Darren K. Patten

Breast cancer: Current and future endocrine therapies

Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.

New Approaches in the Management of Male Breast Cancer

Male breast cancer (MBC) is a rare condition that accounts for 0.1% of all male cancers. Our current evidence base for treatment is derived from female breast cancer (FBC) patients. Risk factors for MBC include age, genetic predisposition, race, sex hormone exposure, and environmental factors. Most patients present later and with more advanced disease than comparable FBC patients. Tumors are likely to be estrogen receptor and progesterone receptor positive, with the most common histologic type being invasive ductal carcinoma. Triple assessment remains the criterion standard for diagnosis. Primary MBC is mostly managed initially by simple mastectomy, with the option of breast conserving surgery, which carries an increased risk of recurrence. Sentinel node biopsy is recommended as the initial procedure for staging the axilla. Reconstructive surgery focuses on achieving primary skin closure, and radiotherapy largely follows treatment protocols validated in FBC. We recommend chemotherapy for men with more advanced disease, in particular, those with estrogen receptor negative histology. MBC responds well to endocrine therapy, although it is associated with significant adverse effects. Third-generation aromatase inhibitors are promising but raise concerns due to their failure to prevent estrogen synthesis in the testes. Fulvestrant remains unproven as a therapy, and data on trastuzumab is equivocal with HER2 receptor expression and functionality unclear in MBC. In metastatic disease, drug-based hormonal manipulation remains a first-line therapy, followed by systemic chemotherapy for hormone-refractory disease. Prognosis for MBC has improved over the past 30 years, with survival affected by disease staging, histologic classification, and comorbidity.

Sporadic medullary thyroid carcinoma with a pedunculated intraluminal internal jugular vein recurrence: A case report and literature review

Medullary thyroid carcinoma (MTC) is an uncommon usually slowly progressing neuroendocrine tumour that arises from calcitonin (CT) producing parafollicular C cells of the thyroid gland. It accounts for approximately 5% of all thyroid cancers. The majority of MTCs are sporadic (75%) whilst 25% are part of the MEN 2 hereditary syndrome (MEN 2A and MEN 2B and familial MTC). Mutations of the proto-oncogene, RET (Rearranged during Transfection), found on chromosome 10q11, are present in more than 95% of hereditary MTCs and about 25% of sporadic MTCs. MTC metastasizes primarily via lymphatic spread, to central, and lateral nodal neck compartments and the anterior and superior mediastinum. Distant haematogenous spread targets the lungs, liver, bone and brain, and is presumed to be secondary to a lymphatic pathway. There are no previously documented reports of a focal pedunculated metastases located within the jugular vein. We present the first reported case of a metastatic MTC lesion found in the right internal jugular vein in a man with recurrent MTC.

Is the presence of small volume disease in the sentinel node an indication for axillary clearance

The finding of micrometastases (M(i)) and isolated tumour cells (ITC) within the axillary lymph nodes of patients with breast cancer has raised the question whether either/both have some prognostic significance. Several studies have shown that compared to node-negative patients, prognosis is significantly poorer in patients with M(i) and ITC. The fact that patients with M(i)/ITC in their sentinel lymph nodes have a systemic relapse risk that is higher than that of node-negative patients may be considered as an indication for systemic treatment. Most studies in the literature suggest that in patients with M(i) or ITC in their sentinel nodes who receive systemic therapy and whole breast radiotherapy, the risk of axillary relapse without axillary lymphadenectomy is under 2%. Given the fact that axillary lymphadenectomy is associated with a 5-25% risk of lymphoedema, we propose that a policy of close follow up should be adopted in these patients rather than axillary lymphadenectomy.

Solitary extramedullary plasmacytoma of the thyroid involved by papillary carcinoma: a case report and review of the literature.

Plasmacytoma is a malignant proliferation of plasma cells that can arise in the bone marrow (osseous) and in the soft tissues (extramedullary). Multifocal osseous lesions are often termed multiple myelomas [1]. Extramedullary plasmacytomas are usually seen in aggressive forms of the disease, frequently occurring in the soft tissues of the head and neck, especially in the upper airways [2]. They may occur as an extramedullary manifestation of multiple myeloma, which must be excluded or present as a solitary primary tumour [3]. Extramedullary plasmacytomas are uncommon, and their occurrence in the thyroid is rare. These lesions have often been associated with Hashimoto’s thyroiditis. There have been 54 cases of solitary extramedullary plasmacytoma (SEP) of the thyroid gland described in world literature [4– 7]. Current literature documents a papillary thyroid carcinoma involved by malignant plasma cell disease without confirmation of the diagnosis of SEP of the thyroid [8]. We present a unique case of a SEP of the thyroid involved by multifocal micropapillary carcinoma. Case

Splenic Laceration After Endoscopic Retrograde Cholangiopancreatography

The advent of endoscopic retrograde cholangio-pancreatography (ERCP) has enabled physicians and surgeons to carry out a range of diagnostic and therapeutic procedures pertaining to various pathologies found within the hepato-biliary system. Despite being relatively less invasive when compared to traditional methods of surgery, ERCP still carries recognized complications that are a cause for morbidity amongst patients. Furthermore, rarer complications can occur in difficult circumstances that are potentially fatal. We report two cases whereby the patients sustained serious splenic injuries as a consequence of the procedure. Splenic lacerations were diagnosed on computer tomography scanning in both patients who subsequently underwent emergency splenectomy. The patients made an uneventful recovery and returned home after surgery. To date twelve cases have been reported in current medical literature regarding injury to the spleen following ERCP. These aforementioned injuries have arisen particularly when the endoscopist has encountered difficult or variations in anatomy whilst performing ERCP. In addition to presenting two cases, we review the literature and discuss the implications of these complications and how this may affect the way in which clinicians take informed consent from patients before conducting ERCP.

Anaplastic Spindle Cell Squamous Carcinoma Arising from Tall Cell Variant Papillary Carcinoma of the Thyroid Gland: A Case Report and Review of the Literature

Tall cell variant (TCV) of papillary thyroid carcinoma (PTC), an aggressive form of thyroid cancer, is characterised by 50% of cells with height that is three times greater than the width. Very rarely, some of these cancers can progress to spindle cell squamous carcinoma (SCSC) resulting in cancers with elements of both SCSC and TCV PTC. Here we report a case of SCSC arising from TCV PTC. In addition to this case, we have performed a literature review and compiled all published reports of SCSC arising from TCV PTC, including the nature of treatment and the prognosis for each of the 20 patients recorded. This is intended for use as a guide for clinicians in what the most appropriate treatment options may be for a newly diagnosed patient. Due to the rarity coupled with diagnosis occurring at a very advanced stage of disease progression, performing clinical trials is difficult and therefore drawing conclusions on optimal treatment methods remains a challenge.

Prior exposure to chemotherapy: a marker of sensitivity and selection for antiangiogenic therapy in breast cancer?

The identification of patients who are more likely to derive benefit from antiangiogenic therapy is a key to refine patient selection and so maximize clinical benefit, and reduce unnecessary treatment costs. Improved patient selection will equally be effective in minimizing the exposure of non-eligible patients to ineffectual treatment which could be associated with adverse effects as well as delaying effective treatment. Herein, we review the literature from clinical trials suggesting that the addition of antiangiogenic agents to chemotherapy for the treatment of HER-2 negative metastatic breast cancer in patients previously exposed to chemotherapy may deliver differential therapeutic benefit and may serve as a selection criteria in the current absence of a robust biomarker.

Occult bladder injury after laparoscopic appendicectomy.

Minimally invasive procedures have revolutionised surgery by reducing pain and the length of hospital stay for patients. These are not simple procedures and training in laparoscopic surgery is an arduous process. Meticulous preparation prior to surgery is paramount to prevent complications. We report a rare complication involving a 35-year-old patient who underwent a laparoscopic appendicectomy for a perforated appendix. Two days after surgery the patient experienced redness and swelling in the lower abdominal region and oliguria. A delayed computer tomography (CT) scan revealed contrast leakage around the bladder spreading within the peritoneal cavity consistent with an intraperitoneal bladder perforation. She underwent urinary catheterisation for 6 days. A follow-up CT cystogram showed no evidence of leakage into the peritoneal cavity. This case highlights the need for thorough preparation prior to laparoscopic surgery and careful manipulation of instruments during routine procedures to minimise the risk of serious patient complications such as the aforementioned.