Practice Patterns of Pancreatic Surgery Within the Military.

INTRODUCTION: Pancreatic surgery is technically challenging, with mortality rates at high-volume centers ranging from 0% to 5%. An inverse relationship between surgeon volume and perioperative mortality has been reported suggesting that patients benefit from experienced surgeons at high-volume centers. There is little published on the volume of pancreatic surgeries performed in military treatment facilities (MTF) and there is no centralization policy regarding pancreatic surgery. This study evaluates pancreatic procedures at MTFs. We hypothesize that a small group of MTFs perform most pancreatic procedures, including more complex pancreatic surgeries. METHODS: This is a retrospective review of de-identified data from MHS Mart (M2) from 2014 to 2020. The database contains patient data from all Defense Health Agency treatment facilities. Variables collected include number and types of pancreatic procedures performed and patient demographics. The primary endpoint was the number and type of surgery for each MTF. RESULTS: Twenty-six MTFs performed pancreatic surgeries from 2014 to 2020. There was a significant decrease in the number of cases from 2014 to 2020. Nine hospitals performed one surgery over eight years. The most common surgery was a distal pancreatectomy, followed by a pancreaticoduodenectomy. There was a decrease in the number of pancreaticoduodenectomies and distal pancreatectomies performed over this period. CONCLUSIONS: Pancreatic surgery is being performed at few MTFs with a downward trajectory over time. Further studies would be needed to assess the impact on patient care regarding postoperative complications, barriers to timely patient care, and impact on readiness of military surgeons.

Practice patterns of hepatobiliary surgery within the military.

BACKGROUND: The purpose of this study is to evaluate the trends of hepatobiliary surgeries performed at military hospitals and to discuss potential implications on resident training and military readiness. While there is data to suggest centralization of surgical specialty services leads to improved patient outcomes, the military does not currently have a specific centralization policy. Implementation of such a policy could potentially impact resident training and readiness of military surgeons. Even in the absence of such a policy, there may still be a trend toward centralization of more complex surgeries like hepatobiliary surgeries. The present study evaluates the numbers and types of hepatobiliary procedures performed at military hospitals. METHODS: This study is a retrospective review of de-identified data from Military Health System Mart (M2) from 2014 to 2020. The M2 database contains patient data from all Defense Health Agency treatment facilities, encompassing all branches of the United States Military. Variables collected include number and types of hepatobiliary procedures performed and patient demographics. The primary endpoint was the number and type of surgery for each medical facility. Linear regression was used to evaluate significant trends in numbers of surgeries over time. RESULTS: Fifty-five military hospitals performed hepatobiliary surgeries from 2014 to 2020. A total of 1,087 hepatobiliary surgeries were performed during this time; cholecystectomies, percutaneous procedures, and endoscopic procedures were excluded. There was no significant decrease in overall case volume. The most commonly performed hepatobiliary surgery was "unlisted laparoscopic liver procedure." The military training facility with the most hepatobiliary cases was Brooke Army Medical Center. CONCLUSION: The number of hepatobiliary surgeries performed in military hospitals has not significantly decreased over the years 2014-2020, despite a national trend toward centralization. Centralization of hepatobiliary surgeries in the future may impact residency training as well as military medical readiness.

Effect of three-dimensional intraoperative imaging on surgical outcomes with breast conservation therapy.

BACKGROUND: Breast conservation therapy (BCT) is frequently performed for breast cancer and associated with a significant risk for positive margins. Intraoperative three-dimensional (3-D) tomosynthesis potentially could limit the risk of positive margins. METHODS: Retrospective review of an institutional breast cancer registry. Evaluated BCT cases for a two year time period prior to and after the introduction of intraoperative 3-D tomosynthesis. Primary outcome was the effect of 3-D tomosynthesis on margin positivity rates. Secondary measures were the impact of 3-D tomosynthesis on additional margin procurements at the index surgery and operative time. RESULTS: A total of 228 cases were evaluated with 106 cases utilizing 3-D tomosynthesis and 122 cases with standard imaging. No significant difference in margin positivity rates between the cohorts at 23.9% versus 15.8% for 3-D tomosynthesis and standard imaging respectively (OR 1.53, CI 0.772-3.032, P = 0.221). 3-D tomosynthesis was associated with increased margin procurement rates (OR 2.34, 95%CI 1.303-4.190, P = 0.004) and longer operative times (P < 0.001). CONCLUSION: Intraoperative 3-D tomosynthesis was not found to limit margin positivity rates or improve the performance of the procedure.

Disparities in Risk Reduction Therapy Recommendations for Young Women With Lobular Carcinoma In-Situ.

BACKGROUND: Endocrine therapy (ET) significantly reduces the risk of breast cancer development in high-risk patients diagnosed with lobular carcinoma in situ (LCIS). However, the variables impacting recommendation and use of ET in young adults (YAs) is not well-studied. We examined the role of provider recommendation and patient acceptance for ET for YAs with LCIS. MATERIALS AND METHODS: The National Cancer Database was queried for women aged < 40 years with primary LCIS between 2000 and 2012. Socioeconomic, demographic, and treatment variables were examined to determine their impact on ET provider recommendation and initial patient acceptance of risk-reducing therapy. RESULTS: Among 1650 YA patients with LCIS, only 749 (45.4%) were recommended ET. On multivariable analysis, women > 30 years of age were more likely recommended ET than women < 30 years (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.10-2.47), African Americans more than other ethnicities (OR, 1.48; 95% CI, 1.1-2.0), and YAs treated in New England were more likely than those in the rest of the country (OR, 3.26; 95% CI, 2.0-5.2). Among YA women recommended ET, only 20.2% had a documented refusal. Only geography appeared to independently impact the likelihood of refusal, with YAs in the Southeastern-Central United States being most likely to refuse ET (OR, 5.4; 95% CI, 1.2-24.0). CONCLUSION: ET is underutilized for risk-reduction in YAs with LCIS. This underuse appears dependent on disparities in provider recommendation practices rather than non-acceptance of therapy. This may reflect regional practice patterns, community standards of care, or provider bias regarding the significance of LCIS as a risk factor for development of invasive cancer.

Evaluation of Operative Waste in a Military Medical Center: Analysis of Operating Room Cost and Waste during Surgical Cases.

Operating rooms (ORs) contribute to at least 40 per cent of hospital costs. There is an existing cost waste in ORs for surgical devices that are opened without being used. There is a paucity of data evaluating the hospital cost of opened but unused OR supplies. The goal of this observational study is to examine the cost of opened but unused OR supplies for general surgery cases. We performed a quality improvement project of OR cost waste by observing 30 cases. Surgical cases of a senior surgeon who had been at the institution for more than five years were evaluated for items opened appropriately and whether the items are used. The cases evaluated ranged from open hernia repairs to robotic-assisted hernia repairs. We found that the cost of instruments opened but not used was $4528.18. Of the cases evaluated, we found that a range of 0 per cent to 27 per cent of total items were wasted, an average of 8.3 per cent. We found that for the open inguinal hernia case, there was minimal waste. The highest waste was among complex cases such as the robotic-assisted inguinal hernia with an average waste and cost of 15.8 per cent and $379. We found that on average for less complex cases such as open inguinal hernia repairs, $1.44 was potentially wasted per case, whereas for more complex cases up to $379 was wasted per case. We identified the outdated preference cards, lack of instrument knowledge, circulating nurse, and surgical technician distractions as reasons for contributing to waste.

Improved hemostasis with major hepatic resection in the current surgical era.

BACKGROUND: Major hepatic resection, predominantly performed for oncologic intent, is a complex procedure with the potential for severe intraoperative hemorrhage. The current surgical era has the ability to improve hemostasis throughout the performance of major hepatic resections which decreases blood transfusions and the detrimental effects associated with transfusion. We evaluated hemostasis and outcomes in the current surgical era of performing hepatic resections. METHODS: Utilizing the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database all major hepatic resections performed between 2012 and 2016 were analyzed in regards to hemostasis. Hemostasis was evaluated by the need for and magnitude of blood transfusions. Additional perioperative variables (including operative time, length of hospital stay, and mortality rates) were analyzed to assess for outcomes with hemostasis. The NSQIP results were compared to previous publications involving major hepatic resections to detect improvement in hemostasis and outcomes in the current surgical era. RESULTS: A total of 22777 major hepatic resections met the inclusion criteria for analysis in the NSQIP database. An additional 21198 cases were compiled within the selected publications for comparative analysis. The transfusion rate in the current surgical era was 13.3% versus 38.7% in the previous era (P = 0.0001). When a transfusion was required in the current surgical era there was a two-fold reduction in the number of units transfused (1.5 U vs. 3.8 U, P = 0.0001). Statistically significant improvements in operative time and length of hospital stay were presented within the current surgical era (P = 0.0001). When a transfusion was required there was an increased relative risk score of 7 for mortality (4.9% vs. 0.7%, P = 0.0001), however, improvement in mortality rates did not reach statistical significance across surgical eras (1.3% vs. 4.0%, P = 0.0001). CONCLUSIONS: The conduction of major hepatic resection in the current surgical era is more hemostatic. Correlated with improved hemostasis are better outcomes for both clinical and financial endpoints. These findings should encourage continued and increased performance of major hepatic resections.

Bile duct injuries (BDI) in the advanced laparoscopic cholecystectomy era.

BACKGROUND: Laparoscopic cholecystectomy is the most commonly performed laparoscopic procedure. It is superior in nearly every regard compared to open cholecystectomies. The one significant aspect where the laparoscopic approach is inferior regards the association with bile duct injuries (BDI). The BDI rate with laparoscopic cholecystectomy is approximately 0.5%; nearly triple the rate compared to the open approach. We propose that 0.5% BDI rate with the laparoscopic approach is no longer accurate. METHODS: The National Surgical Quality Improvement Program (NSQIP) registry was retrospectively reviewed. All laparoscopic cholecystectomies performed between 2012 and 2016 were extracted. A total of 217,774 cases meeting inclusion criteria were analyzed. The primary data points were the overall BDI incidence rate and time of diagnosis. BDI were identified by ICD-9 and ICD-10 codes. Secondary data points were variables associated with BDI. RESULTS: The BDI rate was 0.19%. 77% of cases were diagnosed after the index surgical admission. Intra-operative cholangiography (IOC) use was associated with a higher BDI rate and higher identification rate of a BDI intraoperatively (P value < 0.0001). Resident teaching cases were protective with a RR score of 0.56 (P value < 0.0001). The presence of cholecystitis increased the risk of a BDI with a RR score of 1.20 (P value < 0.0001). There was a low conversion rate of 0.04% however converted cases had a nearly hundredfold increase in BDI at 15% (P value < 0.0001). CONCLUSIONS: The performance of laparoscopic cholecystectomies in North America is no longer associated with higher BDI rates compared to open. IOC use still is not protective against BDI, and cholecystitis continues to be a risk factor for BDI. When a cholecystectomy requires conversion from a laparoscopic to an open approach the BDI increases a hundredfold; which may raise the concern if this approach is still a safe bailout method for a difficult laparoscopic dissection.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial.

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.

Variations in cancer care for adolescents and young adults (AYAs) with ductal carcinoma in situ.

NCCN guidelines recommend tamoxifen (TAM) for adjuvant treatment of ductal carcinoma in situ (DCIS). TAM has side effects that can potentially complicate treatment recommendations and patient acceptance. It is unknown how well-accepted this recommended therapy is for the adolescent and young adult (AYA) patient population with DCIS. The NCDB was used to identify patients aged 15-39 with DCIS treated between 2000 and 2012. Patient demographic, socioeconomic, and treatment data were collected. Chi-squared test and multivariate analysis were used for statistical assessment. A total of 3988 women were identified of which 1795 (45%) were recommended for endocrine therapy. Age > 30 (OR 1.31, 95%CI 1.01-1.70), Black (OR 1.40, 95% CI 1.12-1.65), or Asian (OR 1.45, 95% CI 1.08-1.94) race, treatment at a nonacademic facility (OR 0.71, 95% CI 0.56-0.91), geographic location of treating facility, receipt of radiation (OR 5.30, 95% CI 4.59-6.11), and negative margins (OR 2.14, 95% CI 1.47-3.11) were significant predictors of recommendation for endocrine therapy. Of those recommended, 1484 (83%) accepted treatment. Age, race, and annual income were significant variables affecting acceptance. Overall, only 37.2% (1484 of 3988) of women in this study initiated endocrine therapy for treatment of DCIS. Our results demonstrate that little over a third of patients in the AYA cohort receive endocrine therapy as treatment for DCIS. The bias appears to lie in physician recommendation because when recommended, the majority of patients accept treatment. Factors exist both medical and nonmedical that appear to influence these treatment decisions.

Pediatric-protocol of multimodal therapy is associated with improved survival in AYAs and adults with rhabdomyosarcoma.

BACKGROUND: Multimodal therapy is the standard treatment for pediatric rhabdomyosarcoma, but for adolescents and young adults (AYAs: ages 15-39) and older adults with rhabdomyosarcoma, the use of adjuvant therapy is variable, and survival is greatly decreased compared with younger patients. METHODS: All patients with rhabdomyosarcoma who had a curative operative were identified from the 1998-2012 National Cancer Database. Regression analyses identified independent factors relating to receipt of multimodal therapy (resection + chemotherapy + radiation) and the influence of multimodal therapy on 5-year overall survival. RESULTS: Of 2,312 patients, 44% were pediatric (age < 15 years), 22% AYA (ages 15-39), and 34% adult (age ≥ 40 years). Adults received multimodal therapy least often (pediatric: 62%, AYA: 46%, adults: 24%; P < .001), even after controlling for demographic characteristics, tumor features, and stage. In the entire cohort, multimodal therapy was associated with a decreased risk of death within 5 years (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.84), with similar findings after stratification by age (pediatric: HR 0.64, 95% CI 0.48-0.85; AYA: HR 0.72, 95% CI 0.55-0.95; adult: HR 0.74, 95% CI 0.58-0.93). In AYAs only, black and Hispanic patients had an increased risk of death within 5 years (black patients: HR 1.64, 95% CI 1.14-2.37; Hispanic patients: HR 1.62, 95% CI 1.11-2.36). CONCLUSION: This first large national study suggests that multimodal therapy is independently associated with improved survival for both AYAs and adults with rhabdomyosarcoma, similar to pediatric patients, but multimodal therapy is appreciably underused. Implementation of multimodal therapy for all patients could potentially improve overall outcomes of patients with rhabdomyosarcoma.

Anatomic Location Is the Primary Determinant of Survival for Paragangliomas.

Paragangliomas (PGL) are rare neuroendocrine tumors. This study describes the largest collection of PGLs and evaluates factors that impact survival. Patients with PGL from 1998 to 2013 in the NCDB were reviewed. Independent predictors of overall survival (OS) were identified for patients with non-central nervous system (CNS) tumors. Of 867 PGLs, the primary site was CNS (39.9%), abdomen/pelvis (A&P) (21.0%), head and neck (H&N) (17.5%), thoracic (15.1%), bladder (3%), or unspecified (3.5%). Of 521 non-central nervous system (CNS) PGLs, there were differences in sex, comorbidities, treatment facility, tumor size, treatment modality (P < 0.001). Five-year OS for this cohort was 66 per cent and 10-year OS was 51 per cent. Median OS differed significantly between primary sites (H&N 106.0 months, thoracic 89.0 months, A&P 81.7 months, bladder 69.7 months, and unspecified 27.2, P < 0.001). After controlling for multiple factors, age greater than 50 (HR 1.97; CI 1.38-2.81), primary site A&P (HR 2.01; CI) 1.17-3.48) or bladder (HR 4.03; CI 1.64-9.89) as compared with H&N, distant metastasis (HR 2.25; CI 1.44-3.53) and those who did not receive surgery (HR 2.85; CI 1.89-4.31) all exhibited decreased OS. This is the largest series of PGLs and the first to demonstrate significant survival differences based on PGL site. Abdominal/pelvic and bladder PGLs had the lowest survival in addition to patients that did not have a surgical resection, those with distant metastases, and >50 years of age.

Treatment of unicentric Castleman disease with neoadjuvant rituximab.

Angiofollicular lymph node hyperplasia, known more commonly as Castleman disease, is a rare lymphoproliferative disorder. Castleman disease has two distinct clinical manifestations described as unicentric and multicentric disease. These presentations have distinct treatment algorithms and portend very different prognoses. Standard treatment of unicentric disease is complete surgical resection, which confers a cure rate approaching 100%. To our knowledge, this case report is the first to describe the use of neoadjuvant rituximab in the treatment of unicentric Castleman disease to enable a less morbid surgical resection. Given the vascularity of the tumor, proximity to the pulmonary artery and superior vena cava, and possible intimate association with the lung parenchyma, the tumor was treated preoperatively with rituximab, an anti-CD20 monoclonal antibody, at doses of 375 mg/m² weekly for 4 weeks. Rituximab therapy successfully decreased the diameter of the tumor from 4.79 cm×2.67 cm to 2.8 cm×1.5 cm, as confirmed by CT imaging. Postoperative surgical pathology confirmed the diagnosis of Castleman disease, hyaline vascular type, with negative margins. Notably, the lymph node tissue in the rituximab-treated specimen demonstrated reduced mantle zone thickness, decreased size of follicles, and increased hyalinization of vessels. Rituximab shows promise in neoadjuvant treatment of unresectable or partially resectable unicentric Castleman disease.

Role of growth factors in improved skin flap viability caused by phosphodiesterase-5 inhibitor.

Flap necrosis is one of the major complications of reconstructive surgery and sildenafil citrate has been shown to decrease flap necrosis in preclinical animal models. However, the mechanisms underlying sildenafil's therapeutic efficacy are not known. As with other phosphodiesterase 5 selective inhibitors, sildenafil causes vasodilation and enhanced blood flow. In addition, sildenafil can also alter gene expression. This study is designed to test the hypothesis that increased expression of angiogenic growth factors may be responsible for therapeutic efficacy of sildenafil. A modified McFarlane flap measuring 3 x 10 cm was created on the dorsal skin of male Sprague-Dawley rats. For growth factor expression experiment, rats were administered either vehicle or sildenafil 10 mg/Kg intraperitoneal (IP). Ribonucleic acid (RNA) extracted from skin flap was analyzed to assess the messenger ribonucleic acid (mRNA) levels of different angiogenic growth factors. For skin flap viability experiment, fibrin film impregnated with vehicle, fibroblast growth factor (FGF) (5.0 microg) or vascular endothelial growth factor (VEGF) (2.0 microg) was applied to the wound. The skin flap was then returned to its native position and stapled in place. Total affected area (area of necrosis and blood flow stasis) of each rat on postoperative day 14 was analyzed with orthogonal polarization spectral imaging. Daily systemic treatment with sildenafil significantly (P < 0.05) increased the expression of FGF1 and FGF Receptor 3 on postoperative day 3 by 5.08- and 4.78-fold, respectively. In addition, sildenafil increased the expression of VEGF-A, VEGF-B, and VEGF-C by 2.66-, 2.02-, and 2.00-fold, respectively. Subcutaneous treatment with FGF but not VEGF-A tended to decrease total affected area in rats. These data demonstrate that sildenafil altered the expression of FGF and VEGF. Altered expression of growth factors may be, at least partly, responsible for the beneficial effects of sildenafil citrate on skin viability.