Foot Arch Changes after Endoscopic Plantar Fascia Release for Recalcitrant Plantar Fasciitis.

Introduction: Endoscopic plantar fascia release (EPFR) is a minimally invasive surgical intervention for recalcitrant plantar fasciitis. Its efficacy has been convincing but the in vivo effect on medial longitudinal foot arch and footprint has not been studied. Our objective is to evaluate the changes of foot posture using radiographs and footprints following endoscopic plantar fascia release in recalcitrant plantar fasciitis. Materials and methods: This prospective cohort involved patients with recalcitrant plantar fasciitis who failed six months of conservative treatment. Two-portal endoscopic release of not more than 50% of plantar fascia width was performed. Footprint and standard weight-bearing anteroposterior and lateral radiographs of the foot were taken pre-operatively and at 12 months post-surgery. Arch index, normalised navicular height truncated, calcaneal inclination angle, calcano-1st metatarsal angle, talonavicular coverage angle and talus-2nd metatarsal angle were measured. Results: Sixteen patients (18 feet) were reported. Patients' follow-up ranged from 14 to 31 months after surgery (mean±SD: 23.44±5.76). The increase of arch index, calcano-1st metatarsal angle and reduction of calcaneal inclination angle were found statistically significant (p<0.05). Two normal arch patients progressed to asymptomatic flat arch feet. Three complications were noted between three to nine months post-surgery, one with medial column and two with lateral column symptoms. Conclusion: There is evidence of reduction in medial longitudinal arch of the foot after EPFR. Although the reduction remains asymptomatic, post-operative complications related to changes in biomechanics of the foot can occur between three to nine months. Patients should be monitored at least for 12 months and longer for those who are symptomatic.

Legacy effect of short-term alirocumab in familial hypercholesterolaemia: A case report.

Homozygous familial hypercholesterolaemia (FH) is a rare genetic disorder with aberrantly high level of low-density lipoprotein cholesterol (LDL-C) requiring multiple combined aggressive lipidlowering therapy to reduce the progression of atherosclerotic cardiovascular disease. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) has been approved for treatment of FH, which requires further lowering of LDL-C in addition to diet modification and maximally tolerated statin therapy. We report the response of short-term alirocumab treatment on a young patient with clinically and genetically confirmed FH, who suffered from acute coronary syndrome, and in particular, discussed the hypothesised legacy effect of PCSK9i. The patient was initially treated with a combination of high-intensity statin and ezetimibe for 12 weeks. Subsequently, alirocumab was added to the patient's lipid-lowering regime and he managed to attain guideline recommended LDL-C target within 10 weeks. However, alirocumab was stopped at week 54 due to financial constraint. Interestingly, despite cessation of PCSK9i therapy for a period of 30 weeks, the patient's LDL-C level rose slightly not returning to his baseline level.

Antimicrobial gauze as a dressing reduces pin site infection: a randomized controlled trial.

BACKGROUND: Pin site infection is a common problem in external fixation. Plain gauze wetted with normal saline is commonly used for a pin site dressing owing to the simplicity and low cost. Evidence to support adding an antimicrobial agent in the dressing material is lacking. QUESTIONS/PURPOSES: We compared the rate of pin tract infection using plain gauze and gauze impregnated with polyhexamethylene biguanide in patients undergoing limb lengthening procedures. PATIENTS AND METHODS: We included 38 patients (40 limbs) undergoing limb lengthening or deformity correction using an external fixator between July 2009 and June 2010. There were 23 male patients and 15 female patients, with a mean age of 26.3 years (range, 5-68 years). The patients were randomized into two groups: a polyhexamethylene biguanide group (22 limbs) and a control group (18 limbs). The metal-skin interfaces were assessed by a researcher blinded to the type of gauze at 2, 4, 8, and 12 weeks after surgery for the pin site infection based on a predetermined grading system. There were a total of 483 metal-skin interfaces, with 1932 total observations. Infection rates were compared using the chi square test and relative risk with 95% confidence interval. RESULTS: The infection rate was lower (χ(2) [1, n = 1932] = 23.00) and the risk for infection was lower (relative risk, 0.228; 95% confidence interval, 0.118, 0.443) for the polyhexamethylene biguanide group (n = 1068; 1.0%) than for the control group (n = 864; 4.5%). CONCLUSIONS: Use of polyhexamethylene biguanide-impregnated gauze can reduce the risk of pin tract infection in external fixation. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection.

BACKGROUND: Perioperative chemotherapy improves outcome in resectable colorectal liver-only metastasis (CLM). This study aimed to evaluate perioperative CAPOX (capecitabine-oxaliplatin) plus bevacizumab in patients with poor-risk CLM not selected for upfront resection. PATIENTS AND METHODS: Poor-risk CLM was defined as follows: more than four metastases, diameter >5 cm, R0 resection unlikely, inadequate viable liver function if undergoing upfront resection, inability to retain liver vascular supply, or synchronous colorectal primary presentation. Patients underwent baseline computed tomography, magnetic resonance imaging, and/or positron emission tomography (PET) for staging and received neoadjuvant CAPOX plus bevacizumab, with resectability assessed every four cycles. Primary end point was radiological objective response rate (ORR). RESULTS: Forty-six patients were recruited, of which 91% underwent PET to ensure metastases confined to liver. Following neoadjuvant CAPOX plus bevacizumab, the ORR was 78% (95% confidence interval 63% to 89%). This allowed 12 of 30 (40%) patients with initial nonsynchronous unresectable CLM to be converted to resectability. In addition, 10 of 15 (67%) patients with synchronous resectable CLM underwent liver resection, with four additional patients being observed alone due to excellent response to neoadjuvant therapy. No grade 3-4 perioperative complications were seen. CONCLUSION: Neoadjuvant CAPOX plus bevacizumab resulted in a high response rate for patients with CLMs with poor-risk features not selected for upfront resection and converted 40% of patients to resectability.

Percutaneous transcatheter aortic valve replacement: first transapical implant in Asia.

Percutaneous transcatheter implantation of the aortic valve has been demonstrated as an alternative to open heart surgery in high-risk patients with symptomatic severe aortic stenosis (AS) who are not suitable for open surgery. The majority of these new devices are delivered via the transfemoral approach. However, due to the current size of delivery sheaths, the small and tortuous iliofemoral anatomy makes this approach challenging. The transapical approach provides a viable option for this patient subgroup. The first-in-Asia transcatheter aortic valve implantation via the transapical route is described. A 79-year-old Chinese woman with symptomatic severe AS and peripheral arterial disease, who was at high surgical risk, was successfully treated, and had good functional and haemodynamic results at the three-month follow-up.

The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene.

Neuregulin-1 (NRG1) is both a candidate oncogene and a candidate tumour suppressor gene. It not only encodes the heregulins and other mitogenic ligands for the ERBB family, but also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than that in various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, whereas normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. Small interfering RNA (siRNA)-mediated depletion of NRG1 increased net proliferation in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is antiproliferative and is silenced in many breast cancers.

Resection of a giant malignant mediastinal peripheral nerve sheath tumour under cardiopulmonary bypass.

Malignant peripheral nerve sheath tumour (MPNST) is a rare occurrence in the mediastinum. It is biologically aggressive and is generally resistant to chemoradiation therapy. The mainstay of treatment is complete surgical resection. We report a large MPNST which invaded into the adjacent aortic wall in a 50-year-old man. Extensive resection, which included aortic reconstruction under cardiopulmonary bypass and deep hypothermic arrest, was necessary for a good long-term outcome.

Percutaneous transcatheter aortic valve replacement: first transfemoral implant in Asia.

Surgical aortic valve replacement (AVR) is the standard of care for patients with symptomatic severe aortic stenosis (AS), providing relief of symptoms and prolonging survival. However, many patients are either denied or not offered surgery due to high surgical risk or non-operability for open AVR. The technology of percutaneous aortic valve implantation emerged in 2002, and has since evolved rapidly with satisfactory results. Currently, almost all the procedures are performed predominantly in Europe and North America. The first-in-Asia percutaneous transcatheter aortic valve implantation via the transfemoral route is described. A 77-year-old man with symptomatic severe AS and at high surgical risk was successfully treated, with sustained clinical improvement and satisfactory haemodynamic results at 30-day follow-up.

Pancreatic cancer--is the wall crumbling?

In spite of advances made in the management of the other more common cancers of the gastrointestinal tract, significant progress in the treatment of pancreatic cancer remains elusive, more so with the recent negative results of several much anticipated randomized trials. Gemcitabine has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil (5-FU). Since then, clinical trials have explored the pharmacokinetic modulation of gemcitabine by fixed dose administration and the combination of gemcitabine with other cytotoxics or the biological 'targeted' agents. Against a background of numerous negative randomized trials of gemcitabine-based combination treatment, two trials have recently reported modest survival improvements with the use of combination treatment: the United Kingdom National Cancer Research GEMCAP trial of gemcitabine with the orally administered precursor of 5-FU-capecitabine and the National Cancer Institute of Canada Clinical Trials Group PA.3 trial in which the tyrosine kinase inhibitor erlotinib was used with gemcitabine. This review will summarize the results of several recent randomized trials of combination treatment in advanced pancreatic cancer and discuss their implications for clinical practice and for future research in this disease.

Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes.

Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.

Ovarian tumors of borderline malignancy: a review of 247 patients from 1991 to 2004.

Borderline ovarian tumors account for 15% of epithelial ovarian cancers and are different from invasive malignant carcinoma. Majority are early stage, occurring in women in the reproductive age group, where fertility is important. We reviewed retrospectively 247 such cases treated at the Gynaecological-Oncology Unit, KK Women's and Children's Hospital, between January 1991 and December 2004. The mean age was 38 years (16-89 years). Majority of the cases (92%) were FIGO stage I (Ia, 75%; Ib, 1%; and Ic, 16%). Seven (3.5%) patients were diagnosed as having stage II disease, six (2.5%) as stage IIIa, two (1%) as stage IIIb, and four (2%) as stage IIIc. Histological origin was as follows: mucinous (68%), serous (26%), endometrioid (2.6%), and clear cell (1.2%). Primary surgical procedures undertaken were as follows: hysterectomy with bilateral salpingo-oophorectomy (52%), unilateral salpingo-oophorectomy (33%), or ovarian cystectomy (15%). Adjuvant chemotherapy was administered in 13 patients (5.2% of cases), of which 4 patients were given chemotherapy only because of synchronous malignancies. There were six recurrences (2.4% of cases). Overall mean time to recurrence was 59 months. Recurrence rate for patients who underwent a primary pelvic clearance was 1.6% compared to fertility-sparing conservative surgery (3.3%; although P= 0.683). No significant difference was noted in recurrence and mortality between staged versus unstaged procedures. The overall survival rate was 98.0%. There were a total of five deaths (2.8%): three (1.5%) from invasive ovarian/peritoneal carcinoma and two from synchronous uterine malignancies. It appears that surgical resection is the mainstay of treatment, with conservative surgery where fertility is desired or pelvic clearance if the family is complete. Surgical staging is important to identify invasive extraovarian implants that portend an adverse prognosis. The role of adjuvant chemotherapy is not established.

Oesophageal-impacted denture requiring open surgery.

The successful removal of impacted denture in the oesophagus in a patient is reported, with a review of the literature. A 36-year-old Malay man complained of dysphagia after swallowing his denture. Following unsuccessful attempts at removal via a rigid oesophagoscope, open surgery was performed. Without further delay, the impacted denture was removed by cervical oesophagotomy, and the patient recovered uneventfully. Oesophageal foreign bodies are usually removed by endoscopy. However, in situations where this appears potentially hazardous, such as with impacted denture, open surgical extraction that is promptly performed is a safe option.

Emerging therapies for rectal cancer.

Preoperative treatment with either short-course radiotherapy or chemo-radiotherapy (CRT) is used routinely in some centres to reduce local recurrence rates in patients with operable rectal cancer prior to optimal surgery. However, there is a need for new treatment strategies to further improve the outcomes of these patients, particularly with regard to survival. Advances in the treatment of metastatic disease, such as the use of combination chemotherapy with oxaliplatin and irinotecan, and the targeted agents bevacizumab and cetuximab, have led to clinical research into alternative radio-sensitizers during CRT and the novel use of neo-adjuvant (preoperative) chemotherapy prior to preoperative CRT and surgery. Whilst these remain experimental, it is likely that these will serve as a platform for developing an expanded range of treatment options so that clinicians will be better able to tailor treatment to the needs of different patients.

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-alpha in human aortic smooth muscle and embryonic kidney cells.

NADPH oxidases are important sources of vascular superoxide, which has been linked to the pathogenesis of atherosclerosis. Previously we demonstrated that the Nox4 subunit of NADPH oxidase is a critical catalytic component for superoxide production in quiescent vascular smooth muscle cells. In this study we sought to determine the role of Nox4 in superoxide production in human aortic smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under proinflammatory conditions. Incubation with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) for 12 h increased superoxide production in both cell types, whereas angiotensin II, platelet-derived growth factor or interleukin-1beta had little effects. Superoxide production was completely abolished by the NADPH oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF-alpha upregulated the expression of Nox4 in AoSMC at both message and protein levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2 appeared to mediate the enhanced superoxide production by TNF-alpha in HEK293 cells. We suggest that Nox4 may be involved in increased superoxide generation in vascular smooth muscle cells under proinflammatory conditions.

5-Fluorouracil can cross brain-blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma.

PURPOSE: Capecitabine is a relatively new oral fluoropyrimidine currently licensed for the treatment of colorectal and breast cancer. RESULTS: It has the advantage of oral administration with good tolerability and comparable activity to intravenous 5-fluorouracil. Central neurotoxicity has been described in 5-fluorouracil-treated patients but there is little data regarding capecitabine. We report here a case of reversible capecitabine-induced encephalopathy progressing to coma. DISCUSSION: Literature on fluoropyrimidine-related neurotoxicity will also be reviewed and possible mechanisms of the drug or its metabolites crossing the blood-brain barrier will be discussed.

Operative treatment of trochanteric fractures with dynamic hip screw--is perioperative blood transfusion needed?

The need for perioperative blood transfusion in elderly patients with trochanteric fracture scheduled for elective dynamic hip screw fixation has recently been questioned following reports on the association between allogeneic blood transfusion and post-operative infections. This retrospective study was undertaken to assess the amount of per operative blood loss and transfusion requirement in relation to pre-operative haemoglobin level in 198 patients with trochanteric fractures. The average per operative blood loss was 409 ml and it correlated well with the duration of the operation. More than half of the patients (52.5%) required blood transfusion and nearly three-quarters were anaemic prior to the surgery. Proactive pre-operative measures to optimize the patient's haemoglobin level and intra-operative minimization of blood loss are essential steps to obviate the need for perioperative allogeneic blood transfusion.

Beyond Ortner's syndrome--unusual pulmonary complications of the giant left atrium.

INTRODUCTION: The giant left atrium (GLA) is a complication of severe mitral valve disease and causes morbidity by compressing adjacent intra-thoracic structures. CLINICAL PICTURE: We report 2 cases of unusual pulmonary complications of the GLA. Case 1 developed recurrent collapse of the left lung due to left main bronchus compression. Case 2 was diagnosed with right middle lobe compression and collapse. TREATMENT AND OUTCOME: Case 1 was successfully treated by mitral valve replacement and left atrial reduction surgery. Case 2 was treated conservatively. CONCLUSION: Pulmonary atelectasis may occur in patients with GLA due to bronchopulmonary compression. Surgical management with valve replacement and atrial reduction may be necessary to relieve airway compression.