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Richard J. Barth Jr, MD

Contact Information

Professional Interests

1. Development of novel methods to increase the precision of breast conserving surgery
2. Appropriate opioid prescribing after surgery
3. Surgical entrepreneurship
4. Increasing the safety of liver surgery

Biography

I had the good fortune to do a research fellowship during my surgical residency in Steve Rosenberg’s lab, Surgery Branch, NCI. This provided me with the training and insight to pursue my core research efforts in immunotherapy and the immune response to cancer. As a research fellow I made seminal observations about adoptive immunotherapy with tumor infiltrating lymphocytes (TIL). Using low dose IL-2, I was able to culture tumor specific TIL (JI 1990), a principle utilized when TIL were subsequently cultured in clinical trials. I also discovered that the mechanism whereby TIL caused tumor regressions was not necessarily direct cytolysis (the prevailing concept in the lab at the time), but through secretion of cytokines like IFN-γ and TNF (J Exp Med 1991).
I maintained an active immunotherapy lab at Dartmouth for 15 years. In collaboration with Randy Noelle (and funded with an NCI R29 award) we made the novel observation that anti-tumor immunity required signaling between CD40, on dendritic cells, and CD40 ligand, on T cells (Ca Res 1997). I proceeded to embark on several studies of dendritic cell (DC) immunotherapy in mice. Our most important finding was that injection of DCs directly into lymph nodes (compared to sc or iv routes that others were utilizing) resulted in the development of much more potent T cell immune responses (Ca Res 2001). This finding was confirmed by others in a clinical trial. In a classic example of translational research, we then utilized the insights from our murine studies to design a DC vaccine trial in patients. This is the most significant study I have conducted. I obtained an IND from the FDA and was funded as a project PI on the Dartmouth Immunology COBRE grant. We performed a first in man trial of an adjuvant DC vaccine using a whole cell source of antigen in patients with metastatic colorectal cancer (Clin Ca Res 2010). We were able to induce immune responses against the patient’s own tumor in 2/3 of the patients we immunized and observed that the patients who developed an immune response were much more likely to be recurrence free 5 years later. I then worked with the NCC Genomics Shared Resource to deep sequence the tumors and evaluated the T cell immune response present in situ in liver metastases of these patients to try to understand why some responded to vaccination and others did not (Clin Ca Res 2017). My expertise in the field of immunotherapy has led me to be appointed to the Editorial Boards of Annals of Surgical Oncology and the Journal of Immunotherapy.
I have also performed several clinical studies which have yielded novel results and have changed patient care. While a surgical oncology fellow I designed a study which was the first in the US to show that core needle biopsy could be used to diagnose sarcomas (Surgery 1992). The standard of care for biopsy of soft tissue masses soon changed from incisional biopsy to core needle biopsy. In collaboration with one of my surgical mentors, Dr. Cady, we published that a novel method of inking breast cancer specimens after lumpectomy allowed us to minimize the amount of tissue removed when re-excision was performed to obtain negative margins (Ann Surg Onc 2001). This practice is now the standard of care at Dartmouth and many other institutions. I have been integrally involved in several clinical trials of neoadjuvant chemoradiotherapy for pancreatic cancer patients. These trials have been designed and executed by our multidisciplinary GI tumor group at Dartmouth. We have uniquely demonstrated a specific benefit of administering chemoradiation therapy prior to surgery: a decreased rate of subsequent local recurrence (J Am Coll Surg 2008). I am quite fond of my study of patients with phyllodes tumors, an unusual type of breast cancer. The local recurrence rate after margin negative lumpectomy for these patients is 25%. In the only prospective study ever performed on patients with phyllodes tumors, we demonstrated that adding radiation therapy to lumpectomy resulted in no local recurrences in 46 patients (Ann Surg Onc 2009). This paper was selected as one of the 10 most influential papers of the year by the American Society of Breast Surgeons and has changed the standard of care of treatment for these patients. Building on our novel observation that a short term low calorie diet prior to liver resection greatly decreased hepatic steatosis and decreased the risk of bleeding during liver surgery, I designed and obtained funding for a prospective clinical trial to evaluate the effectiveness of this diet on clinical outcomes after liver resection. We have shown that the use of a pre-op diet can decrease blood loss in hepatic surgery by 50% and makes it much easier for the surgeon to manipulate the liver intra-operatively (Ann Surg 2019).
Another set of very interesting clinical studies we have recently completed was motivated by the nation’s opioid epidemic. We evaluated 650 patients undergoing common general surgical operations at Dartmouth and showed that there was very wide variability in opioid prescription practices. Furthermore, opioids are being way over-prescribed: only 25% of the pills are being used by patients (Ann Surg 2017). By merely educating surgeons about this problem and providing a guideline for rational opioid prescribing we were able to cut opioid prescriptions by over 50% and still take care of patients’ pain (Ann Surg 2018). We have also found that the number of opioids prescribed to surgical inpatients the day prior to discharge is the best predictor of outpatient opioid use, and used this to develop a general guideline for opioid prescription after discharge (JACS 2018). I am currently PI on a prospective clinical trial at Dartmouth that focuses on maximizing disposal of excess opioid pills after surgery.
Another line of research has led me to co-found a company to develop a new device designed to improve the precision of breast conserving surgery. In collaboration with engineers Keith Paulsen and Venkat Krishnaswamy we have shown in a funded pilot study that obtaining a breast MRI in the supine position (rather than the standard prone position) allows us to accurately localize breast cancers in the operating room. We received a NIH R21 grant to fund a randomized prospective clinical trial which we accrued 138 patient to at Dartmouth. This study showed that the positive margin rate was cut in half: from 23% to 12%, using supine MRI guided surgery (Ann Surg Onc 2019). Pushing this technology to the next level, I invented a 3-D printed device called the Breast Cancer Locator, which we have tested in a pilot clinical trial (Ann Surg Onc 2017). We formed a company, CairnSurgical, Inc., to develop this device. We received SBIR phase 1 and 2 grants and are actively accruing to a second pilot clinical trial to demonstrate its feasibility at sites outside of Dartmouth. We have submitted an IDE application to the FDA, have secured series A investor funding and are poised to begin a pivotal randomized prospective trial of the Breast Cancer Locator vs standard of care localization at a dozen medical centers.
Teaching has been an important priority for me throughout my career. I initiated, organized, and taught in a weekly clinical teaching conference for senior surgical residents from 1993-2007. Twenty five residents, medical and PhD students have been involved in research projects with me that have resulted in presentations at national meetings and publications. Two have gone on to faculty appointments in surgical oncology at academic medical centers. I have received 5 teaching awards from medical students and surgery residents, including the Arthur Naitove Award, the Surgery Chief Resident’s Award for teaching excellence, the Dartmouth Mosenthal Surgical Fellowship, the DMS Excellence in Teaching Award and election to AOA by medical students. Outside of Dartmouth I have been honored to serve on the Program Committee of the New England Surgical Society (NESS) from 2003 to the present. In 2008, as Chair of that committee, I was responsible for organizing and leading the annual scientific meeting. As Recorder of the NESS (a 5 year senior leadership position in the Society) I initiated a “Paper of the Year Award” and a Publications Committee. I was elected Vice-President of the Society in 2015 and served as President of the NESS in 2019.
I have held major administrative positions in both the Norris Cotton Cancer Center and the Department of Surgery. For 8 years I was Director of the GI Oncology Program, a multidisciplinary group of physicians who meet on a weekly basis to determine the treatment of individual patients, and also develop, prioritize and accrue patients to clinical research studies. For 3 years I chaired the Clinical Cancer Care Committee, the committee that oversees the workings of all of the NCCC clinical oncology programs. I co-directed the Immunology and Cancer Immunotherapy Research Program (one of the 6 core research programs of the NCCC) for 7 years, facilitating interactions between clinical and basic science investigators. I recently helped direct a strategic planning effort for the NCCC.
During the past 16 years my main administrative responsibilities have focused on the Section of General Surgery. As Section Chief, I have expanded our Section from 10 to 24 surgical faculty. I have successfully launched several initiatives. We initiated a Division of Colorectal Surgery 8 years ago and now have 3 busy full time colorectal surgeons and a physician’s assistant. We have expanded and transformed our Acute Care/Trauma Division to be available in-house 24/7 for urgent surgical patients. In addition, I initiated a mutually beneficial collaboration with four local community hospitals whereby DHMC general surgeons operate and provide care to patients at these local hospitals.
Clinical care comprises the majority of my time (55%), with about 20% in research, 5% in teaching and 20% in administration. I perform approximately 250 operations and see over 1000 patients in the clinic annually. I take general surgery call for emergency patients. I receive regional referrals of patients with breast cancer, melanoma, pancreas cancer and metastatic liver tumors. Over 95% of my patients rate my overall care as excellent. I have been recognized as a Leading Physician in Breast and General Surgery by physician colleagues in NH Magazine. As an oncologist, I am particularly grateful for being recognized by my physician colleagues for compassionate patient care, twice as a finalist for the Leonard Tow Humanism in Medicine Award and for receiving the Alma Hass Milham Award for clinical excellence and compassionate patient care.
On a personal note, I have been happily married for 32 years to my wife Kathy.
We have 3 wonderful boys, Erik (Bates 2012), Matthew (Skidmore 2015) and Brendan (Dartmouth 2017). I enjoy hiking, tennis, biking, skiing and sailing.