Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model

BackgroundWe inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes in fluorescent orthotopic nude mouse models of human colon cancer.MethodsWe established fluorescent orthotopic mouse models of human colon cancer expressing a fluorescent protein. Tumors were resected under bright light surgery (BLS) or FGS. Pre- and post-operative images with the OV-100 Small Animal Imaging System (Olympus Corp, Tokyo Japan) were obtained to assess the extent of surgical resection.ResultsAll mice with primary tumor that had undergone FGS had complete resection compared with 58% of mice in the BLS group (P = 0.001). FGS resulted in decreased recurrence compared with BLS (33% versus 62%, P = 0.049) and lengthened disease-free median survival from 9 to >36 wk. The median overall survival increased from 16 wk in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice (alive without evidence of tumor at >6 mo after surgery) compared with only 37% of mice that underwent BLS (P = 0.049).ConclusionsSurgical outcomes in orthotopic nude mouse models of human colon cancer were significantly improved with FGS. The present study can be translated to the clinic by various effective methods of fluorescently labeling tumors.     

In vivo serial selection of human pancreatic cancer cells in orthotopic mouse models produces high metastatic variants irrespective of Kras status

Introduction

Kras mutations have been thought to play an important role in pancreatic cancer progression. In this study, we evaluated how serially passaging primary pancreatic tumors with and without Kras mutations, in nude mice, can generate more aggressive variants of human pancreatic cancer.

Materials & methods

Orthotopic mouse models of human pancreatic cancer were established by injecting 1 × 10⁶ cells of the Kras wildtype BxPC-3 cell line, expressing red fluorescent protein or the Kras mutant Panc-1 cell line expressing green fluorescent protein, into the pancreas. Pancreatic tumors were harvested from premorbid mice to establish cell lines. One million passaged cells were then orthotopically injected into another set of mice. Serial passaging continued until decreasing lifespan of the implanted mice stabilized, which occurred by six passages. Mice harboring serially-passaged cell lines were followed with weekly imaging.

Results

Serially passaging generated more aggressive variants of both human pancreatic cancer cell lines, one of which was Kras wild-type (BXPC-3) and the other Kras mutant, Panc-1, which displayed faster tumor growth and shortened survival time. Overall survival decreased from 18 wk in mice with the parental cell line (passage 0) tumor to ∼6 wk in mice by passage 6. Average time to metastasis was shortened from 14 wk to ∼3 wk or less. At termination, mice with the passaged tumor demonstrated a greater extent of distant metastasis.

Conclusions

Serial passaging of tumor creates more aggressive variants of human pancreatic cancer cell lines regardless of Kras mutation. The aggressive variants can be used to study the molecular basis of highly malignant pancreatic cancer and to screen for effective agents against this disease.     

Traumatic abdominal wall hernia: Delayed repair: Advantageous or taxing

INTRODUCTIONTraumatic abdominal wall hernia (TAWH) is a rare entity. Most cases occur in children, following an injury from the bicycle handle bar. In adults, it usually results from road traffic accidents (RTA). We present one of the largest reported cases of TAWH following RTA managed by delayed mesh repair.PRESENTATION OF CASEA 35 yr old obese male with RTA was diagnosed with TAWH with 19 cm × 15 cm defect in left flank. As there were no intra abdominal injuries and overlying skin was abraded, he was planned for elective repair after 6 months. On exploration a defect of 30 cm × 45 cm was found extending from midline anteriorly to 8 cm short of midline posteriorly in transverse axis and costal margin to iliac crest in craniocaudal axis. After restoration of bowel into abdominal cavity, primary closure or even approximation of muscular defect was not possible thus a mesh closure using 60 cm × 60 cm prolene mesh in subcutaneous plane was done. After 4 months follow up, patient is healthy and has no recurrence.DISCUSSIONEmergent surgical management of TAWH is usually favoured due to high incidence of associated intra abdominal injuries. Delayed repair may be undertaken in selected cases.CONCLUSIONTAWH, although rare, should be suspected in cases of RTA with abdominal wall swellings. With time, the hernia defect may enlarge and muscles may undergo atrophy making delayed repair difficult.     

Parathyroid lesions: Difficult diagnosis on cytology

Cytology of parathyroid lesion (PL) is often confused with that of thyroid lesions. Differentiation between thyroid and PL is very difficult on cytomorphology because of their similar features and close anatomical proximity. Three cases of PLs reported on cytology in last one year were retrieved from archives of cytology department. Their cytomorphological details were studied and were correlated with the available biochemical parameters. Histopathology was available in two cases. Radiological assistance and parathyroid hormone (PTH) assessment in our cases formed the basis of diagnosing PLs on cytology. We discuss the differential diagnosis and pitfalls in cytological diagnosis of PLs. However, histopathology remains the gold standard for diagnosis. Interpretation of PLs on cytology remains problematic due to its rarity and limited available literature. The cytomorphology combined with clinical and biochemical data supported by histopathology are necessary to improve the diagnostic sensitivity of PLs. Diagn. Cytopathol. 2016;44:704–709. © 2016 Wiley Periodicals, Inc.     

Individualism-Collectivism,Social Self-Control and Adolescent Substance Use and Risky Sexual Behavior

Individualism and collectivism are cultural syndromes that have been associated with adolescent problem behavior in studies conducted in the U.S. and Southeast Asia. However, research investigating the mechanisms of how cultural orientation impacts health risk behaviors has been limited. This study tested a new model explaining the relationship between cultural orientation (i.e., individualism, collectivism) and adolescent problem behavior (i.e., substance use and risky sex) in terms of interpersonal self-regulation (i.e., social self-control). As such, the study is rooted in theories of the role of culture in developing self-regulation. Participants were high school students (N = 716) from the Bashkirtostan Republic of the Russian Federation. Adolescents from the Russian Federation tend to show high prevalence of cigarette smoking and binge drinking. People of the Russian Federation in general are traditionally collectivist in orientation, although increased globalization and post-Soviet capitalism may indicate high individualist values in younger generation Russians. Using path analysis we found that in addition to having direct effects, higher individualism indirectly affected substance use and risky sexual behavior through social self-control and negative life events. Higher collectivism was found to have a direct protective effect on risky sexual behavior and a direct effect on social self-control. However, collectivism was not found to have indirect effects on substance use or risky sexual behavior. Higher individualism appears to function as a risk factor for adolescent problem behavior and this relationship may be mediated by lower social self-control. Culturally-tailored prevention programs utilizing the individualism-collectivism framework may benefit from addressing social self-control.     

Costs of adverse events in intensive care units

CONTEXT: Iatrogenic injuries are very common in critically ill adults. However, the financial implications of these events are incompletely understood. OBJECTIVE: To determine the costs of adverse events in patients in the medical intensive care unit and in the cardiac intensive care unit. DESIGN, SETTING, AND PATIENTS: We performed a matched case-control analysis on data collected during a prospective 1-yr observation study (July 2002 to June 2003) of medical intensive care unit and cardiac intensive care unit patients at an academic, tertiary care urban hospital. A total of 108 cases were matched with 375 controls in our study. MAIN OUTCOME MEASURES: Costs of care and lengths of stay were determined from hospital billing systems for patients in the medical and cardiac intensive care units. We then determined the incremental costs and lengths of stay for patients with adverse events compared with patients without events while in the intensive care unit. Costs were truncated for patients with a second adverse event on a subsequent day during the intensive care unit stay. RESULTS: For 56 medical intensive care unit patients, the cost of an adverse event was $3,961 (p = .010) and the increase in length of stay was 0.77 days (p = .048). This extrapolated to annual costs of $853,000 for adverse events in the medical intensive care unit. Similarly, for 52 cardiac intensive care unit patients, the cost of an adverse event was $3,857 (p = .023), corresponding to $630,000 in annual costs. On average, patients with events in the cardiac intensive care unit had an increase of 1.08 days in length of stay (p = .003). CONCLUSIONS: Patients who require intensive care are especially at risk for adverse events, and the associated costs with such events are substantial. The costs of adverse events may justify further investment in prevention strategies.     

Case report of a uniocular topography guided laser-assisted in situ keratomileusis enhancement following an incorrectly treated astigmatic axis

A 23-year-old male presented to us wanting spectacle removal for cosmetic purposes. He underwent bilateral wavefront optimized (WFO) laser-assisted in situ keratomileusis (LASIK) on the Alcon Wavelight^® EX-500 excimer laser with an incorrectly treated astigmatism axis for left eye due to a manual data entry error in the laser. WFO LASIK treats the sphere and cylinder only. LASIK enhancement with topographic-guided ablation resulted in the elimination of all refractive errors and gave excellent results. Wavelight^® topographic-guided treatment can perform two separate layers of correction in the same ablation: The first is to treat the corneal irregularities for the higher order aberration (HOA) removal, the second one meant to treat the sphere and cylinder if indicated.     

Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology.