laparoscopy did not influence postoperative requirements for RBC transfusions after elective colorectal surgery. Preoperative anaemia and occurrence of postoperative complications represent the major determinants for postoperative transfusions after open as well as laparoscopic surgery.

Intriguing Role of the Mesentery in Ileocolic Crohn's Disease.

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease with unknown etiology. Up to 80% of patients will eventually require surgery throughout their lifetime, and often repeated resections are required for disease recurrence. Observations of "creeping fat" surrounding the diseased intestine renewed interest in the mesentery, recently defined as an organ with endocrine and immune functions. According to the inside-out model, the mesentery may be primarily affected in CD and subsequent cause alterations in the mucosa. Recently, lower surgical recurrence rates have been reported with en-bloc excision of the mesentery adjoining the diseased intestine. Results of ongoing randomized controlled trials may clarify the role of the mesentery in CD and possibly lead to its adoption as standard during surgery for Crohn's disease.

Analgesic efficacy of pre-emptive local wound infiltration plus laparoscopic-assisted transversus abdominis plane block versus wound infiltration in patients undergoing laparoscopic colorectal resection: results from a randomized, multicenter, single-blind, non-inferiority trial.

BACKGROUND: Transversus abdominis plane (TAP) block is considered a reliable locoregional technique for pain control after laparoscopic colorectal surgery. However, no clear benefit of TAP block over wound infiltration has been demonstrated by the current literature. This multicenter randomized clinical trial tested the non-inferiority of wound infiltration (WI) compared to WI plus laparoscopic-assisted TAP block (L-TAP). METHODS: All patients with colorectal cancer and diverticular disease scheduled for laparoscopic resection at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust, Verona, Italy and at the Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University, Daegu, Korea, between April 2018 and March 2019 were considered for the trial. Patients were randomly allocated to either the WI group or the WI plus L-TAP group in a 1:1 allocation ratio. In total, 108 patients entered the study and 102 patients were analyzed; 50 patients received WI plus L-TAP and 52 patients received WI. The primary end point was the efficacy in pain control at 6 h measured according to Numeric Rating Scale (NRS). Secondary aims evaluated pain control at 12, 24, 48 and 72 h and other short-term results related to pain management. RESULTS: Estimation of pain intensity at 6 h was comparable between the two groups (p = 0.16) with a mean (95% CI) difference in pain scores of 0.94 (- 0.13 to 2.02). No differences in pain scores were observed at other interval times or considering analgesic consumption, return of bowel function, postoperative complications and length of hospital stay. CONCLUSION: This study suggests that adding TAP block to WI does not affect pain control, amount of analgesics and other short-term outcomes. TRIAL REGISTRATION: NCT03376048 ( https://www.clinicaltrials.gov ).

Visceral obesity enhances inflammatory response after laparoscopic colorectal resection.

AIMS: C-reactive protein (CRP) is used for monitoring postoperative inflammation (POI) and detecting infectious complications. The aim of this study was to assess the effect of visceral obesity (VO) on acute POI measured through CRP after elective laparoscopic colorectal resection. METHODS: Pre-operative Computed tomography images of 357 patients who underwent laparoscopic colorectal resection were analyzed. Visceral adipose tissue (VAT) area was measured for each patient. VO was defined as VAT area >163.8 cm2 in men and >80.1 cm2 in women according to accepted sex-specific cut-offs. Postoperative outcomes and CRP values were compared between VO and non-VO groups. The most appropriate CRP value for identifying infectious complications in the two groups was assessed with receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were conducted for factors affecting POI including VO. RESULTS: No differences in postoperative outcomes and infectious complications were found in VO patients (62.2% of the overall population). Both in the overall cohort and in patients without infectious complications, VO was associated with higher CRP values on postoperative day (POD) 1, POD2, POD3, and POD5. A positive correlation was found between VAT and CRP on all PODs. VO independently predicted higher CRP on POD1-3 in patients without infectious complications but not in those who developed complications. ROC curves analysis showed optimal accuracy for detection of infectious complications for CRP on POD3 in both groups, though the optimal cut-off value was higher in VO group (154 vs 136 mg/L). CONCLUSIONS: VO is not associated to increased complications after laparoscopic colorectal resection. Nevertheless, it is independently associated to higher CRP in the overall population and in patients without infectious complications. Consequently, CRP values on POD3 higher than cut-offs commonly adopted in the clinical practice should be carefully evaluated in VO patients to assess the occurrence of infectious complications.

Clinical-Pathologic Characteristics and Long-term Outcomes of Left Flexure Colonic Cancer: A Retrospective Analysis of an International Multicenter Cohort.

BACKGROUND: Colorectal cancer seldom presents at the splenic flexure. Small series on left flexure tumors reported a high occurrence of negative prognostic factors called into question as causes of poor prognosis. However, because of the small number of cases, no definite conclusions can be drawn. OBJECTIVE: The aim of this study was to compare clinical-pathologic characteristics and short- and long-term outcomes of left flexure tumors with other colonic locations. DESIGN: This was a retrospective analysis of consecutive patients who underwent surgery for tumors at the splenic flexure. Each tumor was paired in a 1 to 1 fashion with a right-sided and sigmoid tumor. SETTINGS: The study was conducted in 10 international centers. PATIENTS: A total of 641 patients with left flexure tumors were included in the study. MAIN OUTCOME MEASURES: Overall survival and cancer-specific survival were measured. RESULTS: Left flexure tumors presented more frequently with stenosis (30.5%; p < 0.001), with lesions infiltrating beyond the serosa (21.9%; p = 0.001) and with a high rate of mucinous histology (8.8%; p = 0.001). Looking at long-term prognosis, no differences were observed among the 3 groups, both considering overall and cancer-specific survival. However, left flexure tumors recurred more frequently as peritoneal carcinomatosis (20.6%; p < 0.001). LIMITATIONS: This study was limited because of its retrospective nature. CONCLUSIONS: Although left flexure tumors display several negative prognostic factors, they are not characterized by a worse prognosis compared with other colon cancer locations. See Video Abstract at http://links.lww.com/DCR/B395. CARACTERÍSTICAS CLÍNICO-PATOLÓGICAS Y RESULTADOS A LARGO PLAZO DEL CÁNCER DE COLON DE ÁNGULO IZQUIERDO: UN ANÁLISIS RETROSPECTIVO DE UNA COHORTE MULTICÉNTRICA INTERNACIONAL: El cáncer colorrectal rara vez se presenta en el ángulo esplénico. Pequeñas series sobre tumores de ángulo izquierdo informaron una alta incidencia de factores pronósticos negativos cuestionados como causas de mal pronóstico. Sin embargo, debido al pequeño número de casos, no se pueden sacar conclusiones definitivas.El objetivo de este estudio fue comparar las características clínico-patológicas, los resultados a corto y largo plazo de los tumores de ángulo izquierdo con otras ubicaciones de colon.Análisis retrospectivo de pacientes consecutivos que se sometieron a cirugía por tumores en el ángulo esplénico. Cada tumor se emparejó de forma individual con un tumor del lado derecho y sigmoide.El estudio se realizó en 10 centros internacionales.Se incluyeron en el estudio un total de 641 pacientes con tumores del ángulo izquierdo.Supervivencia general y específica del cáncerLos tumores de ángulo izquierda se presentaron con mayor frecuencia con estenosis (30.5%, p <0.001), con lesiones infiltradas más allá de la serosa (21.9%, p = 0.001), y con una alta tasa de histología mucinosa (8.8%, p = 0.001). En cuanto al pronóstico a largo plazo, no se observaron diferencias entre los tres grupos, considerando la supervivencia general y específica del cáncer. Sin embargo, los tumores de ángulo izquierdo recurrieron con mayor frecuencia como carcinomatosis peritoneal (20,6%; p <0,001).Este estudio fue limitado debido a su naturaleza retrospectiva.Aunque los tumores de ángulo izquierdo muestran varios factores pronósticos negativos, no se caracterizan por un peor pronóstico en comparación con otras ubicaciones de cáncer de colon. Consulte Video Resumen en http://links.lww.com/DCR/B395.

The dispersion of myocardial repolarization in ischemic stroke and intracranial hemorrhage.

BACKGROUND: Markers of dispersion of myocardial repolarization have been proposed to identify the patients at higher risk of malignant arrhythmic events. The aim of the present study is to assess a possible association of the electrocardiografic (ECG) markers of the dispersion of repolarization with the type of stroke, involvement of insula, neurological severity (National Institutes of Health Stroke Scale, NIHSS score), and disability (modified Rankin Scale, mRS score) in patients with a cerebrovascular event. METHODS: We conducted a retrospective analysis based on data prospectively collected from consecutive patients with a cerebrovascular event who underwent 12­lead ECG at admission to the Verona Stroke Unit. RESULTS: Of the 63 patients included in the study, 55 had ischemic stroke and 8 intracranial hemorrhage. TpTe (time between the peak and the end of the T wave) and TpTe/QTc (TpTe/corrected time between the start of the Q wave and the end of the T wave) in lead V5 were higher in intracranial hemorrhage than in ischemic stroke (p = 0.03 and p = 0.04, respectively) and QT max (the longest QT calculated in the 12 leads) was higher in patients with involvement of insula (p ≤ 0.01). A correlation was found between QTc max and NIHSS score at admission (p = 0.02), QT max and NIHSS score at discharge (p = 0.05), and QT max and mRS score at discharge (p = 0.02). CONCLUSIONS: TpTe and TpTe/QTc in V5 lead were associated with intracranial hemorrhage and QT max was associated with involvement of insula. The prolongation of QT was correlated with neurological severity and disability.

Clinical outcomes of secondary prevention strategies for young patients with cryptogenic stroke and patent foramen ovale.

Background The aim of this study was to compare the immediate and long-term clinical outcomes of medical therapy and percutaneous patent foramen ovale (PFO) closure as secondary prevention strategies in patients younger than 55 years of age presenting with cryptogenic stroke and PFO. Methods Between January 2006 and April 2015, all patients with the diagnosis of cryptogenic stroke and PFO were analysed and prospectively followed. Stroke was confirmed in 159 out of 309 patients (51%). In the remaining cases, other neurological conditions were found and therefore excluded from further analysis. Patients received PFO closure or medical therapy on the basis of a pre-specified algorithm. Primary outcome was the assessment of recurrent ischaemic events at follow-up. Results Percutaneous PFO closure was performed in 77 patients (48%) and 82 (52%) were treated medically. Mean follow-up was 51.6 ± 34.8 months. Two ischaemic strokes occurred in the medical group only (2.4% vs 0%; P = 0.16) and no complications related to the invasive procedure were observed. Conclusions The diagnosis of stroke in patients with PFO could be confirmed in 50% of cases only, underlining the importance of a multidisciplinary evaluation of these patients. A very low ischaemic recurrence rate was observed in the medical therapy group, suggesting that a personalized treatment based on a prespecified diagnostic algorithm yields good clinical results irrespective of the treatment modality. Given the low number of recurrences, larger cohorts may be needed to prove significant differences.

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

OBJECTIVE: Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. METHODS: Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. RESULTS: Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. DISCUSSION: Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs.

Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis.

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective: To assess the efficacy and tolerability of TNT protocols for LARC. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study Selection: Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data Extraction and Synthesis: Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main Outcomes and Measures: The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results: Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and Relevance: In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.

The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.