Single ventricle congenital heart defects, which are characterized by cyanotic mixing between the oxygenated and de-oxygenated blood, afflict 2 per every 1000 live births. These defects are surgically treated by connecting the superior and inferior vena cava to the pulmonary arteries. However, such a configuration (also known as the total cavopulmonary connection), results in high energy losses and therefore the optimization of this connection prior to the surgery could significantly improve post-operative performance. In this paper, a surgical planning framework is proposed. It is exemplified on a patient with pre and post surgical MRI data. A pediatric surgeon performed a ";virtual surgery"; on the reconstruction of the patient's anatomy prior to the actual surgery. Post-operative hemodynamics in the virtually designed post-surgical anatomy and in the actual one are computed using computational fluid dynamics and compared to each other. This framework provides the surgeon to envision numerous scenarios of possible surgical options, and accordingly predict the post operative hemodynamics.
Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centuries. However, the discipline has not been subjected systematically and thoroughly to the rigors of scientific testing. Objective: This article reviews experimental evidence in regard to the vascular mechanisms of acupuncture and herbal medicine in hypertension. We focus on our hypothesis that acupuncture and herbal medicine reduce hypertension through activation of microvascular endothelial nitric oxide synthesis (eNOS). We also examine whether or not our results in experimental renovascular hypertension conform to the meridian theory. Results and conclusion: Acupuncture and herbal medicine 1) reduce experimental renovascular hypertension; 2) increase production of nitric oxide (NO), and contribute to vasodilation in the microvasculature and reduction of peripheral vascular resistance. We concluded that acupuncture and herbal medicine target eNOS and activate its signaling mechanisms, and that the benefits of acupuncture proceed along the meridian of the stimulated acupoint.
Abstract Background: Although patients (pts) with hormone receptor-positive (HR+)/HER2-negative breast cancer (BC) frequently experience disease response to neoadjuvant therapy, fewer than 10% achieve a pathologic complete response (pCR) with standard chemotherapy or endocrine therapy, even in combination with CDK4/6 inhibitors. Thus, finding more effective therapies for this disease remains an unmet need. HER2 is expressed at a low level (IHC 1+ or 2+) in approximately 60-70% of HR+ BC. Trastuzumab deruxtecan (DS-8201a, T-DXd) is a novel HER2-targeting antibody drug conjugate (ADC) that is FDA approved in the US for HER2-positive and HER2-low metastatic BC (with boxed warnings for interstitial lung disease). However, the efficacy of T-DXd in the neoadjuvant setting is not known. The primary objective of TALENT (TRIO-US B-12, NCT04553770) is to evaluate the clinical activity and safety of neoadjuvant T-DXd alone or in combination with endocrine therapy in pts with HR+/HER2-low early BC. Methods: Men and women with previously untreated, operable invasive early stage, non-recurrent, HR+, HER2-low (IHC 1+ or 2+/ISH- by local or central review) BC measuring > 2 cm were eligible. In stage 1 of clinical trial, participants were randomized 1:1 to receive T-DXd (5.4 mg/kg IV q21 days) alone, Arm A, or in combination with anastrozole AI (1 mg PO QD), Arm B. Originally 6 cycles (cy) were given but in 02/2022, an amendment increased the number of treatment cy from 6 to 8 for newly enrolled pts, or those who had not yet had surgery. Men and pre/peri-menopausal women randomized to Arm B also received a GnRH agonist. Stratification factors were HER2 expression (1+ vs. 2+) and menopausal status (men as postmenopausal). Tumor tissue collected at baseline, cy 1 day 17-21, and at surgery. Breast imaging performed at baseline, cy 2 and pre-surgery/EOT. Primary endpoint is pCR rate (ypT0/is ypN0) at surgery. In stage 1, intent was to randomize 58 pts (if at least 2 pCR occurred in an arm, arm progresses to Stage 2 and an additional 15 pts to be enrolled). Other endpoints include safety, objective response rate (ORR), changes in Ki67 expression, Residual Cancer Burden index, exploratory biomarker analysis, and health-related quality of life. Here we present results from stage 1 of the trial. Results: From 09/21/2020 to 10/13/2022, 58 pts were enrolled and treated (29 Arm A, 29 Arm B) in stage 1 of trial. Five pts came off study before completing study therapy (2 after cy 1, 2 after cy 2, 1 after cy 3). As of data cut-off (10/05/2022), 33 pts completed study treatment and have had surgery (17 Arm A, 16 Arm B), 13 are on treatment and 7 are pending surgery; 27 pts completed 6 cy and 13 completed 8 cy. Baseline characteristics were balanced between arms. 19/58 pts were Stage IIA, 26/58 Stage IIB, 12/58 Stage IIIA, and 1/58 Stage IIIB at baseline. 46/58 pts had baseline HER2 expression (from central review) of 1+, 4/58 were 0, 6/58 were 2+, 1/58 had multicentric lesion 1+ and 2+, and 1/58 had a single lesion with 1+ and 2+. In Arm A, 1/17 pt had pCR after 8 cy, 2/17 pts had RCB-I after 6 cy (17.6% RCB 0/1). In Arm B, 1/16 pt had RCB-I after 8 cy (6.3%). The ORR for response-evaluable pts in Arm A was 75% (12/16, 1 CR, 11 PR) and in Arm B was 63.2% (12/19, 2 CR, 10 PR); 1 patient (Arm B) had PD. ILD occurred in 1 pt (1.7%), Gr 2 and resolved 11 days after stopping therapy. Most common treatment-related Grade ≥ 3 AEs in Arms A and B, respectively, include hypokalemia (1.7%, 5.2%), diarrhea (3.4%, 3.4%), neutropenia (3.4%, 1.7%), fatigue (1.7%, 3.4%), headache (3.4%, 1.7%), vomiting (3.4%, 1.7%), dehydration (1.7%, 1.7%) and nausea (3.4%, 0%). Conclusions: This is the first report of a trial evaluating neoadjuvant T-DXd in HER2 low breast cancer. T-DXd +/- endocrine therapy demonstrates promising clinical activity for pts with HR+ BC. Updated study results will be provided at the time of presentation. Citation Format: Aditya Bardia, Sara Hurvitz, Michael F. Press, Lisa S. Wang, Nicholas P. McAndrew, David Chan, Vu Phan, Deborah Villa, Merry L. Tetef, Erin Chamberlain, Nihal Abdulla, Thomas Lomis, Laura M. Spring, Steven Applebaum, Shaker Dakhil, Brian DiCarlo, David D. Kim, Evangelia Kirimis, William E. Lawler, Aashini K. Master, Kelly McCann, Edwin Hayashi, Christine Kivork, James Chauv. GS2-03 TRIO-US B-12 TALENT: Neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-03.
INTRODUCTION: Treatment of pancreatic cancer depends on the stage of disease. For patients with tumors deemed resectable, the best chance for prolonged survival is with early curative resection. However, it is not clear that this is the best general approach because of the high morbidity and mortality of pancreatic resection, and because tumors often are found to be unresectable at the time of surgery. The aim of this study was to compare survivals of patients who had early curative resection of their pancreatic tumors with those who did not. METHODS: We reviewed medical records of all patients diagnosed with pancreatic cancer at our VA Medical Center from 2005 through 2010, and gathered data on multiple demographic and clinical variables. Survivals of patients with and without tumor resection were compared using Kaplan Meier analysis. RESULTS: We identified 116 patients with pancreatic cancer (all men, 66% white, 29% black, 90% adenocarcinoma, 8% neuroendocrine tumor). Tumor location was head (66%), body (10%), tail (16%) and body/tail of pancreas (4%). Stage at presentation was: I (3%); II (22%); III (12%); IV (63%). 28 patients had tumors deemed resectable (group R) (mean age 64±1.7 years [SEM], 64% white, 81% adenocarcinoma), and 88 had non-resectable (group NR) tumors (mean age 67.1±9.7 years, 66% white, 92% adenocarcinoma). Ultimate treatments overall included surgery (21%), neoadjuvant therapy (4%), adjuvant therapy (10%) and palliative chemotherapy (35%). Kaplan-Meier analysis demonstrated an overall median survival of 153 days (95% CI 93195) for the total group of patients with pancreatic cancer. A total of 17 (14.7%) patients underwent surgery with curative intent (group R+) including 13 Whipple procedures and 4 pancreatic tail resections. 11 patients initially deemed resectable did not undergo tumor resection (group R-) because they were later deemed unfit for surgery (n=4), declined surgery (n=1) or were found to have unresectable disease with intraoperative metastases during surgery (n=6). Both groups (R+ and R-) had similar mean ages (63.6±2.2 vs. 64.5±2.7 years, p=0.80), weight at diagnosis (85.7±5.4 vs. 81.2±3.9, p=0.56), race, stage, tumor size, Ca 19-9 and serum albumin levels. Median survival of the R+ group (401±95 days) was significantly longer than that of the Rgroup (162±70, p =0.03) and the NR group (112±33, p=0.0009). Survival for the 6 patients who had surgery revealing unresectable tumors was poorer than that for the 17 patients who had tumor resections with curative intent (R+), but did not reach significance (246.5 days vs. 401 days, p=0.18). CONCLUSIONS: Early surgery for patients with resectable pancreatic cancer is associated with improved survival. The finding of unresectable disease at surgery is a poor prognostic sign, but the surgery itself does not appear to be the factor influencing the shortened survival.
Abstract Neuroendocrine tumors (NETs) constitute ~0.5% of all diagnosed malignancies. In our case, a 72-year-old male, who was asymptomatic aside from mild left lower abdominal pain, was scheduled for elective ventral hernia repair, evident on computed tomography. The laparoscopic ventral hernia repair necessitated the conversion to laparotomy due to extensive adhesions and the incorporation of surgical mesh into the small bowel wall. The patient suffered from delayed small bowel injury resulting in the second emergent laparotomy when numerous calcified lesions were incidentally noted in the small bowel wall. Pathology confirmed Grade 1 well-differentiated NETs of the jejunum. This case highlights the importance of considering NETs as part of a differential diagnosis in patients with nonspecific symptoms and negative imaging studies. This case also emphasizes the importance of early detection of this rare pathology to improve prognosis and outcome.
Renal cell carcinoma (RCC) is an unpredictable malignancy, with 25%–30% of patients developing metastatic disease. The most common sites of metastasis are the lung, bones, liver and brain, with small intestine metastasis being minimally reported in the literature. This report describes a case of small bowel obstruction caused by metastatic RCC in a male patient in his 60 s who had previously undergone a radical nephrectomy with adjuvant pembrolizumab therapy 6 years prior. The patient underwent a diagnostic laparoscopy converted to a laparotomy due to the complexity of the case. During surgical exploration, an enterectomy and end-to-end anastomosis were performed. This case emphasises the possibility of RCC metastasising to the small intestine, which may present with small bowel obstruction, while highlighting the importance of patient education for early detection to improve prognosis. Additionally, this report discusses treatment options for managing RCC metastasis to the small intestine.
