CT-guided blood tattoo for thoracoscopic excision of lung lesions in pediatric patients.

BACKGROUND: To describe a single-institutional experience with an innovative technique using CT-guided injection of autologous blood for localization of nonpleural-based pulmonary nodules prior to thoracoscopic excisional biopsy in pediatric patients. METHODS: A retrospective review of all patients under the age of 18 with lung lesions suspected to be malignant that were not pleural-based lesions and were not of adequate size to visualize at thoracoscopy, who underwent CT-guided blood tattoo (CGBT) localization between 2006-2019. CGBT was performed under general anesthesia by injecting 0.5-10 mL of autologous blood into the area of the lesions. The patients were then immediately transferred from interventional radiology to the operating room for thoracoscopic excision of the lesion. Demographics, location of lesions, indication for biopsy, and pathology were reviewed. RESULTS: In eleven pediatric patients (ages ranging from 4-18 years), preoperative CGBT localization of pulmonary nodules resulted in successful thoracoscopic excisional biopsy. All resections were diagnostic and 82% (9/11 cases) represented a metastatic malignancy as confirmed by pathology. Malignant nodules ranged from 2 to 14 mm in size, while a 13 mm nodule in a patient with history of AML was determined to be an organizing pneumonia and a 12 mm nodule in a second patient revealed a caseating granuloma consistent with Crohn's disease. One patient with a failed attempt at excisional biopsy without preoperative localization then underwent CGBT one week later with successful thoracoscopic excision of the nodule. CONCLUSIONS: CT-guided blood tattoo is a safe option for localization of nonpleural-based lung nodules prior to thoracoscopic excision in pediatric patients.

Stoma closure and reinforcement (SCAR): A study protocol for a pilot trial.

A quality metric for centers performing rectal cancer surgery is a high percentage of sphincter sparing procedures. These procedures often involve temporary bowel diversion to minimize the complications of an anastomotic leak. The most common strategy is a diverting loop ileostomy which is then closed after completion of adjuvant therapy or the patient recovers from surgery. Loop ileostomy is not without complications and the closure is complicated by a one in three chance of incisional hernia development. Strategies to prevent this problem have been designed using a variety of techniques with and without mesh placement. This proposed pilot study will test the safety and efficacy of a novel stoma closure technique involving permanent mesh in the retro rectus position during ileostomy closure. The study will prospectively follow 20 patients undergoing ileostomy closure using this technique and evaluate for safety of the procedure, quality of life, and feasibility for a larger randomized controlled trial. Patients will be followed post procedurally and evaluated for 30-day complications, as well as followed up with routine cancer surveillance computed tomography every 6 months in which the presence of stoma site incisional hernias will be evaluated. The results of this pilot study will inform the design of a multiple center, blinded randomized controlled trial to evaluate the utility of permanent mesh placement to decrease the incidence of prior stoma site incisional hernias.

Plasma DNA as a "liquid biopsy" incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer.

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

A case report of papillary thyroid carcinoma dedifferentiated to squamous cell carcinoma presenting as a lung metastasis: A potential diagnostic pitfall.

Papillary thyroid carcinoma (PTC) tall cell variant (TCV) with squamous dedifferentiation is a rare entity. We present a case of 90-year-old woman who initially had a 2.8 cm conventional PTC in right lobe of thyroid who, couple decades later, had metastatic dedifferentiated PTC to right neck lymph nodes level II and IV with tall cell features; to right level IV and V lymph nodes with tall cell and squamous components, which recently presented exclusively as squamous cell carcinoma (SCC) metastasizing to lung. The squamous component in the lymph node and SCC in the lung were both positive for squamous marker p63 and PTC markers TTF1, PAX-8 and BRAF V600E while negative for thyroglobulin and p16. The papillary component was positive for TTF-1, BRAF V600E and P63 (majority); negative for thyroglobulin and p16. Final diagnoses were rendered based on combination of cytological features and immunohistochemical profiles. This report highlights the utilization of current biomarkers to distinguish between metastatic dedifferentiated PTC with squamous features and primary lung SCC, as well as the importance of recognizing this rare entity.

Pancreatic mixed acinar-neuroendocrine carcinoma, a unique diagnostic challenge on FNA cytology: A small series of two cases with literature review.

Mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas is a rare tumor. We present two cases of MANEC diagnosed on endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA). The first patient is a 33-year-old male who had a 3.6 cm mass in the uncinate process and liver metastasis. The second patient is a 66-year-old male with a 10 cm mass in the pancreatic tail. The FNA smears from both cases were hypercellular with neoplastic cells in loosely cohesive clusters and many naked nuclei. In both cases, the tumor cells were positive for CKAE1/3, synaptophysin, chromogranin, and trypsin by immunohistochemistry. Final diagnoses of MANEC were rendered based on cytological features and immunohistochemical profiles. To date, 44 cases of MANEC have been reported in the English literature, only three of which were diagnosed on cytopathology specimens before surgical resection. Our report adds two more cases diagnosed on cytopathology alone. Herein, we discuss the various cytomorphologic and clinical features of MANEC and present a brief review of the literature. Diagn. Cytopathol.

Changing the paradigm for diagnostic MRI in pediatrics: Don't hold your breath.

Increasingly complex pediatric patients and improvements in technology warrant reevaluation of the risk associated with anesthesia for diagnostic imaging. Although magnetic resonance imaging is the imaging modality of choice for children given the potentially harmful effects of computerized tomography-associated ionizing radiation, we dare to suggest that certain patients would benefit from the liberalization of our current standard. Incorporating the use of newer computerized tomography technology may improve safety for those that are already at higher risk for adverse events. Furthermore, magnetic resonance imaging is not risk-free-what is often overlooked is the need for controlled ventilation and breath-holding to minimize motion artifact. As physicians at the forefront of the development and sustainability of the perioperative surgical home, anesthesiologists must work to not only optimize patients preoperatively but should also act as gatekeepers for procedural safety.

Nodular Fasciitis of the Posterior Chest Wall With Bone Invasion Mimicking a Malignant Neoplasm.

Nodular fasciitis is a self-limiting benign fibroblastic/myofibroblastic proliferation, which typically presents as a rapidly growing mass resembling an aggressive lesion clinically. It can also mimic a sarcoma histologically, hence the frequent characterization as "pseudosarcoma." We describe a case of a 53-year-old man who presented with a posterior chest wall mass that on imaging showed erosion into the adjacent ribs. After resection, the diagnosis of nodular fasciitis was rendered. Bone erosion by nodular fasciitis is extremely rare and can resemble a malignant neoplasm radiologically.

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

BACKGROUND AND AIMS: The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes. METHODS: In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP. The primary outcomes were time to stent occlusion, attempted surgical resection, or death after the initiation of neoadjuvant therapy, and the secondary outcomes were total patient costs associated with the stent, including the index ERCP cost, downstream hospitalization cost due to stent occlusion, and the cost associated with procedural adverse event. RESULTS: Fifty-four patients were randomized and reached the primary end point: 16 in the fcSEMS group, 17 in the uSEMS group, and 21 in the plastic stent group. No baseline demographic or tumor characteristic differences were noted among the groups. The fcSEMSs had a longer time to stent occlusion compared with uSEMSs and plastic stents (220 vs 74 and 76 days, P < .01), although the groups had equivalent rates of stent occlusion, attempted surgical resection, and death. Although SEMS placement cost more during the index ERCP (uSEMS = $24,874 and fcSEMS = $22,729 vs plastic = $18,701; P < .01), they resulted in higher procedural AE costs per patient (uSEMS = $5522 and fcSEMS = $12,701 vs plastic = $0; P < .01). Conversely, plastic stents resulted in an $11,458 hospitalization cost per patient due to stent occlusion compared with $2301 for uSEMSs and $0 for fcSEMSs (P < .01). CONCLUSIONS: In a prospective trial comparing fcSEMSs, uSEMSs, and plastic stents for malignant biliary obstruction in patients undergoing neoadjuvant therapy with curative intent for pancreatic adenocarcinoma, no stent type was superior in optimizing cost-effectiveness, although fcSEMSs resulted in fewer days of neoadjuvant treatment delay and a longer time to stent occlusion. (Clincial trial registration number: NCT01038713.).

Cytologic rapid on-site evaluation of transthoracic computed tomography-guided lung needle biopsies: who should perform ROSE? A cross-institutional analysis of procedural and diagnostic outcomes.

INTRODUCTION: Cytologic rapid on-site evaluation (ROSE) during minimally invasive biopsy procedures is an increasingly important service provided by cytopathology to increase diagnostic yield and appropriately triage cellular material. Although ROSE can be performed by cytopathologists, cytotechnologists, or cytopathology fellows, few studies have directly compared both procedural and diagnostic outcome measures among different ROSE personnel. MATERIALS AND METHODS: We evaluated all transthoracic computed tomography (CT)-guided lung biopsies in which ROSE was performed during a 1-year period at 2 academic institutions with similar patient populations and procedural methods: Dartmouth-Hitchcock Medical Center (DHMC) (where ROSE is performed by cytopathologists) and the Beth Israel Deaconess Medical Center (BIDMC) (where ROSE is rendered by either cytotechnologists or cytopathology fellows). RESULTS: A total of 273 CT-guided transthoracic lung biopsies (190 DHMC, 83 BIDMC) were analyzed. There was no major difference in procedure time with respect to ROSE personnel. The repeat procedure rate for nondiagnostic biopsies was similar at DHMC (cytopathologists) and BIDMC (cytotechnologists or cytology fellows) (2.1% versus 2.3%, P = 1.0). Adequacy rates for cytopathologists, cytotechnologists, and cytopathology fellows were comparable (P = 0.23). ROSE assessments by cytopathologists were more concordant with the final diagnosis (87%) than those by cytotechnologists (82%) or cytopathology fellows (79%); this difference was not statistically significant (P = 0.28). CONCLUSIONS: ROSE procedural and diagnostic outcomes for transthoracic CT-guided lung biopsies were similar among cytopathologists, cytotechnologists, and cytopathology fellows.

The effect of neoadjuvant chemoradiation on pancreatic cancer-associated diabetes mellitus.

OBJECTIVES: Pancreatic cancer-associated diabetes mellitus (PaCDM) occurs in approximately 50% of patients. In patients with new-onset PaCDM undergoing neoadjuvant chemoradiation therapy before surgical resection, we hypothesized that pancreatic tumor destruction would lead to improvement in fasting glucose levels. METHODS: A retrospective chart review was performed on patients with newly diagnosed pancreatic adenocarcinoma without a history of DM treated with neoadjuvant therapy at our center. All patients underwent combined modality neoadjuvant chemoradiation therapy, followed by surgical excision of the primary tumor. RESULTS: Sixty-nine patients (31 with PaCDM) met inclusion criteria for the study; 18 had Evans grade II tumor kill response, 10 had grade III response, and 3 had grade IV response. In patients with grade IV response, the odds ratio (OR) for achieving a normal preoperative glucose was 5.0 (95% confidence interval [CI], 0.4-63.2), compared with grade III (OR, 0.5; 95% CI, 0.1-3.0) and grade II (OR, 1.1; 95% CI, 0.2-5.2). When adjusted for percent kilogram weight loss and tumor size in a multivariable regression model, the grade IV response became significant to an OR of 6.5 (95% CI, 1.2-77.3). CONCLUSIONS: In patients with new-onset PaCDM undergoing neoadjuvant chemoradiation therapy, fasting glucose response may mirror the extent of tumor destruction.

Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations.

BACKGROUND: Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2. METHODS: Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer. RESULTS: A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes. CONCLUSIONS: Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts have identified mutational spectra in several subtypes of these tumors that may suggest a phenotypic heterogeneity showing mutations that are relevant for targeted therapies.

Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults.

OBJECTIVES: The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. METHODS: This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. RESULTS: Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). CONCLUSIONS: Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.

Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique.

PURPOSE: To develop an interventional hindlimb ischemic model and compare its angiogenic effect versus surgical ligation (SL) and excision of the femoral artery in rats treated with transplantation of bone marrow mononuclear cells (MNCs) as an angiogenic stimulator. MATERIALS AND METHODS: Forty-eight Lewis rats randomly received interventional embolization (IE) with hydrogel wire or SL and excision of the right femoral artery. Rodents were intraarterially transplanted with 1.5 × 10(7) MNCs in 500 µL medium from 24 isogenic donor rats. Functional and structural recovery was evaluated by laser Doppler imaging (LDI), cytokine/chemokine assay, and histologic staining. RESULTS: In vivo microscopic images showed significantly dilated vasa vasorum around the embolized segment of the right femoral artery at 3 days compared with disorganized tissue structure in the SL group. However, the LDI index was significantly higher in the SL group at 3 days compared with the IE group. LDI did not significantly differ between the two groups at 2 weeks after transplantation. Cytokine assay showed higher levels of interleukin (IL)-1α and IL-18 in the SL group; the IE group had higher levels of interferon-γ, IL-6, IL-13, and granulocyte colony-stimulating factor. Histologic examination demonstrated inflammatory infiltration near the incision within nerve fibers with dilated capillaries, showing nerve degeneration in the SL group. At 2 weeks, histologic analysis demonstrated massive scarring under the skin spreading into the musculature in the SL group. CONCLUSIONS: A minimally invasive hindlimb ischemia model has been successfully developed that preserves tissue integrity and minimizes inflammation and confounding factors in the early stages of angiogenesis and arteriogenesis.

Effect of initiating a multidisciplinary care clinic on access and time to treatment in patients with pancreatic adenocarcinoma.

PURPOSE: Neoadjuvant therapy for pancreatic adenocarcinoma requires referral to multiple specialists before initiating therapy. We evaluated the effect of establishing a multidisciplinary clinic (MDC) for patients with newly diagnosed pancreatic adenocarcinoma on treatment access and time to therapy. METHODS: Patients with newly diagnosed pancreatic adenocarcinoma diagnosed and treated at our center were included. Two patient groups were defined: preclinic represented those patients diagnosed before 2008 and MDC represented those patients diagnosed since 2009 who were treated in the newly created MDC and were initially candidates for neoadjuvant therapy. The primary outcomes were days from diagnosis to first treatment (initiation of chemotherapy or external beam radiation), days to completion of all required consultations, and number of visits needed before initiation of therapy. RESULTS: Ninety-seven patients were diagnosed and treated at our medical center from 2003 to 2008; 22 were treated in 2009 after the implementation of the MDC. Compared with the preclinic group, patients treated in the MDC had shorter times from biopsy to treatment (7.7 days v 29.5 days, P < .001), shorter time to completion of all required pretreatment consultations (7.1 days v 13.9 days, P < .001), and fewer visits to complete all consultations (1.1 v 4.3, P < .001). Thirty-three percent of patients seen in the MDC enrolled onto clinical research trials. CONCLUSION: In patients with pancreatic adenocarcinoma undergoing neoadjuvant therapy, the establishment of a multidisciplinary pancreas tumor clinic led to improved patient access to consultations and shorter time to initial treatment.

Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: Pancreatic cancer remains highly lethal. Previous attempts with neoadjuvant therapy in this disease have been inconclusive, but a potential for benefit exists. We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. METHODS: Patients with stage I to III disease were eligible. Docetaxel 65 mg/m(2) intravenously over 1 hour and gemcitabine 4000 mg/m(2) given intravenously over 30 minutes were given on days 1, 15, and 29. On day 43, radiotherapy was begun at 50.4 Gy with gemcitabine 50 mg/m(2) intravenously over 30 minutes twice weekly for 12 doses. After treatment, patients were considered for resection. RESULTS: Twenty-four assessable patients were recruited onto the trial. All but one patient completed a full 12 weeks of therapy. Grade 3 and 4 hematological and nonhematological toxicities were common but manageable, and neutropenic fever did not occur. No patient had local tumor progression. Twelve patients (50%) responded by Response Evaluation Criteria in Solid Tumors Group (RECIST) criteria, including one radiographic complete response. Seventeen patients underwent resection after therapy. Margin-negative resections were performed in 13 patients, including 9 patients whose disease was borderline or unresectable before treatment. A treatment effect was seen in all resection specimens. There have been no local recurrences of tumor, and several patients remain alive without evidence of disease. CONCLUSIONS: Docetaxel/gemcitabine followed by gemcitabine/radiotherapy is active in the treatment of pancreatic adenocarcinoma, with manageable toxicity. Tumor downstaging occurs in some patients to allow complete resection. Further investigation of this regimen is warranted.