Kasai-Like Portoenterostomy for Multiple Biliary Duct Reconstruction After Extended Liver Resection of Perihilar Cholangiocarcinoma.

BACKGROUND: Surgical resection remains the best therapeutic option for the long-term survival of patients with perihilar cholangiocarcinoma (PCC).1 For patients presenting with Bismuth type 3 or 4 tumors, left or right extended liver resection has been shown to be feasible.2 The Achilles heel of the procedure remains biliary reconstruction due to multiple small-diameter remnant liver bile ducts.3 This study showed how a Kasai-like portoenterostomy allows circumvention of this difficulty. METHODS: A 57-year-old woman with a type 3a PCC invading the main portal vein bifurcation underwent a right hepatectomy with en bloc resection of segment 4b, the caudate lobe, and the extrahepatic common bile duct; hepatic pedicle lymphadenectomy; and main portal vein bifurcation reconstruction.4 The cross-section of the left biliary plate was tumor-free at frozen section analysis but involved three small biliary ducts originating from segments 2, 3, and 4a. The biliary plate and the distance between each duct were too large to allow unification. A Roux-en-Y portoenterostomy, inspired by the Kasai procedure,5 was performed between the umbilical plate and the extramucosal wall of an efferent Roux-en-Y jejunal limb. Two temporary external trans-portoenterostomy drains were placed according to the Voelker technique. RESULTS: The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The two trans-portoenterostomy drains were removed after 6 weeks, and patient was disease-free at the 2-year follow-up evaluation. CONCLUSIONS: In extended PCC, Kasai-like portoenterostomy may facilitate complex biliodigestive reconstructions when multiple biliary ducts are involved.

Prospective Evaluation of Intrahepatic Microscopic Occult Tumor Foci in Patients with Numerous Colorectal Liver Metastases.

BACKGROUND: Patients with numerous colorectal liver metastases (CLM) have high risk of early recurrence after liver resection (LR). The presence of intrahepatic occult microscopic metastases missed by imaging has been hypothesized, but it has never been assessed by pathology analyses. METHODS: All patients with > 10 CLM who underwent LR between September 2015 and September 2016 were considered. A large sample of liver without evidence of disease ("healthy liver") was taken from the resected specimen and sent to the pathologist. One mm-thick sections were analyzed. Any metastasis, undetected by preoperative and intraoperative imaging, but identified by the pathologist was classified as occult microscopic metastasis. RESULTS: Ten patients were prospectively enrolled (median number of CLM n = 15). In a per-lesion analysis, the sensitivity of computed tomography and magnetic resonance imaging was 91 and 98% respectively. The pathology examination confirmed all the CLM. All patients had an adequate sample of "healthy liver" (median number of examined blocks per sample n = 14 [5-33]). No occult microscopic metastases were detected. After a median follow-up of 15 months, 5 patients were disease-free. Recurrence was hepatic and bilobar in all patients. CONCLUSIONS: Clinically relevant occult microscopic disease in patients with numerous CLM is excluded. These results support the indication to resection in such patients and exclude the need for de principe major hepatectomy to increase the completeness of surgery.

Extended Right Hepatectomy and Inferior Vena Cava Graft Replacement for En Bloc Resection of Hepatocellular Carcinoma with Cavo-Hepatic Venous Confluence Invasion.

BACKGROUND: Hepatocellular carcinoma (HCC) associated with tumor extension in the portal vein, hepatic vein, or inferior vena cava (IVC) is traditionally considered an advanced stage of disease to which palliative radiotherapy or sorafenib chemotherapy is proposed.1,2 Recent studies have shown a significant survival benefit in patients treated with R0 liver resection.3-5 METHODS: We describe the case of a 45-year-old female patient presenting with a voluminous HCC developed in a non-cirrhotic liver with a tumor thrombus obstructing the retrohepatic IVC and the middle hepatic vein termination. Initial treatment included two cycles of selective internal radiation therapy with Yttrium 90 and sorafenib treatment for 1 year. Re-evaluation revealed a significant reduction of the tumor and compensative hypertrophy of the left liver lobe, enabling surgical resection. RESULTS: The procedure included anatomic right hepatic trisectionectomy with caudate lobectomy and retrohepatic IVC graft replacement. Total liver vascular exclusion with intrapericardial IVC control enabled en bloc R0 resection of the tumor and the floating tumor thrombus in the cavo-hepatic venous confluence. Total liver vascular exclusion duration was 20 min, for a total warm liver ischemia of 40 min. The duration of the operation was 240 min and blood loss was 700 mL. The patient was discharged on postoperative day 15 and was free of disease 6 months post-surgery. CONCLUSION: Liver surgery with complex vascular resections for HCC with major vascular invasion should be considered a valid therapeutic option in high-volume hepatobiliary centers.

Filamin A expression predicts early recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) after hepatectomy is very high. A predictive marker of early recurrence (ER) capable of personalizing follow-up and developing a new target therapy would be beneficial. The overexpression of Filamin-A (FLNA), a cytoskeleton protein with scaffolding properties, has recently been associated with progression in tumours. The aim of this study was to test the expression of FLNA in a cohort of patients operated for HCC. METHODS: A retrospective cohort of patients who underwent hepatic resection at Humanitas Clinical and Research Center between January 2004 and December 2014 was analysed. FLNA was tested, using a tissue microarray, in the HCC and in the surrounding tissues. The endpoint was the role of FLNA expression in predicting ER of HCC after hepatectomy. Analyses were performed following the REMARK guidelines. RESULTS: A total of 113 patients were considered. FLNA was expressed only in the tumoral tissue. Several variables, including T stage, tumour number, tumour size, type of viral hepatitis, type of hepatectomy and intra and peritumoral immune-reactivity to FLNA were significantly associated with ER by univariate analysis. With multivariate analysis, only T stage (HR=2.108; P=.002), tumour number (HR=1.586; P=.023), intra-tumoral (HR=2.672; P<.001) and peritumoral immune-reactivity to FLNA (HR=2.569; P<.001), significantly correlated with ER. The logistic regression analysis revealed that advanced T stage (OR=2.985; P=.001), HCV-infection (OR=1.219; P=.008) and advanced tumour grading (OR=2.781; P=.002) were associated with intratumoral FLNA immune-reactivity. CONCLUSIONS: FLNA expression predicts recurrence of HCC after hepatectomy. This finding provides important insights that would help physicians to personalize follow-up strategies.

Measurement of Total Liver Volume Using the Energy Expenditure: A New Formula.

BACKGROUND: The assessment of liver volume (LV) is important before surgical resection or transplantation to reduce the risk of hepatic insufficiency. LV is usually measured using computed tomography or with some formulas. The aim of this study was to develop a new dynamic formula to predict LV. METHODS: Using computed tomography, LV was calculated in 101 patients without liver disease. LV was correlated with patient metabolic status, calculated with the Harris-Benedict equation for basal energy expenditure (BEE). Activity energy expenditure (AEE) was also calculated. Using linear regression analysis, a new formula was derived and was compared with Heinmann's, Urata's, Emre's, Vauthey's, Yoshizumi's, Yu's, and Hashimoto's formulas. RESULTS: A new basal formula was established: LV = (0.789 × BEE) + 272. It was found to be the most accurate (R2 = 0.39, p < 0.001). Heinmann's, Emre's, and Vauthey's formulas tend to overestimate LV, while Urata's, Yoshizumi's, Yu's, and Hashimoto's formulas tend to underestimate LV. A new AEE formula was also established: LV = (0.789 × AEE) + 272. CONCLUSIONS: These formulas give a dynamic perspective of LV, which may be influenced by the patient's actual clinical status. Using these formulas, it is possible to estimate an increased value of LV, which may contribute to a reduction in the risk of postoperative hepatic insufficiency.

Hepatectomy with or without the thoraco-abdominal approach: impact on perioperative outcome.

BACKGROUND: Hepatectomy using the thoraco-abdominal approach (TAA) compared to the abdominal approach (AA) remains under debate. This study assessed the perioperative outcomes of patients operated with or without TAA. METHODS: 1:1 propensity score-matched analysis was applied in 744 patients operated between 2007 and 2013, identifying 246 patients who underwent hepatectomy with TAA compared to 246 patients with AA. These groups were matched for demographics, liver disease, comorbidity, tumor features, and extent of resection. Rates of morbidity and mortality were the study endpoints. RESULTS: The rates of morbidity or mortality were not different. With the TAA length of the operations (P = 0.002), length of the Pringle maneuver (P = 0.012), and rate of blood transfusions (P = 0.041) were significantly different. Hospital stay was similar. Independent significant prognostic factors for adverse perioperative outcome were: renal comorbidity (OR = 2.7; P = 0.001), extent of the resection (OR = 3.7; P = 0.001), and increased BILCHE score (OR = 2.4; P = 0.002). CONCLUSIONS: Hepatectomy using the TAA was not associated with adverse perioperative outcome. The associations with length of operation, Pringle maneuver and blood transfusions may have reflected the complexity of the tumor presentation rather than the technical approach.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation.

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

Neoadjuvant chemotherapy for borderline resectable and upfront resectable pancreatic cancer increasing overall survival and disease-free survival?

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients. Methods: One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed. Results: One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS. Conclusions: Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.

Microwave Ablation for Colorectal Liver Metastases: A Systematic Review and Pooled Oncological Analyses.

(1) Background: colorectal liver metastases (CRLM) are the most common extra-lymphatic metastases in colorectal cancer; however, few patients are fit for curative surgery. Microwave ablation (MWA) showed promising outcomes in this cohort of patients. This systematic review and pooled analysis aimed to analyze the oncological results of MWA for CRLM. (2) Methods: Following PRISMA guidelines, PubMed, Scopus, EMBASE, Google Scholar, Science Direct, and the Wiley Online Library databases were searched for reports published before January 2021. We included papers assessing MWA, treating resectable CRLM with curative intention. We evaluated the reported MWA-related complications and oncological outcomes as being recurrence-free (RF), free from local recurrence (FFLR), and overall survival rates (OS). (3) Results: Twelve out of 4822 papers (395 patients) were finally included. Global RF rates at 1, 3, and 5 years were 65.1%, 44.6%, and 34.3%, respectively. Global FFLR rates at 3, 6, and 12 months were 96.3%, 89.6%, and 83.7%, respectively. Global OS at 1, 3, and 5 years were 86.7%, 59.6%, and 44.8%, respectively. A better FFLR was reached using the MWA surgical approach at 3, 6, and 12 months, with reported rates of 97.1%, 92.7%, and 88.6%, respectively. (4) Conclusions: Surgical MWA treatment for CRLM smaller than 3 cm is a safe and valid option. This approach can be safely included for selected patients in the curative intent approaches to treating CRLM.

Laparoscopic hybrid pancreaticoduodenectomy: Initial single center experience.

BACKGROUNDS/AIMS: Pancreaticoduodenectomy (PD) is the gold standard for the treatment of periampullary tumors. Many specialized centers have adopted the totally laparoscopic or hybrid laparoscopic PD (LPD). However, this procedure has not yet been standardized and serious debate is taking place towards its safety and feasibility. Herein, we report our recent experience whit hybrid-LPD. METHODS: During 2019 in our department 56 PD were performed and 21 (37.5%) underwent hybrid-LPD. We have retrospectively reviewed the short-term outcomes of these patients. RESULTS: Main indication was pancreatic adenocarcinoma (71,4%). The median operative time and intraoperative blood loss were respectively 425 min (range, 226 to 576) and 317 ml (range 60 to 800 ml). Conversion to an open procedure was required in 4 patients (19%): 2 with suspected vein involvement, 1 for mesenteric panniculitis and 1 for biliary injury. The post-operative complication rate was 42.8% (9/21). Regarding post-operative pancreatic fistula, three patients (14.2%) had grade B and 1 grade C (4.7%). Median length of hospital stay was 14 days (range 9-23) and 90- days mortality was 4.7%. The mean number of harvested lymph nodes was 17.7 (range 12 to 26). The rate of margins R0 was 80%; R1 ＞0<1 mm was 10.5% and R1 0 mm was 9.5%. CONCLUSIONS: Hydrid-LPD is safe and feasible. Careful patient selection and increasing experience can reduce the risk of post-operative complications.

The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: results from the NutriCatt protocol.

BACKGROUND: Malnutrition in liver surgery is correlated with higher postoperative complications and longer length of hospital stay (LOHS), the same items that ERAS programs try to optimize. However, to date, standardized dietary protocols have not been defined within ERAS programs. Aim of this study was to evaluate the impact on LOHS and postoperative complications, of a personalized nutritional protocol (NutriCatt) with diet and oral branched-chain amino acid (BCAA) supplementation, adopted within the ERAS program. METHODS: 1960 consecutive liver resections were performed from January 2000 to September 2018. EXCLUSION CRITERIA: perihilar cholangiocarcinoma, simultaneous colorectal and liver resections. Four groups for analysis: resections before 2009 (1st period); from 2009 to 2016 (2nd period, including laparoscopic resections); between 2016 and September 2017 (ERAS); after September 2017 (ERAS + NutriCatt). RESULTS: LOHS declined (p < 0.0001), from a median of 10 days (1st period) to 8, 7 and 6 in 2nd period, ERAS and ERAS + NutriCatt groups, respectively. At multivariable analysis for risk of LOHS > 8 days, the 2nd period, ERAS and ERAS + NutriCatt groups showed a protective effect. These results were confirmed for both minor and major resections. LOHS was significantly lower in ERAS + Nutricatt group than in ERAS group, without increasing risk of postoperative complications, although the rate of laparoscopic resections was similar in these two groups and complexity of liver resections was significantly higher in the last period. CONCLUSIONS: Adoption of a personalized nutritional protocol with BCAA supplementation within the ERAS program for liver resections was a safe and effective approach that may impact on reducing the LOHS.

Oncologic superiority of anatomic resection of hepatocellular carcinoma by ultrasound-guided compression of the portal tributaries compared with nonanatomic resection: An analysis of patients matched for tumor characteristics and liver function.

BACKGROUND: The superiority of anatomic resection compared with nonanatomic resection for hepatocellular carcinoma remains a matter of debate. Further, the technique for anatomic resection (dye injection) is difficult to reproduce. Anatomic resection using a compression technique is an easy and reversible procedure based on liver discoloration after ultrasound-guided compression of the tumor-feeding portal tributaries. We compared the oncologic efficacy of compression technique anatomic resection with that of nonanatomic resection. METHODS: Among patients with resected hepatocellular carcinoma, patients who underwent compression technique anatomic resection were matched 1-to-2 with nonanatomic resection cases based on the Child-Pugh class, Model for End-Stage Liver Disease score, cirrhosis, hepatocellular carcinoma number (1/>1), and hepatocellular carcinoma size (>30, 30-50, and >50 mm). The exclusion criteria were nonanatomic resection because of severe cirrhosis, major hepatectomy, 90-day mortality (0 compression technique anatomic resection), non-cancer-related death, and follow-up <12 months. A total of 47 patients who underwent compression technique anatomic resection were matched with 94 nonanatomic resection cases. RESULTS: All patients were Child-Pugh A, and 53% were cirrhotic. Liver function tests and signs of portal hypertension were similar between the groups. There was 1 hepatocellular carcinoma in 81% of the patients, and the hepatocellular carcinoma was ≥30 mm in 68%. Patients undergoing anatomic resection with compression had better 5-year survival (77% vs 60%; risk ratio = 0.423; P = .032; multivariable analysis), less local recurrences (4% vs 20%; P = .012), and better 2-year local recurrence-free survival (94% vs 78%; P = .012). Nonlocal recurrence-free survival was similar between the groups. The compression technique anatomic resection group more often had repeat radical treatment for recurrence (68% vs 28%; P = .0004) and had better 3-year survival after recurrence (65% vs 42%; P = .043). CONCLUSION: Compression technique anatomic resection appears to provide a more complete removal of the hepatocellular carcinoma-bearing portal territory. Local disease control and survival are better with compression technique anatomic resection than with nonanatomic resection.

Refining the management of patients with hepatocellular carcinoma integrating 11C-choline PET/CT scan into the multidisciplinary team discussion.

OBJECTIVE: The aim of this study was to report the impact of C-choline PET/CT on the management of patients with hepatocellular carcinoma (HCC) and incorporate into a refined algorithm combining diagnostic imaging and multidisciplinary team (MDT) discussion. PATIENTS AND METHODS: From February 2010 to February 2016, the charts of all patients discussed in the liver MDT were revised. Suspected or confirmed HCC lesions or Barcelona Clinic Liver Cancer stages A, B or C with a C-choline PET/CT performed in our hospital were included in the analyses. Overall, 73 patients (male : female=59 : 14; median age: 75 years) were enrolled. Forty-two (57%) patients were newly diagnosed, whereas 31 (43%) came to our attention at disease recurrence. Seven (10%) patients were Barcelona Clinic Liver Cancer stage 0, 31 (42%) patients were stage A, 15 (20%) patients were stage B, and 18 (25%) patients were stage C. The reference standards for ultimate imaging validation were either histology or MDT consensus. A minimum follow-up of 6 months was established. RESULTS: Overall eight (10%) patients were initially referred for chemotherapy (sorafenib), 43 (59%) for surgery, two (3%) for surgery or transarterial embolization, five (7%) for follow-up only, one (1%) for extrahepatic radiotherapy, seven (10%) for stereotactic body radiation therapy of the liver, six (8%) for transarterial embolization, and one (1%) for liver transplant. After C-choline PET/CT and MDT discussion, in seven patients the diagnosis changed, in six patients the treatment was changed, and in nine patients both the diagnosis and the treatment were changed. Overall, in 30% of our patients, the diagnosis or treatment was altered on the basis of our algorithm of management. CONCLUSION: The incorporation of C-choline PET/CT into the MDT discussion altered the diagnosis/treatment of one-third of HCC patients. We propose a novel diagnostic algorithm to be refined in referral centers for HCC management.

Absence of viable HCC in the native liver is an independent protective factor of tumor recurrence after liver transplantation.

BACKGROUND: Prognostic factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) are still a matter of debate. The absence of viable tumor in the native liver, due to effectiveness of pre-LT locoregional treatment or liver resection, is an intriguing prognostic factor that had never been evaluated. METHODS: Between November 2000 and December 2011, 210 LTs were performed in patients with evidence of HCC and cirrhosis. RESULTS: Fifty-three (25.2%) patients did not show any evidence of active residual HCC in the native liver (Group NVH), whereas 157 (74.8%) patients showed viable HCC (Group VH). All patients in Group NVH were treated before LT with a multimodal approach combining transarterial chemoembolization, liver resection, radiofrequency ablation, percutaneous ethanol injection, or sorafenib, whereas, in Group VH, 110 of the 157 (70.1%) patients received bridging therapy (P<0.001). HCC recurrence occurred in none of the patients in Group NVH (0%) and in 25 (15.9%) patients in Group VH (P=0.003). Liver resection was the most effective treatment in obtaining absence of HCC on liver explantation. The results of multivariate analysis showed that existence of pathologic HCC findings outside of the University of California-San Francisco criteria (P=0.001; odds ratio, 4; confidence interval, 1.7-9.2) and the presence of viable HCC (P=0.003; odds ratio, 5.9; confidence interval, 1.5-17.6) were independently associated with HCC recurrence. CONCLUSIONS: The histologic absence of viable HCC in the native liver after LT and morphologic criteria, due to the high effectiveness of pre-LT bridging treatments, is a highly positive prognostic factor against HCC recurrence after LT.