Serial electrodiagnostic testing: Utility and indications in adult neurological disorders.

Although existing guidelines address electrodiagnostic (EDX) testing in identifying neuromuscular conditions, guidance regarding the uses and limitations of serial (or repeat) EDX testing is limited. By assessing neurophysiological change longitudinally across time, serial electrodiagnosis can clarify a diagnosis and potentially provide valuable prognostic information. This monograph presents four broad indications for serial electrodiagnosis in adult peripheral neurological disorders. First, where clinical change has raised suspicion for a new or ongoing lesion, EDX reassessment for spatial spread of abnormality, involvement of previously normal muscle or nerve, and/or evolving pathophysiology can clarify a diagnosis. Second, where diagnosis of a progressive neuromuscular condition is uncertain, electrophysiological data from a second time point can confirm or refute suspicion. Third, to establish prognosis after a static nerve injury, a repeat study can assess the presence and extent of reinnervation. Finally, faced with a limited initial study (as when complicated by patient or environmental factors), a repeat EDX study can supplement missing or limited data to provide needed clarity. Repeat EDX studies carry certain limitations, however, such as with prognostication in the setting of remote or chronic lesions, sensory predominant fascicular injury, or mild axonal injury. Nevertheless, serial electrodiagnosis remains a valuable and underused tool in the diagnostic and prognostic evaluation of neuromuscular conditions.

Tumor extent impacts survival benefit in minimally invasive colectomy for T4 colon cancer: A propensity matched national cohort analysis.

BACKGROUND: T4 colon cancers have been underrepresented in randomized trials comparing minimally invasive colectomy (MC) versus open colectomy (OC). Retrospective studies suggest improved survival with MC versus OC, but have not addressed the impact of tumor extent. METHODS: Using the National Cancer Database (NCDB), we analyzed patients undergoing colectomy for T4 colon adenocarcinoma from 2010 to 2014. Propensity score matching was performed between MC and OC patients. Tumor extent was defined by zones based on adjacent organ involvement. RESULTS: Of the 19 178 eligible patients, 6564 (34%) underwent MC. After matching, MC was associated with improved overall survival (hazard ratios: 0.71, 95% confidence interval: 0.67-0.76; median OS 59 vs. 42 months, p < 0.001). Compared to MC patients, those undergoing OC had: a higher margin positive rate (p = 0.009); lower median nodes examined (p < 0.001); a lower rate of adjuvant chemotherapy (p < 0.001); and a longer median time to chemotherapy (p < 0.001). Stratified survival analyses demonstrated that MC was associated with improved overall survival compared to OC in all zones except zone 3 and 4. CONCLUSIONS: Compared to OC, MC for T4 colon cancer is associated with improved oncologic outcomes when performed for zone 0-2 tumors. For, zone 3 and 4 tumors MC and OC have similar oncologic outcomes and patients should be cautiously selected.

Do You Really Need a Hand Surgeon? Common Tendinopathies of the Upper Extremity.

Lateral epicondylitis, de Quervain tenosynovitis, and trigger finger are among the most common tendinopathies of the upper extremity. Lateral epicondylitis is a common condition with a prolonged course that can be frustrating for patients. Nonetheless, most patients improve with a simple wait-and-see approach. Therapy has been shown to be helpful and surgical management is usually successful in recalcitrant cases. Cortisone, although commonly used in the past, has been shown to have worse results than placebo in the medium and long term. de Quervain tenosynovitis responds well to nonsurgical measures including bracing treatment, therapy, and cortisone. Surgery is effective, although neuritis of the radial sensory nerve is a notable complication. Trigger finger is strongly associated with diabetes and is typically treated with cortisone or surgery. With a thoughtful and well-researched approach, any of these conditions can be successfully managed by a community orthopaedic specialist.

Emotional Distress and Financial Toxicity in Younger Adult Patients Undergoing Oncologic Surgery.

BACKGROUND: There has been an alarming increase in the number of young adults (YA) diagnosed with cancer. The emotional, psychosocial, and financial distress experienced by newly diagnosed YA undergoing cancer surgery remains largely unknown. METHODS: A validated biopsychosocial distress screening tool (SupportScreen) was administered to patients diagnosed with cancer before surgery between 2009 and 2017 in a National Cancer Institute Comprehensive Cancer Center. Patients were stratified into YA less than or equal to 45 years and older adults (OA) above 45 years. Descriptive statistics and logistic regression were used to analyze distress outcomes. RESULTS: In total, 4297 patients were identified, with YA comprising 13.3% (n=573) of the cohort. YA reported higher emotional distress, including increased anxiety (33.8% vs 27.4%, P =0.002), greater fear of procedures (26.7% vs 22%, P =0.018), and difficulty managing emotions (26% vs 20.7%, P =0.006). YA struggled more frequently to manage work/school (29.5% vs 19.3%, P <0.001), finding resources (17.8% vs 11.8%, P <0.001), changes in physical appearance (22.2% vs 13.4%, P <0.001), fatigue (36% vs 27.3%, P <0.001), and ability to have children (18.4% vs 3%, P <0.001). Financial toxicity was significantly higher in the YA group (40.5% vs 28%, P <0.001). While income level was strongly protective against emotional distress and financial toxicity in OAs, it was less protective against the risk of financial toxicity in YA. Younger age was an independent predictor of financial toxicity in a model adjusted to income (odds ratio=1.52, P =0.020). CONCLUSIONS: YA in the prime of their personal and professional years of productivity require special attention when undergoing surgical evaluation for cancer. Resource allocation and counseling interventions should be integrated as part of their routine care to expedite their return to optimal physical and holistic health and mitigate psychosocial distress and financial toxicity.

PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial.

BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.

Global trends in esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal Cancer (EC) is a lethal malignancy with poor prognosis and significant variations in the incidence, mortality, and histopathology based on geographic regions. The aim of this study was to quantitatively analyze these variations to identify patterns and areas for further research. METHODS: We utilized the GLOBOCAN 2012, and Cancer Incidence in five Continents, Volume X (CI5X) database to analyze variations in EC incidence and mortality. RESULTS: We found the EC incidence and mortality is geographically varied with a particularly high burden in East Asia and Eastern/Southern Africa where esophageal squamous cell carcinoma (SCC) predominates over adenocarcinoma (AC). Interestingly, there is a dichotomy between the high incidence of esophageal SCC in East Africa and low incidence in West Africa. The global incidence and mortality from EC is expected to rise in the coming decades. Asia, and China in particular, will continue to be the areas most burdened by EC, while Africa is expected to surpass the incidence and mortality rates of Europe. CONCLUSIONS: The global burden of EC is expected to rise in the coming years. Understanding the geographic, environmental, and genetic contributors to the development of EC will be essential in combating its prevalence.

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients.

BACKGROUND: Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed. METHODS: PubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched. RESULTS: A total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ≥ 3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0-16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were > 80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively. CONCLUSIONS: The current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.

The role of Sox9 in mouse mammary gland development and maintenance of mammary stem and luminal progenitor cells.

BACKGROUND: Identification and characterization of molecular controls that regulate mammary stem and progenitor cell homeostasis are critical to our understanding of normal mammary gland development and its pathology. RESULTS: We demonstrate that conditional knockout of Sox9 in the mouse mammary gland results in impaired postnatal development. In short-term lineage tracing in the postnatal mouse mammary gland using Sox9-CreER driven reporters, Sox9 marked primarily the luminal progenitors and bipotent stem/progenitor cells within the basal mammary epithelial compartment. In contrast, long-term lineage tracing studies demonstrate that Sox9+ precursors gave rise to both luminal and myoepithelial cell lineages. Finally, fate mapping of Sox9 deleted cells demonstrates that Sox9 is essential for luminal, but not myoepithelial, lineage commitment and proliferation. CONCLUSIONS: These studies identify Sox9 as a key regulator of mammary gland development and stem/progenitor maintenance.

Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate.

There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type by oncogenic insults, or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in Dana-Farber Cancer Institute 1 (DFCI-1) medium retain a fraction with progenitor cell properties. These cells coexpress basal (K5, K14, and vimentin), luminal (E-cadherin, K8, K18, or K19), and stem/progenitor (CD49f, CD29, CD44, and p63) cell markers. Clonal derivatives of progenitors coexpressing these markers fall into two distinct types--a K5(+)/K19(-) type and a K5(+)/K19(+) type. We show that both types of progenitor cells have self-renewal and differentiation ability. Microarray analyses confirmed the differential expression of components of stem/progenitor-associated pathways, such as Notch, Wnt, Hedgehog, and LIF, in progenitor cells compared with differentiated cells. Given the emerging evidence that stem/progenitor cells serve as precursors for cancers, these cellular reagents represent a timely and invaluable resource to explore unresolved questions related to stem/progenitor origin of breast cancer.

Defining MRI Superiority over CT for Colorectal and Neuroendocrine Liver Metastases.

BACKGROUND: We compared CT and MRI for staging metastatic colorectal or neuroendocrine liver metastases (CRLMs and NELMs, respectively) to assess their impact on tumor burden. METHODS: A prospectively maintained database was queried for patients who underwent both imaging modalities within 3 months, with two blinded radiologists (R1 and R2) independently assessing the images for liver lesions. To minimize recall bias, studies were grouped by modality, and were randomized and evaluated separately. RESULTS: Our query yielded 76 patients (42 CRLMs; 34 NELMs) with low interrater variability (intraclass correlation coefficients: CT = 0.941, MRI = 0.975). For CRLMs, there were no significant differences in lesion number or size between CT and MRI. However, in NELMs, Eovist®-enhanced MRI detected more lesions (R1: 14.3 vs. 12.1, p = 0.02; R2: 14.4 vs. 12.4, p = 0.01) and smaller lesions (R1: 5.7 vs. 4.4, p = 0.03; R2: 4.8 vs. 2.9, p = 0.02) than CT. CONCLUSIONS: CT and MRI are equivalent for CRLMs, but for NELMs, MRI outperforms CT in detecting more and smaller lesions, potentially influencing treatment planning and surgery.

The Atlantic divide: contrasting surgical robotics training in the USA, UK and Ireland.

The uptake of robotic surgery is rapidly increasing worldwide across surgical specialties. However, there is currently a much higher use of robotic surgery in the United States of America (USA) compared to the United Kingdom (UK) and Ireland. Reduced exposure to robotic surgery in training may lead to longer learning curves and worse patient outcomes. We aimed to identify whether any difference exists in exposure to robotic surgery during general surgical training between trainees in the USA, UK and Ireland. Over a 15-week period from September 2021, a survey was distributed through the professional networks of the research team. Participants were USA, UK or Irish trainees who were part of a formal general surgical training curriculum. 116 survey responses were received. US trainees (n = 34) had all had robotic simulator experience, compared to only 37.93% of UK (n = 58) and 75.00% of Irish (n = 24) trainees (p < 0.00001). 91.18% of US trainees had performed 15 or more cases as the console surgeon, compared to only 3.44% of UK and 16.67% of Irish trainees (p < 0.00001). Fifty UK trainees (86.21%) and 22 Irish trainees (91.67%) compared to 12 US trainees (35.29%) do not think they have had adequate robotics training (p < 0.00001). Surgical trainees in the USA have had significantly more exposure to training in robotic surgery than their UK and Irish counterparts.

Sternal fixation for isolated traumatic sternal fractures improves pain and upper extremity range of motion.

INTRODUCTION: Sternal fractures are debilitating due to intractable pain, constant fracture movement and limited range of motion (ROM) of the upper extremities (UE). Traditional treatment comprises mainly of pain control, delaying return to daily activities. Recently, sternal fixation has gained popularity. There is, however, a lack of literature demonstrating efficacy. We report our experience of traumatically fractured sternal fixation. METHODS: Following IRB approval, a retrospective chart review was completed for all patients undergoing sternal fixation by a single trauma surgeon at our Level I trauma center. Basic demographics were obtained. Primary outcomes included average cumulative pain scores, total cumulative narcotic amounts and total number of pain medication agents utilized prior to and after sternal fixation. Secondary outcome included physical therapy UE ROM before and after surgery. Paired t tests were used for comparison; significance set at p < 0.05. RESULTS: Thirteen patients underwent sternal fixation from 8/2016 to 2/2018. Average age was 54.4 ± 20.8 years; 54% were female. All patients experienced blunt trauma; average injury severity score was 15.8 ± 10.9 and abbreviated chest injury score was 2.5 ± 0.51. Average intensive care unit/hospital length of stay was 2.3/10.2 days. Average pain scores significantly improved by a score of 3.5 postoperatively (preoperative = 7.08 ± 2.3, postoperative = 3.54 ± 2.5; p = 0.001). Total pain medications required by sternal fixation patients significantly decreased by 1 medication postoperatively (preoperative = 4.2 medications, postoperative = 3.2 medications; p = 0.002). Average narcotic requirements significantly decreased by 7.59 morphine milligram milliequivalents (MME) after sternal fixation (preoperative amount = 71.78 MME, postoperative amount = 64.19 MME; p = 0.041). Every patient had limited UE ROM preoperatively; however, all but one patient resumed full UE ROM postoperatively (p < 0.001). There were no postoperative complications. CONCLUSIONS: Sternal fixation is a safe and effective procedure resulting in improved pain, decreased narcotic requirements, and faster recovery.

Pandemic Operating Room Supply Shortage and Surgical Site Infection: Considerations as We Emerge from the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic created shortages of operating room (OR) supplies, forcing healthcare systems to make concessions regarding "standard" OR attire. At our institution, we were required to reduce shoe covers, reuse face masks, and allow washable head coverings. We determined if these changes affected surgical site infection (SSI) rates. STUDY DESIGN: A single institutional study was performed to compare the SSI rates reported to the National Healthcare Safety Network in the 2 years preceding COVID-19 (PRE, January 1, 2018, to December 31, 2020) with the first 12 months after the pandemic (POST, April 1, 2020, to March 31, 2021). We confirmed our findings using propensity score matching and multivariate analysis. RESULTS: Elimination of traditional shoe covers, disposable head covers, and single-use face masks was associated with a decreased SSI rate from 5.1% PRE to 2.6% POST (p < 0.001). Furthermore, this was despite a 14% increase in surgical volume and an increase in the number of contaminated/dirty cases (2.2% PRE vs 7.4% POST, p < 0.001). Use of disposable face masks decreased by 4.3-fold during this period from 3.5 million/y PRE to 0.8 million/y POST. Of note, inpatient hand hygiene throughout the hospital increased from 71% PRE to 85% POST (p < 0.001). CONCLUSIONS: This analysis has practical applications as we emerge from the pandemic and make decisions regarding OR attire. These data suggest that disposable head covers and shoe covers and frequent changes of face masks are unnecessary, and discontinuation of these practices will have significant cost and environmental implications. These data also reinforce the importance of good hand hygiene for infection prevention.

Salvage regional therapy using hepatic artery infusion pump in unresectable chemotherapy resistant colorectal liver metastases.

BACKGROUND: Little is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. METHODS: Patients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. RESULTS: A total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). CONCLUSIONS: Our findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Shared signaling pathways in normal and breast cancer stem cells.

Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs). These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog); with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes.

INTRODUCTION: Emerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. MATERIALS AND METHODS: In the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells. RESULTS: The results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC. CONCLUSIONS: Our studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers.

Breast cancer subtypes: two decades of journey from cell culture to patients.

Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.

The "swimmer's view" as alternative when lateral view is inadequate during interlaminar cervical epidural steroid injections.

OBJECTIVE: To present a technique that better visualizes the needle during interlaminar cervical epidural steroid injection (ICESI) in patients where the lateral view is inadequate. DESIGN: Case report. SETTING: Private group practice. SUBJECT: A 57-year-old morbidly obese male presenting for ICESI for left neck and upper limb pain after a motor vehicle accident. Magnetic resonance imaging revealed left C6-7 herniated nucleus pulposis and C4-5 osteophytic disc-ridge complex. Electrodiagnostic evaluation revealed activity consistent with a left C7 radiculopathy. INTERVENTION: Left C7-T1 ICESI. Needle was obscured in the lateral view by the patient's shoulders. Needle was made visible by positioning the patient for Swimmer's view. RESULTS: Full resolution of symptoms without associated complications. CONCLUSIONS: Grave complications have been associated with ICESI necessitating impeccable and systematic technique with substantial knowledge of anatomy. Although injection at lower levels is advocated for safety concerns, the needle during lateral view may be obscured by the shoulders in some patients. The "Swimmer's View" position may be attempted when lateral view is insufficient to visualize needle during ICESI.

Managing Squamous Cell Esophageal Cancer.

This article reviews the pathophysiology, risk factors, clinical presentation/diagnosis, and management of SCC.