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Relative survival and disease-specific survival are two statistics that measure net survival from a cancer diagnosis, excluding other causes of death. In most cases, these two rates are comparable. However, in some cancer types for which cancer screening is performed, relative survival is often greater than disease-specific survival. This divergence has been attributed to mechanisms such as the "healthy user effect" and overdiagnosis of indolent tumors detected by screening. Using relative survival rate as a marker of these mechanisms, we examined the association of breast cancer screening with relative survival rates for women diagnosed with early-stage breast cancer. In population-based data from the National Cancer Institute's Surveillance, Epidemiology and End Results registry, we examined relative survival rates in women diagnosed with stage I breast cancer or ductal carcinoma in situ who were in highly screened vs less-highly screened groups, based on time period, age group, and insurance status. In this analysis, relative survival rates for early-stage breast cancer were higher than disease-specific survival, even exceeding 100% in populations experiencing higher rates of screening (ie, women diagnosed during the era of widespread uptake of mammography, age older than 40 years, and women with health insurance coverage). The favorable outcomes observed in screen-detected breast cancers are at least in part attributable to the healthy user effect and overdiagnosis of indolent tumors. Therefore, survival rates may not accurately reflect the effectiveness of cancer screening. These findings have implications for counseling of patients and future clinical studies of active monitoring approaches in breast cancer.

The invasion of nerves by cancer cells, or perineural invasion (PNI), is potentiated by the nerve microenvironment and is associated with adverse clinical outcomes. However, the cancer cell characteristics that enable PNI are poorly defined. Here, we generated cell lines enriched for a rapid neuroinvasive phenotype by serially passaging pancreatic cancer cells in a murine sciatic nerve model of PNI. Cancer cells isolated from the leading edge of nerve invasion showed a progressively increasing nerve invasion velocity with higher passage number. Transcriptome analysis revealed an upregulation of proteins involving the plasma membrane, cell leading edge, and cell movement in the leading neuroinvasive cells. Leading cells progressively became round and blebbed, lost focal adhesions and filipodia, and transitioned from a mesenchymal to amoeboid phenotype. Leading cells acquired an increased ability to migrate through microchannel constrictions and associated more with dorsal root ganglia than nonleading cells. ROCK inhibition reverted leading cells from an amoeboid to mesenchymal phenotype, reduced migration through microchannel constrictions, reduced neurite association, and reduced PNI in a murine sciatic nerve model. Cancer cells with rapid PNI exhibit an amoeboid phenotype, highlighting the plasticity of cancer migration mode in enabling rapid nerve invasion.

Nerve mediated inflammatory monocyte recruitment in perineural invasion.

Tables contain information on the list of candidate genes screened from murine macrophages and clinical data on human pancreatic samples. This file contains 2 tables (Supplemental Tables 1 and 2).

Analysis of human prostate cancer and adenoid cystic carcinoma specimens demonstrates macrophage infiltration around the majority of invaded nerves. This file contains two supplemental figures (S10-S11).

Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI, but the contributing conditions within the tumor microenvironment are not well understood. Here, we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B–mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2–CCR2 signaling or cathepsin B function significantly impaired PNI in vivo. Correlative studies in human specimens demonstrated that cathepsin B–producing macrophages were enriched in invaded nerves, which was associated with increased local tumor recurrence. These findings deepen our understanding of PNI pathogenesis and illuminate how PNI is driven in part by corruption of a nerve repair program. Further, they support the exploration of inhibiting IM recruitment and function as a targeted therapy for PNI. Cancer Res; 77(22); 6400–14. ©2017 AACR.

Esophageal anastomotic stricture is a well-known complication after transhiatal esophagectomy (THE), but there is limited data regarding the initial management and subsequent outcomes after stricture dilation. There is concern that dilating to larger diameters upon the initial encounter, specifically with high-grade strictures, will lead to increased risk for complications. We therefore reviewed one surgeon’s experience with esophageal dilations after THE and provided data and treatment recommendations based upon these findings. A retrospective review of patients who underwent esophageal dilations ≥ 18 mm up to 20 mm after THE between 2006 and 2019 at our institution was performed. Patient demographics were n = 97, age = 70, 81 males. For all cases, the mean location, length, diameter of the stricture, and number of days from surgery and initial dilation were 20 cm, 1.9 cm, 6.7 mm, and 106 days, respectively. Most dilations (79%) occurred within 2 weeks to 3 months from surgery. 29.9% were dilated up to 18 mm, 10.3% were dilated up to 19 mm, and 59.8% were dilated up to 20 mm upon initial dilation. Even 1-mm-diameter lesions could be safely dilated upon 18–20 mm. In this study group there were no complications after endoscopic dilation that required hospitalization or further surgical or endoscopic interventions. These results suggest that early aggressive endoscopic management of esophageal anastomotic strictures after THE can be safely performed.

In the era of subspecialization and duty-hour restrictions, many General Surgery residents desire additional training in their future subspecialty areas. This study examines the relationship between case distributions performed by General Surgery residents and their chosen future subspecialty.A retrospective review of Accreditation Council for Graduate Medical Education case logs of 101 graduated General Surgery residents at a single academic institution (2002-2018) was performed. The total number of operative cases performed during General Surgery residency overall and in Accreditation Council for Graduate Medical Education-defined categories were compared between residents with differing areas of future subspecialization.Residents pursuing surgical fellowships in Endocrine, Cardiothoracic, Vascular, and Trauma/Critical Care Surgery logged respectively more endocrine (63 [11] vs 32 [13]; P.001), thoracic (61 [15] vs 41 [13]; P.001), vascular (225 [38] vs 162 [38]; P.001), and operative trauma (83 [29] vs 71 [25]; P = .045) cases, compared with program average. Residents pursuing General Surgery (no fellowship) performed significantly more endoscopies (131 [47] vs 105 [28]; P = .029) than peers. Residents pursuing Breast, Oncology, Colorectal, and Pediatric Surgery fellowships performed numerically (non-significantly) more breast (94 [16] vs 78 [20]; P = .180), liver/pancreas (39 [3.1] vs 33 [8.0]; P = .173), large intestinal (132 [30] vs 125 [24]; P = .507), and pediatric (173 [27] vs 155 [37]; P = .832) cases, respectively, compared with peers. The majority of these additional cases were performed in postgraduate years 3 to 5.In this single-institution study, many General Surgery residents perform more cases than peers in respective areas of future subspecialization. This may reflect residents at the reporting institution, and similar large, university-based programs seeking focused training in preparation for fellowship while still meeting case-volume minimums in all Accreditation Council for Graduate Medical Education-defined categories.

BackgroundThe ThyroSeq v2 next-generation sequencing assay (ThyroSeq) estimates the probability of malignancy in indeterminate thyroid nodules (ITN). Its diagnostic accuracy in different practice settings and patient populations is not well understood.MethodsWe analyzed 273 Bethesda III/IV ITN evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n=98 and 102), a multicenter healthcare system (n=60), and an academic medical center (n=13). The positive (PPV) and negative predictive values (NPV) of ThyroSeq, and distribution of final pathology were analyzed and compared to values predicted by Bayes Theorem.ResultsAcross 4 institutions, the PPV was 35% (22-43%), and NPV was 93% (88-100%). Predictive values correlated closely with Bayes Theorem estimates (r2=.84), although PPVs were lower than expected. RAS mutations were the most frequent molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10-37%), and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12-85%, NIFTP 5-46%).ConclusionsIn a multi-institutional analysis, ThyroSeq PPVs were variable and lower than expected. This is attributable to differences in the prevalence of malignancy, and variability in pathologist interpretations of non-invasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.

Purpose of review Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer that is associated with significant morbidity and mortality. Because ATC is locally invasive, airway management is a critical component of treating these patients. Timely decisions regarding airway interventions can contribute to symptom relief and supportive care for patients. Over the last decade, there has been a paradigm shift in our recommendations for airway management. The purpose of this review is to summarize airway management, symptom relief and best supportive care for patients with ATC. Recent findings More recent literature discusses the morbidities associated with tracheostomy and instead focuses on the benefits of supportive care and surgical resection. The multidisciplinary treating team should initiate early discussions for airway management, end-of-life care and palliative goals for patients with ATC. Tracheostomy should be offered to patients with careful thought and preoperative planning. Summary Our goal in symptom relief and airway management is to improve the quality of life of patients with ATC and avoid the unnecessary morbidity of tracheostomy until clinically indicated.

Background Common measures of evaluating surgical resident progression include American Board of Surgery In-Training Exam scores and Accreditation Council for Graduate Medical Education operative case logs. This study evaluates the relationship between operative cases performed and American Board of Surgery In-Training Exam scores in general surgery residents. Methods A retrospective review of American Board of Surgery In-Training Exam scores and operative case logs was performed for postgraduate year 1–5 general surgery residents at a single academic institution (2008–2017). For each resident, the total number of operative cases logged from the start of their postgraduate year 1 until the end of each academic year was calculated and compared to their American Board of Surgery In-Training Exam scores for that corresponding year. Results At all postgraduate-year levels, there was a positive linear relationship between the number of cases logged and American Board of Surgery In-Training Exam percentile (slope, m = 0.23–5.2, R2 .01–.17) and scaled (m = 0.29–5.3, R2 .13–.37) scores. At the postgraduate year 1, 2, 3, and 5 levels, and with all residents combined, residents in the top quartile of cases logged performed significantly better on the American Board of Surgery In-Training Exam than those in the bottom quartile (P Conclusion Surgical residents who perform more operative cases do significantly better on the American Board of Surgery In-Training Exam than their peers. This association may be due to increased clinical experience, exposure to pathology, and/or individual resident motivation.

Background The effect of altered parathyroid hormone metabolism in renal insufficiency on intraoperative parathyroid hormone monitoring during parathyroidectomy is not well known. This study evaluates operative outcomes in patients undergoing parathyroidectomy guided by intraoperative parathyroid hormone monitoring for primary hyperparathyroidism with mild and moderate renal insufficiency. Methods A retrospective review of prospectively collected data in 604 patients with sporadic primary hyperparathyroidism undergoing parathyroidectomy guided by intraoperative parathyroid hormone monitoring was performed. Patients were stratified by stage of chronic kidney disease (CKD); those with overt secondary hyperparathyroidism (CKD stages IV and V) were excluded. Rates of bilateral neck exploration, multiglandular disease, and long-term operative outcomes, including success, failure, and recurrence were compared. Results Of the 604 patients, 38% (230/604) had normal renal function or stage I CKD, 44% (268/604) had stage II CKD, and 18% (106/604) had stage III CKD. Overall, there were no differences in the rates of bilateral neck exploration or multiglandular disease or in rates of operative success, failure, or recurrence in patients with normal renal function and stages I to III CKD. Conclusion Parathyroidectomy guided by intraoperative parathyroid hormone monitoring is performed with high operative success uniformly in primary hyperparathyroidism patients with mild and moderate renal insufficiency with outcomes similar to those with normal renal function.

Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI, but the contributing conditions within the tumor microenvironment are not well understood. Here, we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B–mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2–CCR2 signaling or cathepsin B function significantly impaired PNI in vivo. Correlative studies in human specimens demonstrated that cathepsin B–producing macrophages were enriched in invaded nerves, which was associated with increased local tumor recurrence. These findings deepen our understanding of PNI pathogenesis and illuminate how PNI is driven in part by corruption of a nerve repair program. Further, they support the exploration of inhibiting IM recruitment and function as a targeted therapy for PNI. Cancer Res; 77(22); 6400–14. ©2017 AACR.

Undifferentiated (anaplastic) thyroid cancer (ATC) is the rarest yet most aggressive thyroid cancer. Most patients present with a rapidly enlarging thyroid mass, and the majority die within 6 months of diagnosis. ATC commonly occurs from dedifferentiation of a previously well-differentiated thyroid cancer, though it may arise de novo in some cases. Optimal management of ATC involves a multidisciplinary approach with a combination of surgery, radiotherapy, chemotherapy, and most recently, immunotherapy, to provide the best quality of life with the longest survival. Despite advances in ATC management, there is still much work ahead to improve survival for this lethal disease.

This cohort study examines the relative and disease-specific survival rates for patients with 10 early-stage cancers.

Only 43% of ureteral trauma cases present with hematuria, and therefore there are no pathognomonic signs of ureteral trauma. The diagnosis is usually performed by the visualization of contrast leakage into the retroperitoneum on helical computed tomography (CT) with late cuts. Excretory urography and retrograde pyelography are more precise exams. Grade I and II injuries can be treated by ureteral stent implantation or nephrostomy.

The initial management of a patient with cardiac or great vessel trauma is to ensure airway and ventilation with adequate oxygenation, and treat shock according to ATLS protocol. FAST is a very useful adjunct tool in cardiac trauma because it allows diagnosis of injuries in the emergency room. Penetrating wounds to the anatomic area, known as the “cardiac box” (bordered superiorly by the clavicles, inferiorly by the xiphoid, and by the nipples laterally), should increase the suspicion of cardiac injury. Firearm injuries to the heart are more often associated with bleeding and exsanguination rather than tamponade. Definitive treatment involves surgical exposure through an anterior thoracotomy or median sternotomy with subsequent tamponade relief and/or hemorrhage control. The primary management of blunt cardiac injury (BCI) is supportive care. The role of surgery in BCI should be restricted to patients with structural abnormalities and/or a positive FAST. The clinical picture of great vessel trauma includes hypotension, unequal arterial pressures or pulses in the extremities, external evidence of major thoracic trauma, and palpable fracture of the sternum or thoracic spine. Indications for emergency thoracotomy include hemodynamic instability, significant bleeding in the thoracic drains, or radiographic evidence of a rapidly expanding mediastinal hematoma.

The thoracic spine and lumbar spine are the most frequent sites of fracture. The presence of spinal cord injury (SCI) must be assumed in all polytrauma patients until proven otherwise. For this reason, the cervical collar should be placed in all polytrauma patients until SCI is ruled out. Tingling or paralysis of a limb suggests severe injury to the spinal cord. Rectal examination is an essential part of the neurological examination and should assess anal sphincter tone, anal and perianal sensitivity, and anal and bulbocavernosus reflexes. In contrast to spinal shock, which is a transient reflex depression of cord function below the level of injury, neurogenic shock is characterized by hypotension and bradycardia resulting from the loss of vasomotor tone and sympathetic innervation to the heart. Paraplegia and quadriplegia from SCI can be either complete or incomplete. Recent studies have demonstrated the lack of efficacy of high-dose methylprednisolone in the acute treatment of patients with spinal cord injuries.

Cancer cells invade nerves through a process termed perineural invasion (PNI), in which cancer cells proliferate and migrate in the nerve microenvironment. This type of invasion is exhibited by a variety of cancer types, and very frequently is found in pancreatic cancer. The microscopic size of nerve fibers within mouse pancreas renders the study of PNI difficult in orthotopic murine models. Here, we describe a heterotopic in vivo model of PNI, where we inject syngeneic pancreatic cancer cell line Panc02-H7 into the murine sciatic nerve. In this model, sciatic nerves of anesthetized mice are exposed and injected with cancer cells. The cancer cells invade in the nerves proximally toward the spinal cord from the point of injection. The invaded sciatic nerves are then extracted and processed with OCT for frozen sectioning. H&E and immunofluorescence staining of these sections allow quantification of both the degree of invasion and changes in protein expression. This model can be applied to a variety of studies on PNI given its versatility. Using mice with different genetic modifications and/or different types of cancer cells allows for investigation of the cellular and molecular mechanisms of PNI and for different cancer types. Furthermore, the effects of therapeutic agents on nerve invasion can be studied by applying treatment to these mice.

Background Parathyroidectomy guided by intraoperative parathormone (ioPTH) monitoring for primary hyperparathyroidism (pHPT) confirms removal of all hyperfunctioning parathyroid glands. This study evaluates the utility of an additional 20-min ioPTH measurement in patients who fail to meet the >50% ioPTH drop criterion. Methods A retrospective review of prospectively collected data of 706 patients with pHPT who underwent parathyroidectomy guided by ioPTH monitoring was performed. When a >50% ioPTH decrease from the highest either preincision or preexcision level was achieved after 10 min, parathyroidectomy was completed. If this criterion was not met, further exploration was performed or an additional 20-min ioPTH measurement was obtained. Results Of 706 patients, 72 (10%) patients did not meet the >50% ioPTH drop criterion at 10 min. Of these patients, 67% (48/72) underwent immediate bilateral neck exploration (BNE). For the other 33% of patients (24/72), a 20-min parathormone (PTH) measurement was drawn. Of patients with an additional 20-min PTH measurement, 46% (11/24) had a >50% ioPTH decrease at 20 min where BNE was avoided and parathyroidectomy completed, whereas 54% (13/24) did not. Compared to patients with insufficient ioPTH drop at 10 min and subsequent BNE, there was a statistically significant 46% reduction of BNE in patients with a 20-min PTH level (P Conclusions A 20-min ioPTH measurement is useful in preventing unnecessary BNE in some patients who undergo focused parathyroidectomy with a delayed >50% ioPTH drop.

Duodenal stenosis is one of the leading causes of duodenal obstruction in the pediatric population, usually diagnosed in newborns and in Down syndrome patients. It has historically been treated with duodeno-duodenostomy, an operation that is now commonly performed laparoscopically. We present a case of a 10-year-old child with a rare chromosomal abnormality who was diagnosed with a duodenal stricture after presenting with failure to thrive and inability to tolerate tube feeds. Duodeno-duodenostomy was performed using the da Vinci® robot, allowing for improved intra-operative range of motion and control during anastomosis creation, with the same cosmetic benefits of laparoscopic surgery, and subsequent improvement in symptoms postoperatively. This case highlights the utility of robotic surgery in complex operations in the pediatric population.

Cancer staging allows patients to be stratified based on aggressiveness of their disease and provides important prognostic information to both the patient and clinician. The tumor-nodal-metastasis (TNM) system from the American Joint Committee on Cancer (AJCC) is the most commonly used staging system for many cancers, including thyroid cancer, and has been shown to predict differentiated thyroid cancer-related death [1]. While most patients with thyroid carcinoma have well-differentiated tumors that have an excellent prognosis, there are certain characteristics that carry a worse prognosis, including older age, larger primary tumor size, aggressive tumor histology, extrathyroidal tumor extension (ETE), and distant metastasis [2].

This study uses Surveillance, Epidemiology, and End Results (SEER) registry data to describe trends in thyroid cancer incidence overall and by tumor size in the United States from 1992 to 2016.

The importance of intraoperative parathormone "spikes" during parathyroidectomy remains unclear. This study compared patients with and without intraoperative parathormone spikes during parathyroidectomy using the criterion of a 50% parathormone and determined the effect of intraoperative parathormone spikes on operative outcome.We performed a retrospective review of prospectively collected data on 683 patients who underwent parathyroidectomy guided by intraoperative parathormone monitoring. An intraoperative parathormone "spike value" was calculated by subtracting the preincision intraoperative parathormone value from the pre-excision intraoperative parathormone value (SV = PE - PI). An intraoperative parathormone spike was defined as having a positive spike value ≥9 pg/mL (≥10th percentile of all spike values).Of 683 patients, 224 (33%) had intraoperative parathormone spikes and a greater rate of multiglandular disease (8% vs. 3%, P 0.05) and bilateral neck exploration (10% vs. 5%, P 0.05) compared with patients without intraoperative parathormone spikes. Overall, there were no differences between parathyroidectomy patients with and without intraoperative parathormone spikes in terms of operative success (98.2% vs. 98.0%), failure (1.8% vs. 2.0%), or recurrence rates (0.4% vs. 1.3%).Although the presence of intraoperative parathormone spikes may increase suspicion for multiglandular disease, the ability of intraoperative parathormone monitoring to predict operative success after parathyroidectomy is not affected by spikes.

Both functional (hormone hypersecreting) and nonfunctional (nonhypersecreting) adrenal tumors can have benign or malignant pathology. This study compares perioperative in-hospital outcomes after adrenalectomy in patients with benign versus malignant nonfunctional primary adrenal tumors.A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database (2006-2011) to identify patients who underwent unilateral open or laparoscopic adrenalectomy for nonfunctional primary adrenal tumors. Patients were subdivided by benign and malignant final pathology. Demographics, comorbidities, and perioperative complications were compared between groups using bivariate and multivariate logistic regression.Of 23,297 patients, 89.7% (n = 20,897) had benign tumors, whereas 10.3% (n = 2400) had malignant tumors. Those with malignant tumors had higher Charlson Comorbidity Index scores and were more likely to undergo adrenalectomy at high volume centers. For both laparoscopic and open approach, patients with malignant nonfunctional tumors had higher rates of intraoperative complications including vascular and splenic injury (P 0.01), as well as postoperative complications including hematoma, shock, acute kidney injury, venous thromboembolism, and pneumothorax (P 0.01). In addition, the malignant group had higher rates of blood transfusions, longer hospital stay, and higher in-hospital mortality (P 0.05) than benign counterparts. On risk-adjusted multivariate analysis, malignant nonfunctional primary adrenal tumors were independently associated with increased risk of complications following adrenalectomy.Patients with malignant nonfunctional primary adrenal tumors have higher perioperative morbidity and mortality compared to patients with benign nonfunctional adrenal tumors. Such patients should be medically optimized before adrenalectomy, and surgeons must remain vigilant in preventing perioperative complications.

Physical appearance has a significant effect on social and psychological aspects of self-esteem and overall wellbeing. With physical appearance so highly emphasized by current society, many are seeking ways to look younger and healthier. As a result, ant aging therapies are in demand and the market is constantly inundated with new products claiming to be the next best therapy for aging skin. Consumers as well as physicians often encounter difficulty in making informed decisions when choosing among treatment options.