Effect of Prior Salter or Chiari Osteotomy on THA with Developmental Hip Dysplasia

Background  

Controversy exists regarding the outcome of THA after prior pelvic osteotomy.     

A rare presentation of sarcoidosis, back pain and spondylolisthesis

A 48-year old man presented with back pain that was resistant to treatment. An MR scan showed spondylolisthesis at L4-5 and narrowing of the exit foraminae. He had a posterior fusion which did not relieve his symptoms. He continued to have back pain and developed subcutaneous nodules in both forearms. Biopsy from the skin revealed cutaneous sarcoidosis, and one from the lumbar spine showed sarcoidosis granuloma between the bone trabeculae. A CT scan of the abdomen and chest revealed axillary lymphadenopathy, mediastinal enlarged nodes, apical nodular nodes and splenomegaly. The patient was started on large doses of methotrexate and steroids. His angiotensin-converting enzyme and calcium levels returned to normal and the back pain resolved.     

An observational study of 256 cases of vascular trauma in the north western province of Pakistan.

During the past 10 years Peshawar has dealt with increasing casualties with penetrating trauma inflicted by a wide variety of missiles. The aim of this study was to assess whether delay in arrival and mode of presentation affects the outcome of patients with penetrating vascular trauma. Prospective data were collected on 256 vascular injuries in 248 patients (median age, 29 years; range, 7-60 years) between January 1995 and June 1998. Early presentation (group A, 55 cases, < 12 h) was compared with late presentation (group B, 201 cases, > 12 h). The majority of injuries (93%) were caused by fire-arms. Arterial injuries accounted for 71% of the total, venous injuries accounted for 10% and 19% were mixed. The site of injury was the lower limb (61%), upper limb (32%), abdominal cavity (5%) and neck (2%). Patients presented with absent pulses (56%), haemorrhage (46%), false aneurysms (8%), A-V fistula (5%) and 11% presented with more than one sign. There were significantly more lower limb amputations in group A than group B (23% versus 5%; P < 0.05), with fractures having a positive association with lower limb amputations (odds ratio, 0.32; 95% CI, 0.13-0.94; P < 0.05). Group A had a higher mortality than group B (18% versus 7%; P < 0.05). This study shows that patients with vascular trauma can be managed successfully with clinical assessment alone. Patients with fractures were more likely to suffer eventually from lower limb loss. Due to self-selection, arrival at the hospital less than 12 h after sustaining vascular injury was associated with a higher mortality than those presenting after 12 h.     

Valvular heart operation in patients with previous mediastinal radiation therapy

Background. The outcome of valvular heart operations in patients with previous mediastinal radiation therapy was studied.

Methods. This is a single center retrospective study of 60 patients (37 females, 23 males) with a mean age of 62 ± 15 years (28 to 88 years old) operated on from January 1976 to December 1998. Valvular heart operations performed included aortic valve replacements (n = 26), mitral valve procedures (n = 16), tricuspid valve procedures (n = 6), and multiple valve procedures (n = 12). A total of 264 clinical, hemodynamic, electrocardiographic and echocardiographic variables were analyzed.

Results. Total follow-up was 199 patient-years with a mean of 3.3 ± 3.1 years and a range of 0 to 12.4 years old. Early mortality was 7 patients (12%). Early mortality in patients with constrictive pericarditis was 40% (4 of 10) compared with 6% (3 of 50) in patients without constrictive pericarditis. By univariate analysis, early mortality was associated with constrictive pericarditis (p = 0.011), reduced preoperative ejection fraction (p = 0.015), and longer cardiopulmonary bypass times (p = 0.037). A total of 14 patients (23%) required permanent pacemaker placement before (n = 7), during (n = 1), or early (n = 6) after valvular heart operations. There were 19 late deaths (malignancies, 7; heart failures, 5; other cardiac, 4; and other noncardiac, 3). Overall survival and freedom from late cardiac death and cardiac reoperation at 5 years for hospital survivors were 66% ± 8%, 82% ± 7%, and 93% ± 4%, respectively. By univariate analysis, late cardiac death was associated with low ejection fraction (p = 0.002), New York Heart Association (NYHA) functional class IV (p = 0.004), preoperative congestive heart failure (p = 0.02), and preoperative atrial fibrillation (p = 0.038). Eighty-five percent of the discharged patients were in NYHA functional class I or II at follow-up.

Conclusions. Early results of valve replacement after mediastinal radiation therapy were good except in the presence of constrictive pericarditis. Long-term outcome was limited by malignancy and heart failure. Early surgical intervention is recommended before the development of risk factors for late death, namely, severe symptoms, left ventricular dysfunction, and atrial fibrillation.     

Spilled gallstones during laparoscopic cholecystectomy

Introduction

Incidental gallbladder cancer is found in 0.6–2.1% of patients undergoing laparoscopic cholecystectomy for symptomatic gallstones. Patients with Tis or T1a tumours generally undergo no further intervention. However, spilled stones during surgery may have catastrophic consequences. We present a case and suggest aggressive management in patients with incidental gallbladder cancer who had spilled gallstones at surgery.

Case History

A 37-year-old woman underwent a laparoscopic cholecystectomy for symptomatic gallstones, during which some stones were spilled into the peritoneal cavity. Subsequent histological examination confirmed incidental pT1a gallbladder cancer. Hepatopancreatobiliary multidisciplinary team discussion agreed on regular six-monthly follow-up. The patient developed recurrent pain two years after surgery. Computed tomography revealed a lesion in segment 6 of the liver. At laparotomy, multiple tumour embedded gallstones were found on the diaphragm. Histological examination showed features (akin to the original pathology) consistent with a metastatic gallbladder tumour.

Conclusions

This case highlights the potential for recurrence of early stage disease resulting from implantation of dysplastic or malignant cells carried through spilled gallstones. It is therefore important to know if stones were spilled during original surgery in patients with incidental gallbladder cancer following a laparoscopic cholecystectomy. Aggressive and early surgical management should be considered for these patients.     

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Background

Approximately 20 % of patients diagnosed with colorectal cancer will have distant metastases at first presentation (stage IV disease). The effect of removing the primary tumor on survival for patients with stage IV disease with unresectable metastases remains unclear. To address this a meta-analysis of all studies comparing primary tumor resection with chemotherapy alone in cases of stage IV colorectal cancer with unresectable metastases was performed.

Methods

A comprehensive search for published studies examining the effect of primary tumor resection in the setting of colorectal cancer with unresectable metastases was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data.

Results

There were 21 studies including a total of 44,226 patients that met the inclusion criteria. Resection of the primary tumor in patients with unresectable metastases compared with chemotherapy alone was associated with a lower mortality risk (OR 0.28; 95 % CI 0.165–0.474; P < 0.001), translating into a difference in mean survival of 6.4 months in favor of resection (95 % CI 5.025–7.858, P < 0.001). Patients who underwent resection of the primary tumor were more likely to have liver metastasis only (OR 1.551; 95 % CI 1.247–1.929; P < 0.001), were less likely to have ≥2 metastasis (OR 0.653; 95 % CI 0.508–0.839; P = 0.001), and were less likely to have rectal cancer (OR 0.495; 95 % CI 0.390–0.629; P < 0.001). There was significant cross-study heterogeneity.

Conclusions

Resection of the primary tumor may confer a survival advantage in stage IV colorectal cancer with unresectable metastases but significant selection bias exists in current studies. Randomized controlled trials are essential to validate these findings.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

Electroporation enhances transfection efficiency in murine cutaneous wounds

Transfection of wounds with DNA-encoding growth factors has the potential to improve healing, but current means of nonviral gene delivery are inefficient. Repeated high doses of DNA, necessary to achieve reliable gene expression, are detrimental to healing. We assessed the ability of in vivo electroporation to enhance gene expression. Full-thickness cutaneous excisional wounds were created on the dorsum of female mice. A luciferase- encoding plasmid driven by a CMV promoter was injected at the wound border. Following plasmid administration, electroporative pulses were applied to injection sites. Pulse parameters were varied over a range of voltage, duration, and number. Animals were euthanized at intervals after transfection and the luciferase activity measured. Application of electric pulses consistently increased luciferase expression. The electroporative effect was most marked at a plasmid dose of 50 micro g, where an approximate tenfold increase was seen. Six 100- micro s-duration pulses of 1750 V/cm were found to be the most effective in increasing luciferase activity. High numbers of pulses tended to be less effective than smaller numbers. This optimal electroporation regimen had no detrimental effect on wound healing. We conclude that electroporation increases the efficiency of transgene expression and may have a role in gene therapy to enhance wound healing.