Dr. Robin Cisco is a board certified general surgeon and fellowship-trained endocrine surgeon. She specializes in surgery of the thyroid, parathyroid and adrenal glands and has expertise in lymph node dissection for thyroid cancer. Dr Cisco received her medical degree at Duke University before moving to Stanford for general surgery residency. During her residency, she completed a two-year research fellowship in surgical oncology, with a focus on cancer immunology.
After residency, she completed an endocrine surgery fellowship with the internationally recognized UCSF Division of Endocrine Surgery. She is the author of multiple publications related to endocrine surgery and surgical oncology and has an interest in minimally invasive approaches to thyroid, parathyroid and adrenal surgery. She is currently the Physician Leader of Stanford's Endocrine Oncology Cancer Care Program (CCP).
Dr. Cisco focuses on providing outstanding surgical care in an environment that is supportive of her patients and their families. She enjoys patient education and preoperative counseling, and seeks to lessen the anxiety that often comes with a recommendation for surgery. She currently sees patients both in San Jose at Stanford's Cancer Center South Bay and in Palo Alto in the Endocrine Oncology and Surgery clinic.
- General Surgery
- Endocrine Surgery
Clinical Associate Professor, Surgery - General Surgery
Physician Leader, Endocrine Oncology Cancer Care Program (2021 - Present)
Boards, Advisory Committees, Professional Organizations
Active Member, American Association of Endocrine Surgeons (2018 - Present)
Member, Association of Women Surgeons (2018 - Present)
Member, Pacific Coast Surgical Association (2017 - Present)
Fellow, American College of Surgeons (2014 - Present)
Residency: Stanford University Dept of Surgery (2011) CA
Internship: Stanford University Dept of Surgery (2005) CA
Fellowship: University of California, San Francisco (2012) CA
Board Certification: American Board of Surgery, General Surgery (2011)
Medical Education: Duke University School of Medicine (2004) NC
BA, Stanford University, English and Economics (1997)
Risk of permanent hypoparathyroidism requiring calcitriol therapy in a population-based cohort of adults older than 65 undergoing total thyroidectomy for Graves' disease.
Thyroid : official journal of the American Thyroid Association
Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contribute to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the U.S.We performed a population-based cohort study using 100% Medicare claims from beneficiaries older than 65 with GD who underwent total thyroidectomy from 2007 to 2017. We required continuous enrollment in Medicare Parts A, B, and D for 12 months before and after surgery to ensure access to comprehensive claims data. Patients were excluded if they had a preoperative diagnosis of thyroid cancer or were on long-term preoperative calcitriol. Our primary outcome was permanent hypoparathyroidism, which was identified based on persistent use of calcitriol between 6-12 months following thyroidectomy. We used multivariable logistic regression to identify characteristics associated with permanent hypoparathyroidism, including patient age, sex, race/ethnicity, neighborhood disadvantage, Charlson-Deyo Comorbidity Index, urban or rural residence, and frailty.We identified 4,650 patients who underwent total thyroidectomy for GD during the study period and met inclusion criteria (mean age 72.8 years [SD 5.5], 86% female, and 79% white). Among this surgical cohort, 104 (2.2%, 95% CI: 1.8-2.7%) patients developed permanent hypoparathyroidism requiring calcitriol therapy. Patients who developed permanent hypoparathyroidism were on average older (mean age 74.1 vs. 72.8 years) than those who did not develop permanent hypoparathyroidism (p=0.04). On multivariable regression, older age was the only patient characteristic associated with permanent hypoparathyroidism (odds ratio [OR] age ≥ 76 years 1.68 [95% CI 1.13-2.51] compared to age 66-75 years).The risk of permanent hypoparathyroidism requiring calcitriol therapy among this national, U.S. population-based cohort of older adults with GD treated with total thyroidectomy was low, even when considering operations performed by a heterogeneous group of surgeons. These findings suggest the risk of hypoparathyroidism should not be a deterrent to operative management for GD in older adults who are appropriate surgical candidates.
View details for DOI 10.1089/thy.2022.0140
View details for PubMedID 36416252
Adverse Cardiovascular Outcomes Among Older Adults with Primary Hyperparathyroidism Treated with Parathyroidectomy vs. non-operative Management.
Annals of surgery
We sought to compare the incidence of adverse cardiovascular events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus non-operative management.PHPT is a common endocrine disorder that is associated with increased cardiovascular mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse cardiovascular events.We conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006-2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACE), cardiovascular disease-related hospitalization, and cardiovascular hospitalization-associated mortality.We identified 210,206 beneficiaries diagnosed with PHPT from 2006-2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed non-operatively within one year of diagnosis, the unadjusted incidence of MACE was 10.0% (mean follow-up 59.1 [SD 35.6] months) and 11.5% (mean follow-up 54.1 [SD 34.0] months), respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE (HR 0.92 [95%CI 0.90-0.94]), cardiovascular disease-related hospitalization (HR 0.89 [95%CI 0.87-0.91]), and cardiovascular hospitalization-associated mortality (HR 0.76 [95%CI 0.71-0.81]) compared to non-operative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95%CI 1.3%-2.1%), for cardiovascular disease-related hospitalization of 2.5% (95%CI 2.1%-2.9%), and for cardiovascular hospitalization-associated mortality of 1.4% (95%CI 1.2%-1.6%).In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse cardiovascular outcomes when compared with non-operative management for older adults with PHPT, which is relevant to surgical decision-making for patients with a long life expectancy.
View details for DOI 10.1097/SLA.0000000000005691
View details for PubMedID 36005546
Factors associated with postoperative complications and costs for adrenalectomy in benign adrenal disorders.
BACKGROUND: The incidence of adrenal incidentaloma has been increasing, and indications of and approaches to adrenalectomy are diverse. Drivers of complications and costs are not well identified.METHODS: The 2016 National Inpatient Sample data were used to identify patients who underwent adrenalectomy for benign adrenal disorders, such as Cushing syndrome, primary hyperaldosteronism, pheochromocytoma, and other benign neoplasms defined using the 10th Revision of the International Classification of Diseases. The primary outcome was determining the factors associated with clinical outcomes, perioperative complications, and hospitalization costs.RESULTS: Using weighted estimates of the national sample data, 5,140 patients were identified. The mean age was 55 years. The majority of adrenalectomies were performed laparoscopically (48.5%) followed by a robotic approach (32.7%). The postoperative complication rate was 7.6%. In adjusted multivariable analyses, independent risk factors for perioperative complications included Hispanic race (odds ratio, 2.5; P = .01), and perioperative comorbid heart failure (odds ratio, 6.3; P < .001) and respiratory failure (odds ratio, 9.9; P < .001). The mean cost was $18,122. Independent risk factors associated with decrease of cost were female sex and primary hyperaldosteronism; factors associated with increased cost were pheochromocytoma, intraoperative complications, perioperative underlying comorbid respiratory failure and heart failure, and postoperative complications (P < .001).CONCLUSION: Among patients undergoing adrenalectomy for benign adrenal disorders, underlying comorbidities, including heart and respiratory failure, should be considered when recommending adrenalectomy, as these may increase the postoperative complication rates and hospitalization costs.
View details for DOI 10.1016/j.surg.2021.10.065
View details for PubMedID 34857386
Racial disparities in the utilization of parathyroidectomy among patients with primary hyperparathyroidism: Evidence from a nationwide analysis of Medicare claims.
BACKGROUND: Among patients with primary hyperparathyroidism, parathyroidectomy offers a chance of cure and mitigation of disease-related complications. The impact of race/ethnicity on referral and utilization of parathyroidectomy has not been fully explored.METHODS: Population-based, retrospective cohort study using 100% Medicare claims from beneficiaries with primary hyperparathyroidism from 2006 to 2016. Associations of race/ethnicity with disease severity, surgeon evaluation, and subsequent parathyroidectomy were analyzed using adjusted multivariable logistic regression models.RESULTS: Among 210,206 beneficiaries with primary hyperparathyroidism, 63,136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Black patients were more likely than other races/ethnicities to have stage 3 chronic kidney disease (10.8%) but had lower prevalence of osteoporosis and nephrolithiasis compared to White patients, Black and Hispanic patients were more likely to have been hospitalized for primaryhyperparathyroidism-associated conditions (White 4.8%, Black 8.1%, Hispanic 5.8%; P < .001). Patients who were White and met operative criteria were more likely to undergo parathyroidectomy than Black, Hispanic, or Asian patients (White 30.5%, Black 23.0%, Hispanic 21.4%, Asian 18.7%; P < .001). Black and Hispanicpatients had lower adjusted odds of being evaluated by a surgeon (odds ratios 0.71 [95% confidenceinterval 0.69-0.74], 0.68 [95% confidence interval 0.61-0.74], respectively) and undergoing parathyroidectomy if evaluated by a surgeon (odds ratios 0.72 [95% confidence interval 0.68-0.77], 0.82 [95%confidence interval 0.67-0.99]). Asian race was associated with lower adjusted odds of being evaluated by a surgeon (odds ratio 0.64 [95% confidence interval 0.57-0.71]), but no difference in odds of parathyroidectomy.CONCLUSION: Racial/ethnic disparities exist in the management of primary hyperparathyroidism among older adults. Determining the factors that account for this disparity require urgent attention to achieve parity in the management of primary hyperparathyroidism.
View details for DOI 10.1016/j.surg.2021.05.037
View details for PubMedID 34229901
Undertreatment of primary hyperparathyroidism in a privately insured US population: Decreasing utilization of parathyroidectomy despite expanding surgical guidelines.
BACKGROUND: Primary hyperparathyroidism is associated with substantial morbidity, including osteoporosis, nephrolithiasis, and chronic kidney disease. Parathyroidectomy can prevent these sequelae but is poorly utilized in many practice settings.METHODS: We performed a retrospective cohort study using the national Optum de-identified Clinformatics Data Mart Database. We identified patients aged ≥35 with a first observed primary hyperparathyroidism diagnosis from 2004 to 2016. Multivariable logistic regression was used to determine patient/provider characteristics associated with parathyroidectomy.RESULTS: Of 26,522 patients with primary hyperparathyroidism, 10,101 (38.1%) underwent parathyroidectomy. Of the 14,896 patients with any operative indication, 5,791 (38.9%) underwent parathyroidectomy. Over time, there was a decreasing trend in the rate of parathyroidectomy overall (2004: 54.4% to 2016: 32.4%, P < .001) and among groups with and without an operative indication. On multivariable analysis, increasing age and comorbidities were strongly, inversely associated with parathyroidectomy (age 75-84, odds ratio 0.50 [95% confidence interval 0.45-0.55]; age ≥85, odds ratio 0.21 [95% confidence interval 0.17-0.26] vs age 35-49; Charlson Comorbidity Index ≥2 vs 0 odds ratio 0.62 [95% confidence interval 0.58-0.66]).CONCLUSION: The majority of US privately insured patients with primary hyperparathyroidism are not treated with parathyroidectomy. Having an operative indication only modestly increases the likelihood of parathyroidectomy. Further research is needed to address barriers to treatment and the gap between guidelines and clinical care in primary hyperparathyroidism.
View details for DOI 10.1016/j.surg.2020.04.066
View details for PubMedID 32654861
Resection of the Primary Tumor in Patients with Distant Thyroid Cancer Metastasis Is Associated with Longer Survival
ELSEVIER SCIENCE INC. 2019: S82
View details for Web of Science ID 000492740900141
Pediatric vs Adult Adrenocortical Carcinoma: Different Rate of Surgical Treatment and Patient Outcome
ELSEVIER SCIENCE INC. 2019: S81–S82
View details for Web of Science ID 000492740900139
Aggressive resection of neuroendocrine tumor (NET) liver metastases: NET neutral or gain?
View details for PubMedID 30266442
Differences Between Bilateral Adrenal Incidentalomas and Unilateral Lesions.
2015; 150 (10): 974–78
Adrenal incidentalomas are found in 1% to 5% of abdominal cross-sectional imaging studies. Although the workup and management of unilateral lesions are well established, limited information exists for bilateral incidentalomas.To compare the natural history of patients having bilateral incidentalomas with those having unilateral incidentalomas.Retrospective analysis of a prospective database of consecutive patients referred to an academic multidisciplinary adrenal conference. The setting was a tertiary care university hospital among a cohort of 500 patients with adrenal lesions between July 1, 2009, and July 1, 2014.Prevalence, age, imaging characteristics, biochemical workup, any intervention, and final diagnosis.Twenty-three patients with bilateral incidentalomas and 112 patients with unilateral incidentalomas were identified. The mean age at diagnosis of bilateral lesions was 58.7 years. The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side. Bilateral incidentalomas were associated with a significantly higher prevalence of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009) and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6% [22 of 112]) (P = .003) compared with unilateral lesions, while rates of hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of 112]) (P > .99). Only one patient with bilateral incidentalomas underwent unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years). There were no occult adrenocortical carcinomas.Bilateral incidentalomas are more likely to be associated with subclinical Cushing syndrome and less likely to be pheochromocytomas. Although patients with bilateral incidentalomas undergo a workup similar to that in patients with unilateral lesions, differences in their natural history warrant a greater index of suspicion for subclinical Cushing syndrome.
View details for DOI 10.1001/jamasurg.2015.1683
View details for PubMedID 26200882
- Pheochromocytoma crisis resulting in acute heart failure and cardioembolic stroke in a 37-year-old man. Surgery 2014; 155 (4): 726-7
Variant adrenal venous anatomy in 546 laparoscopic adrenalectomies.
2013; 148 (4): 378-83
Knowing the types and frequency of adrenal vein variants would help surgeons identify and control the adrenal vein during laparoscopic adrenalectomy.To establish the surgical anatomy of the main vein and its variants for laparoscopic adrenalectomy and to analyze the relationship between variant adrenal venous anatomy and tumor size, pathologic diagnosis, and operative outcomes.In a retrospective review of patients at a tertiary referral hospital, 506 patients underwent 546 consecutive laparoscopic adrenalectomies between April 22, 1993, and October 21, 2011. Patients with variant adrenal venous anatomy were compared with patients with normal adrenal venous anatomy regarding preoperative variables (patient and tumor characteristics [size and location] and clinical diagnosis), intraoperative variables (details on the main adrenal venous drainage, any variant venous anatomy, duration of operation, rate of conversion to hand-assisted or open procedure, and estimated blood loss), and postoperative variables (transfusion requirement, reoperation for bleeding, duration of hospital stay, and histologic diagnosis).Laparoscopic adrenalectomy.Prevalence of variant adrenal venous anatomy and its relationship to tumor characteristics, pathologic diagnosis, and operative outcomes.Variant venous anatomy was encountered in 70 of 546 adrenalectomies (13%). Variants included no main adrenal vein identifiable (n = 18), 1 main adrenal vein with additional small veins (n = 11), 2 adrenal veins (n = 20), more than 2 adrenal veins (n = 14), and variants of the adrenal vein drainage to the inferior vena cava and hepatic vein or of the inferior phrenic vein (n = 7). Variants occurred more often on the right side than on the left side (42 of 250 glands [17%] vs. 28 of 296 glands [9%], respectively; P = .02). Patients with variant anatomy compared with those with normal anatomy had larger tumors (mean, 5.1 vs 3.3 cm, respectively; P < .001), more pheochromocytomas (24 of 70 [35%] vs. 100 of 476 [21%], respectively; P = .02), and more estimated blood loss (mean, 134 vs. 67 mL, respectively; P = .01). For patients with variant anatomy vs those with normal anatomy, the rates of transfusion requirement (2 of 70 [3%] vs. 10 of 476 [2%], respectively; P = .69) and reoperation for bleeding (1 of 70 [1%] vs. 3 of 476 [1%]; P = .46) were similar between groups.Understanding variant adrenal venous anatomy is important to avoid bleeding during laparoscopic adrenalectomy, particularly in patients with large tumors or pheochromocytomas. Surgeons should anticipate a higher probability of adrenal vein variants when operating on pheochromocytomas and larger adrenal tumors.
View details for DOI 10.1001/jamasurg.2013.610
View details for PubMedID 23715888
Pheochromocytoma crisis is not a surgical emergency.
The Journal of clinical endocrinology and metabolism
2013; 98 (2): 581-91
Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma.We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated.Retrospective cohort study (1993-2011); literature review (1944-2011).Tertiary referral center.There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature.Medical management of pheochromocytoma crisis; adrenalectomy.Perioperative complications, conversion, and mortality.In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002).Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.
View details for DOI 10.1210/jc.2012-3020
View details for PubMedID 23284003
Practice patterns and job satisfaction in fellowship-trained endocrine surgeons.
2012; 152 (6): 953-6
Debates about the difficult job market for young endocrine surgeons are ongoing. This study aimed to analyze the practice patterns and work-related satisfaction levels of recently trained endocrine surgeons.An anonymous survey was utilized. Participants were divided into 3 groups: "Young" (<3 years in practice), "middle" (3-5 years), and "older" (>5 years).Fifty-six of 78 surgeons (72%) responded to the survey. Time in practice ranged from 1 to 9 years (mean, 3.9 ± 0.28). Forty-five (80%) described their practice as academic. Participants performed 244.1 ± 17.8 operations within the last year; 75.4 ± 3.3% were endocrine cases. More surgeons in the "young" group have academic practices (92%) and joined established endocrine surgery groups (54%) versus older surgeons (67% and 42%; P = .05). Of surgeons in the "young" group, 4% started their own practice versus 33% in the "older" group (P = .04). Level of satisfaction with financial compensation (3.2 on a 4-point scale versus 2.9) and lifestyle (3.6 vs 3.1) was also higher in the younger group (P = .009).Despite widespread speculation about scarcity of academic jobs after fellowship, recently trained endocrine surgeons are more likely to practice in academic settings and join established endocrine surgery practices when compared with older surgeons. Overall satisfaction level is higher among recently trained surgeons.
View details for DOI 10.1016/j.surg.2012.08.032
View details for PubMedID 23102635
Impact of race on intraoperative parathyroid hormone kinetics: an analysis of 910 patients undergoing parathyroidectomy for primary hyperparathyroidism.
Archives of surgery (Chicago, Ill. : 1960)
2012; 147 (11): 1036-40
HYPOTHESIS African American patients exhibit different intraoperative parathyroid hormone (IOPTH) profiles than non-African American patients. DESIGN Retrospective review. SETTING University medical center. PATIENTS Nine hundred ten patients who underwent parathyroidectomy for primary hyperparathyroidism between July 2005 and August 2010. INTERVENTIONS All patients underwent preoperative imaging with ultrasonography and sestamibi; operative exploration; and IOPTH measurement at 2 points preexcision and 5 and 10 minutes postexcision. MAIN OUTCOME MEASURES Preexcision and postexcision IOPTH measurements. RESULTS Of the 910 patients, 734 self-reported their race as white (81%); 91, Latino/other (10%); 56, Asian (6%); and 28, African American (3%). African American patients had significantly higher initial preexcision IOPTH levels compared with white patients (348 vs 202 pg/mL; P = .048) and significantly higher 5-minute postexcision IOPTH levels (151 vs 80 pg/mL; P = .01). The 10-minute postexcision IOPTH levels were similar between the 2 groups (52 vs 50 pg/mL). A similar percentage of white and African American patients had a 50% drop in IOPTH level at 10 minutes postexcision. No differences in IOPTH kinetics were observed in the other racial groups examined. CONCLUSIONS African American patients with primary hyperparathyroidism exhibit significantly higher preincision and 5-minute postexcision IOPTH values when compared with white patients. The 10-minute postexcision IOPTH values did not differ between races. The altered IOPTH kinetics identified in African American patients may reflect the severity of biochemical disease but may also be related to genetically predetermined differences in parathyroid hormone metabolism.
View details for DOI 10.1001/archsurg.2012.1476
View details for PubMedID 22801754
Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.
Current treatment options in oncology
2012; 13 (1): 1-10
Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.
View details for DOI 10.1007/s11864-011-0175-z
View details for PubMedID 22278672
- The role of surgery in cancer prevention. Current problems in surgery 2010; 47 (10): 750-830
- Solid Pseudopapillary Tumor of the Pancreas: An Unexpected Finding After Minor Abdominal Trauma DIGESTIVE DISEASES AND SCIENCES 2010; 55 (2): 240-241
Hereditary diffuse gastric cancer - Implications of genetic testing for screening and prophylactic surgery
2008; 113 (7): 1850-1856
Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative. The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.
View details for DOI 10.1002/cncr.23650
View details for PubMedID 18798546
Hereditary diffuse gastric cancer: surgery, surveillance and unanswered questions
2008; 4 (4): 553-559
Hereditary diffuse gastric cancer (HDGC) is an inherited cancer-susceptibility syndrome characterized by autosomal dominance and high penetrance. In 30-50% of cases, a causative germline mutation in CDH1, the E-cadherin gene, may be identified. Female carriers of CDH1 mutations also have an increased (20-40%) risk of lobular breast cancer. Endoscopic surveillance of patients with CDH1 mutations is ineffective because early foci of HDGC are typically small and underlie normal mucosa. CDH1 mutation carriers are therefore offered the option of prophylactic gastrectomy, which commonly reveals early foci of invasive signet-ring cell cancer. We review recommendations for genetic testing, surveillance and prophylactic surgery in HDGC. Areas for future research are discussed, including development of new screening modalities, optimal timing of prophylactic gastrectomy, identification of additional causative mutations in HDGC, management of patients with CDH1 missense mutations and prevention/early detection of lobular breast cancer in CDH1 mutation carriers.
View details for DOI 10.2217/147966220.127.116.113
View details for PubMedID 18684065
Surgery for gastrinoma.
Advances in surgery
2007; 41: 165-176
Surgery has been demonstrated to offer potential for cure in patients who have sporadic ZES and improved tumor-related survival in all patients who have ZES with gastrinomas larger than 2.5 cm. Techniques such as preoperative localization with SRS and intraoperative localization with duodenotomy have improved the effectiveness of surgical intervention for ZES. Future directions for investigation should include better defining the role of preoperative EUS and developing new, more sensitive techniques for preoperative localization. More research also is needed to define the appropriate indications for pancreaticoduodenectomy in ZES and to determine whether proximal vagotomy should be performed at the time of surgical exploration.
View details for PubMedID 17972563
Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses.
The Journal of surgical research
2005; 124 (2): 264-73
Cotransfection of dendritic cells (DC) with MART-1 and constitutively active TLR4 (caTLR4) RNA enhances the maturation of DC.Immature DC were cotransfected with RNA constructs encoding MART-1 and caTLR4, and CTL responses were analyzed.Cotransfection of DC with MART-1 + caTLR4 enhanced the expression of CD80 and CD83 surface markers and increased the secretion of cytokines IL-6, IL-12, and TNFalpha. Neither the native nor the A27L-modified MART-1 RNA could induce significant DC maturation or cytokine secretion. More importantly, DC cotransfected with caTLR4 + MART-1 RNA induced MART-1-specific CTL responses of a higher magnitude than DC transfected with either the native or A27L MART-1 RNA. When the MART-1 RNA-transfected DC were treated with DC-maturing cytokines, the induced CTL were less frequent and less lytic than those induced with MART-1 + caTLR4. A 2- to 100-fold increase in MART-1 tetramer+ cells and 2- to 10-fold increases in IFNgamma secretion and cytotoxicity were seen in CTL induced with MART-1 + caTLR4 compared to CTL induced with either MART-1 or A27L RNA. CTL induced with the mixed RNA displayed high percentages of CD8+ cells coexpressing CD45RA, CD56, and 2B4 antigens. Transfection with caTLR4 alone induced DC maturation, but did not induce lytic CTL, suggesting that CTL responses were induced solely by MART-1 epitopes.caTLR4 increases the CTL-inducing capacity of DC generating a lytic response specific for the accompanying antigen. These results demonstrate the possibility of enhancing the immunogenicity of the native MART-1 and other RNA derived from weakly immunogenic tumors in DC-based immunotherapy.
View details for DOI 10.1016/j.jss.2004.10.002
View details for PubMedID 15820257
Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4.
Journal of immunology (Baltimore, Md. : 1950)
2004; 172 (11): 7162-8
Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. However, clinical use of LPS is limited due to potential toxicity. Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human DC with RNA encoding caTLR4 led to IL-12 and TNF-alpha secretion. Transfection with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of DC with caTLR4 RNA enhanced allostimulation of CD4(+) T cells. DC transfected with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced the generation of MART-specific CTL. This CTL activity was superior to that seen when DC maturation was induced using either LPS or a standard mixture of cytokines (TNF-alpha, IL-6, IL-1beta, and PGE(2)). We conclude that transfection of DC with RNA encoding a functional signaling protein, such as caTLR4, may provide a new tool for studying TLR signaling in DC and may be a promising approach for the induction of DC maturation for tumor immunotherapy.
View details for PubMedID 15153540
Induction of anti-melanoma CTL response using DC transfected with mutated mRNA encoding full-length Melan-A/MART-1 antigen with an A27L amino acid substitution.
2003; 224 (2): 86-97
Modification of the parental immunodominant Melan-A/MART-1 peptide (MART-1(26-35)) by replacing the alanine with leucine (A27L) enhances its immunogenicity. Because of the reported advantages of RNA over peptides in DC vaccines, we sought to mutate the MART-1 gene to encode a full-length MART-1 antigen with an A27L amino acid substitution. Human DC were transfected with A27L-mutated MART-1 RNA (A27L RNA) or native MART-1 RNA, and then used to stimulate autologous T cells from a series of 8 HLA-A2+ volunteers. After three stimulations, all CTL induced with DC/A27L RNA exhibited more tetramer+ cells, and demonstrated stronger antigen-specific IFNgamma-secreting activity compared to CTL induced with DC/native RNA. A potent MART-1-specific, and predominantly class-I-restricted lysis was detected in most CTL induced with DC/A27L RNA, while native RNA-induced CTL showed minimal and non-specific lysis. HLA-A2+ DC and MART-1 negative/A2+ melanoma cells transfected with the A27L RNA were recognized and killed by MART-1-specific CTL, suggesting that these APC efficiently processed the A27L RNA and presented correct MART-1-specific epitope(s). In summary, introducing an A27L mutation into the MART-1 full-length mRNA sequence enhanced the immunogenicity of the encoded MART-1 Ag. The ease with which such a mutation can be made in RNA presents another potential advantage of using RNA for immunotherapy. Our results support considering this strategy for enhancing the immunogenicity of DC-based RNA vaccines.
View details for PubMedID 14609574