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Sirolimus is an mTOR inhibitor that stabilizes lung function and improves some measures of life in LAM patients. It is approved by the FDA for use in LAM, based on the results of the Multicenter International LAM Efficacy and Safety of Sirolimus (MILES) Trial. MILES data supports the use of sirolimus in patients who have abnormal lung function (i.e. FEV1<70% predicted). Whether the benefits of treatment outweigh the risks for asymptomatic LAM patients with normal lung function is not clear, but some physicians consider treatment for declining patients who are approaching the abnormal range for FEV1. Sirolimus also appears to be effective for the treatment chylous effusions and lymphangioleiomyomatosis. The benefits of sirolimus only persist while treatment continues. The safety of long term therapy has not been studied.
Potential side effects from mTOR inhibitors include swelling in the ankles, acne, oral ulcers, dyspepsia, diarrhea, elevation of cholesterol and triglycerides, hypertension and headache. Sirolimus pneumonitis and latent malignancy are more serious concerns, but occur infrequently. Sirolimus inhibits wound healing. It is important to stop therapy with the drug for 1–2 weeks before and after elective procedures that require optimal wound healing. Precautions must be taken to avoid prolonged sun exposure due to increased skin cancer risk.
Treatment with another mTOR inhibitor, everolimus, was reported in a small, open-label trial to be associated with improvement in FEV1 and six-minute walk distance. Serum levels of VEGF-D and collagen IV were reduced by treatment. Adverse events were generally consistent with those known to be associated with mTOR inhibitors, although some were serious and included peripheral edema, pneumonia, cardiac failure and "Pneumocystis jirovecii" infection. Escalating doses of everolimus were used, up to 10 mg per day; higher than what is typically used clinically for LAM.
Serum VEGF-D concentration is useful, predictive and prognostic biomarker. Higher baseline VEGF-D levels predicts more rapid disease progression and a more robust treatment response.
Hormonal approaches to treatment have never been tested in proper trials. In the absence of proven benefit, therapy with progesterone, GnRh agonists (e.g., Lupron, goserelin) and tamoxifen are not routinely recommended. Doxycycline had no effect on the rate of lung function decline in a double blind trial.
Sirolimus is often effective as first-line management for chylothorax. If chylous leakage or accumulations persist despite treatment, imaging with heavy T2 weighted MRI, MRI lymphangiography or thoracic duct lymphangiography can be considered. Pleural fusion procedures can be considered in refractory cases.
Estrogen-containing medications can exacerbate LAM and are contraindicated. Agents that antagonize the effects of estrogen have not been proven to be effective for treatment, but no proper trials have been done. A trial of bronchodilators should be considered in LAM patients, because up to 17% to 25% have bronchodilator-responsive airflow obstruction. Oxygen should be administered to maintain oxyhemoglobin saturations of greater than 90% with rest, exercise and sleep. Bone densitometry should be considered in all patients who are immobilized and/or on antiestrogen therapies, and appropriate therapy instituted for osteoporotic patients. Proper attention should be paid to cardiovascular health following natural or induced menopause. Immunizations for pneumococcus and influenza should be kept up to date. Pulmonary rehabilitation seems to be particularly rewarding in young, motivated patients with obstructive lung disease, but studies to assess this intervention's effect on exercise tolerance, conditioning and quality of life have not been done.
To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired.
Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases.
The treatment of choice in any patient with BAC is complete surgical resection, typically via lobectomy or pneumonectomy, with concurrent ipsilateral lymphadenectomy.
Non-mucinous BACs are highly associated with classical EGFR mutations, and thus are often responsive to targeted chemotherapy with erlotinib and gefitinib. K-ras mutations are rare in nm-BAC.
Mucinous BAC, in contrast, is much more highly associated with K-ras mutations and wild-type EGFR, and are thus usually insensitive to the EGFR tyrosine kinase inhibitors. In fact, there is some evidence that suggests that the administration of EGFR-pathway inhibitors to patients with K-ras mutated BACs may even be harmful.
Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis has been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gys for children, 24-30 Gys for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.
Multifocal micronodular pneumocyte hyperplasia (MMPH) is a subtype of pneumocytic hyperplasia (hyperplasia of pneumocytes lining pulmonary alveoli).
Several synonymous terms have been done for this entity: adenomatoid proliferation of alveolar epithelium, papillary alveolar hamartoma, multifocal alveolar hyperplasia, multinodular pneumocyte hyperplasia.
These multifocal lesions are observed in tuberous sclerosis, and can be associated with lymphangioleiomyomatosis and perivascular epithelioid cell tumour (PEComa or clear cell "sugar tumor")).
It can be diagnosed through lung biopsy using thoracoscopy.
The treatment of hyperplasia would consist upon "which"; in the case of benign prostate hyperplasia the combination of alpha-1-receptor blockers and 5-alpha-reductase inhibitors are effective.
Treatment is by surgical excision (complete removal) of the fibrous tissue overgrowth and addressing the causative factor to prevent recurrence of the lesion. Other sources suggest that surgical excision may not be required in all cases. Common techniques for removal of the excess tissue include traditional removal with a surgical scalpel, electrical scalpel, or laser excision with a laser scalpel, e.g. a carbon dioxide laser, , Neodymium-YAG laser, or diode laser. The poorly fitting denture can be adapted to fit better (a "reline") or a new denture constructed. Alternatively, the section of flange that is sharp/over-extended can be smoothed and reduced with a drill.
When BAC recurs after surgery, the recurrences are local in about three-quarters of cases, a rate higher than other forms of NSCLC, which tends to recur distantly.
Treatment may involve smoking cessation and prescription of topical or systemic antifungal medication. Usually the mucosal changes resolve with antifungal therapy, but sometimes the lesion is resistant to complete resolution.
Levothyroxine is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.
Excellent for single-focus disease. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.
Pneumocytic hyperplasia is an hyperplasia of pneumocytes lining pulmonary alveoli.
An alternative using high intensity focused ultrasound or HIFU has recently proved its effectiveness in treating benign thyroid nodules. This method is noninvasive, without general anesthesia and is performed in an ambulatory setting. Ultrasound waves are focused and produce heat enabling to destroy thyroid nodules.
Focused ultrasounds have been used to treat other benign tumors, such as breast fibroadenomas and fibroid disease in the uterus.
Treatment of endometrial hyperplasia is individualized, and may include hormonal therapy, such as cyclic or continuous progestin therapy, or hysterectomy.
Atypical adenomatous hyperplasia is a subtype of pneumocytic hyperplasia in the lung. It can be a precursor lesion of in situ adenocarcinoma of the lung (bronchioloalveolar carcinoma).
In prostate tissue biopsy, it can be confused for adenocarcinoma of the prostate. The needle biopsy rate is less than 1%.
The first line management of gingival overgrowth is improved oral hygiene, ensuring that the irritative plaque is removed from around the necks of the teeth and gums. Situations in which the chronic inflammatory gingival enlargement include significant fibrotic components that do not respond to and undergo shrinkage when exposed to scaling and root planing are treated with surgical removal of the excess tissue, most often with a procedure known as gingivectomy.
In DIGO, improved oral hygiene and plaque control is still important to help reduce any inflammatory component that may be contributing to the overgrowth. Reversing and preventing gingival enlargement caused by drugs is as easy as ceasing drug therapy or substituting to another drug. However, this is not always an option; in such a situation, alternative drug therapy may be employed, if possible, to avoid this deleterious side effect. In the case of immunosuppression, tacrolimus is an available alternative which results in much less severe gingival overgrowth than cyclosporin, but is similarly as nephrotoxic. The dihydropyridine derivative isradipidine can replace nifedipine for some uses of calcium channel blocking and does not induce gingival overgrowth.
Photodynamic therapy (PDT) is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types. The 2008 study reported that PDT was a good treatment option for primary superficial BCCs, reasonable for primary low-risk nodular BCCs, but a 'relatively poor' option for high-risk lesions.
Immunotherapy research suggests that treatment using "Euphorbia peplus", a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC. Imiquimod is an immunotherapy but is listed here under chemotherapy.
Treatment is usually surgical removal of the gland(s) containing adenomas, but medication may also be required.
Bisphosphonate therapy has been suggested as a first-line therapeutic option in many case reports and series.
Treatment with tumor necrosis factor alpha antagonists (TNF inhibitors) have been tried in few patients with limited success. Other drugs that are used in psoriatic arthritis, to which SAPHO syndrome is closely related, have also been used in this condition. They include NSAIDs, corticosteroids, sulfasalazine, methotrexate, ciclosporin and leflunomide.
Some patients have responded to antibiotics. The rationale for their use is that Propionibacterium acnes, a bacterium known for its role in acne, has been isolated from bone biopsies of SAPHO patients.
Salivary gland hyperplasia is hyperplasia of the terminal duct of salivary glands.
There are two types:
- Acinar adenomatoid hyperplasia
- Ductal adenomatoid hyperplasia
If the causative factor persists, tissue will become more fibrous over time.
Atypical hyperplasia is a benign (noncancerous) cellular hyperplasia in which cells show some atypia. In this condition, cells look abnormal under a microscope and are increased in number.
Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery.
Another treatment option is injection of ethanol into the nodules.