SBIR-STTR Award

Anastomotic failure is one of the most feared complications of gastrointestinal surgery due to the resultant morbidity and mortality. Failure of an anastomosis, or intestinal junction, can cause a spectrum of morbidities to the patient including local abscess formation - requiring procedural drainage, tumor recurrence, debilitating pain, dysfunctional defecation, and overwhelming bacterial sepsis resulting in death. Despite improvements in surgical technique, and the widely accepted use of surgical staplers, anastomotic failure in the form of leakage or stricture occurs at unacceptable high levels given the severe consequences. In the performance of a low anterior resection (LAR) for excision of rectal cancer, anastomotic failure has been reported to occur in up to 30% of cases. One large multicenter, observational study of 2729 patients reported a leak rate of 14.3%. These anastomotic failures cause a significant and avoidable economic burden on the healthcare system, as well as an incalculable amount of pain, suffering, and hardship for the patients in which the failure occurs. As a precaution many surgeons will tunnel a proximal segment of the bowel through the abdominal wall to form a diverting stoma. The rationale of this maneuver is to prevent the leakage of fecal matter into the abdominal cavity from a potential failure at the newly formed anastomotic site. Many times the surgeons will perform another procedure to reverse the stoma months after the initial procedure. In the same multicenter study 881 patients were given a temporary diverting stoma to mitigate the risk of an anastomotic leak, however, within this group only 128 patients developed a leak. Thus up to 85% of those patients underwent an additional surgical procedure to reverse the stoma that provided questionable benefit. The arbitrary creation of a temporary diverting stoma, and the eventual reversing procedure presents a significant and avoidable economic burden on the healthcare system, as well as exposes numerous patients to arguably unnecessary surgical risk. Presently, there is neither a clinically practical method nor device available for predicting anastomotic failure, nor objective criteria by which the operative team can decide when a diverting stoma is indicated. Our objective is to create a clinically transparent device that reduces anastomotic failures through analysis of target tissues before, during, and after creation of an anastomosis. If the tissues are deemed unsuitable for reliable formation of an anastomosis, the device alerts the operative team to take corrective action. Our approach is to design a device that: integrates into the surgical workflow by coupling to a commercially available, off-the-shelf surgical stapling instrument, employs an array of multimodality sensors to assess the viability of the tissues at the staple line, and wirelessly transmits sensor data to a base station where the real-time feedback is displayed to the operative team. Phase I of this study will focus on the evaluation of in-vivo oxygen dependent quenching of phosphorescence as the primary modality capable of assessing tissue viability, while maintaining clinical and commercial feasibility. , ,

Public Health Relevance:
The proposed research is the first step to realizing a clinically transparent device capable of providing real-time assessment of anastomotic viability not currently available to the operative team;the operative team will be able to take appropriate measures to reduce anastomotic failures by ensuring adequate tissue perfusion. The proposed device will assist the operative team by objectively determining the optimal staple gap, minimizing tension across the anastomosis, and indicating when the creation of a diverting ostomy or the provision of an alternative therapy is in the best interest of the patient. The proposed device could significantly reduce patient suffering, while saving $2 billion dollars annually in excess healthcare costs.

Thesaurus Terms:
Abdominal Cavity;Abdominal Wall;Abdominal Wall Structure;Abscess;Abscission;Alternative Therapies;Anastomosis;Anastomosis - Action;Animals;Anterior;Blood;Blood Flow;Body Tissues;Carcinoma Of The Rectum;Cavitas Abdominis;Cessation Of Life;Characteristics;Clinical;Clinical Research;Clinical Study;Colon;Colorectal Cancer;Coupling;Custom;Data;Death;Defecation;Devices;Disadvantaged;Drainage;Drainage Procedure;Economic Burden;Ensure;Evaluation;Excision;Extirpation;Extravasation;Flr;Failure (Biologic Function);Family Suidae;Fear;Feedback;Fluorescence;Fright;Gastrointestinal Surgical Procedures;Grant;Health Care Costs;Health Costs;Healthcare Costs;Healthcare Systems;Injectable;Injection Of Therapeutic Agent;Injections;Intestinal;Intestines;Ischemia;Leakage;Measurement;Measures;Methods;Methods And Techniques;Methods, Other;Miniaturisations;Miniaturization;Miniaturizations;Modality;Monitor;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Multi-Institutional Clinical Trial;Multi-Center Clinical Study;Multi-Center Clinical Trial;Multi-Site Clinical Study;Multi-Site Clinical Trial;Multicenter Studies;O Element;O2 Element;Observational Study;Operation;Operative Procedures;Operative Surgical Procedures;Ostomy;Outcome;Oximetry;Oxygen;Oxygen Consumption;Oxygen Saturation Measurement;Pain;Painful;Patients;Performance;Perfusion;Phase;Pigs;Pressure;Pressure- Physical Agent;Procedures;Property;Property, Loinc Axis 2;Reaction Time;Rectal Cancer;Rectal Carcinoma;Rectum Cancer;Recurrence;Recurrent;Removal;Reporting;Research;Response Rt;Response Time;Reticuloendothelial System, Blood;Risk;Sepsis;Series;Side;Site;Spillage;Standardization;Stomas;Suidae;Surface;Surgeon;Surgical;Surgical Interventions;Surgical Procedure;Surgical Removal;Surgical Staplers;Surgical Staples;Surgical Stapling;Swine;System;System, Loinc Axis 4;Systems, Health Care;Techniques;Testing;Time;Tissue Sample;Tissue Viability;Tissues;Validation;Venous;Work;Abdominal Wall;Abstracting;Base;Bloodstream Infection;Bowel;Bowel Movement;Commercialization;Cost;Design;Designing;Dosage;Failure;Gastrointestinal Surgery;Improved;In Vivo;Instrument;Interest;Luminescence;Miniaturize;Multi Center Clinical Study;Multi Center Clinical Trial;Multi Site Clinical Study;Multi Site Clinical Trial;Multimodality;Operative Procedure On The Gastrointestinal System;Phase 1 Study;Phosphorescence;Porcine;Preclinical Evaluation;Pressure;Prevent;Preventing;Psychomotor Reaction Time;Resection;Sensor;Suid;Surgery;Surgical Construction Of A Stoma;Time Use;Tissue Oxygen Saturation;Tissue Oxygenation;Tumor

Standard of care for surgical resection of rectal cancer is the performance of low anterior resection (LAR). After removal of the cancerous segment, a surgical stapler is used to restore continuity by creating an anastomosis between the resulting ends of disjointed bowel. Anastomotic leak is one of the most dreaded complications of colorectal surgery due to the morbidity and mortality caused by fecal contamination of the abdominal cavity. Anastomotic leak, after LAR for rectal cancer, has been reported to occur in as many as 14% of patients;three times more frequently than with other bowel resections. The sequela of anastomotic leak can include local abscess formation, debilitating pain, dysfunctional defecation, overwhelming bacterial sepsis, and death. The consequences are so severe that surgeons subjectively opt to divert the fecal stream away from the healing anastomosis to an ostomy;many months later the patient is then subject to an additional operation to restore normal defecation. While creation of a diverting ostomy can lessen the impact of anastomotic leak, it does not prevent the leak, and poses a high risk for additional complications while significantly compromising the lifestyle of the recovering patient. There is neither a clinically practical method available for predicting which patients will experience an anastomotic leak, nor an objective set of criteria by which a surgeon can select those patients that would benefit from an ostomy. The long term goal of the proposed research is to reduce the rate of anastomotic leak and unnecessary ostomy diversion through the creation of an objective, repeatable means by which to screen patients intra-operatively. Patients at low risk will avoid an unnecessary ostomy. Patients at high risk of leak, despite efforts to improve tissue viability, would likely be better served by a permanent ostomy instead of a failed, painful attempt at a restorative procedure. Postulated mechanisms for the increased incidence of leak after resection of rectal cancer can each contribute to inadequate oxygen delivery to the healing anastomosis;each of which are present at the time of surgery. The Stapled Anastomosis Viability Evaluation (SAVE) System integrates into the surgical workflow by replacing the anvil of commercially available, circular staplers with a sensing anvil. The SAVE Anvil uses an array of multi-modality sensors to enable the surgeon to perform the procedure in a standardized manner while assessing the viability of the anastomosis at the staple line throughout its formation. Sensor data is transmitted to a base station where actionable information is displayed to the surgical team. Phase I demonstrated the feasibility of measuring interstitial oxygenation levels at the anastomotic site using oxygen dependent quenching of phosphorescence via a locally injected phosphor. Initial toxicity studies of the probe indicate non-toxicity at dose-response levels. Phase II of this study will establish the relationship between interstitial oxygen level and integrity of the anastomosis through survival studies in animal models. Concurrently the candidate phosphor with undergo requisite screening, and pharmacokinetic evaluation in preparation for pre-IND discussion.

Public Health Relevance:
Colorectal cancer afflicts 1.2 million people annually, the mainstay of treatment being surgical removal of the afflicted segment of bowel. After the surgical procedure the intestine fails to heal in as many as 14% of patients resulting in life threatening illness as fecal material contaminates the abdominal cavity. Surgisense's Stapled Anastomosis Viability Evaluation (SAVE) System strives to reduce the occurrence of this complication as the first, clinically relevant, intra-operative device capable of providing real-tie assessment of an intestinal tissue's ability to heal;reducing patient suffering, while saving $2 billion dollars annually in excess healthcare costs.