"The Prognostic Role of Aspartate Transaminase to Platelet Ratio Index (APRI) on Outcomes Following Non-emergent Minor Hepatectomy".

INTRODUCTION: Fibrosis and cirrhosis are associated with worse outcomes after hepatectomy. Aspartate transaminase to platelet ratio index (APRI) is associated with fibrosis and cirrhosis in hepatitis C patients. However, APRI has not been studied to predict outcomes after hepatectomy in patients without viral hepatitis. METHODS: We reviewed the ACS-NSQIP dataset to identify patients who underwent a minor hepatectomy between 2014 and 2021. We excluded patients with viral hepatitis or ascites as well as patients who underwent emergent operations or biliary reconstruction. APRI was calculated using the following equation: (AST/40)/(platelet count) × 100. APRI ≥0.7 was used to identify significant fibrosis. Univariable analysis was performed to identify factors associated with APRI ≥0.7, transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression was performed to identify adjusted predictors of these outcomes. RESULTS: Of the 18,069 patients who met inclusion criteria, 1630 (9.0%) patients had an APRI ≥0.7. A perioperative blood transfusion was administered to 2139 (11.8%). Overall morbidity, serious morbidity, and mortality were experienced by 3162 (17.5%), 2475 (13.7%), and 131 (.7%) patients, respectively. APRI ≥0.7 was an independent predictor of transfusion (adjusted OR: 1.48 [1.26-1.74], P < .001), overall morbidity (1.17 [1.02-1.33], P = .022), and mortality (1.97 [1.22-3.06], P = .004). Transfusion was an independent predictor of overall morbidity (3.31 [2.99-3.65], P < .001), serious morbidity (3.70 [3.33-4.11], P < .001), and mortality (5.73 [4.01-8.14], P < .001). CONCLUSIONS: APRI ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. APRI may serve as a noninvasive tool to risk stratify patients prior to elective minor hepatectomy.

Oncologic and Functional Outcomes After Stereotactic Body Radiation Therapy for High-Grade Malignant Spinal Cord Compression.

Purpose: Although surgical decompression is the gold standard for metastatic epidural spinal cord compression (MESCC) from solid tumors, not all patients are candidates or undergo successful surgical Bilsky downgrading. We report oncologic and functional outcomes for patients treated with stereotactic body radiation therapy (SBRT) to high-grade MESCC. Methods and Materials: Patients with Bilsky grade 2 to 3 MESCC from solid tumor metastases treated with SBRT at a single institution from 2009 to 2020 were retrospectively reviewed. Patients who received upfront surgery before SBRT were included only if postsurgical Bilsky grade remained ≥2. Neurologic examinations, magnetic resonance imaging, pain assessments, and analgesic usage were assessed every 3 to 4 months post-SBRT. Cumulative incidence of local recurrence was calculated with death as a competing risk, and overall survival was estimated by Kaplan-Meier. Results: One hundred forty-three patients were included. The cumulative incidence of local recurrence was 5.1%, 7.5%, and 14.1% at 6, 12, and 24 months, respectively. At first post-SBRT imaging, 16.2% of patients with initial Bilsky grade 2 improved to grade 1, and 53.8% of patients were stable. Five of 13 patients (38.4%) with initial Bilsky grade 3 improved to grade 1 to 2. Pain response at 3 and 6 months post-SBRT was complete in 45.4% and 55.7%, partial in 26.9% and 13.1%, stable in 24.1% and 27.9%, and worse in 3.7% and 3.3% of patients, respectively. At 3 and 6 months after SBRT, 17.8% and 25.0% of patients had improved ambulatory status and 79.7% and 72.4% had stable status. Conclusions: We report the largest series to date of patients with high-grade MESCC treated with SBRT. The excellent local control and functional outcomes suggest SBRT is a reasonable approach in inoperable patients or cases unable to be successfully surgically downgraded.

Gender and the Receipt of the Association of Residents in Radiation Oncology Educator of the Year Award.

Purpose: We hypothesized that there may be a gender disparity in the receipt of the Association of Residents in Radiation Oncology (ARRO) Educator of the Year Award and sought to elucidate factors that contribute to differences in award receipt. Methods and Materials: Using a database provided by the American Society for Radiation Oncology, award recipients were identified from 2010 to 2022. Publicly available websites were accessed to obtain data regarding gender, years since residency graduation, percentage of female faculty, size of residency program, and program director designation. A 1-sample Z-test was used to assess whether the proportion of female ARRO award winners, defined as the proportion of female radiation oncology faculty members in the nominating universities that year, was significantly less than the population average. Secondary analyses used univariable binary logistic regression to identify global associations between gender, year since gradation, or program size. Results: The lowest proportion of female awardees occurred in 2013 (14.3%) and the greatest proportion in 2022 (30.6%). Compared with the proportion of female faculty members in nominating programs for the respective year, there were significantly fewer female awardees in 2010 (18% female awardees vs 32% female faculty members; P = .02) and 2013 (14% female awardees vs 31% female faculty members; P = .01). There was a statistically significant increase in female awardees during the study period (P < .01). On logistic regression analysis, large program size (≥10 residents) (odds ratio [OR], 6.86; 95% CI, 2.71-23.1; P < .001) and medium program size (5-9 residents) (OR, 4.05; 95% CI, 1.60-13.7; P < .001) were associated with a greater proportion of female awardees compared with small program size (1-4 residents). There was no association between awardee gender and years since graduation. Conclusions: A gender disparity was present in the receipt of ARRO Educator Awards. Residency chiefs, program directors, and chairs should work to ensure that a diverse slate of faculty is considered annually for the ARRO Educator Award.

The Kidney Transplant: Maintaining Excellent Outcomes While Increasing Skills Acquisition.

OBJECTIVE/BACKGROUND: Kidney transplantation is a complex operation that incorporates multiple fundamental surgical techniques and is an excellent opportunity for surgical skill development during residency training. We hypothesized that increasing resident competency, measured as anastomosis time, could be demonstrated while maintaining high-quality surgical outcomes during the learning process. METHODS: We performed a retrospective cohort study of surgical resident involvement in kidney transplantation and recorded the anastomosis time. The study population comprised adult, single organ kidney transplants (n = 2052) at a large academic transplant center between 2006 and 2019. Descriptive statistics included frequencies, medians, and means. A mixed model of anastomosis time on number of procedures was fitted. Poisson models were fitted with outcomes of the number of patients with delayed graft function and number of patients that underwent reoperation postoperatively, with the exposure being number of kidney transplants performed by resident. RESULTS: Results from the mixed model suggest that as the number of times a resident performs the surgery increases, the time to conduct the operation decreases with statistical significance. The Poisson regression demonstrated no significant relationship between the operative volume of a resident and postoperative complications. CONCLUSION: This study demonstrated statistical evidence that with an increase in the number of renal transplantations performed by a surgical resident, anastomosis time decreased. It also demonstrated no significant relationship between number of kidney transplants performed by a resident and postoperative complications, suggesting that patient outcomes for this operation are not adversely affected by resident involvement.

Recognition and Management of the Long-term Effects of Cranial Radiation.

OPINION STATEMENT: Cranial radiation is ubiquitous in the treatment of primary malignant and benign brain tumors as well as brain metastases. Improvement in radiotherapy targeting and delivery has led to prolongation of survival outcomes. As long-term survivorship improves, we also focus on prevention of permanent side effects of radiation and mitigating the impact when they do occur. Such chronic treatment-related morbidity is a major concern with significant negative impact on patient's and caregiver's respective quality of life. The actual mechanisms responsible for radiation-induced brain injury remain incompletely understood. Multiple interventions have been introduced to potentially prevent, minimize, or reverse the cognitive deterioration. Hippocampal-sparing intensity modulated radiotherapy and memantine represent effective interventions to avoid damage to regions of adult neurogenesis. Radiation necrosis frequently develops in the high radiation dose region encompassing the tumor and surrounding normal tissue. The radiographic findings in addition to the clinical course of the patients' symptoms are taken into consideration to differentiate between tissue necrosis and tumor recurrence. Radiation-induced neuroendocrine dysfunction becomes more pronounced when the hypothalamo-pituitary (HP) axis is included in the radiation treatment field. Baseline and post-treatment evaluation of hormonal profile is warranted. Radiation-induced injury of the cataract and optic system can develop when these structures receive an amount of radiation that exceeds their tolerance. Special attention should always be paid to avoid irradiation of these sensitive structures, if possible, or minimize their dose to the lowest limit.

Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis.

OBJECTIVE: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes. METHODS: The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort. RESULTS: Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non-small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti-PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07-1.78, p = 0.012). CONCLUSIONS: Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

Upfront immunotherapy leads to lower brain metastasis velocity in patients undergoing stereotactic radiosurgery for brain metastases.

Background: While immunotherapy has been shown to improve survival and decrease neurologic death in patients with brain metastases, it remains unclear whether this improvement is due to prevention of new metastasis to the brain. Method: We performed a retrospective review of patients presenting with brain metastases simultaneously with the first diagnosis of metastatic disease and were treated with upfront immunotherapy as part of their treatment regimen and stereotactic radiosurgery (SRS) to the brain metastases. We compared this cohort with a historical control population (prior to the immunotherapy era) who were treated with pre-immunotherapy standard of care systemic therapy and with SRS to the brain metastases. Results: Median overall survival time was improved in the patients receiving upfront immunotherapy compared to the historical cohort (48 months vs 8.4 months, p=0.001). Median time to distant brain failure was statistically equivalent (p=0.3) between the upfront immunotherapy cohort and historical control cohort (10.3 vs 12.6 months). Brain metastasis velocity was lower in the upfront immunotherapy cohort (median 3.72 metastases per year) than in the historical controls (median 9.48 metastases per year, p=0.001). Cumulative incidence of neurologic death at one year was 12% in the upfront immunotherapy cohort and 28% in the historical control cohort (p=0.1). Conclusions: Upfront immunotherapy appears to improve overall survival and decrease BMV compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent immunotherapy with SRS.

Deviation from consensus contouring guidelines predicts inferior local control after spine stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To analyze the impact of target delineation on local control (LC) after stereotactic body radiotherapy (SBRT) for spine metastasis. MATERIALS AND METHODS: Patients with de novo metastasis of the spine treated with SBRT, excluding those with prostate or hematologic malignancies, were retrospectively reviewed. Deviations from consensus contouring guidelines included incomplete coverage of involved vertebral compartments, omission of adjacent compartments, or unnecessary circumferential coverage. Univariable and multivariable Cox proportional hazard analyses were performed using death as a competing risk. RESULTS: 283 patients with 360 discrete lesions were included with a median follow up of 14.6 months (range 1.2-131.3). The prescription dose was 24-27 Gy in 2-3 fractions for the majority of lesions. Median survival after SBRT was 18.3 months (95 % confidence interval [CI]: 14.8-22.8). The 1 and 2-year local control (LC) rates were 81.1 % (95 % CI: 75.5-85.6 %) and 70.6 % (95 % CI: 63.2-76.8 %), respectively. In total, 60 deviations (16.7 %) from consensus contouring guidelines were identified. Deviation from guidelines was associated with inferior LC (1-year LC 63.0 % vs 85.5 %, p < 0.001). Gastrointestinal primary, epidural extension, and paraspinal extension were all associated with inferior LC on univariable analyses. After adjusting for confounding factors, deviation from guidelines was the strongest predictor of inferior LC (HR 3.52, 95 % CI: 2.11-5.86, p < 0.001). Among guideline-compliant treatments, progressions were mainly in field (61 %) and/or epidural (49 %), while marginal (42 %) and/or epidural progressions (58 %) were most common for those with deviations. CONCLUSIONS: Adherence to consensus contouring guidelines for spine SBRT is associated with superior LC and fewer marginal misses.

Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum: A case series and systematic literature review.

BACKGROUND: Heterotopic pancreas (HP) is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract. While the majority of heterotopic pancreatic lesions are asymptomatic, many manifest severe clinical symptoms which require surgical or endoscopic intervention. Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature. The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease. AIM: To classify the common clinical manifestations of heterotopic pancreas. METHODS: A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018. Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location. Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated. These were compared to a systematic review of the literature utilizing PubMed and Embase searches for papers pertaining to heterotopic pancreas. Publications describing symptomatic presentation of HP were selected for review. Information including demographics, symptoms, presentation and treatment were compiled and analyzed. RESULTS: Twenty-nine patient were identified with HP at a single center, with six of these identified has having clinical symptoms. Clinical manifestations included, gastrointestinal bleeding, gastric ulceration with/without perforation, pancreatitis, and gastric outlet obstruction. Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients. Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients. The majority of patients presented with abdominal pain (67%) combined with one of the following clinical categories: (1) Dyspepsia, (n = 445, 48%); (2) Pancreatitis (n = 260, 28%); (3) Gastrointestinal bleeding (n = 80, 9%); and (4) Gastric outlet obstruction (n = 80, 9%). The majority of cases (n = 832, 90%) underwent surgical or endoscopic resection with 85% reporting resolution or improvement in their symptoms. CONCLUSION: Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract. Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation.

Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases.

BACKGROUND: Previous series have demonstrated CNS activity for immune checkpoint inhibitors, yet no prior data exists regarding whether this activity can improve outcomes of stereotactic radiosurgery. METHODS: In this single institution retrospective series, the clinical outcomes of 80 consecutive lung cancer patients treated with concurrent immune checkpoint inhibitors and stereotactic radiosurgery were compared to 235 in the historical control cohort in which patients were treated prior to immune checkpoint inhibition being standard upfront therapy. Overall survival was estimated using the Kaplan Meier method. Cumulative incidence of local progression was estimated using a competing risk model. RESULTS: Median overall survival time was improved in patients receiving upfront immunotherapy compared to the historical control group (40 months vs 8 months, p < 0.001). Factors affected overall survival include concurrent immunotherapy (HR 0.23, p < 0.0001) and KPS (HR 0.97, p = 0.0001). Cumulative incidence of local failure in the historical control group was 10% at 1 year, compared to 1.1% at 1 year in the concurrent immunotherapy group (p = 0.025). Factors affected local control included use of concurrent immunotherapy (HR 0.09, p = 0.012), and lowest margin dose delivered to a metastasis (HR 0.8, p = 0.0018). CONCLUSION: Local control and overall survival were both improved in patients receiving concurrent immune checkpoint inhibitors with radiosurgery compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent use of immunotherapy with SRS.

Improved outcomes with minimally invasive pancreaticoduodenectomy in patients with dilated pancreatic ducts: a prospective study.

BACKGROUND: Little is known about what factors predict better outcomes for patients who undergo minimally invasive pancreaticoduodenectomy (MIPD) versus open pancreaticoduodenectomy (OPD). We hypothesized that patients with dilated pancreatic ducts have improved postoperative outcomes with MIPD compared to OPD. METHODS: All patients undergoing pancreaticoduodenectomy were prospectively followed over a time period of 47 months, and perioperative and pathologic covariates and outcomes were compared. Ideal outcome after PD was defined as follows: (1) no complications, (2) postoperative length of stay < 7 days, and (3) negative (R0) margins on pathology. Patients with dilated pancreatic ducts (≥ 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with dilated ducts who underwent OPD and outcomes compared. Likewise, patients with non-dilated pancreatic ducts (< 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with non-dilated ducts who underwent OPD and outcomes were compared. RESULTS: 371 patients underwent PD-74 (19.9%) MIPD and 297 (80.1%) underwent OPD. Overall, patients who underwent MIPD had significantly less intraoperative blood loss. After 1:3 propensity score matching, patients with dilated pancreatic ducts who underwent MIPD (n = 45) had significantly lower overall complication and 90-day readmission rates compared to matched OPD patients (n = 135) with dilated ducts. Patients with dilated duct who underwent MIPD were more likely to have an ideal outcome than patients with OPD (29 vs 15%, p = 0.035). There were no significant differences in postoperative outcomes among propensity score-matched patients with non-dilated pancreatic ducts who underwent MIPD (n = 29) compared to matched patients undergoing OPD (n = 87) with non-dilated ducts. CONCLUSIONS: MIPD is safe with comparable perioperative outcomes to OPD. Patients with pancreatic ducts ≥ 3 mm appear to derive the most benefit from MIPD in terms of fewer complications, lower readmission rates, and higher likelihood of ideal outcome.

A Single-Institution Retrospective Study of Patients Treated With Laser-Interstitial Thermal Therapy for Radiation Necrosis of the Brain.

Object Laser-interstitial thermal therapy (LITT) has been proposed as an alternative treatment to surgery for radiation necrosis (RN) in patients treated with stereotactic radiosurgery (SRS) for brain metastases. The present study sought to retrospectively analyze LITT outcomes in patients with RN from SRS. Methods This was a single-institution retrospective study of 30 patients treated from 2011-2018 with pathologically-proven RN after SRS for brain metastases (n=28) or proximally treated extracranial lesions treated with external beam radiotherapy (n=2). Same-day biopsy was performed in all cases. Patients were prospectively followed with Functional Assessment of Cancer Therapy - Brain (FACT-Br), EuroQol-5 Dimension (EQ-5D), Hopkins Verbal Learning Test (HVLT) and clinical history and examination. Adjusted means, standard errors and tests comparing visits to pre-LITT were generated. Kaplan-Meier method was used to estimate time overall survival. Competing risk analysis was used to estimate cumulative incidence of LITT failure. Results In our patient population, median time from radiotherapy to LITT was 13.1 months. Median SRS dose and median LITT treatment target volume were 20 Gy (IQR 18-22) and 3.5 cc (IQR 2.2-4.6), respectively. Seventy-seven percent of our patients tapered off steroids within one month. There were only two instances of RN recurrence after LITT, with recurrence defined as recurrence of symptoms after initial improvement. These recurrences occurred at 1.9 and 3.4 months. The three-, six- and nine-month freedom from recurrence rates were 95.7%, 90.9%, and 90.9%. Median survival in our patient population with pathologically confirmed RN treated with LITT was 2.1 years. Regarding the quality of life questionnaires with which some patients were followed as part of different prospective studies, completion rates were 22/30 for FACT-Br, 16/30 for the EQ-5D and 8/30 for HVLT. Quality of life questionnaire results were overall stable from baseline. Mean FACT-Br scores were stable from baseline (17.9, 16.6, 21.4 and 22.8) to three months (18.8, 15.4, 18.4 and 23.4) (p=0.38, 0.53, 0.09 and 0.59). The mean EQ-5D Aggregate score was stable from baseline (7.1) to one month (7.6) (p=0.25). Mean HVLT-R Total Recall was stable from baseline (20.6) to three months (18.4) (p=0.09). There was a statistically significant decrease in mean Karnofsky Performance Scale (KPS) score from baseline (84) to three-month follow-up (75) (p=0.03). Conclusions LITT represents a safe and durably effective treatment option for RN in the brain. Results demonstrate a median survival of 2.1 years from LITT with only two recurrences, both within four months of treatment and salvageable. Patient-reported outcomes showed no severe declines after LITT. Quality of life questionnaires demonstrated stable well-being and functionality from baseline. LITT should be considered for definitive treatment of RN, especially in cases where patients have significant side effects from standards medical therapies such as steroids or if steroids are minimally effective.

Less is more in the difficult gallbladder: recent evolution of subtotal cholecystectomy in a single HPB unit.

INTRODUCTION: Subtotal cholecystectomy (SC) is a technique to manage the difficult gallbladder and avoid hazardous dissection and biliary injury. Until recently it was used infrequently. However, because of reduced exposure to open total cholecystectomy in resident training, we recently adopted subtotal cholecystectomy as the bail-out procedure of choice for resident teaching. This study reports our experience and outcomes with subtotal cholecystectomy in the years immediately preceding adoption and since adoption. METHODS: A retrospective analysis was conducted of patients undergoing SC from July 2010 to June 2019. Outcomes, including bile leak, reoperation and need for additional procedures, were analyzed. Complications were graded by the Modified Accordion Grading Scale (MAGS). RESULTS: 1571 cholecystectomies were performed of which 71 were SC. Subtotal cholecystectomy patients had several indicators of difficulty including prior attempted cholecystectomy and previous cholecystostomy tube insertion. The most common indication for SC was marked inflammation in the hepatocystic triangle (51%). As our experience increased, fewer patients required open conversion to accomplish SC and SC was completed laparoscopically, usually subtotal fenestrating cholecystectomy (SFC). Most patients (85%) had a drain placed and 28% were discharged with a drain. The highest MAGS complication observed was grade 3 (11 patients, 15%). Six patients had a bile leak from the cystic duct resolved by ERCP. At mean follow-up of about 1 year no patient returned with recurrent symptoms. CONCLUSIONS: Subtotal fenestrating cholecystectomy is a useful technique to avoid biliary injury in the difficult gallbladder and can be performed with very satisfactory rates of bile fistula, ERCP, and reoperation.

Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity.

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose-response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones.

Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery.

PURPOSE: Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS). METHODS: From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF). Eighty-seven patients were treated within the immunotherapy era. Brain metastasis velocity (BMV) was calculated for each patient. In general, the institutional philosophy for use of salvage SRS vs whole brain radiotherapy (WBRT) was to postpone the use of WBRT for as long as possible and to treat with salvage SRS when feasible. No further treatment was reserved for patients with poor life expectancy and who were not expected to benefit from salvage treatment. RESULTS: Two hundred and eighty-five patients were treated with repeat SRS, 91 patients were treated with salvage WBRT, and 64 patients received no salvage radiation therapy. One-year cumulative incidence of neurologic death after salvage SRS vs WBRT was 15% vs 23% for the low- (p = 0.06), 30% vs 37% for the intermediate- (p < 0.01), and 31% vs 48% (p < 0.01) for the high-BMV group. Salvage WBRT was associated with increased incidence of neurologic death on multivariate analysis (HR 1.64, 95% CI 1.13-2.39, p = 0.01) when compared to repeat SRS. One-year cumulative incidence of neurologic death for patients treated within the immunotherapy era was 9%, 38%, and 38% for low-, intermediate-, and high-BMV groups, respectively (p = 0.01). CONCLUSION: Intermediate and high risk BMV groups are predictive of neurologic death. The association between BMV and neurologic death remains strong for patients treated within the immunotherapy era.

Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries.

BACKGROUND: The effect of immunotherapy on brain metastasis patients remains incompletely understood. Our goal was to evaluate its effect on survival, neurologic death, and patterns of failure after stereotactic radiosurgery (SRS) without prior whole-brain radiation therapy (WBRT) in patients with lung and melanoma primaries metastatic to the brain. METHODS: We performed a retrospective analysis of 271 consecutive lung or melanoma patients treated with upfront SRS for brain metastases between 2013 and 2018. Of these patients, 101 (37%) received immunotherapy and 170 (63%) did not. Forty-three percent were treated with nivolumab. Thirty-seven percent were treated with pembrolizumab. Fifteen percent were treated with ipilimumab. One percent were treated with a combination of nivolumab and ipilimumab. One percent were treated with atezolizumab. Three percent were treated with another immunotherapy regimen. Survival was estimated by the Kaplan-Meier method and cumulative incidences of neurologic death, and local and distant brain failure were estimated using death as a competing risk. RESULTS: The median overall survival (OS) of patients treated with immunotherapy vs without was 15.9 (95% CI: 13.3 to 24.8) vs 6.1 (95% CI: 5.1 to 8.8) months (P < .01). The 1-year cumulative incidence of neurologic death was 9% in patients treated with immunotherapy vs 23% in those treated without (P = .01), while nonneurologic death was not significantly different (29% vs 41%, P = .51). Median brain metastasis velocity (BMV) did not differ between groups, and rates of salvage SRS and WBRT were similar. CONCLUSIONS: The use of immunotherapy in patients with lung cancer or melanoma metastatic to the brain treated with SRS is associated with improved OS and decreased incidence of neurologic death.

Simple and Rapid Creation of Customized 3-dimensional Printed Bolus Using iPhone X True Depth Camera.

PURPOSE: Three-dimensional printing has produced customized bolus during radiation therapy for superficial tumors along irregular skin surfaces. In comparison, traditional bolus materials are often difficult to manipulate for a proper fit. Current 3-dimensional printed boluses are made from either preexisting computed tomography scans or complex surface scanning methods. Herein, we introduce an inexpensive, convenient approach to generate a 3-dimensional printed bolus from surface scanning technology available in common smartphones. METHODS AND MATERIALS: A three-dimensional printed bolus was designed using surface scans from iPhone X true depth cameras and a low-cost 3-dimensional printer. The percentage density infill was adjusted to achieve tissue equivalence. To evaluate the clinical feasibility, fit against the skin surface and radiation dose distribution were compared with those of the traditional bolus. RESULTS: We fabricated a customized 3-dimensional printed bolus for different areas of the face using an iPhone X camera and inexpensive commercially available 3-dimensional printer. When printed at 100% density, the bolus material approximated soft tissue/water and provided an equivalent dose distribution to that found with standard bolus materials on direct comparison. The bolus material is inexpensive and produces an ideal fit with the scanned anatomy. CONCLUSIONS: We present a simplified method of highly customized bolus production that requires minimal experience with computer modeling programs and can be accomplished with an iPhone true depth camera.