Ten-year experience in optimizing neoadjuvant therapy for localized pancreatic cancer-Medical college of Wisconsin perspective.

Treatment of localized pancreatic cancer has also evolved to prioritize preoperative (neoadjuvant) multimodality therapy over a surgery-first approach. Given the complexities of pancreatic cancer staging and the challenge of delivering multiple treatment modalities (chemotherapy, radiation therapy, and surgery), an experienced and highly integrated multidisciplinary team is necessary to achieve the best outcomes. In this review, we will discuss our institutional experience with neoadjuvant therapy, guiding principles for treatment, and outline the landscape for future investigations.

Challenges in Clinical Trial Implementation: Results from a Survey of the National Accreditation Program of Breast Centers (NAPBC).

BACKGROUND: Although the results of clinical trials often guide best practices, changing clinical practice based on clinical trial results can be challenging. The objective of this study was to examine provider-reported barriers to adopting best clinical practices according to clinical trial data. METHODS: A cross-sectional survey was conducted of providers from the National Accreditation Program for Breast Centers about barriers that prevent the incorporation of trial findings. Descriptive analyses and multivariable analyses were performed to determine provider characteristics that were significantly associated with reported barriers. RESULTS: Overall, 383 institutions participated (63.5% response rate), with a total of 1226 physicians responding to the survey (80% response rate). Providers identified national guidelines and meetings as the most compelling way to receive practice-changing information. They reported the following internal barriers to trial implementation: patient preference (45%), strongly held beliefs by partners/colleagues (37%), and insufficient time to discuss new practices (30%). External barriers preventing trial implementation included a lack of agreement from multidisciplinary tumor boards (32%), fear of reimbursement loss (23%), and resistance from clinical staff (20%). Reported barriers differed by provider specialty, with plastic surgeons and radiation oncologists reporting that strongly held beliefs by partners/colleagues and disagreement from multidisciplinary tumor boards were the most significant factors preventing clinical trial implementation. CONCLUSIONS: Physician beliefs and patient preferences are the most frequently reported barriers to clinical trial implementation. Tactics to better educate providers about how to explain new clinical trial data to their patients and colleagues are needed.

Doppler Ultrasound-Visible SignalMark Microspheres are Better Identified than HydroMARK® Clips in a Simulated Intraoperative Setting in Breast and Lung Tissue.

BACKGROUND: Preoperative breast and lung markers have significant drawbacks, including migration, patient discomfort, and scheduling difficulties. SignalMark is a novel localizer device with a unique signal on Doppler ultrasound. OBJECTIVE: We aimed to evaluate intraoperative identification of SignalMark microspheres compared with HydroMARK® clips. We also assessed the safety and efficacy of SignalMark in the lung. METHODS: Twelve breasts of lactating pigs were injected with SignalMark or HydroMARK® by a breast radiologist, and subsequently identified using a standard ultrasound machine by three surgeons blinded to marker location. Time to identification of each marker was recorded, with a maximum allotted time of 300 s. To further demonstrate efficacy in lung parenchyma, a second cohort of pigs underwent lung injections. RESULTS: A total of eight SignalMark markers and four HydroMARK® clips were placed in pig breasts. Overall, the surgeons correctly identified SignalMark 95.8% of the time (n = 23/24) and HydroMARK® clips 41.7% of the time (n = 5/12) within 300 s (p < 0.001). The mean time to identification was significantly faster for SignalMark, at 80.8 ± 20.1 s, than for HydroMARK®, at 209.4 ± 35.2 s (p < 0.002). For the lung injections, all 10 SignalMark markers were visible on Doppler ultrasound at the time of placement, and at the 7- and 21-day time points. CONCLUSIONS: Surgeons identified SignalMark in significantly less time than HydroMARK® clips in a simulated intraoperative setting, and SignalMark was easily viewed in the lung. These results suggest that SignalMark is a feasible option for efficient intraoperative localization of non-palpable breast and lung tumors using ultrasound guidance.

Cirrhosis is not a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in highly selected patients.

BACKGROUND: Patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critically important to optimizing outcomes. There is currently no literature regarding the safety of CRS/HIPEC in patients with cirrhosis. The aim of this case series is to report the outcomes of three patients with well-compensated cirrhosis who underwent CRS/HIPEC. METHODS: Patients were identified from a prospectively maintained peritoneal surface malignancy database. Patient, tumor, and operative-related details were recorded as short-term postoperative outcomes. Results were analyzed using descriptive statistics. RESULTS: All patients had well-compensated (Child-Pugh Class A) cirrhosis and Eastern Cooperative Oncology Group (ECOG) performance status of 0. One patient had preoperative evidence of portal hypertension. All safely underwent CRS/HIPEC with completeness of cytoreduction (CC) scores of 0. The postoperative morbidity profile was unique, but all complications were manageable and resulted in full recovery to preoperative baseline status. CONCLUSIONS: Patient selection for CRS/HIPEC is critical for optimization of short- and long-term outcomes. This small series suggests that well-compensated cirrhosis should not be an absolute contraindication to CRS/HIPEC.

Incidence and treatments of DCIS in octogenarians: grade matters.

PURPOSE: The purpose of this study is to better characterize the current incidence and treatment patterns of DCIS in women greater than 80 years of age (>80) and to evaluate the effect of grade on treatment efficacy. METHODS: Retrospective observational study of women diagnosed with single primary DCIS from 2000 to 2012 in SEER. Statistics including incidence, multivariable Cox proportional hazards model and subset analysis were performed. RESULTS: 42,899 female patients with DCIS were identified, 2566 (5.98%) were >80. Incidence of DCIS in the less than 80 (<80) cohort was 8 per 100,000 and 11.7 per 100,000 for >80. >80 patients have a similar incidence of high grade DCIS (9.8%) as compared to <80 cohort (10.7%, P = 0.246). Compared to the <80 population the >80 population received significantly less surgery (97 vs. 92%, P < 0.001) and radiation (22 vs. 47%, P < 0.001). Although on multivariate analysis surgery did not provide a survival benefit for >80 population, it conveyed a survival benefit for high grade DCIS (HR 0.14, 95% CI 02-0.68) that was not observed for low grade DCIS (HR 0.46, 95% CI 0.1-2.03). CONCLUSIONS: Patients over 80 years of age have a relatively high incidence of DCIS and receive low relative rates of treatment. Although surgery does not provide a survival benefit for all patients over 80, it does provide a significant survival benefit for patients with high grade DCIS. Our results suggest that perhaps the biology of the DCIS, not the age of the patient should direct who warrants treatment.

Influence of Distance to Hospital and Insurance Status on the Rates of Contralateral Prophylactic Mastectomy, a National Cancer Data Base study.

INTRODUCTION: We evaluated the impact of travel distance and insurance status on contralateral prophylactic mastectomy (CPM) rates in breast cancer. METHODS: We queried the National Cancer Data Base (NCDB) for women >18 years of age with a nonmetastatic primary breast cancer of ductal, lobular, or mixed histology. Patient- and facility-specific CPM rates were calculated based on insurance, race, and distance to treatment center. Standard univariable and multivariable regression analysis was performed. RESULTS: Overall, the CPM rate was 6.5% for the 864,105 patients identified. Most patients traveled <20 miles to a treatment center (79.5%) and had private insurance or Medicare (58.3 and 33.4%, respectively). In general, younger, White, non-Hispanic, and privately insured patients residing further from a treatment center was associated with increased rates of CPM. However, distance to the treatment center and insurance type had a greater absolute impact on rates of CPM for Black and Hispanic patients. Absolute CPM rate increases for patients >100 miles from a treatment center compared with those <20 miles from a treatment center were observed to be greater for Black and Hispanic patients (3.5 and 3.9%, respectively) compared with White and non-Hispanic patients (2.5 and 2.6%). Additionally, further patient travel distance was associated with higher treatment center-specific CPM rates. CONCLUSION: Increased travel distance is independently associated with increased rates of CPM for all patients and increased facility-specific rates of CPM. Black and Hispanic patients were found to be more vulnerable to the impact of travel distance and insurance status on rates of CPM.

Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques.

BACKGROUND: Currently, the gold standard diagnostic examination for significant aortoiliac lesions is angiography. Fractional flow reserve (FFR) has a growing body of literature in coronary artery disease as a minimally invasive diagnostic procedure. Improvements in numerical hemodynamics have allowed for an accurate and minimally invasive approach to estimating FFR, utilizing cross-sectional imaging. We aim to demonstrate a similar approach to aortoiliac occlusive disease (AIOD). METHODS: A retrospective review evaluated 7 patients with claudication and cross-sectional imaging showing AIOD. FFR was subsequently measured during conventional angiogram with pull-back pressures in a retrograde fashion. To estimate computed tomography (CT) FFR, CT angiography (CTA) image data were analyzed using the SimVascular software suite to create a computational fluid dynamics model of the aortoiliac system. Inlet flow conditions were derived based on cardiac output, while 3-element Windkessel outlet boundary conditions were optimized to match the expected systolic and diastolic pressures, with outlet resistance distributed based on Murray's law. The data were evaluated with a Student's t-test and receiver operating characteristic curve. RESULTS: All patients had evidence of AIOD on CT and FFR was successfully measured during angiography. The modeled data were found to have high sensitivity and specificity between the measured and CT FFR (P = 0.986, area under the curve = 1). The average difference between the measured and calculated FFRs was 0.136, with a range from 0.03 to 0.30. CONCLUSIONS: CT FFR successfully identified aortoiliac lesions with significant pressure drops that were identified with angiographically measured FFR. CT FFR has the potential to provide a minimally invasive approach to identify flow-limiting stenosis for AIOD.

Median arcuate ligament release at the time of pancreaticoduodenectomy or total pancreatectomy.

BACKGROUND: Celiac artery compression can complicate the performance of pancreaticoduodenectomy or total pancreatectomy due to the need for ligation of the gastroduodenal artery. Median arcuate ligament release restores normal arterial flow to the liver, spleen, and stomach and may avoid complications related to poor perfusion of the foregut. METHODS: All patients who underwent median arcuate ligament release for celiac artery compression at the time of pancreatectomy between 2009 and 2023 were reviewed. Pre- and postoperative computed tomography was used to categorize celiac artery compression by the extent of compression (types A [<50%], B [50%-80%], and C [>80%]). RESULTS: Of 695 patients who underwent pancreatectomy, 22 (3%) had celiac artery compression, and a majority (17) were identified on preoperative imaging. Median celiac artery compression was 52% (interquartile range = 18); 8 (36%) patients had type A and 14 (64%) had type B compression with a median celiac artery compression of 39% (interquartile range = 18) and 59% (interquartile range = 14), respectively (P < .001). Postoperative imaging was available for 20 (90%) patients, and a reduction in the median celiac artery compression occurred in all patients: type A, 14%, and type B, 31%. Complications included 1 (5%) death after hospital discharge, 1 (5%) pancreatic fistula, 1 (5%) delayed gastric emptying, and 4 (18%) readmissions. No patient had evidence of a biliary leak or liver dysfunction. CONCLUSION: Preoperative computed tomography allows accurate identification of celiac artery compression. Ligation of the gastroduodenal artery during pancreaticoduodenectomy or total pancreatectomy in the setting of celiac artery compression requires median arcuate ligament release to restore normal arterial flow to the foregut and avoid preventable complications.

Current Controversies in Neoadjuvant Therapy for Pancreatic Cancer.

Over the last two decades, there have been significant changes in the management of patients with localized pancreatic cancer. The rationale for an evolution toward a neoadjuvant approach and summary of relevant clinical trials is reviewed. Controversies in identifying optimal neoadjuvant therapeutic approaches are discussed.

Ki67 does not predict recurrence for low-grade appendiceal mucinous neoplasms with peritoneal dissemination after cytoreductive surgery and HIPEC.

Low-grade appendiceal mucinous neoplasms (LAMN) can disseminate to become low-grade mucinous carcinoma peritonei (LGMCP), which is optimally treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Approximately half of the patients with LGMCP recur despite complete cytoreduction, and risk factors for recurrence are poorly understood. We sought to evaluate if Ki67 predicts progression of LGMCP after CRS/HIPEC. A retrospective review of a prospectively maintained database was performed to identify patients treated with complete CRS/HIPEC for LGMCP from 2008 to 2019 with Ki67 assessed. Patient characteristics, histologic data, average and focally high "hotspot") Ki67 index, progression-free survival (PFS), and overall survival (OS) were analyzed. Ki-67 immunostain was performed on the histologic section with the highest cellularity and architectural complexity. Forty-four patients with LGMCP (55% male, median age 61) were identified. The median Ki67 score and hotspot Ki67 score was 15% (1-70) and 50% (1-90), respectively. On univariate analysis, average Ki67 and hotspot Ki67 were not predictive of PFS when analyzed as continuous normalized values (HR 1.0, p = 0.79 and HR 1.1, p = 0.38, respectively) or as categorical values when stratified by the median (HR 0.9, p = 0.67 and HR 1.0, p = 0.93). This remained true on multivariate analysis when stratified for peritoneal cancer index, CEA, and completeness of cytoreduction score for both normalized Ki67 and hotspot Ki67 (HR 0.9 [95% CI 0.8-1.3], p = 0.94 and HR 1.04 [95% CI 0.8-1.3], p = 0.73, respectively). Ki67 failed to predict disease recurrence for patients with LGMCP in this cohort.

Indocyanine green fluorescence-guided parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Our aim was to evaluate the ease and utility of using indocyanine green fluorescence angiography for intraoperative localization of the parathyroid glands. METHODS: Indocyanine green fluorescence angiography was performed during 60 parathyroidectomies for primary hyperparathyroidism during a 22-month period. Indocyanine green was administered intravenously to guide operative navigation using a commercially available fluorescence imaging system. Video files were graded by 3 independent surgeons for strength of enhancement using an adapted numeric scoring system. RESULTS: There were 46 (77%) female patients and 14 (23%) male patients whose ages ranged from 17 to 87 (average 60) years old. Of the 60 patients, 43 (71.6%) showed strong enhancement, 13 (21.7%) demonstrated mild to moderate vascular enhancement, and 4 (6.7%) exhibited little or no vascular enhancement. Of the 54 patients who had a preoperative sestamibi scan, a parathyroid adenoma was identified in 36, while 18 failed to localize. Of the 18 patients who failed to localize, all 18 patients (100%) had an adenoma that fluoresced on indocyanine green imaging. The operations were performed safely with minimal blood loss and short operative times. CONCLUSION: Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly with minimal risk.

Identifying lost surgical needles with visible and near infrared fluorescent light emitting microscale coating.

BACKGROUND: Retained foreign bodies (RFOs) have substantial clinical and financial consequences. In laparoscopic surgery, RFOs can be a cause of needing to convert a minimally invasive surgery (MIS) procedure to an open operation. A coating for surgical models was developed to augment localization of needles using fluorescence appropriate for open and minimally invasive surgeries procedures. METHODS: An epoxy matrix containing both dansyl chloride and indocyanine green was coated as visible and near infrared labels, respectively. With ultraviolet excitation, dansyl chloride emits green fluorescence and with NIR excitation, the ICG dye emits radiation observable with specialized near infrared capable laparoscopes. To evaluate the coatings, open and laproscopic surgeries were simulated in rabbits. Surgeons blinded to the type of needles (coated or non-coated) were timed while finding needles in standard conditions and with the use of the adjunct coatings. Control needles not located within 300 seconds were researched with the corresponding near infrared or ultraviolet light. Localization time was evaluated for statistical significance, P < .05. RESULTS: All dual dye coated needles searched utilizing the near infrared camera (n = 26) or ultraviolet light (n= 26) were located within 300 seconds. Conversely, 9 needles in both control settings (no dye usage) were not located within 300 seconds. Mean time to locate control needles in open surgery and laparoscopic surgery was statistically 2-3× greater than time to localization with the use of dye as an adjunct (P = .0027 open, P < .001 laparoscopic). CONCLUSION: Incorporation of a dual-dye fluorescent coating on surgical needles improved the efficiency of locating needles, may minimize the need to convert minimally invasive surgeries procedures to open, and may decrease the consequences of a missed RFO.

Preemptive Ladd Procedure in congenital diaphragmatic hernia and Abdominal Wall defects does not reduce the risk of future volvulus.

INTRODUCTION: Patients with congenital diaphragmatic hernia (CDH), gastroschisis, and omphalocele are prone to abnormalities of intestinal rotation and thus future midgut volvulus. Controversy exists whether routine preemptive Ladd procedure in this subgroup of asymptomatic patients is of value to reduce future volvulus. METHODS: The Pediatric Health Information System (PHIS) database was queried for neonates with CDH, gastroschisis, and omphalocele between January 2009 and September 2015. Standard univariate and multivariate analysis was completed to compare risk of volvulus between patients treated with a preemptive Ladd versus no Ladd (p<0.05). RESULTS: Seven thousand seven hundred forty-nine neonates with CDH (40%), gastroschisis (38%), omphalocele (14%), and abdominal wall malformation (NOS) (9%) were identified. Overall, 3.6% (n=279) had a preemptive. Thirty-two patients had subsequent volvulus. Ladd procedure did not reduce volvulus readmissions for any diagnosis and was associated with a significantly increased risk of volvulus for omphalocele patients (9.1% vs 0.1%, p<0.001). Overall, a Ladd procedure during the index admission was associated with a higher risk for volvulus (1.4% vs. 0.4%, p=0.021) and was associated with a 3.28 increased odds ratio of future volvulus (95% CI 1.12-9.68). CONCLUSION: Ladd procedure performed prophylactically in patients with CDH, gastroschisis, and omphalocele did not reduce subsequent volvulus. LEVEL OF EVIDENCE: III, Retrospective Comparative Study.

Utilization of iron (III)-doped nanoshells for in vivo marking of nonpalpable tumors using a VX2 rabbit model.

BACKGROUND: We aimed to evaluate the potential for ultrasound (US) visible biodegradable nanoshells (NS) as an alternative to wire-guided localization for nonpalpable tumors in vivo. METHODS: VX2 tumor was injected in bilateral thighs of 22 New Zealand rabbits and after 5 to 10 days, 1 tumor was marked with a wire as a control and the contralateral tumor was injected with 1 mL of 500 nm gas-filled silica NS under Doppler US. Tumors were excised after 24 hours. Chi-square was used for significance, P = .05. RESULTS: One rabbit was excluded on postoperative day 1 due to equipment failure, no ill effects were observed from the NS. The NS were used to localize and resect 100% of marked tissue, 4/21 wires were displaced (P < .05). CONCLUSIONS: We have shown that preoperatively injected US visible silica NS can be successfully used to mark nonpalpable tumors in vivo more consistently than WL.