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RISULTATI E FATTORI PROGNOSTICI DEL COLANGIOCARCINOMA INTRAEPATICO E PERI-ILARE DOPO TRATTAMENTO CHIRURGICO
Full text linkIntroduzione: La prognosi del colangiocarcinoma peri-ilare ed intraepatico è scarsa. La resezione radicale è l'unico possibilità di sopravvivenza in questi pazienti. Tuttavia,i fattori prognostici di sopravvivenza dopo la resezione, l'insorgenza e il trattamento della recidiva e I miglioramenti nel tempo del trattamento di questi tumori sono ancora oggetto di dibattito in letteratura.
Materiali e Metodi: Sono stati prospetticamente analizzati i dati di 95 pazienti affetti da colangiocarcinoma peri-ilare (PCC) ed 84 affetti da intraepatico (ICC), sottoposti a resezione epatica nella Divisione di Chirurgia Generale dell'Università di Verona tra il settembre 1990 e il settembre 2012.
Risultati: Riguardo i pazienti affetti da PCC I livelli sierici preoperatori di Ca 19.9 e CEA, l'esecuzione di una epatectomia maggiore, la resezione del lobo caudato, la resezione e la ricostruzione portale, l'estesa dissezione linfonodale, l'assenza di noduli satelliti, lo stato N0 e un basso grado secondo TNM stage sono fattori prognosticamente positivi per la sopravvivenza. L'analisi multivariata ha confermato che un basso valore di Ca 19.9 e l'assenza di coinvolgimento linfonodale fattori fortemente correlati con la sopravvivenza. La sopravvivenza mediana è stata di 28.8 mesi, la sopravvivenza a 3 e 5 anni è risultata del 43.2% e 23.9%. Nei pazienti ICC, all'analisi univariata, il CEA> 5 ng / dL, la presenza di metastasi linfonodali, l'invasione vascolare macroscopica, la presenza di metastasi intraepatiche, un più alto grado di differenziazione, uno stadio TNM superiore e margini di resezione positivi (R + ) erano significativamente correlate alla sopravvivenza. L'analisi multivariata ha identificato l'alto valore sierico del CEA, la presenza di metastasi intraepatiche e la radicalità come significativamente correlata alla sopravvivenza con HR di 9.8, 2.2 e 2.3, rispettivamente. La sopravvivenza mediana è stata di 31.8 months, con una sopravvivenza a 3 e 5 anni del 44.5% e 26.8%. Globalmente, la sopravvivenza libera da malattia a 1 e 5 anni è stata del 69.4% e del 21.1%. Nei pazienti affetti da PCC, le sede di recidiva è stata più frequentemente extraepatica (71%). La multifocalità, la resezione / ricostruzione portale, l'invasione perineurale ed elevati livelli sierici di CEA sono risultati significativamente associati alla recidiva. Nove (19,1%) pazienti sono stati sottoposti a intervento chirurgico, 29 pazienti sono stati sottoposti a chemio o radioterapia (61,8%), 9 pazienti (19,1%) hanno ricevuto terapia di supporto. Nei pazienti affetti da ICC la sede direcidiva si è verificata più frequentemente nel fegato (52%). Un alto livello di Ca 19.9, una dimensione del tumore superiore a 30 mm, una resezione R1, la multifocalità e un grading istologico sono risultati fattori correlati alla recidiva. Sei (19.6%) pazienti sono stati sottoposti a resezione chirurgica come terapia della recidiva, la chemioterapia è stata eseguita in 14 pazienti (45,2%) e le rimanenti 11 pazienti hanno ricevuto terapia di supporto. Quando la recidiva è trattata chirurgicamente i pazientihanno mostrato una sopravvivenza più lunga dopo la recidiva rispetto ai pazienti sottoposti a chemio o radioterapia, con una sopravvivenza a1 e 3 anni del 64,8% e del 25,9% contro il 60,3% e il 18,8%, rispettivamente, p = 0,005.
Tra i pazienti affetti da PCC, 29 sono stati sottoposti all'intervneto prima del 2005 e 55 dopo il 2005. La sopravvivenza globale a 5 anni è risultato significativamente aumentata dopo il 2005 (12,5% prima del 2005 e 39,4% dopo il 2005, p = 0,01). In pazienti sottoposti a intervento chirurgico dopo il 2005 rispetto a quelli trattati prima del 2005, si è mostrato un tasso più basso di recidiva (51,7% vs 78,9%, p = 0,07) e una sopravvivenza libera da malattia a 3 anni più alta (49,6% vs. 26,3 % rispettivamente, p = 0,01). Sorprendentemente, in pazienti sottoposti a intervento chirurgico dopo il 2005 con resezione radicale e senza metastasi linfonodali, la sopravvivenza a 5 anni è stata del 73,8%, rispetto al 13,6% degli stessi pazienti sottoposti a intervento chirurgico prima del 2005. Nei pazienti affetti da ICC, 25 sono stati sottoposti a chirurgia prima e 58 dopo il 1 ° gennaio 2005. I pazienti avevano un'età più elevata dopo il 2005. Lo stadio tumorale è risultato essere più avanzato dopo il 2005: infatti, i tumori erano di dimesioni maggiori e con maggiore coinvolgimento macrovascolare in pazienti sottoposti a intervento chirurgico dopo il 2005 rispetto ai pazienti sottoposti prima del 2005. Dopo il 2005 sono state eseguite un maggior numeor di epatectomie maggiori e più ampie dissezioni linfonodali, anche se i tassi di complicanze non hanno dimostrato differenze. Le resezioni radicali sono state più eseguite in maggior numero dopo il 2005 rispetto a prima. Tuttavia, questi risultati non hanno permesso un guadagno di sopravvivenza in pazienti prima e dopo il 2005 (p = 0,48).
Conclusioni: nei pazienti con PCC un basso livello sierico preoperatorio di Ca 19.9 e CEA, l'esecuzione di una epatectomia maggiore, la resezione del lobo caudato, la resezione e ricostruzione della vena porta, e unb'ampia dissezione linfonodale sono risultati fattori prognostici positivi per la sopravvivenza. Nel nostro istituto, i pazienti trattati per PCC negli ultimi 10 anni ha ottenuto un significativo miglioramento dei tassi di sopravvivenza globale rispetto ai pazienti trattati in precedenza, soprattutto se sono stati eseguite resezioni radicali senza linfonodi coinvolti. Per quanto riguarda i pazienti con ICC, CEA> 5 ng / dL, la presenza di metastasi linfonodali, l'invasione vascolare macroscopica, la presenza di metastasi intraepatiche, un più alto grado di differenziazione, uno stadio TNM superiore e margini di resezione positivi (R +) erano significativamente correlate alla sopravvivenza. Il tipo MF ha dimostrato di avere una migliore prognosi rispetto ad altri tipi di ICC. La recidiva si conferma essere un importante fattore prognostico. Quando possibile, la resezione chirurgica aggressiva di recidiva può migliorare la prognosi in questi pazienti, soprattutto nei pazienti con ICC. Nei pazienti con PCC, in cui ricorrenza è più spesso resecabile, protocollo di trattamento adiuvante aggressivo potrebbe migliorare la sopravvivenza ridurre la frequenza delle recidive.Introduction: Prognosis of perihilar and intrahepatic cholangiocarcinoma is dismal. Curative resection is the only chance of survival. Prognostic factors of survival after surgery, onset and treatment of recurrence and the reports of results during the years is still under debate in literature.
Matherial and Methods: Prospectively data of 95 patients with perihilar (PCC) and 84 with intrahepatic cholangiocarcinoma (ICC) submitted to surgical resection in Division of General Surgery of the University of Verona Medical School between September 1990 and September 2012 were evaluate.
Results: for PCC patients, Preoperative serum level of Ca 19.9 and CEA, major hepatectomy, caudate lobe resection, portal vein resection and reconstruction, and lymph node dissection, absence of satellite nodules, N0 status and lower TMN stage resulted as prognostic factors for longer survival at univariate analisys. The multivariate analysis confirmed the serum value of Ca 19.9 lower than 500 U/L, and the absebnce of positive lymphnodal involvement as factor strongly related to survival. Median follow up was of 29 months (range 4-107). Median overall survival was 28.8 months; cumulative proportion survival at 3 and 5 years were 43.2% and 23.9% respectively. For ICC patients, at univariate analysis, the CEA > 5 ng/dL, the presence of lymph node metastases, macroscopic vascular invasion, the presence of intrahepatic metastases, an higher grade of differentiation, an higher TNM stage and positive resection margins (R +) were significantly related to survival. Cox’s regression multivariate model identified the high serum value of CEA, the presence of intrahepatic metastases and the radicality as being significantly related to survival with hazard ratios (HR) of 9.8, 2.2 and 2.3 , respectively. The overall median survival time was 31.8 months, with 3- and 5-year actuarial survival rates of 44.5% and 26.8%, respectively. For all patients, the 1- and 5-year disease-free survival was 69.4% and 21.1%. In patients with PCC, recurrences were more frequently extrahepatic (71%). High lymph-node ratio, multifocality, portal resection/reconstruction, perineural invasion and elevated serum level of CEA were significantly associated with recurrence. Nine (19.1%) patients were submitted to surgery, 29 patients were submitted to chemo or radiotherapy (61.8%), 9 patients (19.1%) received best supportive care. In patients affected by ICC recurrences occurred more frequently into the liver (52%). High level of Ca 19.9, a tumor size higher than 30 mm, R1 resection, multifocality and histological grading are factors correlated to recurrence. Six (19.6%) patients underwent surgical resection of recurrence, chemotherapy was performed in 14 patients (45.2%) and the remnant 11 patients received best supportive care. When recurrence was surgically treated patients showed a longer survival after recurrence than patients submitted to chemo or radiotherapy (1- and 3-year survival of 64.8% and 25.9% vs. 60.3% and 18.8% respectively, p=0.005). Among patients affected by PCC, 29 were submitted before 2005 and 55 after 2005. The 5-year overall survival was significantly increased before and after 2005 (12.5% and 39.4%, respectively, p=0.01). In patients submitted to surgery after 2005 respect than in those treated before 2005, it is shown a lower recurrence rate (51.7% vs. 78.9%, p=0.07) and a higher 3-year disease-free survival (49.6% vs. 26.3%, respectively, p=0.01). Remarkably, in patients submitted to surgery after 2005 with radical resection and with no positive lymph-nodes metastases, the 5-year survival was 73.8%, compared to 13.6% of the same patients submitted to surgery before 2005. In patients affected by ICC, 25 were submitted to surgery before and 58 after 1st January, 2005. Patients were older after 2005. Tumor seemed to be more advanced after 2005: indeed, the tumors were bigger in size and with more macrovascular involvement rate in patients submitted to surgery after 2005 than in patients submitted before 2005. So, the surgery resulted more aggressive after 2005, with more major hepatectomy and more lymph node harvested than before, even if with no difference in complication rate between the two periods. R0 resections were more performed after 2005 than before. Nevertheless, these results did not allow a survival gain in patients before and after 2005 (p=0.48).
Conclusions: in patients with PCC we demonstrated that an low preoperative serum level of Ca 19.9 and CEA, major hepatectomy, caudate lobe resection, portal vein resection and reconstruction, and large lymph node dissection with more than 10 lymph nodes were positive prognostic factors for longer survival. Besides, perioperative and surgical thecniques for the treatment of PCC has been evolved during the years. In our institution, patients treated for PCC in the last 10 years gained a significantly better overall survival rates compared to patients treated before, especially if radical resections were performed with no lymph node involved. Regarding patients with ICC, CEA > 5 ng/dL, the presence of lymph node metastases, macroscopic vascular invasion, the presence of intrahepatic metastases, an higher grade of differentiation, an higher TNM stage and positive resection margins (R +) were significantly related to survival. MF type demonstrated to have better prognosis than other types of ICC. Recurrence is confirmed to be a major prognostic factor. When feasible, aggressive surgical resection of recurrence can improve the prognosis in these patients, especially in patients with ICC. In patients with PCC, in which recurrence is more often unresectable, aggressive adjuvant treatment protocol could improve survival reducing the frequency of recurrences
Role of surgery in the treatment of intrahepatic cholangiocarcinoma
No full textIntrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer, accounting for 10% to 15% of primary hepatic malignancy, and its incidence is increasing in Western Countries. Surgery with curative intent is the only treatment that offers a chance of long-term survival, with a reported 5-year overall survival rate ranging from 17% to 48%. In the most of recent series postoperative mortality is lower than 5% and morbidity varied from 6% to 66%. The macroscopic classification of ICC, proposed by Liver Cancer Study Group of Japan (LCSGJ), reflects different biologic behaviours, pattern of tumor growth and clinicopathological findings. The most important prognostic factors after resection are positive resection margins, lymph-node metastases, tumor size, presence of macrovascular invasion and intrahepatic metastases. Unfortunately, recurrence is still frequent and it is the leading cause of death. The treatment of the recurrence varied according to the location and extension of the disease. Recently, expression of several genes found to be related with the carcinogenesis of ICC. These molecular findings are helpful to differentiate the biological behaviour and will provide evidence for the development of new target therapies
How much remnant is enough in liver resection?
No full textLiver resection represents the first choice of treatment for primary and secondary liver malignancies, offering the patient the best chance of long-term survival. The extensive use of major hepatectomy increases the risk of post-hepatectomy liver failure (PHLF), which is associated with a high frequency of postoperative complications, mortality and increased length of hospital stay.The aim of this review is to investigate the different risk factors related to the occurrence of PHLF and to identify the limits for a safe liver resection in patients with normal liver and injured liver (cirrhosis, cholestasis, steatosis and post-chemotherapy liver injury).A literature search was undertaken in PubMed and related search engines, looking for articles relating to hepatic failure following hepatectomy in normal liver or injured liver.In spite of improvements in surgical and postoperative management, the parameters determining how much liver can be resected are still largely undefined. A number of preoperative, intraoperative and postoperative factors all contribute to the likelihood of liver failure after surgery. The safe limits for liver resection can be estimated from the data of the literature for patients with normal liver and for those with different types of liver injury.Preoperative assessment that includes evaluation of liver volume and function of the remnant liver is a mandatory prerequisite before major hepatectomy. The critical residual liver volume for patients able to predict PHLF is mainly related to the presence of pre-existing liver disease and liver function. Among patients with normal liver, the limit for safe resection ranges from 20 to 30\% future remnant liver of total liver volume. In patients with injured liver (cirrhosis, cholestasis or steatosis), preoperative assessment of the risk of PHLF should include future remnant liver volumetry and accurate liver function evaluation, including different dynamic liver function tests
Laparoscopic double mesh repair of a large Morgagni hernia: a video vignette
No full text: Morgagni hernia (MH) is a rare congenital diaphragmatic hernia (CDH) that accounts for less than 2% of surgically repaired CDH in adulthood. Even if this condition is often asymptomatic, surgery is advised due to the risk of life-threatening complications such as volvulus or bowel strangulation. Surgery for MH repair can be performed by transthoracic, transabdominal, laparoscopic, or thoracoscopic approaches. Though laparoscopy has recently improved surgical outcomes, the use of prosthetic meshes and the need for reduction of the hernia sac are still the most debated issues. We present the video of a laparoscopic repair of a large MH with the use of a double mesh technique and no resection of the hernia sac.: Morgagni hernia (MH) is a rare congenital diaphragmatic hernia (CDH) that accounts for less than 2% of surgically repaired CDH in adulthood. Even if this condition is often asymptomatic, surgery is advised due to the risk of life-threatening complications such as volvulus or bowel strangulation. Surgery for MH repair can be performed by transthoracic, transabdominal, laparoscopic, or thoracoscopic approaches. Though laparoscopy has recently improved surgical outcomes, the use of prosthetic meshes and the need for reduction of the hernia sac are still the most debated issues. We present the video of a laparoscopic repair of a large MH with the use of a double mesh technique and no resection of the hernia sac
Role of Preoperative Biliary Drainage in Jaundiced Patients Who Are Candidates for Pancreatoduodenectomy or Hepatic Resection: Highlights and Drawbacks.
No full textINTRODUCTION:: In this review of the literature, we analyze the indications for preoperative drainage in jaundiced patients who are candidates for pancreaticoduodenectomy (PD) or major hepatectomy due to periampullary or proximal bile duct neoplasms. OBJECTIVE:: The aim of this study is to review the literature and to report on the current management of jaundiced patients with periampullary or proximal bile duct neoplasms who are candidates for PD or major liver resection. BACKGROUND:: Jaundiced patients represent a major challenge for surgeons. Alterations and functional impairment caused by jaundice increase the risk of surgery; therefore, preoperative biliary decompression has been suggested. METHODS:: A literature review was performed in the MEDLINE database to identify studies on the management of jaundice in patients undergoing PD or liver resection. Papers considering palliative drainage in jaundiced patients were excluded. RESULTS:: The first group of papers considered patients affected by middle-distal obstruction from periampullary neoplasms, in which preoperative drainage was applied selectively. The second group of papers evaluated patients with biliary obstructions from proximal biliary neoplasms. In these cases, Asian authors and a few European authors considered it mandatory to drain the future liver remnant (FLR) in all patients, while American and most European authors indicated preoperative drainage only in selected cases (in malnourished patients and in those with hypoalbuminemia, cholangitis or long-term jaundice; with an FLR < 30\% or 40\%) given the high risk of complications of drainage (choleperitoneum, cholangitis, bleeding, and seeding). The optimal type of biliary drainage is still a matter of debate; recent studies have indicated that endoscopy is preferable to percutaneous drainage. Although the type of endoscopic biliary drainage has not been clearly established, the choice is made between plastic stents and short, covered, metallic stents, while other authors suggest the use of nasobiliary drainage. CONCLUSIONS:: A multidisciplinary evaluation (made by a surgeon, biliary endoscopist, gastroenterologist, and radiologist) of jaundiced neoplastic patients should be performed before deciding to perform biliary drainage. Middle-distal obstruction in patients who are candidates for PD does not usually require routine biliary drainage. Proximal obstruction in patients who are candidates for major hepatic resection in the majority of cases requires a drain; however, the type, site, number, and approach must be defined and tailored according to the planned hepatic resection. Recently, the use of preoperative biliary drainage limited to the FLR has been a suggested strategy. However, multicenter, randomized, controlled trials should be conducted to clarify this issue
Prognostic value of portal hypertension after surgical resection of HCC in cirrhotic patients
No full textLiver resection for multinodular hepatocellular carcinoma. Lesson learn from observational study on 464 patients.
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