Interstitial pneumonitis is a frequent complication in liver transplant recipients treated with sirolimus

Background

Sirolimus is a powerful immunosuppressive drug which is being used increasingly after liver transplantation because of its renal sparing and anti-tumour effects. It has been associated with uncommon, but potentially fatal, interstitial pneumonitis.

Aim

To determine the frequency and outcome of sirolimus-associated pneumonitis following liver transplantation.

Methods

Retrospective study in an adult liver transplant centre.

Results

We identified five patients with siromimus-associated pneumonitis, three of whom were transplanted at our centre. Between 1999 and 2008 a total of 522 liver transplants were performed, in our unit, and 45 patients were switched from calcineurin inhibitors to sirolimus. Three of these 45 patients subsequently developed pneumonitis (6.7%). The most common presenting symptoms were cough and dyspnea. The duration of use of sirolimus before diagnosis of pneumonitis varied between 4 and 16?months. Trough serum sirolimus levels were elevated in 3/5 patients with pneumonitis. Sirolimus was withdrawn in all five patients with complete resolution of symptoms and radiological findings.

Conclusions

Pneumonitis is a relatively common side effect of sirolimus in liver transplant patients and can occur despite normal therapeutic blood levels. It is reversible on stopping the medication. Early recognition is important to prevent unnecessary investigations and prolonged morbidity.     

Outcome of infants born to hepatitis C infected women

Background

Hepatitis C virus (HCV) can be transmitted vertically from mother to infant, either late in pregnancy or at delivery.

Aims

To determine the outcome of infants bom to HCV infected women, to characterise epidemiology and to design an appropriate infant monitoring schedule.

Methods

Three hundred and fourteen infants, born to 296 HCV positive women between 1994 and 1999 were monitored for a median of 18 months (range 1–52).

Results

Forty per cent of infants were small for age and 46% had neonatal abstinence syndrome (NAS). Of 173 infants of delned status, 11 were infected (vertical transmission rate [VTR] 6.4%, 95% CI 2.8–10). Infected infants were diagnosed at a median of three months (range 0.5–10). Liver transaminases elevation was documented in 8% of uninfected infants. A negative HCV PCR test before one month of age did not exclude infection but all infected patients had detectable HCV RNA when next tested (range 2–10 months).

Conclusions

94% of infants bom to HCV antibody positive women are not HIV infected. Liver transaminase elevation in exposed infants is not always indicative of infection. A minimum monitoring schedule of testing (PCR and antibody) at six to eight weeks, six and 18 months allows early diagnosis while detecting late seroconversions.     

Prophylactic cranial irradiation in small cell lung cancer: a single institution experience

Background

Prophylactic cranial irradiation (PCI) is used to prevent the development of brain metastases in small cell lung carcinoma. PCI confers an overall survival (OS) benefit in both limited and extensive stage disease.

Aims

We analyze the incidence of symptomatic brain metastases, progression-free survival (PFS) and OS in a cohort of patients who received PCI, in a 5-year period.

Methods

A retrospective review of all patients who had received PCI between 2006 and 2011 at the Whitfield Clinic was completed. Patient- and disease-related characteristics, the number of patients who developed brain metastases, PFS and OS data were collected.

Results

24 patients were identified. 14 (58.3 %) patients were male, 10 (41.7 %) were female, with a mean age of 62.5 years (range 31–78). All patients were smokers. 12 (50 %) patients had limited stage small cell lung cancer (SCLC), 12 (50 %) had extensive stage disease. 2 (8.2 %) patients developed brain metastases post PCI (p = 0.478.) The median PFS for limited stage SCLC was 13 months (range 3–20) and 10 months (range 5–18) for extensive stage SCLC. Median OS was 15 months (range 4–29) in limited stage SCLC, and 11 months (range 5–29) in extensive stage SCLC.

Conclusions

Our study demonstrated a low incidence of symptomatic brain metastases and favourable median PFS and OS in the patients that received PCI, when compared to published phase III data.     

Fludarabine, Cyclophosphamide and Rituximab: an effective chemoimmunotherapy combination with high remission rates for chronic lymphocytic leukaemia

Background

Combined Fludarabine and Cyclophosphamide is now standard first-line therapy in chronic lymphocytic leukaemia (CLL) and the addition of Rituximab improves outcome.

Methods

We adopted a modified Fludarabine, Cyclophosphamide and Rituximab (FCR) protocol in treating 39 patients (median age 57 years) with progressive or advanced CLL. Depending on CR, treatment was given for four or six cycles.

Result

Twenty-six patients were treatment naïve and 13 were pre-treated. Twelve patients had progressive Binet stage A, 16 stage B and 11 stage C disease. The overall response rate (ORR) was 100%, with 75% achieving CR. Neutropenia was the major toxicity in 71/187 (38%) of the cycles. There were five deaths, two from infection and three from progressive disease. Twenty-six of 31 patients have maintained their post-treatment disease status for a median of 17 months (2–41).

Conclusion

We conclude that FCR is a feasible, well-tolerated and effective treatment for patients with CLL.     

Late presentation of HIV despite earlier opportunities for detection, experience from an Irish Tertiary Referral Institution

Objectives

Late presentation of HIV continues to undermine advances in the management of HIV. Opportunities to detect HIV at an earlier stage are often missed. Current estimates suggest that undiagnosed individuals comprise approximately one quarter of all people in the western world living with HIV. ‘Testing-and-treating’ this group has been proposed as a means to curb the HIV epidemic. In this study we assessed the characteristics of individuals newly diagnosed with HIV, and their utilisation of healthcare services in Ireland prior to their diagnosis.

Methods

A retrospective review was undertaken of all patients newly diagnosed with HIV over a 27-month period. Patient demographics were recorded, as were details of healthcare contacts in the year preceding diagnosis. Individuals detected via screening of recent immigrants/asylum seekers were excluded.

Results

In the period studied 114 patients received a new diagnosis of HIV, 59 met inclusion criteria. The majority (54 %) fulfilled the European consensus definition for late presenters (CD4 < 350 cells/µl). ‘Late presenters’ were significantly more likely to be symptomatic at diagnosis (OR = 4.62; 95 % CI 1.45–14.67; p = 0.015), diagnosed by acute tertiary hospital services (p = 0.015), and 56 % reported heterosexual mode of acquisition (OR = 2.12; 95 % CI 0.73–6.16; p = 0.19). Patients detected via screening had significantly higher CD4 counts at diagnosis compared with those diagnosed due to symptoms (Median CD4 422 cells/µl; IQR 285–594 vs. 142 cells/µl; IQR 62–333; p = 0.0007). ‘Symptomatic’ patients were significantly more likely to report prior healthcare contacts (OR 4.71; 95 % CI 1.32–16.79; p = 0.013).

Conclusion

Current screening activities are inadequate. Unfortunately newly diagnosed HIV patients continue to be symptomatic, at advanced stages of disease, to acute hospital services. Heterosexual groups in particular are at risk for late detection.     

Metastatic uterine leiomyosarcoma presenting as a breast lump

Background

It is uncommon to encounter a breast metastasis from an extramammary malignancy and even rarer from a uterine leiomyosarcoma.

Aims

We describe the third case report in the medical literature of a breast metastasis from a uterine leiomyosarcoma.

Methods

We report the management of a 56-year-old patient who presented with a breast lump 3 years after hysterectomy for a fibroid uterus. We conducted a literature review of breast leiomyosarcomas.

Results

The excision of the breast mass revealed a low-grade leiomyosarcoma. Radiographic examinations demonstrated metastases to the lung, liver, pelvis and bone. Retrospective pathology review of her uterus identified a small focus of leiomyosarcoma. She received chemotherapy and palliative radiotherapy but passed away within few months.

Conclusion

Metastasis to the breast from a non-breast primary is generally a sign of disseminated disease and; thus, a poor prognostic indicator.     

Clinical and experimental study on separately decocted and mingly decocted jianweishu granule

Objective

To observe the difference in therapeutic effect of Chinese herbal granule decocted separately and mingly.

Methods

One hundred patients of functional dyspepsia of Spleen deficiency and Liver stagnancy type were treated with Jianweishu Granule (JWSG, ,a self-formulated recipe by the authors). Half of the patients received JWSG decocted separately, half of them received that decocted mingly. The therapeutic effects between the two groups were compared. Experimental observation on the effects of differently decocted remedies in rats was also conducted.

Results

The therapeutic effects obtained in the two groups were similar, with respective cure rate of 72 % and 70 % and the total effective rate 96 % in both group. There was insig1nificant difference between the two groups (P <0.05). Experimental study all showed no difference between the differently decocted remedies in inhibiting gastric acid, pepsin activity, gastric function regulation, small intestine movement improvement and pain alleviation in rats.

Conclusion

The therapeutic effects of JWSG decocted separately or mingly are the same. This fact provides a scientific basis for clinical use of granule form of single Chinese herbs.     

Transplantation after blunt trauma to the liver: a valuable option or just a "waste of organs"?

Objective

Liver injury due to trauma is a rare indication for transplantation. The main indications in such cases were uncontrollable bleeding and insufficient hepatic function. Because of poor results, liver transplantation in these patients is occasionally described as "waste of organs", however based on insufficient data. This study aims to report our experience and to critically question the indication of transplantation in these patients.

Methods

All liver transplantations at our institution were reviewed retrospectively. This covered 1,529 liver transplants between September 1987 and December 2008. Of them, 6 transplants were performed due to motor-vehicle accidents which caused uncontrollable acute liver trauma in 4 patients. The patients'' peri-operative course, short- and long-term outcomes were analyzed.

Results

Five deceased-donor liver transplantations (4 full size, 1 split) and 1 living donor (right) transplantation were performed. The median GCS score was 9/15; the median MELD score was 15. Postoperative complications were observed in 3 patients, requiring re-operation in 2. After a median (range) follow-up of 32.95 (10.3-55.6) months, 2 patients are alive and remain well on immunosuppression.

Conclusion

Liver transplantation in patients with otherwise surgically uncontrollable acute liver injury can be indicated as a life saving procedure and can be performed successfully in highly selected cases.     

Effects of different therapeutic methods and typical recipes of Chinese medicine on activation of c-Jun N-terminal Kinase in Kupffer cells of rats with fatty liver disease

<正>Objective:To observe the effects of different therapeutic methods and the recipes of Chinese medicine(CM) on the activation of c-Jun N-terminal kinase(JNK) in Kupffer cells of rats with fatty liver disease and to explore the mechanisms of these therapeutic methods.Methods:By using a random number table,98 rats were randomly divided into 7 groups:control group,model group,and 5 treatment groups,including soothing Liver(Gan) recipe group,invigorating Spleen(Pi) recipe group,dispelling dampness recipe group,promoting blood recipe group,and complex recipe group.Rats in the control group were fed with normal food and distilled water by gastric perfusion,while rats in the model group were fed with high-fat food and distilled spirits by gastric perfusion.Rats in the 5 treatment groups were fed with high-fat food and corresponding recipes by gastric perfusion.Twelve weeks later,all rats were sacrificed and liver tissues were stained for pathohistological observation.Kupffer cells were isolated from livers of rats to evaluate JNK and phospho-JNK expressions by Western blotting.Results:The grade of hepatic steatosis was higher in the model group than the control group(P0.05).Compared with the model group,the grade of fatty degeneration in soothing Liver recipe group and invigorating Spleen recipe group were significantly ameliorated(P0.05).Expressions of JNK and phospho-JNK in Kupffer cells were significantly higher in the model group than those in the control group(P0.05,P0.01).Compared with the model group,expressions of JNK in all treatment groups decreased,especially in invigorating Spleen recipe group and promoting blood recipe group(P0.05).Compared with the model group,expressions of phospho-JNK in all treatment groups declined significantly(P0.01),especially in soothing Live recipe group and invigorating Spleen recipe group. Conclusions:The high expressions of JNK and phospho-JNK in Kupffer cells might play an important role in the pathogenesis of fatty liver disease in rats.The recipes of CM,especially invigorating Spleen recipe and soothing Liver recipe,might protect liver against injury by reducing the total JNK protein content and inhibiting the activation of JNK protein in Kupffer cells of fatty liver model rats,which showed beneficial effects on fatty liver disease.     

Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience

Background

Stereotactic radiosurgery is frequently used for the treatment of brain metastases. This study provides a retrospective evaluation of patients with secondary lesions of the brain treated with stereotactic radiosurgery (SRS) at our institution.

Aims

To provide outcome data from a single institutional experience with SRS and identify any significant prognostic factors in the cohort.

Methods

Sixty-seven patients received first time SRS to 86 intracranial metastases between 2007 and 2010. Sixteen patients were excluded from this study due to the absence of post-treatment neuroimaging, resulting in 51 patients with 64 treated lesions. Of these patients, 37 (72.5 %) received SRS electively, while 14 (27.5 %) received salvage SRS after brain metastasis progression following whole brain radiotherapy.

Results

Median survival for the entire group was 15 months from the date of radiosurgery. Patients without active extracranial disease had statistically significant survival time than those with active extracranial disease (P = 0.03). 45 (70.3 %) lesions achieved local tumour control in 34 patients (66.7 %) with a mean follow-up period of 10.7 months (range 1.7–33.6 months, 95 % confidence interval 6.6–9.8 months).

Conclusions

The results reported in this study equate to those reported in other series consolidating SRS as an effective treatment option with few serious complications. Developments in systemic disease control will see further improvements in overall survival.     

Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation

Objective

Glutathione-S-Transferase (GST) subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and p may serve as predictive markers for liver surgery, especially transplantations.

Methods

13 patients receiving living donor liver transplantation (LDLT) and their corresponding donors were analyzed for standard serum parameters (ALT, AST, gGT, bilirubin) as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R) and donors (D) were grouped according to graft loss (R1/D1) or positive outcome (R2/D2) and above named serum parameters were compared between the groups.

Results

R1 showed significantly increased GST-α and significantly lower GST-π levels than R2 patients or the donors. There was a positive correlation between GST-α and ALT, AST as well as bilirubin and a negative correlation to γGT. However, γGT correlated positively with GST-π. Graft failure was associated with combined low GST-π levels in donors and their recipients before living donor liver transplantation.

Conclusion

Our data suggest that high GST-α serum levels reflect ongoing liver damage while GST-P indicates the capacity and process of liver regeneration. Additionally, GST-π may be useful as marker for optimizing donor and recipient pairs in living donor liver transplantation.

     

Autologous stem cell transplantation in myeloma: the St James’s Hospital experience, 1997–2003

Background

High-dose treatment with autologous stem cell transplantation (ASCT) has become the standard of care for patients with myeloma below the age of 65 years.

Aims

We report an audit of 60 patients (median age: 52.5 years) who underwent ASCT in the National Bone Marrow Transplant centre in St James’s Hospital in Dublin between 1997 and 2003 inclusive.

Methods

Clinical and laboratory data were retrieved from patient medical records and hospital information management systems.

Results

Thirty-six patients had IgG, 11 IgA, 1 IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received anthracycline-corticosteroid combination chemotherapy prior to autografting. There was no transplant-related mortality (TRM). Complete (CR) and Partial Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54 (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at five years are 13% and 55% respectively.

Conclusion

Centre outcome is comparable to published international series and supports the use of ASCT in the treatment of this malignancy.     

Survival after incidental prostate cancer diagnosis at transurethral resection of prostate: 10-year outcomes

Background

The most appropriate management of incidental prostate cancers diagnosed at transurethral resection of prostate has been debated. It is important to determine the long-term outcomes to establish an appropriate management in patients with incidental prostate cancer.

Aims

We aim to determine 10-year survival and to identify the factors of worse prognosis of incidental prostate cancers diagnosed at transurethral resection of prostate.

Methods

A retrospective analysis of patients with pT1a?CpT1b prostate cancers diagnosed between 1998 and 2003. Medical notes, PSA and pathology results were reviewed. Overall and cancer specific survival was calculated at mean 10-year follow-up.

Results

Sixty patients with incidental prostate cancer were identified (pT1a?=?18, pT1b?=?42). Fifty-one percents of the patients were managed on a watchful waiting strategy with overall 84% survival and 9.7% cancer specific mortality. Twenty patients (all with pT1b) received hormone therapy. Overall survival in this cohort was 50% with 20% cancer specific mortality. Nine patients received curative therapy (Radical prostatectomy?=?4, Radiotherapy?=?5). In this group, overall survival was 88% with no cancer specific mortality.

Conclusions

Stage pT1a disease and preoperative low PSA were associated with favourable survival. However, for pT1b and/or high Gleason score (??7), mortality was comparatively higher. Hence, patients with high Gleason score and/or pT1b disease should be considered for curative therapy. Additionally, active surveillance may have a role in selected men with incidental prostate cancer.     

Collecting Duct Carcinoma of the kidney: A case report with variable immunohistochemistry

Background

Collecting duct carcinoma of the kidney is a rare tumour with distinctive clinical and histopathological features. Management of this malignancy remains a challenge because of advanced stage at presentation and aggressive clinical course.

Aims

We describe a case of Collecting Duct Carcinoma with variable immunohistochemistry and review the pathology and management.

Results

Our patient died shortly after commencing systemic chemotherapy.

Conclusion

Advances in immunohistochemistry have aided in diagnosis of this tumour. Early detection and nephrectomy offer the best chance of cure. Newer chemotherapeutic regimens may improve survival in more advanced disease.     

Inappropriate use of proton pump inhibitors

Background

Proton pump inhibitors (PPIs) are widely used expensive medications.

Aims

We performed a cross-sectional study to determine the extent and indication of PPI use in Irish acute medical wards.

Methods

Fifty-five medical charts were reviewed at the beginning and end of 1 month.

Results and conclusions

Thirty-three patients were prescribed PPIs; 26 prior to admission. The prescribing of PPIs was concordant with guideline recommendations in only 30% of cases. Two-thirds of PPI use was unlicensed.     

An assessment of the long-term health outcome of renal transplant recipients in Ireland

Background

Renal transplantation remains the preferred method of renal replacement therapy in terms of patient survival, quality of life and cost. However, patients have a high risk of complications ranging from rejection episodes, infection and cancer, amongst others.

Aims and methods

In this study, we sought to determine the long-term health outcomes and preventive health measures undertaken for the 1,536 living renal transplant patients in Ireland using a self-reported questionnaire. Outcomes were divided into categories, namely, general health information, allograft-related information, immunosuppression-related complications and preventive health measures.

Results

The results demonstrate a high rate of cardiovascular, neoplastic and infectious complications in our transplant patients. Moreover, preventive health measures are often not undertaken by patients and lifestyle choices can be poor.

Conclusions

This study highlights the work needed by the transplantation community to improve patient education, adjust immunosuppression where necessary and aggressively manage patient risk factors.     

Effect of Acupoint Sanyinjiao（SP6） Moxibustion on the First Stage of Labor and Uterine Contractive Pain in Primiparae

Objective:To observe the effect of acupoint Sanyinjiao(SP6) moxibustion(S-Mox) on the duration of the first labor stage and uterine contractive pain in primiparae.Methods:Sixty primipara women in labor were equally assigned according to their choice to three groups:women in the S-Mox group received bilateral S-Mox for 30 min,women in the non-acupoint group received moxibustion(Mox) applied on non-acupoints for 30 min,and those in the control group did not receive Mox intervention.The duration of the first labor stage was recorded and the degree of labor pain was estimated by a visual analogue scale(VAS) before and after Mox. Results:The duration of the first stage active phase in the S-Mox group was significantly shorter than that in the other two groups(P<0.05,P<0.01);the VAS score after Mox was lower in the S-Mox group,showing a statistical difference in comparison with the control group(P<0.05).Conclusions:Applying S-Mox could markedly shorten the active phase of the first stage of labor and lower the VAS score of uterine contractive pain,which means alleviating the pain caused by vaginal delivery.Its mechanism is worthy of further study.     

Coracoid Impingement Syndrome: A treatable cause of anterior shoulder pain

Background

Coracoid Impingement Syndrome is a relatively uncommon but generally treatable cause of anterior shoulder pain that can be easily overlooked. It typically presents with anterior shoulder joint pain in activities involving forward flexion, adduction and internal rotation.

Aims

To assess the outcome of a cohort of patients diagnosed with Coracoid Impingement Syndrome.

Methods

Patients were investigated clinically and radiologically. They received appropriate therapeutic measures and were followed-up in an orthopaedic outpatient setting.

Results

Twelve patients were identified over a four-year period. All patients have made good progress. Thus far, none have needed operative intervention for symptom relief.

Conclusion

Coracoid impingement syndrome is an uncommon cause of anterior shoulder pain but diagnosed patients can expect good symptomatic relief following referral to a dedicated shoulder unit. An increase in clinical awareness of the condition may prevent undue diagnostic delay in such cases.     

Prognostic implications of p53 and bcl-2 expression in 108 women with stage two breast cancer

Background

The mortality and morbidity of patients with breast cancer can vary even between individuals with similar histological stage at diagnosis. Identification of those individuals with prognostically poorer tumours is an essential prerequisite in planning adjuvant therapies. Some prognostic indices of tumour size, grade, oestrogen receptor status and nodal status are well established.

Aim

The aim of this study was to examine the prognostic role of information relating to proto-oncogene and tumour suppressor gene expression.

Methods

108 women with stage II breast cancer were studied. Tumour expression of p53 and bcl-2 were scored and then correlated with recurrence and mortality.

Results

We have shown that individuals poorly expressing bcl-2 in their tumours have a poorer disease-free and overall survival than those who express bcl-2. When p53 was strongly expressed, it was associated with poorer disease-free and overall survival.

Conclusion

The profiling of individual tumour genetic expression of proto-oncogenes may allow for more specific identification of patients at higher risk’ of recurrence in breast cancer.