ST6GAL1 is associated with poor response to chemoradiation in rectal cancer.

INTRODUCTION: Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues. METHODS: Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured. RESULTS: Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01). CONCLUSION: ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.

4,300 steps per day prior to surgery are associated with improved outcomes after pancreatectomy.

BACKGROUND: Decreased preoperative physical fitness and low physical activity have been associated with preoperative functional reserve and surgical complications. We sought to evaluate daily step count as a measure of physical activity and its relationship with post-pancreatectomy outcomes. METHODS: Patients undergoing pancreatectomy were given a remote telemonitoring device to measure their preoperative levels of physical activity. Patient activity, demographics, and perioperative outcomes were collected and compared in univariate and multivariate logistic regression analysis. RESULTS: 73 patients were included. 45 (61.6%) patients developed complications, with 17 (23.3%) of those patients developing severe complications. These patients walked 3437.8 (SD 1976.7) average daily steps, compared to 5918.8 (SD 2851.1) in patients without severe complications (p < 0.001). In logistic regression analysis, patients who walked less than 4274.5 steps had significantly higher odds of severe complications (OR = 7.5 (CI 2.1, 26.8), p = 0.002). CONCLUSION: Average daily steps below 4274.5 before surgery are associated with severe complications after pancreatectomy. Preoperative physical activity levels may represent a modifiable target for prehabilitation protocols.

Biomechanical comparison of subsidence performance among three modern porous lateral cage designs.

BACKGROUND: Cage subsidence remains a major complication after spinal surgery. The goal of this study was to compare the subsidence performance of three modern porous cage designs. METHODS: Three porous cages were evaluated: a porous titanium cage, a porous polyetheretherketone cage and a truss titanium cage. Mechanical testing was performed for each cage per the American Society for Testing and Materials F2077 and F2267 standards to evaluate cage stiffness and block stiffness, and per a novel clinically relevant dynamic subsidence testing method simulating cyclic spine loading during 3-months postoperatively to evaluate the subsidence displacement. FINDINGS: The porous polyetheretherketone cage demonstrated the lowest cage stiffness (21.0 ± 1.1 kN/mm), less than half of both titanium cages (truss titanium cage, 49.1 kN/mm; porous titanium cage, 43.6 kN/mm). The block stiffness was greatest for the porous titanium cage (2867.7 ± 105.3 N/mm), followed by the porous polyetheretherketone (2563.4 ± 72.9 N/mm) and truss titanium cages (2213.7 ± 21.8 N/mm). The dynamic subsidence displacement was greatest for the truss titanium cage, which was 1.5 and 2.5 times the subsidence displacement as the porous polyetheretherketone and porous titanium cages respectively. INTERPRETATIONS: Specific porous cage design plays a crucial role in the cage subsidence performance, to a greater degree than the selection of cage materials. A porous titanium cage with body lattice and microporous endplates significantly outperformed a truss titanium cage with a similar cage stiffness in subsidence performance, and a porous polyetheretherketone cage with half of its stiffness.

Increased Morbidity and Mortality After Hepatectomy for Colorectal Liver Metastases in Frail Patients is Largely Driven by Worse Outcomes After Minor Hepatectomy: It's Not "Just a Wedge".

BACKGROUND: Frailty is associated with postoperative mortality, but its significance after hepatectomy for colorectal liver metastases (CRLM) is poorly defined. This study evaluated the impact of frailty after hepatectomy for CRLM. METHODS: The study identified 8477 patients in National Surgical Quality Improvement Program databases from 2014 to 2019 and stratified them by frailty score using the risk analysis index as very frail (>90th percentile), frail (75th-90th percentile), or non-frail (< 75th percentile). Multivariate regression models determined the impact of frailty on perioperative outcomes, including by the extent of hepatectomy. RESULTS: The procedures performed were 2752 major hepatectomies (left hepatectomy, right hepatectomy, trisectionectomy) and 5725 minor hepatectomies (≤2 segments) for 870 (10.3%) very frail, 1680 (19.8%) frail, and 5927 (69.9%) non-frail patients. Postoperatively, the very frail and frail patients experienced more complications (very frail [41.8%], frail [35.1%], non-frail [31.0%]), which resulted in a longer hospital stay (very-frail [5.7 days], frail [5.8 days], non-frail [5.1 days]), a higher 30-day mortality (very-frail [2.2%], frail [1.3%], non-frail [0.5%]), and more discharges to a facility (very frail [6.8%], frail [3.7%], non-frail [2.6%]) (p < 0.05) although they underwent similarly extensive (major vs. minor) hepatectomies. In the multivariate analysis, frailty was independently associated with complications (very-frail [odds ratio {OR}, 1.70], frail [OR, 1.25]) and 30-day mortality (very-frail [OR, 4.24], frail [OR, 2.41]) (p < 0.05). After minor hepatectomy, the very frail and frail patients had significantly higher rates of complications and 30-day mortality than the non-frail patients, and in the multivariate analysis, frailty was independently associated with complications (very frail [OR, 1.97], frail [OR, 1.27]) and 30-day mortality (very frail [OR, 6.76], frail [OR, 3.47]) (p < 0.05) after minor hepatectomy. CONCLUSIONS: Frailty predicted significantly poorer outcomes after hepatectomy for CRLM, even after only a minor hepatectomy.

Inhibition of DNA-PK may improve response to neoadjuvant chemoradiotherapy in rectal cancer.

Treatment of locally advanced rectal cancer includes chemoradiation and surgery, but patient response to treatment is variable. Patients who have a complete response have improved outcomes; therefore, there is a critical need to identify mechanisms of resistance to circumvent them. DNA-PK is involved in the repair of DNA double-strand breaks caused by radiation, which we found to be increased in rectal cancer after treatment. We hypothesized that inhibiting this complex with a DNA-PK inhibitor, Peposertib (M3814), would improve treatment response. We assessed pDNA-PK in a rectal cancer cell line and mouse model utilizing western blotting, viability assays, γH2AX staining, and treatment response. The three treatment groups were: standard of care (SOC) (5-fluorouracil (5FU) with radiation), M3814 with radiation, and M3814 with SOC. SOC treatment of rectal cancer cells increased pDNA-PK protein and increased γH2AX foci, but this was abrogated by the addition of M3814. Mice with CT26 tumors treated with M3814 with SOC did not differ in average tumor size but individual tumor response varied. The clinical complete response rate improved significantly with the addition of M3814 but pathological complete response did not. We investigated alterations in DNA repair and found that Kap1 and pATM are increased after M3814 addition suggesting this may mediate resistance. When the DNA-PK inhibitor, M3814, is combined with SOC treatment, response improved in some rectal cancer models but an increase in other repair mechanisms likely diminishes the effect. A clinical trial is ongoing to further explore the role of DNA-PK inhibition in rectal cancer treatment.

Sialyltransferase ST6GAL-1 mediates resistance to chemoradiation in rectal cancer.

Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance.

Subsidence and fusion performance of a 3D-printed porous interbody cage with stress-optimized body lattice and microporous endplates - a comprehensive mechanical and biological analysis.

BACKGROUND CONTEXT: Cage subsidence remains a serious complication after spinal fusion surgery. Novel porous designs in the cage body or endplate offer attractive options to improve subsidence and osseointegration performance. PURPOSE: To elucidate the relative contribution of a porous design in each of the two major domains (body and endplates) to cage stiffness and subsidence performance, using standardized mechanical testing methods, and to analyze the fusion progression via an established ovine interbody fusion model to support the mechanical testing findings. STUDY DESIGN/SETTING: A comparative preclinical study using standardized mechanical testing and established animal model. METHODS: To isolate the subsidence performance contributed by each porous cage design feature, namely the stress-optimized body lattice (vs. a solid body) and microporous endplates (vs. smooth endplates), four groups of cages (two-by-two combination of these two features) were tested in: (1) static axial compression of the cage (per ASTM F2077) and (2) static subsidence (per ASTM F2267). To evaluate the progression of fusion, titanium cages were created with a microporous endplate and internal lattice architecture analogous to commercial implants used in subsidence testing and implanted in an endplate-sparing, ovine intervertebral body fusion model. RESULTS: The cage stiffness was reduced by 16.7% by the porous body lattice, and by 16.6% by the microporous endplates. The porous titanium cage with both porous features showed the lowest stiffness with a value of 40.4±0.3 kN/mm (Mean±SEM) and a block stiffness of 1976.8±27.4 N/mm for subsidence. The body lattice showed no significant impact on the block stiffness (1.4% reduction), while the microporous endplates decreased the block stiffness significantly by 24.9% (p<.0001). All segments implanted with porous titanium cages were deemed rigidly fused by manual palpation, except one at 12 weeks, consistent with robotic ROM testing and radiographic and histologic observations. A reduction in ROM was noted from 12 to 26 weeks (4.1±1.6° to 2.2±1.4° in lateral bending, p<.05; 2.1±0.6° to 1.5±0.3° in axial rotation, p<.05); and 3.3±1.6° to 1.9±1.2° in flexion extension, p=.07). Bone in the available void improved with time in the central aperture (54±35% to 83±13%, p<.05) and porous cage structure (19±26% to 37±21%, p=.15). CONCLUSIONS: Body lattice and microporous endplates features can effectively reduce the cage stiffness, therefore reducing the risk of stress shielding and promoting early fusion. While body lattice showed no impact on block stiffness and the microporous endplates reduced the block stiffness, a titanium cage with microporous endplates and internal lattice supported bone ingrowth and segmental mechanical stability as early as 12 weeks in ovine interbody fusion. CLINICAL SIGNIFICANCE: Porous titanium cage architecture can offer an attractive solution to increase the available space for bone ingrowth and bridging to support successful spinal fusion while mitigating risks of increased subsidence.

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.

Yield of Surveillance Colonoscopy in Older Adults with a History of Polyps: A Systematic Review and Meta-Analysis.

BACKGROUND: The benefit of surveillance colonoscopy in older adults is not well described. AIMS: To quantify the detection of colorectal cancer (CRC) and advanced polyps during surveillance colonoscopy in older adults with a history of colon polyps. METHODS: We conducted a systematic review (MEDLINE, Cochrane Library, Web of Science, and Embase) for all published studies through May 2020 in adults age > 70 undergoing surveillance colonoscopy. The main outcome was CRC and advanced polyps detection. We performed meta-analysis to pool results by age (>70 vs. 50-70). RESULTS: The search identified 6239 studies, of which 569 underwent full-text review and 64 data abstraction, of which 19 were included. The risk of detecting CRC (N = 11) was higher in those >70 compared to 50-70 (risk ratio 1.5 (95% CI 1.1-2.2); risk difference 0.8% (95% CI -0.2%-1.8%)). Similarly, the risk of detecting advanced polyps (N = 8) was higher in those >70 compared to 50-70 (risk ratio 1.3 (95% CI 1.2-1.3), risk difference 2.7% (95% CI 1.3%-4.0%)). Most studies did not stratify results by baseline polyp risk. CONCLUSIONS: The detection of CRC and advanced polyps during surveillance colonoscopy in older individuals was higher than in younger controls; however, the absolute risk increase for both was small. These differences must be weighed against competing medical problems and limited life expectancy in older adults when making decisions about surveillance colonoscopy. More primary data on the risks of CRC and advanced polyps accounting for number of past colonoscopies, prior polyp risk, and duration of time since last polyp are needed.

18 F-FDG positron emission tomography-computed tomography has a low positive predictive value for detecting occult recurrence in asymptomatic patients with high-risk Stages IIB, IIC, and IIIA melanoma.

BACKGROUND AND OBJECTIVES: High recurrence rates of Stages II and IIIA melanoma make close follow-up essential, especially with new adjuvant therapies for metastatic disease. However, there are currently no consensus guidelines for routine imaging for Stages IIB, IIC, and IIIA melanoma. The study's aim is to determine the utility of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting asymptomatic recurrence of melanoma after primary surgical resection. METHODS: This retrospective cohort study included 158 patients with the American Joint Committee on Cancer 8th edition Stages IIB, IIC, or IIIA cutaneous melanoma who underwent an 18 F-FDG PET/CT from 2010 to 2020. We retrospectively analyzed clinical data after a median follow-up time of 39 months. RESULTS: We calculated a positive predictive value (PPV) of 32% (95% confidence interval: 11%-53%) for 154 routine PET/CTs, including six true positives and 13 false positives (FPs). PPV was 33% for Stage IIB, 50% for Stage IIC, and 14% for Stage IIIA. FPs were mostly benign or inflammatory foci (75%), and some other malignancies were found (21%). CONCLUSIONS: This cohort of patients imaged for high-risk melanoma demonstrated a high FP rate and low PPV. These findings suggest that routine surveillance with 18 F-FDG PET/CT may not be indicated for monitoring recurrence in this population.

Enhanced recovery pathway after open pancreaticoduodenectomy reduces postoperative length of hospital stay without reducing composite length of stay.

BACKGROUND/PURPOSE: There is no data regarding the impact of enhanced recovery pathways (ERP) on composite length of stay (CLOS) after procedures with increased risk of morbidity and mortality, such as pancreaticoduodenectomy. METHODS: Patients undergoing open pancreaticoduodenectomy before and after implementation of ERP were prospectively followed for 90 days after surgery and complications were severity graded using the Modified Accordion Grading System. A retrospective analysis of patient outcomes were compared before and after instituting ERP. 1:1 propensity score matching was used to compare ERP patient outcomes to those of matched pre-ERP patients. CLOS is defined as postoperative length of hospital stay (PLOS) plus readmission length of hospital stay within 90 days after surgery. RESULTS: 494 patients underwent open pancreaticoduodenectomy - 359 pre-ERP and 135 ERP. In a 1:1 propensity-score-matched analysis of 110 matched pairs, ERP patients had significantly decreased superficial surgical site infections (5.5% vs 15.5% p = 0.015) and significantly increased rates of urinary retention (29.1% vs 7.3% p < 0.0001) compared to matched pre-ERP patients. However, overall complication rate and 90-day readmission rate were not significantly different between matched groups. Propensity score-matched ERP patients had significantly decreased PLOS (7 days vs 8 days p = 0.046) compared to matched pre-ERP patients, but CLOS was not significantly different (9 days vs 9.5 days p = 0.615). CONCLUSION: ERP may reduce PLOS but might not impact the total postoperative time spent in the hospital (i.e. CLOS) within 90 days after pancreaticoduodenectomy.

Inability to manage non-severe complications on an outpatient basis increases non-white patient readmission rates after pancreaticoduodenectomy: A large metropolitan tertiary care center experience.

BACKGROUND: Pancreaticoduodenectomy (PD) has a high rate of readmission, and racial disparities in care could be an important contributor. METHODS: Patients undergoing PD were prospectively followed, and their complications graded using the Modified Accordion Grading System (MAGS). Patient factors and perioperative outcomes for patients with and without postoperative readmission were compared in univariate and multivariate analysis by severity. RESULTS: 837 patients underwent PD, the overall 90-day readmission rate was 27.5%. Non-white race was independently associated with readmission (OR 1.83, p = 0.007). 51.3% of readmissions were for non-severe complications (MAGS <3). Non-white race was independently associated with MAGS non-severe readmission (OR 2.13, p = 0.006), but not MAGS severe readmission. CONCLUSIONS: Non-white patients are more likely to be readmitted, particularly for non-severe complications. Follow up protocols should be tailored to address race disparities in the rates of readmission as readmission for less severe complications could potentially be avoidable.

Predicting Outcomes in Patients Undergoing Pancreatectomy Using Wearable Technology and Machine Learning: Prospective Cohort Study.

BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related deaths, and although pancreatectomy is currently the only curative treatment, it is associated with significant morbidity. OBJECTIVE: The objective of this study was to evaluate the utility of wearable telemonitoring technologies to predict treatment outcomes using patient activity metrics and machine learning. METHODS: In this prospective, single-center, single-cohort study, patients scheduled for pancreatectomy were provided with a wearable telemonitoring device to be worn prior to surgery. Patient clinical data were collected and all patients were evaluated using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator (ACS-NSQIP SRC). Machine learning models were developed to predict whether patients would have a textbook outcome and compared with the ACS-NSQIP SRC using area under the receiver operating characteristic (AUROC) curves. RESULTS: Between February 2019 and February 2020, 48 patients completed the study. Patient activity metrics were collected over an average of 27.8 days before surgery. Patients took an average of 4162.1 (SD 4052.6) steps per day and had an average heart rate of 75.6 (SD 14.8) beats per minute. Twenty-eight (58%) patients had a textbook outcome after pancreatectomy. The group of 20 (42%) patients who did not have a textbook outcome included 14 patients with severe complications and 11 patients requiring readmission. The ACS-NSQIP SRC had an AUROC curve of 0.6333 to predict failure to achieve a textbook outcome, while our model combining patient clinical characteristics and patient activity data achieved the highest performance with an AUROC curve of 0.7875. CONCLUSIONS: Machine learning models outperformed ACS-NSQIP SRC estimates in predicting textbook outcomes after pancreatectomy. The highest performance was observed when machine learning models incorporated patient clinical characteristics and activity metrics.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

Re-defining a high volume center for pancreaticoduodenectomy.

BACKGROUND: The purpose of this study was to re-evaluate the previously utilized definitions of high volume center for pancreaticoduodenectomy to determine/establish an objective, evidence based threshold of hospital volume associated with improvement in perioperative mortality. METHODS: Patients who underwent pancreaticoduodenectomy were identified using the National Cancer Database from 2004 to 2015. The relationship between hospital volume and 90-day mortality was assessed using a logistic regression model. Receiver Operator Characteristic analysis was performed and Youden's statistic was utilized to calculate the optimal cut offs. RESULTS: 42,402 patients underwent elective Pancreaticoduodenectomy at 1238 unique hospitals. A logistic regression was performed which showed a significant inverse linear association between institutional volume and overall 90 day mortality. The maximum improvement in 90 day mortality is seen if the average annual hospital volume was greater than 9 (OR = 0.647 (0.595-0.702), p < 0.0001). When analysis is limited to hospitals that performed >9 cases per year, the maximum improvement in 90 day mortality was noticed at 36 cases per year (OR = 0.458 (0.399-0.525), p < 0.0001). CONCLUSIONS: Based on our results, we recommend defining low, medium, and high volume centers for pancreaticoduodenectomy as hospitals with average annual volume less than 9, 9 to 35, and more than 35 cases per year, respectively.

Thunderbeat™ Integrated Bipolar and Ultrasonic Forceps in the Whipple Procedure: A Prospective Randomized Trial.

Thunderbeat™ is a device that uses both ultrasonic and advanced bipolar energies to achieve hemostasis. It has been evaluated in a variety of clinical contexts, but no literature exists regarding its application to pancreatic surgery. Using a prospective, randomized controlled trial, we evaluated its safety and efficacy in the Whipple procedure. Thirty-two participants were enrolled in the study. The Thunderbeat™ device during the Whipple procedure showed similar safety profile compared to standard of care.

The safety of hepatectomy after transarterial radioembolization: Single institution experience and review of the literature.

BACKGROUND AND OBJECTIVES: The liver is a frequent site of malignancy, both primary and metastatic. The treatment goal of patients with liver cancer may include transarterial radioembolization (TARE). There are limited reports on the safety of hepatectomy following TARE. Our study's purpose is to review patients who have received TARE followed by hepatectomy. METHODS: A retrospective study was performed on patients diagnosed with any liver cancer from 2013 to 2019 who underwent TARE followed by hepatectomy. Postoperative complications were prospectively collected. Descriptive statistics and the Kaplan-Meier test were used to assess survival outcomes. RESULTS: Twelve patients were treated with a TARE followed by a hepatectomy (nine with ≥4 segments resected). Diagnoses included: six HCC, four cholangiocarcinoma, one metastatic neuroendocrine tumor, and one metastatic colorectal cancer. There were no 90-day post-hepatectomy mortalities and the overall morbidity was 66% (16% severe ≥MAGS 3). Hepatectomy-specific complications after hepatectomy included two (16%) bile leaks and no post-hepatectomy liver failures. The median recurrence free survival was 26 months. Overall survival at 1-year was 78% and at 3 years was 47%. CONCLUSIONS: Our results support the safety of hepatectomy in select patients after TARE. Additional comparison to patients who receive hepatectomy as a first-line treatment for liver cancers should be investigated.

Tumor-insular Complex in Neoadjuvant Treated Pancreatic Ductal Adenocarcinoma Is Associated With Higher Residual Tumor.

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a vital role in treatment response, and therefore, patient survival. We and others have observed an intimate association of neoplastic ductal cells with non-neoplastic islet cells, recapitulating the ductoinsular complex. We define this phenomenon as tumor-insular complex (TIC). Herein, we describe the clinicopathologic characteristics of TIC in neoadjuvant treated PDAC cases for the first time. We retrospectively reviewed the pathology of 105 cases of neoadjuvant treated PDAC resected at our institution. TIC was noted in 35 cases (33.3%), the mean tumor bed size was 2.7±1.0 cm, mean percentage of residual tumor 40±28% and mean Residual Tumor Index (RTI) (an index previously established as a prognostic parameter by our group) was 1.1±1.0. TIC was significantly associated with perineural invasion (P=0.001), higher tumor bed size (P=0.007), percentage of residual tumor (P=0.009), RTI (P=0.001), ypT stage (P=0.045), and poor treatment response, grouped by a previously established criteria (P=0.010). Using our prior binary reported prognostic cutoff for RTI of ≤0.35 and >0.35, TIC was associated with a RTI >0.35 (P=0.002). Moreover, patients who did not receive neoadjuvant radiation were associated with a higher frequency of TIC (P=0.003). In this cohort, RTI but not TIC was also shown to be a significant independent prognosticator for recurrence-free survival and overall survival on multivariate analysis. In conclusion, TIC is significantly associated with a more aggressive neoplasm which shows a poor treatment response. Further studies will be needed to better understand the tumor biology of TICs.

Extending Enhanced Recovery after Surgery Protocols to the Post-Discharge Setting: A Phone Call Intervention to Support Patients after Expedited Discharge after Pancreaticoduodenectomy.

The goal of this pilot study was to track patient outcomes after an expedited discharge after enhanced recovery after surgery (ERAS) pathway for pancreaticoduodenectomy (PD). A quantitative content analysis approach was used. All PD patients in a single academic medical center between February 2017 and June 2018 were called twice by specialized physician extenders after discharge. A semi-structured interview approach was used to identify patient's symptoms or concerns, proactively educate them, and provide outpatient management when indicated. A detailed narrative of the conversation was documented. Ninety patients (mean age 66.3; 58.1% males) were included in the study. Of all, 88.9 per cent of the patients received follow-up phone calls in accordance with our PD ERAS protocol. Among the 80 patients called, 71 (88.8%) reported at least one symptom, issue, or self-care need. The most common issues involved bowel movements and nutrition. A total of 147 interventions were performed to address patient needs including medication management, local care coordination, and outpatient referral to a healthcare provider. The intervention led to the identification of 15 patients for earlier evaluation. This identification was associated with the total number of reported symptoms (X² = 15.6, P = 0.004). Most patients require additional care after discharge after traditional ERAS pathways. ERAS transitional care protocols uncovered an unmet need for additional patient support after PD.

Composite Length of Stay, An Outcome Measure of Postoperative and Readmission Length of Stays in Pancreatoduodenectomy.

PURPOSE: Postoperative length of stay (PLOS) and readmission rate are pancreatoduodenectomy (PD) outcome measures, which are reported individually but may be interrelated. The purpose of this study was to evaluate how well a composite length of stay measure (CLOS) that included PLOS and readmission length of stay describes outcomes. To do so, we evaluated how well CLOS correlated to postoperative complications absolutely and compared to PLOS. METHODS: A total of 668 PDs performed between 2011 and 2018 were evaluated. CLOS was calculated from PLOS and readmission length of stay. Complication severity was judged by the Modified Accordion Grading System (MAGS). Multinomial logistical regression models (MLRM) were used to investigate the relationship between either PLOS or CLOS and complications. Multilevel and pairwise area under curves (AUC) using SAS macro %MultAUC were provided for both models. RESULTS: A total of 432 of 668 patients (65%) developed complications. One hundred seventy-seven patients (27%) were readmitted. Mean PLOS was 10.2 days (7.1 SD) and mean CLOS was 12.3 days (10.1 SD). PLOS and CLOS both were correlated linearly to MAGS grade. Spearman correlation coefficient for CLOS vs. MAGS of 0.68 was higher than that of 0.49 for PLOS vs. MAGS. Multilevel AUC from MLRM using PLOS was 0.66, but multilevel AUC from MLRM using CLOS was 0.71. DISCUSSION: CLOS provides an accurate estimate of hospital day utilization per patient for PD, reflecting not only the basal hospital recovery time for PD but the added time needed because of readmissions due to complications. It is tightly correlated to number and severity of postoperative complications.