Pulmonary toxicities from targeted therapies: a review

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.     

Van der Woude syndrome: dentofacial features and implications for clinical practice

Background:  Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis.
Methods:  A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort.
Results:  The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals.
Conclusions:  Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.     

Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: an open label pilot study

Background  Intralesional immunotherapy with skin test antigens and vaccines has been found to be effective in the management of genital and extragenital warts.
Objective  To evaluate the efficacy and safety of intralesional Mycobacterium w (M w ) vaccine monotherapy for the treatment of ano-genital warts.
Patients and methods  Ten patients clinically diagnosed to have external ano-genital warts, including three with giant ano-genital warts (Buschke Löwenstein tumour), were included in this open-label pilot study. Two patients were human immunodeficiency virus seropositive, and one was on iatrogenic immunosuppression for renal transplantation. M w vaccine (0.1 mL) was initially injected intradermally in the deltoid region on both the sides, followed 2 weeks later by intradermal intralesional injection into the genital warts. Intralesional injections were repeated weekly until either complete clearance or a maximum of 10 injections was achieved.
Results  One patient was lost to follow-up after the first intralesional injection. In 8 out of remaining 9 patients (88.9%), the genital warts cleared completely. In one patient with giant perianal wart, the lesion was reduced to less than 5% of its volume after 10 intralesional injections, which was later electrosurgically excised. The treatment was well tolerated by the majority of the patients. The adverse reactions were noted in four patients, which were reversible. No recurrence was seen after a mean follow-up of 5.1 months.
Conclusion  Intralesional immunotherapy of ano-genital warts with M w vaccine seems to be a promising new approach, which needs to be evaluated in the randomized controlled trials.     

Internal fixation and muscle pedicle bone grafting in femoral neck fractures

Background:

The treatment of displaced intracapsular femoral neck fracture is still an unsolved problem. Non-union and avascular necrosis are the two main complications of this fracture, especially if patient presents late. Muscle pedicle bone grafting has been advocated to provide additional blood supply. We present analysis of our 32 cases of displaced femoral neck fracture treated by internal fixation and quadratus femoris based muscle pedicle bone grafting.

Materials and Methods:

Open reduction and internal fixation with muscle pedicle grafting was done in 32 patients. The age of patients varied from 14-62 years (average age 45 years) with male to female ratio of 13:3. Twenty-nine fractures were more than three weeks old. All the cases were treated by Meyers'' procedure. The fracture was internally fixed after open reduction and then a muscle pedicle graft was applied. It was supplemented by cancellous bone graft in seven cases. Fixation was done by parallel cancellous lag screws (n = 19), crossed Garden''s screws (n = 7), parallel Asnis screws (n = 5) and Moore''s pin (n = 1).Quadratus femoris muscle pedicle graft was used in 32 cases. In the initial 12 cases the graft was fixed with circumferential proline sutures, but later, to provide a secure fixation, the graft was fixed with a cancellous screw (n = 20). Postoperative full weight bearing was deferred to an average of 10 weeks.

Results:

Union was achieved in 26/29 (89.65%) cases which could be followed for an average period of 3.4 years, (2-8.5 years) with good functional results and had the ability to squat and sit cross-legged. Results were based on hip rating system given by Salvatti and Wilson. The results were excellent in 15 cases, good in four cases, fair in four cases and poor in six cases. Complications were avascular necrosis (n = 2), transient foot drop (n = 2), coxa-vara (n = 1) and temporary loss of scrotal sensation (n = 1).

Conclusion:

Muscle pedicle bone grafting with internal fixation is a viable treatment option in displaced femoral neck fractures with late presentation.     

Single‐port appendectomy in obese children: an optimal alternative?

Introduction: The aim of this study was to evaluate our experience with single‐port appendectomy (SPA) in obese children. Methods: From January 2003 to June 2009, 94 SPA (65 women and 29 men, mean age of 12.4 years) were performed in children with appendicitis. Sixty‐five of these patients were found to have normal weight, whereas 29 were obese. Patients’ records were evaluated regarding operative time, intra‐ and post‐operative complications, initiation of oral intake and histopathological findings. Results: There was no significant difference in operative time between obese and normal weight patients. In the obese group, one wound healing disturbance was documented. In the normal weight group, there were one post‐operative bleeding and one wound infection. There was no difference with regards to the introduction of feeds following appendectomy between the groups. Histological examinations revealed 15 normal, 32 acute, 21 phlegmonous, 20 chronic and two perforated cases of appendicitis, three neurogenic appendicopathies and one case of enterobius vermicularis related appendicitis. Conclusions: Our results indicate that the advantages of single‐port appendectomy in the evaluation of the peritoneal cavity, the minimal rate of intra‐operative incidents with this technique and superior cosmetics validate this alternative approach of minimal access appendectomy in obese children.     

Perianal anatomy in non-abused preschool children

The purpose of this study was to describe the normal variation in perianal anatomy in preschool children, selected for non-abuse, and to compare the findings in two examination positions. A letter of invitation was sent to 3773 children, after which 305 children (103 boys and 202 girls) were recruited. Inclusion in the study was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their child gave informed consent to participate. The mean age of the children was 5.63 y (range: 5.13-6.75). An anal examination was performed in the left lateral position (LLP) and the prone knee-chest position (KCP), for approximately 30 s each. A colposcope and a camera were used. All data were systematically analysed for gender differences, and a paired sample test was used to compare findings in LLP and KCP. Venous congestion in LLP and external anal dilatation in both positions were significantly more common in girls, while midline depressions and smooth areas (both positions) were significantly more common in boys. External and total anal dilatation, midline smooth areas and depressions and the occurrence of a prominent anal verge were significantly more common in the KCP. The finding of total anal dilatation was rare. CONCLUSION: We observed several gender and position differences in perianal anatomy, and most of these findings seem to be related to structure and tone in the anal muscles.     

Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma.

Both epidermal growth factor receptor (EGFR) and ErbB-2 play an important role in cancer biology and constitute promising molecular targets of therapy. EGFR and ErbB-2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors. Tissue microarray sections representing 66 rhabdomyosarcoma tumors (34 embryonal rhabdomyosarcoma, 32 alveolar rhabdomyosarcoma) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB-2. Immunostains were assessed for intensity (0: no immunostaining; 1: weak; 2: moderate; 3: strong) and percentage of at least 500 neoplastic cells exhibiting membranous or membranous and cytoplasmic immunostaining. EGFR and ErbB-2 expression was considered positive if the product of intensity and percentage was greater than 10. Patients had a median age of 5.7 years (range 8 months-19.1 years), and of 65/66 patients, 38 were males and 27 were females. Expression of ErbB-2 was identified in 22/66 (33%) cases and tended to be more frequent in the alveolar subtype (13/32, 41%, vs 9/34, 26%, P=0.30). Expression of EGFR was identified in 31/66 (47%) cases and correlated with the embryonal subtype (26/34, 76%, vs 5/32, 16%, P<0.0001) independent of stage, age, and gender. Coexpression of EGFR and ErbB-2 was identified in eight tumors, of which six were embryonal rhabdomyosarcoma. None of the cases exhibited EGFR or ErbB-2 gene amplification, as assessed using fluorescence in situ hybridization. Furthermore, analysis of 11 additional rhabdomyosarcoma tumors (six alveolar; five embryonal) revealed no evidence of mutations in EGFR exons 18, 19, 20, and 21. In summary, expression of EGFR and/or ErbB-2 is detected in a sizeable subset of rhabdomyosarcoma tumors without evidence of EGFR or ErbB-2 amplification or mutations in the EGFR tyrosine kinase domain. Notably, expression of EGFR correlates with the embryonal subtype, which is also more likely to coexpress EGFR and ErbB-2.