Efficacy and safety of near-infrared fluorescence identification of the thoracic duct during left lateral neck dissection.

BACKGROUND: Thoracic duct leaks occur in up to 5% of left lateral neck dissections. No one imaging modality is routinely used to identify the thoracic duct intraoperatively. The goal of our study was to evaluate the efficacy and safety of indocyanine green lymphangiography for intraoperative identification of the thoracic duct compared to traditional methods using ambient and evaluate the optimal timing of indocyanine green administration. METHODS: We enrolled all patients who underwent left lateral neck dissection at our institution from 2018 to 2022 in this prospective clinical trial. After indocyanine green injection into the dorsum of the foot, we performed intraoperative imaging was performed with a near-infrared fluorescence camera. We reported the data using descriptive statistics. RESULTS: Of the 42 patients we enrolled, 14 had prior neck surgery, and 3 had prior external beam radiation. We visualized the thoracic duct with ambient light in 48% of patients and with near-infrared fluorescence visualization in 64%. In 17% of patients, we could identify the thoracic duct only using near-infrared fluorescence visualization, which occurred within 3 minutes of injection, and were required to re-dose 5 patients. We visualized the thoracic duct with near-infrared fluorescence in all patients with prior neck radiation and 77% of patients with prior neck surgery. One adverse reaction occurred (hypotension), and 5 intraoperative thoracic duct injuries occurred that were ligated. There with no chylous fistulas postoperatively. CONCLUSION: This trial demonstrates that near-infrared fluorescence identification of the thoracic duct is feasible and safe with indocyanine green lymphangiography, even in patients with prior neck surgery or radiation.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer-induced cachexia.

Background: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes. Methods: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia. Results: Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males. Conclusions: Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.

Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large, Integrated Health Care System is Feasible and Effective.

BACKGROUND: Intraoperative ultrasound (IUS) localization for breast cancer is a noninvasive localization technique. In 2015, an IUS program for breast-conserving surgery (BCS) was initiated in a large, integrated health care system. This study evaluated the clinical results of IUS implementation. METHODS: The study identified breast cancer patients with BCS from 1 January to 31 October 2015 and from 1 January to 31 October 2019. Clinicopathologic characteristics were collected, and localization types were categorized. Clinical outcomes were analyzed, including localization use, surgeon adoption of IUS, day-of-surgery intervals, and re-excision rates. Multivariate logistic regression analysis was performed to evaluate predictors of re-excision. RESULTS: The number of BCS procedures increased 23%, from 1815 procedures in 2015 to 2226 procedures in 2019. The IUS rate increased from 4% of lumpectomies (n = 79) in 2015 to 28% of lumpectomies (n = 632) in 2019 (p < 0.001). Surgeons using IUS increased from 6% (5 of 88 surgeons) in 2015 to 70% (42 of 60 surgeons) in 2019. In 2019, 76% of IUS surgeons performed at least 25% of lumpectomies with IUS. The mean time from admission to incision was shorter with IUS or seed localization than with wire localization (202 min with IUS, 201 with seed localization, 262 with wire localization in 2019; p < 0.001). The IUS re-excision rates were lower than for other localization techniques (13.6%, vs 19.6% for seed localization and 24.7% for wire localization in 2019; p = 0.006), and IUS predicted lower re-excision rates in a multivariable model (odds ratio [OR], 0.59). CONCLUSIONS: In a high-volume integrated health system, IUS was adopted for BCS by a majority of surgeons. The use of IUS decreased the time from admission to incision compared with wire localization, and decreased re-excision rates compared with other localization techniques.

Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients.

BACKGROUND: Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease. METHODS: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines. RESULTS: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. CONCLUSIONS: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.

Interval Magnetic Resonance Imaging: an Alternative to Guidelines for Indeterminate Nodules Discovered in the Cirrhotic Liver.

BACKGROUND: Current guidelines for the management of indeterminate nodules discovered on surveillance imaging recommend alternate imaging modality or biopsy. This study evaluates the use of short interval MRI rather than immediate CT or biopsy. METHOD: This retrospective cohort study examines outcomes of 111 patients with indeterminate nodules reviewed by a single institution's Liver Tumor Board 2011-2016. Analysis was focused on outcomes stratified by management decision. RESULTS: The tumor board recommended biopsy or immediate repeat CT imaging in 13 (12%), 3-month interval MRI in 64 (58%) and 6-month interval MRI for 34 (30%) patients. Twenty-eight (29%) patients in the interval MRI subgroups were diagnosed with hepatocellular carcinoma (HCC) during the period of follow-up, and 21 (75%) of these were located within the original indeterminate nodule. The median time to diagnosis was 6.5 months. Twenty-three (82%) were eligible for potentially curative therapy at the time of HCC diagnosis. Delay in HCC diagnosis was not the reason for inability to provide potentially curative therapy in any patient. CONCLUSION: This study supports the judicious use of interval MRI at 3 or 6 months in patients with liver cirrhosis and an indeterminate liver nodule rather than immediate CT scan or biopsy.

Indocyanine green fluorescence-guided redo parathyroidectomy.

Re-operative neck surgery for hyperparathyroidism is a technically difficult operation that requires adjunctive studies to assist with finding the parathyroid tissues. Intraoperative tests help minimise exploration of the neck and decrease injuries to the surrounding structures. Indocyanine green is a near-infrared fluorescent dye that in pre-clinical models was found to be useful in locating the parathyroid glands of dogs. No study has yet reported its use as a tool for parathyroid localisation in humans. We investigated the use of indocyanine green to assist with localisation of a recurrent parathyroid adenoma using a near-infrared imaging system. After exposure of the neck tissues, the parathyroid gland fluoresced brightly and directed our dissection. Exploration of the neck was minimal, and allowed for fast localisation and excision of the adenoma. Overall, use of indocyanine green is a simple and safe technique of intraoperative parathyroid localisation that warrants further investigation.