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Despite advances in imaging and biopsy techniques, the management of thyroid nodules often remains a diagnostic and clinical challenge. In particular, patients with cytologically indeterminate nodules often undergo diagnostic thyroidectomy although only a minority of patients are found to have thyroid malignancy on final pathology. More recently, several molecular testing platforms have been developed to improve the stratification of cancer risk for patients with cytologically indeterminate thyroid nodules. Based on numerous studies demonstrating its accuracy, molecular testing has been incorporated as an important diagnostic adjunct in the management of indeterminate thyroid nodules in the National Comprehensive Cancer Network Guidelines as well as in the American Thyroid Association (ATA) and American Association of Endocrine Surgeons (AAES) guidelines. This overview describes the currently available molecular testing platforms and highlights the published data to date on the clinical validity and utility of molecular testing in the contemporary management of thyroid nodules.

Obesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients.Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD.The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P 0.001).Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). The US HIPEC collaborative database (2000–2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. A total of 174 patients were identified. Median PCI was 16 (3–39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59–4.74; MOR-2+ : HR 0.77, 95% CI 0.22–2.69). MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

Adoptive cell therapy (ACT) using tumor-specific tumor-infiltrating lymphocytes (TILs) has demonstrated success in patients where tumor-antigen specific TILs can be harvested from the tumor, expanded, and re-infused in combination with a preparatory regimen and IL2. One major issue for non-immunogenic tumors has been that the isolated TILs lack tumor specificity and thus possess limited in vivo therapeutic function. An oncolytic virus (OV) mediates an immunogenic cell death for cancer cells, leading to elicitation and dramatic enhancement of tumor-specific TILs. We hypothesized that the tumor-specific TILs elicited and promoted by an OV would be a great source for ACT for solid cancer. In this study, we show that a local injection of oncolytic poxvirus in MC38 tumor with low immunogenicity in C57BL/6 mice, led to elicitation and accumulation of tumor-specific TILs in the tumor tissue. Our analyses indicated that IL2-armed OV-elicited TILs contain lower quantities of exhausted PD-1hiTim-3+ CD8+ T cells and regulatory T cells. The isolated TILs from IL2-expressing OV-treated tumor tissue retained high tumor specificity after expansion ex vivo. These TILs resulted in significant tumor regression and improved survival after adoptive transfer in mice with established MC38 tumor. Our study showcases the feasibility of using an OV to induce tumor-reactive TILs that can be expanded for ACT.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan–Meier and Cox estimates were used to assess survival. In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction.Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations.A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P .001; colorectal: r = 0.729; P .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071).In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood.Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula).Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p 0.01), higher complication rate (90% vs 59%; p 0.01), higher reoperation rate (41% vs 9%; p 0.01), more 30-day readmissions (59% vs 22%; p 0.01), greater 30-day mortality (9% vs 1%; p 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p 0.01).Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

We demonstrate a frequency-tunable THz polariton source based on stimulated polariton scattering (SPS) in MgO:LiNbO3. The system produces THz emission using an intracavity shallow-bounce configuration. Continuously tunable THz emission across the frequency range of 1.05–2.89 THz is demonstrated, and a maximum average THz power of 67.5 μ W is detected at 1.34 THz, when pumped with 15.1 W from a continuous-wave laser diode at 880 nm. In contrast to conventional linear configurations, this shallow-bounce configuration offers enhanced THz output power across the systems' entire THz frequency-tuning range, especially at higher frequencies. This is achieved through careful consideration of the THz generation volume, and locating it as close as possible to the emitting surface of the polariton-active crystal, thereby minimizing the deleterious effect of absorption within the SPS crystal. In addition to experimental data, the degree of THz enhancement offered using this configuration, in contrast to a linear configuration is also investigated mathematically.

The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

Laguerre-Gaussian (LG) modes [1] , [2] carry an annual spatial profile and a nonzero orbital angular momentum (OAM) owing to their on-axis phase singularity, and they offer us many applications, such as optical trapping and manipulation, laser nano/micro fabrication, super-resolution microscope, and optical communication.

BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on thesurvivalof patients withappendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.MethodsThe US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsOf the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p

Routine lymphadenectomy (LND) for resectable hepatocellular carcinoma (HCC) remains controversial. We evaluated national LND trends to identify pre-operative factors associated with node-positive disease to determine which patients might benefit from LND.We identified HCC patients in the National Cancer Database (NCDB) treated with surgical resection between 2004 and 2015. Demographic, operative, pathologic, and survival data were compared. Multivariable regression was performed to determine preoperative predictors of pathologic nodal disease.Of 8095 total resected patients, 1442 (17.8%) underwent hepatectomy with LND. Patients who received LND had higher preoperative clinical T (T3-T4: 20.0% vs 12.1%, p 0.001) and N (N1: 3.3% vs 0.6%, p 0.001) stages. The strongest independent predictor of pathologic nodal disease was clinical N stage (OR 106.54, CI 44.10-257.42). Survival was highest in patients whose surgeons omitted LND or were found with LND to be node-negative on final pathology (p 0.001). Clinical node positivity had high negative predictive value (97.9%) but moderate positive predictive value (56.3%) in estimating pathologic nodal status.Defining preoperative clinical nodal status is imperative in HCC patients. Clinical node positivity was the strongest predictor of pathologic nodal disease and its associated worse prognosis. LND can be considered selectively in clinically node-positive patients.

The advent of high-throughput multi-omics technologies has underpinned the expansion in lung microbiome research, increasing our understanding of the nature, complexity and significance of the polymicrobial communities harbored by people with CF (PWCF). Having established that structurally complex microbial communities exist within the airways, the focus of recent research has now widened to investigating the function and dynamics of the resident microbiota during disease as well as in health. With further refinement, multi-omics approaches present the opportunity to untangle the complex interplay between microbe–microbe and microbe–host interactions in the lung and the relationship with respiratory disease progression, offering invaluable opportunities to discover new therapeutic approaches for our management of airway infection in CF.

BACKGROUND Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: Open or closed abdominal technique. AIM To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes. METHODS Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database. Post-operative, recurrence, and overall survival outcomes were compared between those who received open vs closed HIPEC. RESULTS Of the 1812 patients undergoing curative-intent CRS and HIPEC, 372 (21%) patients underwent open HIPEC and 1440 (79%) underwent closed HIPEC. There was no difference in re-operation or severe complications between the two groups. Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities. On multi-variable analysis, closed HIPEC technique was not a significant predictor for overall survival (hazards ratio: 0.75, 95% confidence interval: 0.51-1.10, P = 0.14) or recurrence-free survival (hazards ratio: 1.39, 95% confidence interval: 1.00-1.93, P = 0.05) in the entire cohort. These findings remained consistent in the appendiceal and the colorectal subgroups. CONCLUSION In this multi-institutional analysis, the HIPEC method was not independently associated with relevant post-operative or long-term outcomes. HIPEC technique may be left to the discretion of the operating surgeon.

Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. CA19-9 [HR 2.44, CI 1.2–3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06–23.46] was independently predictive of OS (p

While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM).All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay75th percentile, and non-home discharge.Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p 0.01).Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

BackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000&ndash, 2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

After resection of colorectal liver metastases (CLM), up to 40% of patients will develop intrahepatic recurrence. This study aims to identify patterns of intrahepatic recurrence and their impact on survival after preoperative chemotherapy and CLM resection. A retrospective review was performed of patients developing intrahepatic recurrence after CLM resection following preoperative chemotherapy. Prechemotherapy, preoperative, and postoperative computed tomography scans were reviewed. Recurrences were classified as in situ, de novo, or both in situ and de novo. Median follow-up was 42 months (range 2–144 months). Among 223 patients meeting study criteria, intrahepatic recurrence was identified a median of 9 months after hepatectomy. Isolated de novo or in situ recurrence developed in 105 (47%) and 86 (39%) patients, respectively. Thirty-two patients (14%) developed both in situ and de novo recurrence, which was associated with significantly lower median overall survival of 33 months compared with 49 and 45 months with isolated in situ or de novo recurrence, respectively (p = 0.048). Among 118 patients (53%) who developed in situ recurrence as a component of disease relapse, recurrences resulted from disappearing or missed liver metastases in 47 patients (40%). An intrahepatic recurrence pattern of both in situ and de novo metastases after CLM resection following preoperative chemotherapy predicts significantly worse overall survival compared with isolated in situ or de novo recurrence.

For gallbladder cancer (GBC), the American Joint Committee on Cancer eighth edition (AJCC 8) staging system classifies lymph node (LN) stage by the number of positive LN and recommends sampling of ≥6 LNs. We evaluated the prognostic capability of the AJCC 8 for patients undergoing resection and the current national trends in LN staging in the context of these new recommendations for nodal (N) sampling.Utilizing the National Cancer Data Base, we identified all gallbladder adenocarcinoma patients treated with surgical resection in 2004-2014. Cox regression modeling was used to calculate the concordance index of AJCC 8 in predicting overall survival. N sampling and positivity rates were analyzed over the study period.In our cohort, predicted 5-year overall survival by AJCC 8 was: stage I, 62.5%; II, 50.2%; IIIA, 25.7%; IIIB, 22.1%; IVA, 15.7%; IVB, 6.7% (P 0.01). The concordance index for the staging system was 0.832. Only 50.7% of the patients had any LN sampling to determine the N stage. LN sampling rates improved from 45.6% in 2004 to 55.1% in 2013 (P 0.001). However, only 24.5% of patients with any LN sampling had ≥6 LNs resected (12.4% of eligible cohort), with a median LN sample of two.AJCC 8 offers adequate discrimination for GBC staging, especially for node-positive patients. With actual GBC LN sampling rates at 50.7%, and far short of the ≥6 LN threshold, quality improvement measures may need to focus on requiring any LN sampling before raising the minimum to six LNs.

We report a diode-pumped, intracavity THz laser source based on stimulated polariton scattering in crystalline RbTiOPO4 using a surface-emitting configuration. The system was continuously tunable in four regions, from 3.05 to 3.16 THz, from 3.50 to 4.25 THz, from 4.57 to 4.75 THz, and from 5.40 to 5.98 THz. The laser delivered 124.7 μW average output power at 4.10 THz for only 6.0 W diode pump power at 808 nm, corresponding to a diode-to-THz conversion efficiency of 2.1 × 10−5. The horizontal and vertical beam quality parameters were $M_H^2 and $M_V^2 and the linewidth of the terahertz field was 28 GHz at 4.10 THz. The results demonstrate that the surface-emitting configuration is a very efficient technique to produce high-power THz laser sources with frequency-tunable output suitable for real-world applications.

A 61-year-old white man was referred to the University of Minnesota Department of Ophthalmology with a diagnosis of cystoid macular edema (CME) following bilateral cataract surgery 2 months prior. Chorioretinal folds and CME were present on fundus examination and optical coherence tomography (OCT). His past medical history included diabetes mellitus for 18 years, hypertension for 5 years, and heart disease with bypass surgery. His most recent glycosylated hemoglobin test (HbA1C) was 8.3 (normal

By incorporating an etalon within an intracavity continuous wave terahertz polariton laser, we achieve a ten-fold reduction in linewidth, plus a factor of two increase in the THz output power.

In the Neurology Clerkship at our institution, we introduced a medical education curriculum to increase student competency in providing discharge education to patients with neurologic disease, and to increase knowledge of QI principles. The curriculum was peer-based, in that it was developed by medical students, experienced by medical student clerks, and modified over time with their feedback, which was tracked using exit surveys. Patients counseled were predominantly male (67%) and white (55%), with stroke or TIA together representing the most common diagnoses (58%). A high proportion of students (>85%) agreed that the clerkship project was effective in teaching discharge education, the risk factors for readmission, and increased confidence in providing discharge education. We conclude that medical students are poised to learn QI principals through practice-based curricula, and through practice may improve the quality and safety of care for patients with neurologic disease. This curriculum can be implemented within other services, and with different learners., Highlights • Ninety-one percent (91%) of students felt more confident educating Neurology patients. • About half of patients counseled suffered a stroke or TIA. • The curriculum evolved using ongoing collection of student feedback.

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM). Methods The US HIPEC Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ± HIPEC between 2000 and 2012 (P1) versus 2013–2017 (P2). Results Among 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045). Conclusion CRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.

Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors.

A continuous-wave (CW) single-longitudinal-mode (SLM) intracavity Raman laser is demonstrated for the first time, by virtue of the spatial hole-burning free nature of stimulated Raman scattering (SRS) gain. By using a single etalon in the Nd:GdVO4 fundamental laser cavity, the spectral linewidth of the multimode fundamental field is suppressed below the Raman linewidth of Raman crystal BaWO4; hence power in all the longitudinal modes of fundamental field can be extracted by one single Stokes mode. Therefore, the hole-burning free SRS gain exhibits a spectral cleanup effect whereby a stable SLM Stokes field is derived from the multimode fundamental field within a simple standing-wave cavity arrangement. The low-threshold SLM Raman laser delivered 3.42 W SLM Stokes and 1.53 W SLM one-way yellow harmonic at the guide-star wavelength of 589.16 nm. The results here provide a new approach to SLM laser operation with good simplicity and power dynamic range. Further engineering for power scaling and better stability is also discussed.

Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs.PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (3). Clinicopathologic variables and biomarkers were compared in the two groups.Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P 0.021).PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.

BACKGROUND. No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS. The U.S. HIPEC Collaborative database (2000–2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6–12mos or high-frequency surveillance (HFS) at q2–4mos. Primary outcome was overall survival (OS). RESULTS. Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for noninvasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two postoperative years would potentially save $13–19 M/year to the U.S. healthcare system. CONCLUSIONS. Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Background For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. Methods All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). Results Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. Conclusion The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

We demonstrate a continuous-wave self-Raman Nd:GdVO4 Laguerre-Gaussian (LG) mode laser based on different Raman shifts of 382 cm−1 and 882 cm−1 by shaping the pumping beam with the use of an axicon lens and a focusing lens. Selective generation of LG mode beams at 1108 nm or 1173 nm, or simultaneously 1108 nm and 1173 nm, was achieved by carefully adjusting the alignment of the laser cavity. The maximum Raman LG mode output powers at the wavelengths of 1108 nm (the first-Stokes emission of the 382 cm−1 Raman shift) and 1173 nm (the first-Stokes emission of the 882 cm−1 Raman shift) were measured to be 49.8 mW and 133.4 mW at the absorbed pump power of 5.69 W, respectively. The generated LG modes, formed via the incoherent superposition of two LG mode beams with positive and negative topological charges, carry zero orbital angular momentum. Such LG mode laser sources have the potential to fill in the wavelength gap of lasers in the visible and infrared regions.

In this paper we review the field of terahertz (THz) sources which make use of the nonlinear, stimulated polariton scattering (SPS) process. A historical perspective of the technology is offered, in addition to an investigation of modern SPS-based THz sources. Breakthroughs in these source technologies have coincided with rapid developments in laser technology over the past 10 years. We are now in an age where pulsed SPS-THz sources are generating peak powers in excess of 50 ​kW, and continuous wave SPS-THz sources can be produced using diode pump powers as low as 2.3 ​W. The versatility of this approach to THz generation has enabled the generation of coherent THz radiation across continuous wave (CW), nanosecond-, and picosecond-pulsed modalities, with sources spanning the frequency range 0.5–13 ​THz. Being based on robust and well-developed, crystalline solid-state laser technology, these sources hold great promise as an enabling technology for a plethora of THz applications.

Neoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT.Utilizing the National Cancer Data Base (NCDB), patients with cStage I-II PDAC who underwent pancreatoduodenectomy in 2006-2013 were pathologically staged using the AJCC 8th edition and compared by treatment sequencing.Among 13,871 patients, 15.3% received NT. Despite higher pre-treatment T-stage (cT2: 71.9% vs. 56.3%, p 0.001), NT patients had lower rates of pathologic nodal metastases (46.2% vs. 69.2% in SF, p 0.001), suggesting higher rates of pathologic downstaging. In cStage II, 33.0% were upstaged to stage III after SF, vs. only 14.0% after NT. In cStage I, 65.5% were upstaged following SF, vs. 46.7% after NT (all p 0.001). Patients with NT (HR-0.77, p 0.001) or downstaging (HR-0.80, p 0.001) had improved overall survival (OS).NT is associated with reduction in unexpected upstaging, reduction in nodal positivity, and improved OS, compared to SF approach in putatively early-stage PDAC. Because clinical staging underestimates the underlying disease burden in resectable PDAC, patients with cStage I-II should be considered for NT.

Human prion diseases constitute a group of infectious and invariably fatal neurodegenerative disorders associated with misfolding of the prion protein. Variant Creutzfeldt-Jakob disease (vCJD) is a zoonotic prion disease linked to oral exposure to the infectious agent that causes bovine spongiform encephalopathy (BSE) in cattle. The most recent case of definite vCJD was heterozygous (MV) at polymorphic codon 129 of the prion protein gene PRNP while all of the previous 177 definite or probable vCJD cases who underwent genetic analysis were methionine homozygous (MM). Retrospective prevalence studies conducted on lympho-reticular tissue suggest that the number of asymptomatic vCJD carriers in the United Kingdom might be around 1 in 2000 people. In addition, there have been four known cases of the transmission of vCJD infection via blood transfusion. For these reasons, a sensitive, reliable, and fast diagnostic test is currently needed. We describe a rapid and highly sensitive seeding conversion assay that detects disease-associated prion protein in the brain and cerebrospinal fluid in vCJD after 48-96 h of amplification, with 100% sensitivity and specificity. This method can amplify prions from definite, probable, and possible vCJD cases from patients who are either MM or MV at PRNP-codon 129.

An enhancement in the performance of an intracavity CW THz polariton laser is reported. THz output power of up to 23.1 µW was detected at 1.66 THz, frequency tunability across 1.30 – 2.51 THz was achieved.

We report the application of THz radiation, generated from a solid-state THz laser source, to the detection of water content within plant leaves, and the determination of plant health status.

We detail the operation of a THz laser source based on non-linear stimulated polariton scattering (SPS) in Mg:LiNbOsub3/sub. This system utilizes a fundamental wavelength of 1342 nm to completely avoid the negative effect of free-carrier generation within high-resistivity silicon (Si) prisms used to extract THz radiation from the Mg:LiNbOsub3/subcrystal. THz power of up to 23.6 μW (62.3 μW when chopped at 50% duty cycle) was detected at 1.33 THz, and frequency tunability across the range 1.05-2.2 THz was achieved.

Optical vortices, carrying a doughnut-shaped spatial form and an orbital angular momentum assigned with topological charge), have received attention in diverse application fields, for instance, high spatial resolution microscopies, quantum communications, and chiral materials processing. The aforementioned applications require highly pulsed optical vortex sources with wavelength versatility. In general, a mode conversion technique based on wavefront modulation elements, such as a spiral phase plate and a spatial light modulator, allows us to produce optical vortices; however, these elements, designed for specified frequency, impact highly a power scaling and a frequency versatility of the systems owing to the diffraction losses and optical damege.

An uncoated etalon was incorporated within an intracavity continuous wave terahertz polariton laser, leading to a tenfold reduction in linewidth, plus a factor of 2 increase in the THz output power. The increase in output power is explained in terms of phase matching considerations for the parametric downconversion process.

The goal of this work is to develop a plan-quality evaluation program for clinical routine and multi-institutional clinical trials so that the overall evaluation efficiency is improved. In multi-institutional clinical trials evaluating the plan quality is a time-consuming and labor-intensive process. In this note, we present a semi-automated plan-quality evaluation program which combines MIMVista, Java/MATLAB, and extensible markup language (XML). More specifically, MIMVista is used for data visualization; Java and its powerful function library are implemented for calculating dosimetry parameters; and to improve the clarity of the index definitions, XML is applied. The accuracy and the efficiency of the program were evaluated by comparing the results of the program with the manually recorded results in two RTOG trials. A slight difference of about 0.2% in volume or 0.6 Gy in dose between the semi-automated program and manual recording was observed. According to the criteria of indices, there are minimal differences between the two methods. The evaluation time is reduced from 10-20 min to 2 min by applying the semi-automated plan-quality evaluation program.

We report a very compact, laser diode end-pumped THz laser source, which utilizes two resonators to generate frequency-tunable radiation across the range 1.53-2.82 THz via stimulated polariton scattering (SPS) in a Mg:LiNbO3 crystal. To the best of our knowledge, this THz system operates with the lowest pump power threshold (2.4 W), and highest conversion efficiency (6.45tW average output power at 1.82 THz for 5 W input diode pump power) ever reported for a THz source based on SPS.

We obtained a frequency tunable, low-coherence, picosecond, terahertz (THz) output with a high repetition rate from a picosecond Nd:YVO4 bounce laser in combination with tandem periodically poled stoichiometric lithium tantalate and 4′-dimethylamino-N-methyl-4-stilbazolium tosylate crystals. The frequency of the THz output was tunable in the range 2.1–7.1 THz with a linewidth of ~3.5 THz at 2.2 THz. The THz output had a maximum peak power of ~180 mW and an average power of ~0.65 μW at 3.9 THz. This system has the potential to realize ultra-high speed, THz coherence tomography.

Etalons have been incorporated within an intracavity CW THz laser, leading to both linewidth narrowing and an improvement in THz output power. We report key findings, with a focus on using 100 µm thick coated and uncoated YAG etalons, as these were found to provide the most stable and repeatable operation.

A THz laser source based on stimulated polariton scattering (SPS) in an intracavity RbTiOPO4 (RTP) crystal is reported, with frequency-tunable output from 3.10 to 3.16 THz and from 3.50 to 4.15 THz. The gap exhibited from 3.17 to 3.49 THz is located in the vicinity of the 104 cm−1 absorbing mode in RTP. A maximum average output power of 16.2 μW was measured at 3.80 THz.

Sum frequency generation of the fundamental and Stokes fields within an intracavity self-Raman vortex laser is demonstrated in a linear resonator configuration. In this system, the sum frequency field exhibits different spatial profiles in the near and far fields, and a time-varying topological charge which varies between values of +2 and 0. We present a theoretical model which supports these experimental observations.