Principles of cancer treatment by radiotherapy

Radiotherapy (or radiation therapy) uses ionizing radiation to selectively kill cancer cells, especially for solid tumours. Like surgery, it is meant to be a ‘local’ treatment, although its beneficial systemic effects are being discovered. It is most commonly used in addition to surgery (adjuvant, e.g. breast), but its role in the neoadjuvant setting in combination with chemotherapy for some cancers (e.g. rectum) is also established. In early stages of cancer, it can be the definitive treatment, avoiding surgery and enabling organ preservation (e.g. larynx), while in late stages, it can provide excellent palliation (e.g. bone metastasis). Radiotherapy can be delivered at various energy levels (kiloVolts, megaVolts), with various subatomic particles (e.g. electrons, protons, and high-energy electromagnetic radiation). The traditional bulky equipment (e.g. linear accelerator) needs to be housed in an underground bunker and uses complex imaging to improve precision and avoid radiation to normal tissues. Fractionated regimens spanning several days reduce individual doses. Modern techniques using mobile devices (e.g. TARGIT-IORT) can deliver radiotherapy during surgery with the highest precision and immediacy.     

Heart Transplantation for Giant Cell Myocarditis: A Case Series

BackgroundGiant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown.PurposeTo describe the post-transplant survival of patients with GCM at a large transplant center.MethodsSeven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone.ResultsOne patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant.ConclusionsPatients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.     

Correlates of hopelessness in psychiatrically hospitalized children

The importance of hopelessness within the study of childhood psychiatric disorders is becoming increasingly apparent. The present study divides a child inpatient sample (age 7 to 12 years) into two groups based on scores from the Kazdin Hopelessness Scale for Children. Comparisons made between the two groups on various measures showed that children with high hopelessness had lower cognitive ability, "difficult child" temperament characteristics, more anxiety, lower self-esteem, and a higher degree of psychopathology than the low-hopelessness group. The role of hopelessness in academic success and future psychopathology are discussed.     

Pedicle screw fixation of the C7 vertebra using an anteroposterior fluoroscopic imaging technique

Cervical pedicle screws have been reported to be biomechanically superior to lateral mass screws. However, placement of these implants is a technical challenge. The purpose of this investigation was to use an anatomic and a clinical study to evaluate a technique for placement of the pedicle screws in the C7 vertebra using fluoroscopic imaging in only the anteroposterior (A/P) plane. Ten adult cadaver C7 vertebrae were used to record the pedicle width, inclination and a suitable entry point for placement of pedicle screws. A prospective study of 28 patients undergoing posterior instrumentation of the cervical spine with C7 pedicle screw placement was also performed. A total of 55 C7 pedicle screws were placed using imaging only in the A/P plane with screw trajectory values obtained by the anatomic study. Radiographs and CT scans were performed post-operatively. The average posterior pedicle diameter of C7 vertebra was 9.5 ± 1.2 mm in this study. The average middle pedicle diameter was 7.1 mm and the average anterior pedicle diameter was 9.2 mm. The average transverse pedicle angle was 26.8 on the right and 27.3 on the left. CT scans were obtained on 20 of 28 patients which showed two asymptomatic cortical wall perforations. One screw penetrated the lateral wall of the pedicle and another displayed an anterior vertebral penetration. There were no medial wall perforations. The preliminary results suggest that this technique is safe and suitable for pedicle screw placement in the C7 vertebra.     

Total knee arthroplasty: Limb length discrepancy and functional outcome

Background:

Limb length discrepancy and its effects on patient function have been discussed in depth in the literature with respect to hip arthroplasty but there are few studies that have examined the effect on function of limb length discrepency following total knee arthroplasty (TKA). The aim of this study was to determine whether limb length discrepancy after TKA in patients with bilateral osteoarthritis of knee with varus deformity affects functional outcome.

Materials and Methods:

Fifty-four patients with bilateral osteoarthritis of knee with varus deformity, who were operated for total knee arthroplasty from 1996 to 2008, were reviewed retrospectively. The patients were divided into two groups. Thirty patients (mean age 64 years) were operated for unilateral TKA and thirty patients (mean age 65.8 years) were operated for bilateral total knee arthroplasty. Six patients underwent staged surgery and were included in both groups as the time interval between the two surgeries was more than the minimum 6-month follow-up period specified for inclusion in the study. The limb length discrepancy was measured and statistically correlated with the functional component of the Knee Society Score.

Result:

In the unilateral group (n=30), the mean limb length discrepancy was 1.53 cm (range: 0-3 cm) and the mean functional score was 73 (range: 45-100). In the bilateral group (n=30), the mean limb length discrepancy was 0.5 cm (range: 0-2 cm) and the mean functional score was 80.67 (range: 0-100). A statistically significant negative correlation was found between limb length discrepancy and functional score in the unilateral group (Spearman correlation coefficient, r =−0.52, P=0.006), while no statistically significant correlation was found in the bilateral group (Spearman correlation coefficient, r = −0.141, P=0.458).

Conclusion:

Limb length discrepancy affects functional outcome after total knee arthroplasty, especially so in patients of bilateral osteoarthritis with varus deformity undergoing surgery of only one knee.     

Renal function in type 1 diabetics one year after successful pancreas transplantation

Chatzizacharias NA, Vaidya A, Sinha S, Smith R, Jones G, Sharples E, Friend PJ. Renal function in type 1 diabetics one year after successful pancreas transplantation.
Clin Transplant 2011: 25: E509–E515. © 2011 John Wiley & Sons A/S. Abstract: The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single‐unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty‐nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post‐transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m²) and low (≤45 mL/min/1.73 m²) pre‐transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post‐transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post‐transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre‐existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.     

Interbody fusion with allograft and rhBMP-2 leads to consistent fusion but early subsidence

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.     

Metastasis Suppressors and Their Roles in Breast Carcinoma

Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus distinct from tumor suppressors. As the biology underlying functional mechanisms of metastasis suppressors becomes clearer, it is evident that metastasis suppressors could be harnessed as direct drug targets, prognostic markers, and to understand the fundamental biology of the metastatic process. Metastasis suppressors vary widely in their cellular localization: they are found in every cellular compartment and some are secreted. In general, metastasis suppressors appear to regulate selectively how cells respond to exogenous signals, by affecting signaling cascades which regulate downstream gene expression. This review briefly summarizes current functional and biochemical data on metastasis suppressors implicated in breast cancer. We also present a schematic integrating known mechanisms for these metastasis suppressors highlighting potential targets for therapeutic intervention.