Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results

Background: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). Material and methods: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. Results: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. Conclusions: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations

Fluorescence‐based bowel anastomosis perfusion evaluation: results from the IHU‐IRCAD‐EAES EURO‐FIGS registry

Background: Anastomotic leakage (AL) is one of the dreaded complications following surgery in the digestive tract. Near-infrared fluorescence (NIRF) imaging is a means to intraoperatively visualize anastomotic perfusion, facilitating fluorescence image-guided surgery (FIGS) with the purpose to reduce the incidence of AL. The aim of this study was to analyze the current practices and results of NIRF imaging of the anastomosis in digestive tract surgery through the EURO-FIGS registry. Methods: Analysis of data prospectively collected by the registry members provided patient and procedural data along with the ICG dose, timing, and consequences of NIRF imaging. Among the included upper-GI, colorectal, and bariatric surgeries, subgroup analysis was performed to identify risk factors associated with complications. Results: A total of 1240 patients were included in the study. The included patients, 74.8% of whom were operated on for cancer, originated from 8 European countries and 30 hospitals. A total of 54 surgeons performed the procedures. In 83.8% of cases, a pre-anastomotic ICG dose was administered, and in 60.1% of cases, a post-anastomotic ICG dose was administered. A significant difference (p < 0.001) was found in the ICG dose given in the four pathology groups registered (range: 0.013–0.89 mg/kg) and a significant (p < 0.001) negative correlation was found between the ICG dose and BMI. In 27.3% of the procedures, the choice of the anastomotic level was guided by means of NIRF imaging which means that in these cases NIRF imaging changed the level of anastomosis which was first decided based on visual findings in conventional white light imaging. In 98.7% of the procedures, the use of ICG partly or strongly provided a sense of confidence about the anastomosis. A total of 133 complications occurred, without any statistical significance in the incidence of complications in the anastomoses, whether they were ICG-guided or not. Conclusion: The EURO-FIGS registry provides an insight into the current clinical practice across Europe with respect to NIRF imaging of anastomotic perfusion during digestive tract surgery

Laparoscopic right hemicolectomy: the SICE (Societ\ue0 Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospective trial on 1225 cases comparing intra corporeal versus extra corporeal ileo-colic side-to-side anastomosis

Background: While laparoscopic approach for right hemicolectomy (LRH) is considered appropriate for the surgical treatment of both malignant and benign diseases of right colon, there is still debate about how to perform the ileo-colic anastomosis. The ColonDxItalianGroup (CoDIG) was designed as a cohort, observational, prospective, multi-center national study with the aims of evaluating the surgeons\u2019 attitude regarding the intracorporeal (ICA) or extra-corporeal (ECA) anastomotic technique and the related surgical outcomes. Methods: One hundred and twenty-five Surgical Units experienced in colorectal and advanced laparoscopic surgery were invited and 85 of them joined the study. Each center was asked not to change its surgical habits. Data about demographic characteristics, surgical technique and postoperative outcomes were collected through the official SICE website database. One thousand two hundred and twenty-five patients were enrolled between March 2018 and September 2018. Results: ICA was performed in 70.4% of cases, ECA in 29.6%. Isoperistaltic anastomosis was completed in 85.6%, stapled in 87.9%. Hand-sewn enterotomy closure was adopted in 86%. Postoperative complications were reported in 35.4% for ICA and 50.7% for ECA; no significant difference was found according to patients\u2019 characteristics and technologies used. Median hospital stay was significantly shorter for ICA (7.3 vs. 9 POD). Postoperative pain in patients not prescribed opioids was significantly lower in ICA group. Conclusions: In our survey, a side-to-side isoperistaltic stapled ICA with hand-sewn enterotomy closure is the most frequently adopted technique to perform ileo-colic anastomosis after any indications for elective LRH. According to literature, our study confirmed better short-term outcomes for ICA, with reduction of hospital stay and postoperative pain. Trial registration: Clinical trial (Identifier: NCT03934151)

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

RISULTATI A LUNGO TERMINE SULLA QUALITÀ DI VITA (QOL) IN PAZIENTI CON TUMORE DEL RETTO TRATTATI CON ENDOLUMINAL LOCO-REGIONAL RESECTION BY TEM VS LAPAROSCOPIC TOTAL MESORECTAL EXCISION

Obiettivi: La Endoluminal Loco-Regional Resection tramite Microchirurgia Endoscopica Transanale (ELRR by TEM) può rappresentare in pazienti selezionati con tumore del retto un opzione alternativa alla Total Mesorectal Excision Laparoscopica (LTME). La valutazione della Qualità di Vita (QoL) è un importante parametro delle sequelae funzionali. In un precedente lavoro, gli Autori hanno riportato i risultati a breve e medio termine della QoL in pazienti sottoposti a ELRR by TEM vs LTME. L’obiettivo di quest’analisi retrospettiva di dati raccolti prospetticamente è di valutare la QoL a 3 anni in pazienti con tumore del retto iT2-T3 N0/+ alla presentazione sottoposti a ELRR by TEM o LTME dopo radio-chemioterapia neoadiuvante (n-ChRT). Metodi: In questo studio sono stati arruolati 39 pazienti affetti da tumore del retto iT2-iT3 sottoposti a ELRR by TEM (19) o a LTME (20), in base a criteri predefiniti. La QoL è stata valutata tramite i questionari EORTC QLQ-C30 e QLQ-CR38 al momento dell’arruolamento, dopo n-ChRT, a 1, 6, 12 e 36 mesi dall’intervento. Risultati: Non sono state riscontrate differenze statisticamente significative in termini di QoL tra i due gruppi sia all’arruolamento che dopo n-ChRT. Nel breve termine (1-6 mesi), sono stati osservati migliori risultati nel gruppo ELRR tramite il QLQ-C30 per le voci Global Health Status (p=0.03), Physical Functioning (p=0.026), Role Functioning (p=0.04), Emotional Functioning (p=0.04), Cognitive Functioning, Fatigue (p<=0.05); e tramite il QLQ-CR38 per le voci Body Image (p=0.03) and Defecation (p=0.025). Ad un anno tramite il QLQ-C30 i due gruppi risultavano omogenei, mentre il QLQ-CR38 ancora mostrava migliore risultati nel gruppo ELRR per le voci Body Image (p=0.006), Defecation Problems (p=0.01), and Weight Loss (p=0.005). A 3 anni non erano più evidenziabili differenze statisticamente significative tra i due gruppi. Conclusioni: I risultati a 3 anni dei test sulla QoL, in pazienti selezionati con tumore del retto sottoposti a ELRR by TEM o LTME, non mostrano le differenze rilevate nello studio condotto ad 1 anno

ANGIOGRAFIA A FLUORESCENZA PER L’IDENTIFICAZIONE DEL PUNTO DI SEZIONE IN CHIRURGIA COLORETTALE

Obiettivi: La deiscenza anastomotica (AL) rimane la più importante complicanza chirurgica nel cancro colo-rettale (CRC) con dei tassi variabili riportati in letteratura tra il 3 e il 20% e un aumento della mortalità associata dal 6% al 22%. Attualmente non vi sono dei test intraoperatori validati predittivi della tenuta anastomotica. Diversi fattori come la tensione anastomotica, vascolarizzazione e l’esecuzione di un’appropriata tecnica chirurgica, sono riportati in letteratura essere correlati con il rischio di AL. L’angiografia a fluorescenza (FA) con Verde di Indocianina (ICG) è una metodica utilizzata per valutare la microperfusione in chirurgia epatobiliare, intestinale, dei trapianti e plastica. L’obiettivo di questo studio prospettico è di verificare la fattibilità ed attendibilità della FA con ICG per valutare la vascolarizzazione del moncone colico prossimale in chirurgia colo-rettale al fine di stabilire il punto ottimale di sezione (PoT). Metodi: I risultati preliminari di questo studio prospettico si riferiscono a 18 pazienti sottoposti a emicolectomia sinistra o resezione anteriore del retto VLS per CRC. Dopo legatura e sezione di arteria e vena mesenterica inferiore, ampia mobilizzazione colica sinistra e sezione del moncone colico/rettale distale e prima dell’estrazione del pezzo operatorio, è stato somministrato un bolo di ICG (0.2 mg/kg) per via endovenosa. La perfusione del colon è stata visualizzata e valutata tramite la FA in un tempo medio stimato di 1-2 minuti e la linea di demarcazione del tessuto perfuso è stata confrontata con il PoT precedentemente deciso dall’operatore. Tale PoT clinico è stato quindi valutato come inadeguato, adeguato o ottimale. In tutti i pazienti l’air leak test è risultato negativo. È stato valutato il tasso di variazione del PoT dopo FA e il tasso di AL sia clinicamente nel periodo postoperatorio che con clisma opaco ed endoscopia a 30 giorni dall’intervento chirurgico. Risultati: In 15 pazienti la FA ha confermato come ottimale il PoT identificato dall’operatore, mentre in 2 è stato considerato inadeguato e in un caso adeguato. Nel gruppo “inadeguato” in 1 caso il PoT dopo FA è risultato essere distale di circa 4cm, mentre nell’altro era 3cm craniale. In entrambi i casi il PoT è stato modificato in accordo con il risultato della FA. Nel paziente considerato “adeguato” non è stato modificato il PoT, ma, non essendo questo ottimale alla FA, nonostante l’air-leak test negativo, si è preferito eseguire una ileostomia temporanea. Il controllo a 30 giorni ha mostrato una deiscenza anastomotica. La metodica ha cambiato il programma chirurgico nel 16.6% dei casi (3/18). Non sono state riportate reazioni avverse all’ICG. Conclusioni: I risultati preliminari dello studio mostrano la fattibilità e sicurezza della metodica senza un sensibile prolungamento dei tempi operatori. La dimostrazione dell’adeguata vascolarizzazione del moncone colico dovrà essere validata da maggiori casistiche ai fini della prevenzione della AL

PREDITTIVITÀ DELLA RICERCA DEI LINFONODI SENTINELLA TRAMITE LA NEAR-INFRARED FLUORESCENCE LIGHT PER LA STADIAZIONE DEI TUMORI COLO-RETTALI

Obiettivi: La ricerca dei linfonodi sentinella (SLN) tramite la fluorescenza vicina all’infrarosso (NIRF) è una tecnica sempre più usata per migliorare la stadiazione linfonodale in diversi tipi di tumore, tra i quali testa-collo, mammella e melanoma. L’ultrastadiazione dei SLN ha un potenziale ruolo decisionale nell’indicazione di terapie adiuvanti in presenza di micrometastasi. Inoltre, in base all’ultima edizione (8°) dell’AJCC Cancer Staging Manual, la presenza di micrometastasi nei linfonodi dovrebbe essere direttamente stadiata come N1 e non più come N1mi. In chirurgia colorettale, nei pochi studi condotti il tasso riportato di micrometastasi nei SLN è fino al 20-30%. Obiettivo di questo studio prospettico in corso è di stabilire la predittività della NIRF per la ricerca ex-vivo dei SLN durante chirurgia resettiva oncologica colorettale e la successiva ricerca delle micrometastasi nei pazienti con stadiazione linfonodale N0. Materiali e metodi: Sono stati prospettivamente arruolati 23 pazienti sottoposti a resezioni oncologiche laparoscopiche standard per tumore colorettale. Dopo l’estrazione del pezzo operatorio, è stato iniettato nella sottomucosa 1ml di ICG equidistribuito sui quattro punti cardinali del tumore, su mucosa sana, per rilevare, tramite la NIRF i canali linfatici e i SLN. Ogni SLN N0 all’analisi anatomopatologica convenzionale è stato successivamente analizzato con tecniche di ultrastadiazione per la valutazione della presenza di micrometastasi: sezioni seriate, immunoistochimica coerentemente con tecniche riportate in letteratura. Risultati: Sono stati rinvenuti un totale di 395 linfonodi. 12 pazienti erano N+ e 11 N0. Sono identificati con la NIRF 66 SLN (2.87 in media per caso) e 32 di questi erano N0. Dopo gli esami di ultrastadiazione, non sono state evidenziate micrometastasi nei SLN N0. I SLN localizzati in profondità nel mesocolon e nel mesoretto (anche dopo nChRT) sono stati facilmente identificati dalla NIRF. Conclusioni: In questa serie preliminare, l’assetto istologico dei SLN (sia negli N+ che negli N0) ha correttamente predetto lo stato dei linfonodi loco-regionale. L’assenza di micrometastasi nei SLN indagati, potrebbe essere dovuta alla ridotta numerosità del campione e ulteriori casi dovranno essere raccolti per rivalutare questi risultati

Predictability of Near-Infrared Fluorescence Light Sentinel Lymph Node Mapping for Colorectal Cancer Staging

Background: Sentinel lymph node (SLN) mapping using Near-Infrared (NIR) Fluorescence Light is an increasingly used technique to improve nodal staging in several type of tumors, including gastro-intestinal, head and neck, breast and mel- anoma). The ultrastaging has a potential decision-making role in order to propose adjuvant chemotherapies in case of nodal micro-metastases. As a matter of fact, according to the last edition (8th) of the AJCC Cancer Staging Manual, the presence of LFN micro-metastases should directly be staged as N1 and no longer as N1mi. In colorectal cancer, the reported rate of SLN micro-metastases is up to 30%. The aim of this ongoing prospective study is to assess the predictability of NIR fluorescence imaging for ex-vivo SLN mapping in conventional surgical resection for colorectal tumors and the research of micro-metastases in patients with negative node disease (NND). Materials and Methods: Twenty-two consecutive patients presenting resectable colorectal cancer have been prospectively enrolled. All patients underwent a standard oncological laparoscopic resection. The intact surgical specimen was extracted and opened longitudinally and 1 ml of Indocyanine Green (ICG; 5 mg/ml) was injected submucosally at four corners around the tumor in order to identify the lymphatic pathway and the SLNs. Each NND SLN at conventional histological analysis, was further investigated with ultrastaging techniques in order to detect the presence of micro-metastases, including serial sectioning and additional immuno- histochemistry or reverse transcriptase-polymerase chain reaction. Results: Overall, a total of 363 lymph nodes were retrieved. Twelve patients were N?, and 10 were NND. A total of 41 SLN were identified (mean 1.9 per case) and 19 of those were NND. After ultrastaging investigations, no micro-metastases were found in NND SLN, nor in the remaining nodes. SLN located deeper in the mesenteric and mesorectal (even underwent nChRT) fat could easily be identified by NIR fluorescence. Conclusions: In this preliminary series, the sentinel lymph nodes’ asset (both in N ? than in NND) rightly predicts the status of loco-regional nodes, as confirmed by the histological investigations. The absence of micro-metastases in the SLN investigated may be due to the small sample size and more cases should be collected to confirm this finding