Abstract Background The benefit of adjuvant chemotherapy occurs with early initiation, but is commonly delayed due to postoperative complications. Minimally invasive surgery is proven to ...significantly reduce complications and hospital length of stay. This study compares open versus laparoscopic liver resection in patients requiring adjuvant chemotherapy. Methods 120 consecutive patients with metastatic colorectal liver cancer who underwent liver resection between 2007 through 2012 were reviewed from an IRB prospective database. Results 44 laparoscopic cases were compared to 76 open cases having equivalent resections. Laparoscopic liver resection patients had lower blood loss (276 ml) than patients with open resection (614 ml). Patients with laparoscopy had shorter length of hospital stay (5 days) than patients with open resection (9 days). Patients with laparoscopic resection had a shorter time of chemotherapy initiation postoperatively (24 days v 39 days). Overall complication rates were higher, but statistically insignificant in patients with open resection. Conclusions Our data showed that the shorter LOS with laparoscopic major hepatectomies allows earlier initiation of chemotherapy compared to the open group, without jeopardizing surgical margins or extent of resection. Summary Over the past decade multiple authors have established that, despite occasional longer operating times, laparoscopic liver surgery is associated with reduced blood loss, reduced postoperative morbidity and shorter hospital stay. The purpose of this analysis was to determine if the advantages of a minimally invasive approach correspond to shorter initiation of adjuvant chemotherapy versus an open approach.
Background Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such ...patients may benefit from completion lymph node dissection (CLND). Study Design In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin H and E serial sections and immunohistochemistry IHC) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison. Results A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044). Conclusions Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.
We enumerate the broad range of anesthetic considerations that affect the outcome of patients undergoing laparoscopic liver resection. Key elements for excellent outcomes after laparoscopic liver ...resection are careful patient selection and risk stratification, appropriate monitoring, techniques to reduce blood loss and transfusion, and active recovery management. Although some of these key elements are the same for open liver operation, there are specific anesthetic considerations of which both the surgical and anesthesia teams must be aware to achieve optimal patient outcomes after laparoscopic liver resection. While unique advantages of laparoscopic liver resection typically include decreased intraoperative bleeding, transfusion requirements, and a lower incidence of postoperative ascites, specific challenges include management of the complicated interplay between low-volume anesthesia and increased intraabdominal pressure due to pneumoperitoneum, with additional considerations regarding circulatory support to treat acute blood loss with need for emergent conversion in some cases. This article will address in detail the preoperative, intraoperative, and postoperative anesthetic considerations for patients undergoing laparoscopic liver resection that both the surgical and anesthesia team should be aware of to optimize outcomes.
Background Sentinel lymph node (SLN) biopsy for melanoma results in accurate nodal staging, which guides treatment decisions. Patients with a negative SLN biopsy in general have a favorable ...prognosis, but certain subsets are at increased risk for recurrence and death. This study aimed to identify risk factors predictive of prognosis in patients with a tumor-negative SLN biopsy for cutaneous melanoma. Methods In this post-hoc analysis of data from a multicenter prospective randomized trial, clinicopathologic data of patients with cutaneous melanoma ≥1.0 mm Breslow thickness and tumor-negative SLN were analyzed. Disease-free survival, overall survival (OS), and local and in-transit recurrence-free survival were compared by Kaplan-Meier analysis. Risk factors for worse survival were identified with Cox proportional hazard models. Results This analysis included 1,998 patients with tumor-negative SLN with a median follow-up of 70 months. Ulceration, Breslow thickness, nonextremity tumor location, and age ≥45 years were independent risk factors for worse disease-free survival and OS. Breslow thickness and ulceration were the only factors on multivariate analysis that predicted local and in-transit recurrence-free survival. Estimated 5-year OS rates ranged from 55.5 to 95.4% on the basis of the defined risk factors. Conclusion There is a wide range of prognosis among patients with tumor-negative SLN. Breslow thickness, ulceration, age, and anatomic location of the primary melanoma are important independent factors predicting survival and recurrence among such patients. These factors can be used to stratify prognosis among patients with tumor-negative SLN to formulate rational long-term follow-up strategies as well as identify high-risk, SLN-negative patients for clinical trials of adjuvant therapy.
Background Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification ...scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS). Study Design A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥1.0 mm Breslow thickness who underwent SLN biopsy. The following micrometastatic disease burden measurements were recorded: Starz classification, Dewar classification (microanatomic location), maximum diameter of the largest focus of metastasis, maximum tumor area, and sum of all diameters. Univariate and multivariate models and Kaplan-Meier analysis were used to evaluate each classification system. Results We reviewed 204 tumor-positive SLNs from 157 patients. On univariate analysis, all criteria except Starz classification were statistically significant risk factors for NSN metastasis. On multivariate analysis, including Breslow thickness, ulceration, age, sex, and NSN status, maximum diameter (using a cut-off of 3 mm) was the only classification system that was an independent risk factor predicting DFS (hazard ratio 2.31, p = 0.0181) and OS (hazard ratio 3.53, p = 0.0005). By Kaplan-Meier analysis, DFS and OS were significantly different among groups using maximum diameter cut-offs of 1 and 3 mm. Conclusions Maximum tumor diameter outperformed other measurements of metastatic tumor burden, including microanatomic tumor location (Dewar classification), Starz classification, maximum tumor area, and sum of all diameters for prediction of survival. Maximum tumor diameter is a simple method of assessing micrometastatic tumor burden that should be reported routinely.
Background Hospital readmission is becoming a quality measure, despite poor understanding of the risks of readmission. This study examines readmission risk factors after major hepatectomy and ...develops a predictive model. Study Design A retrospective review was performed on patients who had undergone major hepatectomy at 1 of 3 academic centers between the years 2000 and 2012. Clinicopathologic and perioperative data were analyzed for risk factors of 90-day readmission using logistic regression. A readmission risk score was developed and validated in a separate validation set to determine its predictive value. Results Of 1,184 hepatectomies performed, 17.3% of patients were readmitted within 90 days. Factors associated with readmission include operative blood loss (odds ratio OR = 1.00; 95% CI, 1.000–1.001), any postoperative complication (OR = 4.3; 95% CI, 1.8–10.4), a major postoperative complication (OR = 5.7; 95% CI, 3.2–10.2), postoperative pulmonary embolism (OR = 12.2; 95% CI, 1.9–78.4), no postoperative blood transfusion (OR = 3.3; 95% CI, 1.7–6.2), surgical site infection (OR = 5.3; 95% CI, 2.9–10.0), and post-hepatectomy hyperbilirubinemia (OR = 1.1; 95% CI, 1.1–1.2). A scoring system based on these risk factors accurately predicted readmission in the validation cohort. A score of >20 points had a positive predictive value of 30.8% and negative predictive value of 95.6%, and a score >50 had a positive predictive value of 50.9% and negative predictive value of 87.7%. This risk score accurately stratifies readmission risk. Conclusions The risk of hospital readmission within 90 days after major hepatectomy is high and is reliably predicted with a novel scoring system.
Background Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma. Study Design We reviewed ...patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease. Results The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival. Conclusions The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival.
Abstract Background Advances in small animal imaging have improved the detection and monitoring of cancer in vivo ; although with orthotopic models, precise localization of tumors remains a ...challenge. In this study, we evaluated multispectral optoacoustic tomography (MSOT) as an imaging modality to detect pancreatic adenocarcinoma in an orthotopic murine model. Methods In vitro binding of Syndecan-1 probe to the human pancreatic cancer cell line S2VP10 was evaluated on flow cytometry. For in vivo testing, S2VP10 cells were orthotopically implanted into the pancreas of severe combined immunodeficiency mice. At 7 d after implantation, the mice were intravenously injected with Syndecan-1 probe, and tumor uptake was evaluated with MSOT at multiple time points. Comparison was made with a free-dye control, indocyanine green (ICG). Probe uptake was verified ex vivo with fluorescent imaging. Results Syndecan-1 probe demonstrated partial binding to S2VP10 cells in vitro. In vivo, Syndecan-1 probe preferentially accumulated in the pancreas tumor (480 MSOT a.u.) compared with off-target organs, including the liver (67 MSOT a.u.) and kidney (96 MSOT a.u.). Syndecan-1 probe accumulation peaked at 6 h (480 MSOT a.u.), whereas the ICG control dye failed to demonstrate similar retention within the tumor bed (0.0003 MSOT a.u.). At peak accumulation, signal intensity was 480 MSOT a.u., resulting in several times greater signal in the tumor bed than in the kidney or liver. Ex vivo fluorescent imaging comparing tumor signal with that within off-target organs confirmed the in vivo results. Conclusions MSOT demonstrates successful accumulation of Syndecan-1 probe within pancreatic tumors, and provides high-resolution images, which allow noninvasive, real-time comparison of signal within individual organs. Syndecan-1 probe preferentially accumulates within a pancreatic adenocarcinoma model, with minimal off-target effects.
Abstract Background The BRAF inhibitor vemurafenib (PLX) has shown promise in treating metastatic melanoma, but most patients develop resistance to treatment after 6 mo. We identified a transmembrane ...protein, extracellular matrix metalloproteinase inducer (EMMPRIN) as a cell surface receptor highly expressed by PLX-resistant melanoma. Using an S100A9 ligand, we created an EMMPRIN targeted probe and liposome that binds to melanoma cells in vivo , thus designing a novel drug delivery vehicle. Methods PLX-resistant cells were established through continuous treatment with PLX-4032 over the course of 1 y. Both PLX-resistant and sensitive melanoma cell lines were evaluated for the expression of unique cell surface proteins, which identified EMMPRIN as an overexpressed protein in PLX0-resistant cells and S100A9 is a ligand for EMMPRIN. To design a probe for EMMPRIN, S100A9 ligand was conjugated to a CF-750 near-infrared (NIR) dye. EMMPRIN targeted liposomes were created to encapsulate CF-750 NIR dye. Liposomes were characterized by scanning electron microscopy, flow cytometry, and in vivo analysis. A2058PLX and A2058 cells were subcutaneously injected into athymic mice. S100A9 liposomes were intravenously injected and tumor accumulation was evaluated using NIR fluorescent imaging. Results Western blot and flow cytometry demonstrated that PLX sensitive and resistant A2058 and A375 melanoma cells highly express EMMPRIN. S100A9 liposomes were 200 nm diameter and uniformly sized. Flow cytometry demonstrated 100X more intracellular dye uptake by A2058 cells treated with S100A9 liposomes compared with untargeted liposomes. In vivo accumulation of S100A9 liposomes within subcutaneous A2058 and A2058PLX tumors was observed from 6–48 h, with A2058PLX accumulating significantly higher levels ( P = 0.001626). Conclusions EMMPRIN-targeted liposomes via an S100A9 ligand are a novel, targeted delivery system which could provide improved EMMPRIN specific drug delivery to a tumor.
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