Improved outcomes of liver resection for hepatitis C-related hepatocellular carcinoma after the introduction of direct-acting antiviral therapy.

BACKGROUND: Assess impact of direct-acting antivirals introduction on outcomes after liver resection for hepatocellular carcinoma. METHODS: 391 patients (1991-2021) treated with resection for hepatocellular carcinoma on Hepatitis C background were divided according to receiving Hepatitis C treatment, treatment type, achievement of sustained virological response (SVR), time of resection pre- (Era 1, 1991-2011) and post-direct acting antivirals introduction (Era 2, 2012-2021). Survival was estimated with Kaplan-Meier curves, Cox regression analysis performed to identify survival predictors. RESULTS: Majority of patients had single lesion (67.8%), diameter >2 cm in 60.6%, no evidence of macroscopic vascular invasion on imaging. Pathology showed vascular invasion in 69.6% of patients, 76.5% microvascular. Recurrence developed in 247 patients (63.2%). 194 patients (49.6%) achieved SVR. Overall survival at 1-, 3-, 5-years was 94.6%, 85.7%, 78.8% for patients who achieved SVR, 80.1%, 48.1%, 29.9% in those who did not (p < 0.001). 220 patients (56.3%) were in Era 1, 171 (43.7%) in Era 2. Survival at 1-, 3-, 5-years was 76.1%, 49%, 36% in Era 1, 94.5%, 82.5%, 70.3% in Era 2 (p < 0.001). SVR was an independent predictor of survival on multiple Cox Regression analysis. CONCLUSION: While many aspects of HCC management have evolved, SVR following direct-acting antivirals independently improves HCC resection outcomes.

The Importance of Segment 4 Anatomy on Outcomes Following Living Donor Left Lateral Segmentectomy.

BACKGROUND: During left lateral section (LLS) resection for live liver donation, the vascular inflow and the bile drainage of segment 4 (S4) are compromised. We investigated the long-term changes of S4 after donation and their potential prognostic impact on living liver donors. MATERIALS AND METHODS: This was a retrospective analysis of 42 consecutive left lateral (LLS, S2/3) liver resections for living donation. RESULTS: There were 25 female and 17 male donors. Median age was 33 y and median body mass index was 26. Median LLS, S2/3, volume was 262 cc, and median sS4 volume was 160 cc. Complications were encountered in three donors (7%). An independent extrahepatic S4 artery (S4A) (with a proximal left heptic artery or a right hepatic artery origin) was identified in 41% of the donors. Ligation of the independent S4A was not associated with the rate of post resection liver dysfunction, complications, or the degree of S4 atrophy. Having a dominant S4 portal triad pedicle feeding the right anterior sectors, segment 5/8, of the liver was associated with increased parenchymal damage as evidenced by a higher peak of alanine aminotransferase but was not associated with postoperative complications. The median degree of atrophy of S4 at 1 y post donation as noted on imaging was 66%. The presence of a dominant S4 portal triad pedicle and the peak alanine aminotransferase early postoperatively were both predictors of the degree of S4 atrophy post donation. CONCLUSIONS: The presence of an independent S4A or dominant S4 portal triad pedicle feeding the liver right anterior sectors, segment 5/8, should not be a contraindication for left lateral segment living donation.

Two hundred and fifty-one right hepatectomies for living donation: Association between preoperative risk factors, hepatic dysfunction, and complications.

BACKGROUND: Donor safety is essential in living donor liver transplantation. In this study we assessed the association among perioperative factors, liver dysfunction, and complications in 251 consecutives right hepatectomies for living donation. METHODS: Retrospectively collected data from a prospectively assembled cohort of 251 consecutive living donors who underwent right hepatectomy between 1999 and 2020 were evaluated. RESULTS: Median age was 36 years; 54% were men. There was a statistically significant relationship between standardized liver volume by body surface area and the volumes calculated by imaging, weighting, and volume displacement. (r2 = 0.40, r2 = 0.34, and r2 = 0.34, respectively), with the relationship between standardized liver volume and liver volume by imaging being the strongest. The median remnant liver volume was 35%. Fifty-eight donors (23%) developed postoperative hepatic dysfunction, which was associated with increased length of stay (P = .04), and complications (P < .01). Men had a 2.5 times higher chance of developing postoperative hepatic dysfunction. Age >50 years was an independent predictor of increased bilirubin at postoperative day 4 (P < .01), and remnant liver volume was inversely associated with higher peak international normalized ratio (P < .01). Eighty-one donors (32%) experienced complications. Postoperative hepatic dysfunction was associated with 2.4 times higher chances of complications (odds ratio = 2.4, P < .01). CONCLUSION: Early postoperative hepatic dysfunction is associated with the development of post-live liver donor complications. A thoughtful balancing of preoperative risk factors for postoperative hepatic dysfunction may indeed and by association reduce postoperative complications.

Non-invasive imaging criteria for the diagnosis of hepatocellular carcinoma in non-cirrhotic patients with chronic hepatitis B.

BACKGROUND & AIMS: Criteria defined by the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) enable hepatocellular carcinoma (HCC) diagnosis based on imaging in cirrhosis. Non-cirrhotic patients require biopsy given the lower pre-test probability of HCC. The objective of our study was to assess the performance of EASL and LI-RADS criteria for the diagnosis of HCC in non-cirrhotic patients with chronic HBV infection. METHODS: This was a cross-sectional study performed at a referral center. We included all patients with HBV without cirrhosis with focal liver lesions who underwent contrast-enhanced CT or MRI at our clinic between 2005-2018. Studies were reviewed by 2 radiologists blinded to the diagnosis. RESULTS: We included 280 patients, median age was 56.8 (IQR 48.2-65.45) years and 223 (80%) were male. In 191 (79%) cases the lesion was found as a result of screening. Cirrhosis was excluded based on pathology in 252 (90%) cases. We assessed 338 nodules: 257 (76%) HCC, 40 (12%) non-HCC malignant lesions, and 41 (12%) benign lesions. EASL criteria and LR-5/LR-tumor-in-vein (TIV) categories had a 100% agreement in categorizing lesions as HCC, and 226 nodules (67%) were classified as HCCs. The sensitivity, specificity, positive predictive value, and negative predictive value were 82.1 (76.9-86.6), 81.5 (71.3-89.2), 93.4 (89.3-96.2), and 58.9 (49.2-68.1), respectively. When the pre-test probability of HCC is >70%, estimated as a PAGE-B score above 9, and EASL or LR-5/LR-TIV criteria are met, post-test probability would be >90%. CONCLUSIONS: EASL criteria and LR-5/LR-TIV categories show a positive predictive value in patients with HBV without cirrhosis that is comparable to that seen in patients with cirrhosis. These criteria can be used when the pre-test probability of HCC is >70%. LAY SUMMARY: Current guidelines recommend performing a biopsy to confirm the diagnosis of presumed hepatocellular carcinoma (HCC) in patients without cirrhosis. We showed that specific imaging criteria had a 100% agreement for categorizing lesions as HCC, with a positive predictive value of 93.4%. These imaging criteria could be used to diagnose HCC in HBV patients without cirrhosis with a pre-test probability of HCC of ≥70%, avoiding the need for a liver biopsy.

Limited upper midline incision for major hepatectomy in adults: safety and feasibility.

Objectives: Optimal incision for major hepatectomy remains controversial. In this study, we described our experience with a limited upper midline incision (UMI) for major hepatectomy. The objective was to analyze the feasibility and safety of UMI in major hepatectomy. Material and Methods: Fifty-seven consecutive patients who underwent major hepatectomies performed via an UMI were compared to a control group of 36 patients who underwent major hepatectomies with a conventional incision (CI). Results: In 85% of the patients, the indication was malignancy, with a median tumor size of 6 cm. Fifty-three percent of the patients had underlying chronic liver disease, and liver fibrosis was found in 61% of the patients. Ninteen percent of the patients had previous upper abdominal surgery. Twenty- six patients underwent left hepatectomy, 20 patients had right hepatectomy and 11 patients trisegmentectomy. Additional combined surgical proce- dures were performed in 42% of the patients. Median operative time was 323 minutes, estimated blood loss was 500 ml, and median post-operative hospital stay was seven days. Surgical complications occurred in 22 patients (39%). 5-year overall survival was 67%. When compared with the control group with CI, patients with UMI had no statistical difference on operative time, estimated blood loss, length of hospital stay, complication rate, and overall survival. Conclusion: Major hepatectomies can be safely performed through UMI. This approach should be considered as a reasonable option in addition to conventional and laparoscopic approaches for major hepatectomies.

Can we downstage locally advanced pancreatic cancer to resectable? A phase I/II study of induction oxaliplatin and 5-FU chemoradiation.

BACKGROUND: Half of patients with pancreatic adenocarcinoma (PC) present with regionally advanced disease. This includes borderline resectable and locally advanced unresectable tumors as defined by current NCCN guidelines for resectability. Chemoradiation (CH-RT) is used in this setting in attempt to control local disease, and possibly downstage to resectable disease. We report a phase I/II trial of a combination of 5FU/Oxaliplatin with concurrent radiation in patients presenting with borderline resectable and locally advanced unresectable pancreatic cancer. METHODS: Patients with biopsy-proven borderline resectable or locally advanced unresectable PC were eligible. Chemotherapy included continuous infusion 5FU (200 mg/m2) daily and oxaliplatin weekly for 5 weeks in dose escalation cohorts, ranging from 30 to 60 mg/m2. Concurrent radiation therapy consisted of 4,500 cGy in 25 fractions (180 cGy/fx/d) followed by a comedown to the tumor and margins for an additional 540 cGy ×3 (total dose 5,040 cGy in 28 fractions). Following completion of CH-RT, patients deemed resectable underwent surgery; those who remained unresectable for cure but did not progress (SD, stable disease) received mFOLFOX6 ×6 cycles. Survival was calculated using Kaplan-Meier analysis. End-points of the phase II portion were resectability and overall survival. RESULTS: Overall, 24 subjects (15 men and 9 women, mean age 64.5 years) were enrolled between June 2004 and December 2009 and received CH-RT. Seventeen patients were enrolled in the Phase I component of the study, fifteen of whom completed neoadjuvant therapy. Reasons for not completing treatment included grade 3 toxicities (1 patient) and withdrawal of consent (1 patient). The highest dose of oxaliplatin (60 mg/m2) was well tolerated and it was used as the recommended phase II dose. An additional 7 patients were treated in the phase II portion, 5 of whom completed CH-RT; the remaining 2 patients did not complete treatment because of grade 3 toxicities. Overall, 4/24 did not complete CH-RT. Grade 4 toxicities related to initial CH-RT were observed during phase I (n=2, pulmonary embolism and lymphopenia) and phase II (n=3, fatigue, leukopenia and thrombocytopenia). Following restaging after completion of CH-RT, 4 patients had progressed (PD); 9 patients had SD and received additional chemotherapy with mFOLFOX6 (one of them had a dramatic response after two cycles and underwent curative resection); the remaining 7 patients (29.2%) were noted to have a response and were explored: 2 had PD, 4 had SD, still unresectable, and 1 patient was resected for cure with negative margins. Overall 2 patients (8.3%) in the study received curative resection following neoadjuvant therapy. Median overall survival for the entire study population was 11.4 months. Overall survival for the two resected patients was 41.7 and 21.6 months. CONCLUSIONS: Combined modality treatment for borderline resectable and locally advanced unresectable pancreatic cancer with oxaliplatin, 5FU and radiation was reasonably well tolerated. The majority of patients remained unresectable. Survival data with this regimen were comparable to others for locally advanced pancreas cancer, suggesting the need for more novel approaches.

MRI-Based Apparent Diffusion Coefficient for Predicting Pathologic Response of Rectal Cancer After Neoadjuvant Therapy: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the use of apparent diffusion coefficient (ADC) during DWI for predicting complete pathologic response of rectal cancer after neoadjuvant therapy. MATERIALS AND METHODS: A systematic review of available literature was conducted to retrieve studies focused on the identification of complete pathologic response of locally advanced rectal cancer after neoadjuvant chemoradiation, through the assessment of ADC evaluated before, after, or both before and after treatment, as well as in terms of the difference between pretreatment and posttreatment ADC. Pooled mean pretreatment ADC, posttreatment ADC, and Δ-ADC (calculated as posttreatment ADC minus pretreatment ADC divided by pretreatment ADC and multiplied by 100) in complete responders versus incomplete responders were calculated. For each parameter, we also pooled sensitivity and specificity and calculated the area under the summary ROC curve. RESULTS: We found 10 prospective and eight retrospective studies. Overall, pathologic complete response was observed in 22.2% of patients. Pooled mean pretreatment ADC in complete responders was 0.84 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s in incomplete responders (p = 0.33). Posttreatment ADC values were 1.51 × 10-3 mm2/s and 1.29 × 10-3 mm2/s, in complete and incomplete responders, respectively (p = 0.00001). The Δ-ADC percentages were also significantly higher in complete responders than in incomplete responders (59.7% vs 29.7%, respectively, p = 0.016). Pooled sensitivity, specificity, and AUC were 0.743, 0.755, and 0.841 for pretreatment ADC; 0.800, 0.737, and 0.782 for posttreatment ADC; and 0.832, 0.806, and 0.895 for Δ-ADC. CONCLUSION: Use of ADC during DWI is a promising technique for assessment of results of neoadjuvant treatment of rectal cancer.

Use of the surgical Apgar score to enhance Veterans Affairs Surgical Quality Improvement Program surgical risk assessment in veterans undergoing major intra-abdominal surgery.

BACKGROUND: We investigated whether the surgical Apgar score (SAS) may enhance the Veterans Affairs Surgical Quality Improvement Program (VASQIP) risk assessment for prediction of early postoperative outcomes. METHODS: We retrospectively evaluated demographics, medical history, procedure, SAS, VASQIP assessment, and postoperative data for patients undergoing major/extensive intra-abdominal surgery at the Manhattan Veterans Affairs between October 2006 and September 2011. End points were overall morbidity and 30-, 60- , and 90-day mortality. Pearson's chi-square, ANOVA, and multivariate regression modeling were employed. RESULTS: Six hundred twenty-nine patients were included. Apgar groups did not differ in age, sex, and race. Low SASs were associated with worse functional status, increased postoperative morbidity, and 30-, 60- , and 90-day mortality rates. SAS did not significantly enhance VASQIP prediction of postoperative outcomes, although a trend was detected. Multivariate analysis confirmed SAS as an independent predictor of morbidity and mortality. CONCLUSIONS: SAS effectively identifies veterans at high risk for poor postoperative outcome. Additional studies are necessary to evaluate the role of SAS in enhancing VASQIP risk prediction.

Small bowel obstruction and incisional hernia after laparoscopic and open colorectal surgery: a meta-analysis of comparative trials.

INTRODUCTION: Recent studies show contrasting data on the impact of laparoscopy on long-term complications such as the occurrence of small bowel obstruction (SBO) and incisional hernia (IH). The objective of the study was to assess the impact of the laparoscopic approach on the occurrence of SBO and IH after colorectal resection. METHODS: Two trained investigators independently searched MEDLINE, Embase, PubMed, and the Cochrane Central Register of clinical trials for studies comparing laparoscopy to open surgery for mid- to long-term outcomes after colorectal surgery. No language restriction was set. Sensitivity analyses for study design and quality, conversion rate, type of procedure (colon or rectal surgery), and length of follow-up were performed. RESULTS: Eleven RCTs and 14 non-RCT comparative studies for a total of 6540 patients were included in the analysis. Laparoscopy was associated with a significant reduction in the occurrence of SBO (RR 0.57, [95 %CI 0.42-0.76], 16 trials) and IH (RR 0.60, [95 %CI 0.50-0.72], 19 trials). Sensitivity analysis including only RCTs confirmed the reduction in SBO (RR 0.58, [95 %CI 0.39-0.87], 8 trials), while the difference was close to significance for IH (RR 0.76, [95 %CI 0.56-1.03], 7 trials). Sensitivity analysis including only studies with conversion rate lower than 15 % showed a significant protective effect of laparoscopy for both SBO (RR 0.53, [95 %CI 0.37-0.77], 11 trials) and IH (RR 0.58, [95 %CI 0.47-0.72], 12 trials). No significant difference between laparoscopy and open surgery was found when the analysis was limited to studies with conversion rate >15 % (SBO: RR 0.60 [0.32-1.12], IH: RR 0.70 [0.46-1.06]). Length of follow-up did not substantially impact on results. CONCLUSION: Laparoscopic surgery is associated with a significant reduction in both SBO and IH compared to the open approach. A low conversion rate in the laparoscopic group plays a key role for reduction in both SBO and IH.

Ten-year outcomes following laparoscopic colorectal resection: results of a randomized controlled trial.

PURPOSE: To evaluate the impact of laparoscopy compared to open surgery on long-term outcomes in a large series of patients who participated in a randomized controlled trial comparing short-term results of laparoscopic (LPS) versus open colorectal resection. METHODS: This is a retrospective review of a prospective database including 662 patients with colorectal disease (526, 79 % cancer patients) who were randomly assigned to LPS or open colorectal resection and followed every 6 months by office visits. The primary endpoint of the study was long-term morbidity. Secondary outcomes included 10-year overall, cancer-specific, and disease-free survivals. All patients were analyzed on an intention-to-treat basis. RESULTS: Fifty-eight (8.8 %) patients were lost to follow-up. Median follow-up was 131 (IQR 78-153) months in the LPS group and 126 (IQR 52-152) months in the open group (p = 0.121). Overall, long-term morbidity rate was 11.8 % (36/309) in the LPS versus 12.6 % (37/295) in the open group (p = 0.770). Incisional hernia rate was 5.8 % (18/309) in the LPS group versus 8.1 % (24/295) in the open group (p = 0.264). Adhesion-related small-bowel obstruction occurred in five (1.6 %) patients in the LPS versus four (1.4 %) patients in the open group (p = 1.000). In 497 cancer patients, 10-year overall survival was 45.3 % in the LPS group and 40.9 % in the open group (p = 0.160). No difference was found in cancer-specific and disease-free survivals, also when patients were stratified according to cancer stage. CONCLUSION: In this series, LPS colorectal resection was not associated with a lower long-term morbidity rate when compared to open surgery. Overall, cancer-specific and disease-free survivals were similar in cancer patients who were treated with LPS and open surgeries.