Prognostic role of nodal ratio, LODDS, pN in patients with pancreatic cancer with venous involvement

Background: The UICC/AJCC TNM staging system classifies lymph nodes as N0 and N1 in pancreatic cancer. Aim of the study is to determine whether the number of examine nodes, the nodal ratio (NR) and the logarithm odds of positive lymph nodes (LODDS) may better stratify the prognosis of patients undergoing pancreatectomy combined with venous resection for pancreatic cancer with venous involvement. Methods: A multicenter database of 303 patients undergoing pancreatectomy in 9 Italian referral centers was analyzed. The prognostic impact of number of retrieved and examined nodes, NR, LODDS was analyzed and compared with ROC curves analysis, Pearson test, univariate and multivariate analysis. Results: The number of metastatic nodes, pN, the NR and LODDS was significantly correlated with survival at multivariate analyses. The corresponding AUC for the number of metastatic nodes, pN, the NR and LODDS were 0.66, 0.69, 0.63 and 0.65, respectively. The Pearson test showed a significant correlation between the number of retrieved lymph nodes and number of metastatic nodes, pN and the NR. LODDS had the lower coefficient correlation. Concerning N1 patients, the NR, the LODDS and the number of metastatic nodes were able to significantly further stratify survival (p = 0.040; p = 0.046; p = 0.038, respectively). Conclusions: The number of examined lymph nodes, the NR and LODDS are useful for further prognostic stratification of N1 patients in the setting of pancreatectomy combined with PV/SMV resection. No superiority of one over the others methods was detected

A pre-operative model predicting survival in patients with locally advanced pancreatic cancer undergoing pancreatectomy with arterial resection

Introduction. Pancreatectomy with arterial resection is a treatment option in selected patients with locally advanced pancreatic cancer. This study aimed to identify factors predicting cancer-specific survival in this patient population. Methods. A single-Institution prospective database was used. Pre-operative prognostic factors were identified by using univariate and multivariate proportional hazard models. A nomogram was developed and a prognostic score was calculated for each patient in order to classify them into different categories of risk. Matching with pathologic parameters was used for internal validation. Results. In a patient population with a median Ca 19.9 level of 19.8 U/mL(IQR: 7.1–77), cancer-specific survival was predicted by: metabolic deterioration of diabetes (OR = 0.22, p = 0.0012), platelet count (OR = 1.00; p = 0.0013), serum level of Ca 15.3 (OR = 1.01, p = 0.0018) and Ca 125 (OR = 1.02, p = 0.00000137), neutrophils-to-lymphocytes ratio (OR = 1.16; p = 0.00015), lymphocytes-to-monocytes ratio (OR = 0.88; p = 0.00233), platelets-to-lymphocytes ratio (OR = 0.99; p = 0.00118), and FOLFIRINOX neoadjuvant chemotherapy (OR = 0.57; p = 0.00144). A prognostic score was developed and three risk groups were identified. Harrell’s C-Index was 0.74. Median cancer-specific survival was 16.0 months (IQR: 12.3–28.2) for the high-risk group, 24.7 months (IQR: 17.6–33.4) for the intermediate-risk group, and 39.0 months (IQR: 22.7–NA) for the low-risk group (p = 0.0003). Matching the three risk groups against pathology parameters, N2 rate was 61.9, 42.1, and 23.8% (p = 0.04), median value of lymph-node ratio was 0.07 (IQR: 0.05–0.14), 0.04 (IQR:0.02–0.07), and 0.03 (IQR: 0.01–0.04) (p = 0.008), and mean value of logarithm odds of positive nodes was − 1.07 ± 0.5, − 1.3 ± 0.4, and − 1.4 ± 0.4 (p = 0.03), in the high-risk, intermediate- risk, and low-risk groups, respectively. An online calculator is available at www.survivalcalculator-lapdac-arterialresection.org. Conclusions. The prognostic factors identified in this study predict cancer-specific survival in patients with locally advanced pancreatic cancer and low Ca 19.9 levels undergoing pancreatectomy with arterial resection. Three different categories of risk with statistically different survival were highlighted based on these prognostic factors

I pazienti "high-performing" dopo pancreasectomia con resezione arteriosa per adenocarcinoma duttale del pancreas localmente avanzato: definizione di un modello prognostico

ABSTRACT INTRODUZIONE L’adenocarcinoma duttale del pancreas (ACDP) presenta una sopravvivenza a 5 anni del 5%. La resezione chirurgica radicale rimane il trattamento migliore per prolungare la sopravvivenza e l’unica possibilità di raggiungere la guarigione. Sfortunatamente la diagnosi viene effettuata spesso quando sono già evidenti metastasi a distanza oppure quando il tumore ha già interessato i grandi vasi arteriosi peripancreatici. Quando il tumore interessa arteria mesenterica superiore (SMA) e/o tripode celiaco (CT) viene stadiato come T4 (classificazione TNM dell’AJCC Cancer Staging Manual) e viene definito come “localmente avanzato”. In questi casi il tumore viene tradizionalmente considerato come non resecabile. Tuttavia, dopo la resezione chirurgica, molti pazienti con ACDP “localmente avanzato” presentano la stessa sopravvivenza di pazienti con ACDP resecabili e in alcuni casi possono addirittura raggiungere i cinque anni senza comparsa di recidiva di malattia. Sfortunatamente, non siamo in grado di identificare questi pazienti ad elevata performance prima dell’intervento chirurgico. Infatti, attualmente ci basiamo su alcuni criteri, quali l’ECOG performance status, la risposta radiologica del tumore alla chemioterapia neoadiuvante secondo i criteri RECIST (Response Evaluation Criteria in Solid Tumors) e la risposta sierologica del tumore alla chemioterapia neoadiuvante secondo il dosaggio dei livelli plasmatici di Ca 19.9, che non sono completamente affidabili. Questo studio è volto ad eseguire un’analisi retrospettiva della nostra casistica di pazienti sottoposti a pancreasectomia estesa con resezione arteriosa (P-Ar) per ACDP “localmente avanzato” al fine di valutare la sopravvivenza generale (OS), la sopravvivenza specifica per tumore (DSS) e la sopravvivenza libera da malattia (DFS) e di identificare i pazienti ad elevata performance (“high-performing”) in termini di OS, DSS, DFS. L’obbiettivo principale è quello di identificare i fattori predittivi di OS, DSS e DFS al fine di creare e validare degli score specifici per OS, DSS e DFS, che permettano di predire in fase pre-operatoria la probabilità di un paziente di essere “high-performing”. In questo modo sarebbe possibile creare un modello atto alla selezione esclusiva per l’intervento chirurgico resettivo di quei pazienti con potenziali benefici in termini di sopravvivenza. MATERIALI E METODI Abbiamo eseguito un’analisi retrospettiva di tipo “cross-section” della nostra casistica relativa ai pazienti sottoposti a P-Ar dal marzo 2000 al luglio 2017. Per quanto riguarda la OS e la DFS, sono stati definiti come “high-performing” i pazienti la cui sopravvivenza risulta compresa nel quartile maggiore (più alto) della distribuzione di sopravvivenza (curva di Kaplan-Meier). Per la DSS abbiamo, invece, utilizzato come cut-off il valore arbitrario di 30 mesi. I restanti pazienti, definiti come “normal-performing”, sono stati presi come gruppo di controllo. La curva di Kaplan-Meier è stata utilizzata per stimare la distribuzione della funzione di OS, DSS e DFS nella popolazione. Il Log-rank test è stato considerato appropriato per stimare le differenze in termini di sopravvivenza tra i due gruppi considerati (high-performing e normal-performing). I fattori predittivi di OS, DSS e DFS sono stati identificati dall’analisi univariata e multivariata della regressione di Cox e dei rischi proporzionali e sono stati utilizzati per creare degli score atti a valutare la probabilità di essere “high-performing” per OS, DSS e DFS, rispettivamente, dei pazienti da candidare all’intervento chirurgico resettivo. RISULTATI Sessantaquattro pazienti sono stati sottoposti a P-Ar per ACDP “localmente avanzato”, non metastatico (SMA n=29, CT/arteria epatica=40). Utilizzando come cut-off 29.9, 30 e 21 mesi, rispettivamente per OS, DSS e DFS, abbiamo identificato 9 pazienti “high-performing” per OS e DSS e 10 pazienti “high-performing” per DFS. I gruppi di controllo sono risultati composti da 39, 31 e 37 pazienti, rispettivamente per OS, DSS e DFS. I gruppi individuati differivano in maniera statisticamente significativa (p<0.0001) per quanto riguarda OS, DSS e DFS. Dall’analisi multivariata della regressione di Cox e dei rischi proporzionali sono risultati come fattori prognostici la OS il sesso, il livello plasmatico preoperatorio di leucociti, neutrofili, Ca 15.3 e Ca 125 e la chemioterapia neoadiuvante; come fattori prognostici la DSS il livello plasmatico preoperatorio di leucociti, neutrofili e Ca 15.3, il rapporto tra livelli plasmatici preoperatori di piastrine ed albumina e quello tra livelli plasmatici preoperatori di linfociti e monociti, il tipo di chemioterapia neoadiuvante (FOLFIRINOX), il numero di linfonodi metastatici, la presenza di almeno un linfonodo metastatico (N1 TNM 7°edizione), la presenza di almeno quattro linfonodi metastatici (N2 TNM 8°edizione), la presenza di almeno otto linfonodi metastatici, il rapporto tra linfonodi metastatici e linfonodi esaminati e l’infiltrazione arteriosa all’esame patologico del pezzo operatorio; e come fattori prognostici la DFS il livello plasmatico preoperatorio di Ca 15.3 e il tipo di chemioterapia neoadiuvante (FOLFIRINOX e Gemcitabina). Gli score predittivi identificati, composti esclusivamente dai fattori prognostici pre-operatori, hanno presentato una sensibilità massima del 77.8%, 88.9% e 70.3% rispettivamente per OS, DSS e DFS. Il valore predittivo negativo massimo di questi score è risultato 93.9%, 95.8% e 89.6% rispettivamente per OS, DSS e DFS. La OS, DSS e DFS sono risultate maggiori in maniera statisticamente significativa nei pazienti con score positivo rispetto ai pazienti con score negativo (p=0.03 per OS, p=0.007 per DSS e p=0.01 per DFS). CONCLUSIONI Tra tutti i pazienti sottoposti a P-Ar per ACDP “localmente avanzato” ce ne sono alcuni ad alta performance in termini di OS, DSS e DFS, che noi abbiamo definito “high-performing”. Utilizzando i fattori predittivi della OS, della DSS e della DFS abbiamo creato degli score numerici, capaci di predire la probabilità di un paziente di essere “high-performing” in sede pre-operatoria. Questi score, una volta validati anche in casistiche esterne, potrebbero essere utilizzati per selezionare per la P-Ar solamente quei pazienti con ACDP “localmente avanzato” che possano avere potenziali benefici in termini di sopravvivenza a lungo termine dalla resezione

Pancreasectomie laparoscopiche robot-assistite: esperienza pilota e prospettive future

Viene discussa la casistica delle pancreasectomie laparoscopiche robot-assistite effettuate presso l'UO di Chirurgia Generale nell'Uremico e nel Diabetico dell'AOUP nel periodo compreso tra l'Aprile 2008 e il Giugno 2011. La casistica si riferisce ad un numero complessivo di 68 pazienti operati. Sono stati presi in considerazione i risultati istologici, intraoperatori e perioperatori. Dal punto di vista degli istotipi sono risultati 51 neoplasie di grado lieve-moderato, 11 carcinomi e 6 patologie non neoplastiche. Per i risultati intraoperatori è stata valutata la durata media degli interventi in generale e in base alla tipologia d'intervento. Infine tra i risultati perioperatori sono stati valutati: mortalità perioperatoria, degenza media, prevalenza complicanze postoperatorie, numero di reinterventi, ripresa dell'alimentazione per OS e nuovi ricoveri

The learning curve in robotic distal pancreatectomy

No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8 %), being of Clavien-Dindo grade I-II in 32 patients (58.1 %), including pancreatic fistula in 29 patients (52.7 %). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2 %), three were readmitted (5.4 %) and one required repeat surgery (1.8 %). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6 %; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6 %) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators

Nesidioblastosis and Insulinoma: A Rare Coexistence and a Therapeutic Challenge

Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma. Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels (p &lt; 0.0001) and reduction of nocturnal hypoglycemia episodes (p = 0.0002). Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted

Effects of complete immunosuppression suspension after pancreatic graft loss

Background: In the event of loss of function of a pancreatic graft, there are two safe options: suspension of immunosuppressive therapy followed by explantation of the grafted pancreas, or maintenance of reduced doses of mycophenolate without explanting the graft. Methods: A 73-year-old woman, who had received a pancreas transplant alone in 2001 when she was 54, since 2018 suffered the loss of renal function requiring hemodialysis treatment. In 2019, due to repeated acute rejection episodes, she has lost also the function of the grafted pancreas. First, tacrolimus therapy was suspended then, in March 2020 also mycophenolate was interrupted. In September 2020, the patient has accessed the emergency room for massive hematemesis. A contrast-enhanced computed tomography scan of the abdomen showed infected perigraft hematoma with an anastomotic pseudoaneurysm that fistulized in the graft duodenum. Results: The patient was immediately stabilized and underwent a radiological interventional procedure for stent placement in the native right common iliac artery, excluding the native right internal iliac artery and the anastomosis with the common branch of the Y artery graft for the transplanted pancreas. Two days later the patient underwent graft removal with ligation and section of the native right common iliac artery at the level of the anastomosis serving the transplanted pancreas. Due to acute ischemia of the right lower limb, 24 hours later a femoro-femoral arterial crossover was constructed using a cryo-preserved graft. Despite the full restoration of arterial vascularization to the ischemic limb, the patient died five days later. Conclusions: After the loss of a pancreatic graft, if not explanted, it is advisable to maintain immunosuppression at low doses to avoid recurrence of severe acute rejection phenomena with colliquative evolution of the transplanted organ, potentially leading to anastomotic pseudoaneurysms and/or fistulization in the grafted duodenum