Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with ...neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).
A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluorescently labeled somatostatin analog,
Ga-MMC(IR800)-TOC.
studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.
Direct labeling with
Ga/
Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed
and
at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.
The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) ...imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field.
Background
Advantages of minimally invasive compared with open hepatobiliary surgery include quicker functional recovery, decreased postoperative length of stay, and decreased postoperative opioid ...use. As more complex operations are approached in minimally invasive fashion, it is imperative to maintain safety and excellent oncologic outcomes.
Methods
In this video, we demonstrate the key principles in performing a safe robotic extended right hepatectomy for colorectal liver metastasis following sound oncologic principles.
Results
Key preoperative considerations include (1) early referral to a hepatobiliary surgeon, (2) careful review of cross-sectional imaging to identify the relationship of tumors to major vasculature and any aberrant vascular anatomy, and (3) liver volumetry for every right hepatectomy to determine the need for future liver remnant volume augmentation. Key intraoperative techniques include (1) liberal use of ultrasound before and during transection to determine the relationship of major vasculature to tumor to preserve liver parenchyma without compromising tumor margins, (2) external retraction with vessel loops placed on either side of the transection line as stay sutures to facilitate parenchymal transection, and (3) a crush clamp technique to safely identify and control crossing vessels while dividing liver parenchyma.
Conclusions
With proper preoperative planning and intraoperative use of these techniques, the benefits of a minimally invasive approach can be achieved while maintaining excellence in surgical quality and safety.
Background
Low socioeconomic status (SES) patients with early-stage hepatocellular carcinoma (HCC) receive procedural treatments less often and have shorter survival. Little is known about the extent ...to which these survival disparities result from treatment-related disparities versus other causal pathways. We aimed to estimate the proportion of SES-based survival disparities that are mediated by treatment- and facility-related factors among patients with stage I–II HCC.
Methods
We analyzed patients aged 18–75 years diagnosed with stage I–II HCC in 2008–2016 using the National Cancer Database. Inverse odds weighting mediation analysis was used to calculate the proportion mediated by three mediators: procedure type, facility volume, and facility procedural interventions offered. Intersectional analyses were performed to determine whether treatment disparities played a larger role in survival disparities among Black and Hispanic patients.
Results
Among 46,003 patients, 15.0% had low SES, 71.6% had middle SES, and 13.4% had high SES. Five-year overall survival was 46.9%, 39.9%, and 35.7% among high, middle, and low SES patients, respectively. Procedure type mediated 45.9% (95% confidence interval CI 31.1–60.7%) and 36.7% (95% CI 25.7–47.7%) of overall survival disparities for low and middle SES patients, respectively, which was more than was mediated by the two facility-level mediators. Procedure type mediated a larger proportion of survival disparities among low–middle SES Black (46.6–48.2%) and Hispanic patients (92.9–93.7%) than in White patients (29.5–29.7%).
Conclusions
SES-based disparities in use of procedural interventions mediate a large proportion of survival disparities, particularly among Black and Hispanic patients. Initiatives aimed at attenuating these treatment disparities should be pursued.
Background
Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate ...whether local therapy benefits patients with early recurrence following hepatectomy for CLM.
Methods
Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001–12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival RFS < 6 months), intermediate (RFS 6–12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation.
Results
Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all
p
< 0.001). Following recurrence, treatment with local therapy (hazard ratio HR = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all
p
≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all
p
≤ 0.04).
Conclusions
While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.
Background
Current guidelines recommend radical cholecystectomy with regional lymphadenectomy (RC-RL) for patients with T1b gallbladder cancer (GBC). However, the extent to which these guidelines are ...followed is unclear. This study aimed to evaluate current surgical practices for T1b GBC and their implications for overall management strategies and associated outcomes.
Methods
This retrospective cohort study investigated patients identified from the National Cancer Data Base (2004–2012) with non-metastatic T1b GBC. The patients were categorized according to type of surgical treatment received: simple cholecystectomy (SC) or RC-RL. Among the patients who had lymph nodes pathologically examined, nodal status was classified as pN− or pN+. Use of any adjuvant therapy was ascertained. Overall survival (OS) was compared based on type of surgical treatment and nodal status.
Results
The cohort comprised 464 patients (247 SC and 217 RC-RL cases). The positive margin status did not differ between the two groups (6.1% for SC vs 2.3% for RC-RL;
p
= 0.128). For RC-RL, the pN+ rate was 15%. Adjuvant therapies were used more frequently in pN+ (53.1% vs 9.4% for pN−). By comparison, 10.9% of the SC patients received adjuvant therapy. The OS for RC-RL-pN− (5-years OS, 64.4%) was significantly better than for RC-RL-pN+ (5-years OS, 15.7%) or SC (5-years OS, 48.3%) (
p
< 0.001).
Conclusion
Less than 50% of the patients with a T1b GBC primary tumor undergo the recommended surgical treatment. Given that 15% of these patients have nodal metastasis and in light of the previously described benefits of adjuvant therapy for node positive GBC, failure to perform RC-RL risks incomplete staging and thus undertreatment for patients with T1b GBC.
Background
Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar ...obstruction and long-term outcomes after resection.
Methods
Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0–281 months).
Results
Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1–5779) and 21 U/mL (range 1–681) among patients with malignant and benign strictures, respectively (
p
= 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all
p
< 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3–4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (
p
= 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (
p
= non-significant).
Conclusions
Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.
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