Novel imaging techniques in refractory pituitary adenomas.

Accurate localization of the site(s) of active disease is key to informing decision-making in the management of refractory pituitary adenomas when autonomous hormone secretion and/or continued tumor growth challenge conventional therapeutic approaches. In this context, the use of non-standard MR sequences, alternative post-acquisition image processing, or molecular (functional) imaging may provide valuable additional information to inform patient management.

Modern imaging in Cushing's disease.

Management of Cushing's disease is informed by dedicated imaging of the sella and parasellar regions. Although magnetic resonance imaging (MRI) remains the investigation of choice, a significant proportion (30-50%) of corticotroph tumours are so small as to render MRI indeterminate or negative when using standard clinical sequences. In this context, alternative MR protocols [e.g. 3D gradient (recalled) echo, with acquisition of volumetric data] may allow detection of tumors that have not been previously visualized. The use of hybrid molecular imaging (e.g. 11C-methionine positron emission tomography coregistered with volumetric MRI) has also been proposed as an additional modality for localizing microadenomas.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy.

PURPOSE: To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. PATIENTS AND METHODS: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. RESULTS: In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. CONCLUSIONS: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

The normal-equivalent: a patient-specific assessment of facial harmony.

Evidence-based practice in oral and maxillofacial surgery would greatly benefit from an objective assessment of facial harmony or gestalt. Normal reference faces have previously been introduced, but they describe harmony in facial form as an average only and fail to report on harmonic variations found between non-dysmorphic faces. In this work, facial harmony, in all its complexity, is defined using a face-space, which describes all possible variations within a non-dysmorphic population; this was sampled here, based on 400 healthy subjects. Subsequently, dysmorphometrics, which involves the measurement of morphological abnormalities, is employed to construct the normal-equivalent within the given face-space of a presented dysmorphic face. The normal-equivalent can be seen as a synthetic identical but unaffected twin that is a patient-specific and population-based normal. It is used to extract objective scores of facial discordancy. This technique, along with a comparing approach, was used on healthy subjects to establish ranges of discordancy that are accepted to be normal, as well as on two patient examples before and after surgical intervention. The specificity of the presented normal-equivalent approach was confirmed by correctly attributing abnormality and providing regional depictions of the known dysmorphologies. Furthermore, it proved to be superior to the comparing approach.

SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla.

BACKGROUND: Historical studies of lymphatic drainage of the breast have suggested that the lymphatic drainage of the breast was to lymph nodes lying in the antero-pectoral group of nodes in the axilla just lateral to the pectoral muscles. The purpose of this study was to confirm this is not correct. METHODS: The hybrid imaging method of SPECT/CT allows the exact anatomical position of the sentinel lymph node (SLN) in the axilla to be documented during pre-operative lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a series of 741 patients. The Level I axillary nodes were defined as anterior, mid or posterior. This was related to the anatomical location of the primary cancer in the breast. RESULTS: A SLN was found in the axilla in 97.8% of our patients. Just under 50% of SLNs located in the axilla were not in the anterior group and lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a single node field in 460 patients (63%), two node fields in 261(36%), three node fields in 6 and four node fields in 1 patient. CONCLUSION: Axillary lymphatic drainage from the breast is not exclusively to the anterior (or antero-pectoral) group of Level I nodes. SYNOPSIS: SPECT/CT lymphoscintigraphy shows that the breast does not always drain to the anterior group of Level I lymph nodes in the axilla but may drain to the mid axilla and/or posterior group in about 50% of patients with breast cancer regardless of the location of the cancer in the breast. These data redefine lymph drainage from the breast to axillary lymph nodes.

Supraglottitis and abscess formation.

OBJECTIVE: This case series report aims to raise awareness of the association between supraglottic infection and abscess formation, which has been rarely documented. METHOD: We report a series of four patients who developed cervical abscesses following supraglottic infection. The diagnosis was confirmed by imaging in three patients, and by incision and drainage of pus at direct laryngoscopy in one. RESULTS: All four patients were treated with intravenous antibiotics, steroids and humidification; two also underwent surgical drainage of pus. All made an uneventful recovery. CONCLUSION: The factors that lead to neck abscess formation are poorly understood. Physicians should always be aware of this potential complication. If it is suspected, appropriate neck imaging should be undertaken, after excluding airway copromise; this will aid early diagnosis and treatment.

Reanimation following facial palsy: present and future directions.

BACKGROUND: An understanding of the management of chronic facial palsy is vital for otolaryngologists, due to its common presentation to ENT surgeons. There is currently a lack of consensus on the optimum management of this condition. This article reviews the existing literature and offers a perspective on current management, as well as an insight into future treatments. METHODS: A literature search was performed, using the Medline, Embase and Cochrane databases from 1966 to the present, using the keywords listed below. Articles were reviewed. Selection was limited to English language articles on human subjects. RESULTS AND CONCLUSION: A tailored, multidisciplinary approach using combinatorial therapy should be used for reanimation of the face following facial palsy. Advances in surgical and non-surgical techniques, and the exchange of information from centres of excellence via global databases, will enable objective appraisal of results and the development of an evidence-based approach to facial reanimation.

Overexpression of Cripto and its prognostic significance in breast cancer: a study with long-term survival.

INTRODUCTION: Cripto is a founding member of the EGF-CFC family, and plays an important role in tumourigenesis, tumour cell proliferation and migration. We aimed to determine the significance of Cripto expression on the survival of patients with breast cancer. METHODS: Immunohistochemical detection of Cripto was performed by using mAb C13 on 120 formalin-fixed paraffin-embedded breast tumour specimens in tissue microarrays. This cohort comprises a series of 120 patients with primary operable breast cancer diagnosed between 1989 and 1995, retrieved from the Concord Repatriation General Hospital breast carcinoma database. RESULTS: Using a cutoff value of 80%, Cripto overexpressed in 57 of the 120 (47.5%) patients. We found significant associations between overexpression of Cripto and the Nottingham Prognostic Index (NPI, p<0.01), histological grade (p<0.01), pathological tumour type (p=0.04), PR (p=0.02) as well as Ki-67 (p=0.02). Univariate analysis reveals that there is a significant correlation between overexpression of Cripto and survival (p=0.0003). Cox regression analysis indicates that the overexpression of Cripto is an independent prognostic factor in breast cancer (HR 2.79, 95%CI 1.20-6.50). CONCLUSION: The unique epitope recognized by mAb C13 is overexpressed on breast tumour tissues. In this series of invasive breast cancers, overexpression of Cripto was more often found in high grade and poor prognosis tumours compared to low grade and good prognosis breast cancers. Moreover, overexpression of Cripto was significantly associated with decreased patient survival.

Patterns of breast cancer relapse.

AIMS: Although breast cancer is the major cause of cancer-related death in women, there is little comprehensive information on long-term outcomes, particularly pertaining to site of relapse. The Strathfield Breast Centre (TSBC) is a multidisciplinary breast clinic that has collected patient data prospectively over 14 years. METHODS: All women with invasive, non-metastatic breast cancer, referred to TSBC from 1989 until 2002, were studied (n=2509). After initial treatment, patients were reviewed at 3-12-month intervals, including annual mammography and/or breast ultrasound. Information was collected on demographics, pre- and post-operative management and patient outcomes. Survival was analysed by the method of Kaplan and Meier. RESULTS: The mean age was 58 years and median follow-up 4 years (range <1-14) with complete data for 81%. In total, 456 patients (18%) had a local, nodal or distant relapse. The most common site of first relapse was to bone (in 125 patients), followed by local recurrence (124), lung (73) and liver (57). The median interval from primary breast surgery until recurrence was 2.3 years and disease-free intervals correlated to survival (p<0.0001). After local recurrence the 5-year survival was 41%, vs. 20% for nodal and 13% for distant recurrence (p<0.0001). Following breast-conserving surgery, the 5-year disease-free survival after local recurrence was 49.4%, vs. 33.1% after chest wall recurrence (p=0.0361). Of distant relapses, bone metastases had the best prognosis, with median survival 2.4 years. CONCLUSION: These data provide information on treatment outcomes in a multidisciplinary setting and statistical information that will be useful when discussing the fears and expectations of patients after the diagnosis of breast cancer.

Bone-anchored hearing aids: results of the first eight years of a programme in a district general hospital, assessed by the Glasgow benefit inventory.

OBJECTIVES: To report the clinical results of a bone-anchored hearing aid (BAHA) programme in a district general hospital, compared with those in an established, large, university teaching hospital centre. DESIGN: A retrospective postal questionnaire sent to BAHA patients, with two month waiting time and one reminder, combined with case note analysis. Results compared by appropriate statistical tests with published outcomes data from the largest UK series. SETTING: Public sector (National Health Service) district general hospital, England. Catchment population: 300,000 (mixed rural and small towns). PARTICIPANTS: Case note analysis of sixty-three patients implanted between 1994 and 2003 (age range, six to 88 years). The commonest indication was chronic otitis media, with inability to wear a conventional hearing aid. Otitis externa, otosclerosis and sensorineural hearing loss were other indications. The questionnaire was sent to 59 patients who had worn their aid for at least six months; it was returned by 41 (69 per cent). MAIN OUTCOME MEASURES: Glasgow benefit inventory (GBI, change in health status following otolaryngological intervention); incidence of complications. RESULTS: Bone-anchored hearing aid implantation significantly improved quality of life as measured by the GBI (p<0.001). The degree of improvement was similar to that achieved in Birmingham by Proops et al. (p>0.05, chi-squared test). Minor temporary skin infection was common (33 per cent). Thickening of the skin around the implant occurred in 17 per cent. One implant (2 per cent) failed. There were no serious complications. CONCLUSION: The BAHA is a safe, reliable and effective treatment for selected patients. A successful BAHA programme can be run in a district general hospital.

Imatinib mesylate as a cause of acute liver failure.

A 46-year-old patient diagnosed with chronic myeloid leukemia in whom cytogenetic and molecular remission had never been achieved was commenced on Imatinib Mesylate (Gleevec, Novartis Pharmaceuticals Corp., East Hanover, NJ). After 18 months of treatment, she developed abnormal liver function tests and subsequently acute liver failure, requiring transfer to the regional liver unit. The patient proceeded to liver transplantation but later died. The explanted liver had histological features of severe hepatic necrosis. This is the first case described of fatal hepatic necrosis in a patient who has have been on long-term imatinib therapy. This may have implications for long-term use of the drug and emphasizes the need for regular monitoring of liver function.

Antenatal transabdominal ultrasound detection of cleft lip and palate in Western Australia from 1996 to 2003.

OBJECTIVE: To determine the frequency of detection of cleft lip with or without cleft palate and isolated cleft palate from antenatal ultrasound examinations conducted on mothers of infants born with cleft lip and/or palate and isolated cleft palate in Western Australia from 1996 to 2003. DESIGN: Review of patient records and purpose-designed questionnaire sent to parents of children born with cleft lip and/or palate and isolated cleft palate. RESULTS: There were 308 infants born with cleft lip and/or palate and isolated cleft palate in the study period. Of the 293 parents, 218 responses were available for the study (70.7%), and 2.9 +/- 1.8 SD antenatal ultrasound scans were performed on 216 women. No such scans were performed on two women. Cleft lip and/or palate was detected in 22.2% of cases. There was no detection prior to 15 weeks gestational age in the 137 women screened. Between 15 and 19 weeks gestational age, 174 scans detected 30 cases. Between 20 and 29 weeks gestational age, 84 scans detected 11 cases. Between 30 and 40 weeks gestational age, 66 scans detected 7 cases. The detection rate for bilateral cleft lip and/or palate was 44.4% and for unilateral cleft lip and/or palate, 40.6%. Detection rate for isolated cleft lip was 33.3%. Antenatal ultrasound failed to detect any infants with an isolated cleft palate (n = 95). The rate of detection of cleft lip and/or palate increased through the study period. CONCLUSIONS: The rate of detection of cleft lip and/or palate in Western Australia is comparable to that for referral centers worldwide and is increasing. The rate of detection of the various types of cleft anomalies using antenatal ultrasound ranged from 0% to 44%.

Extra-axillary sentinel node biopsy in the management of early breast cancer.

AIM: To document of our experience with EAS SNB and evaluate its impact on the staging, management and the associated morbidities of patients with early breast cancer. METHOD: A review of two prospective breast cancer databases identifying all SNB procedures performed at two affiliated breast units from 1998 to 2003. RESULTS: A series of 979 patients underwent lymphatic mapping. Sentinel nodes were successfully identified in 903 patients. There were 142 cases in which lymphoscintigraphy identified EAS. In 17 cases extraaxillary sentinel nodes were identified with lymphoscintigraphy but could not be removed. There were 138 cases where internal mammary nodes (IMN) were removed. Of those IMN removed 25 were positive for metastases and in six of these cases only the IMN was positive. Of the 21 cases where other EAS were identified there was one case in which a supraclavicular sentinel node was positive. Twenty-five of the 26 positive sentinel nodes in EAS were macrometastases and one was a micrometastasis. No significant morbidity resulted from biopsy of EAS SNB. During IMN SNB there were eight pleural breeches, which did not result in pneumothoraces, and one case in which bleeding was difficult to control. CONCLUSION: EAS SNB is technically feasible in the majority of cases. Minimal morbidity occurs after an initial learning phase. IMN SNB was shown to have significant impact on the staging and management in 18% of patients when IMNs were identified with lymphoscintigraphy. The impact of other extraaxillary lymph nodes is more difficult to assess due to small numbers. As there is little morbidity and valuable information is gained in a significant percentage of cases we strongly advocate EAS SNB.

Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node positivity.

AIMS: This study evaluates the breast cancer nomogram (BCN), an online tool developed by Memorial Sloan-Kettering Cancer Center to determine the rate of non-SLN positivity, in an independent cohort of SLN positive patients. MATERIAL AND METHODS: Available data between 02/2000 and 06/2004 in two prospective databases, 749 cases had successful SLN biopsy including 149 axillary-SLN metastases study cases. These cases had accurately graded tumours up to 9 cm in size and CAD with a minimum total 10 nodes removed. Histopathological assessment of nodes included hematoxylin and eosin staining and/or immunohistochemistry. Computerized BCN was used to estimate probability of non-SLN positivity and compared with actual probability after grouping into deciles. RESULTS: The trend of actual probability in various decile groups was comparable to the predicted probability. An area under the receiver operating characteristic curve was 0.75 as compared to 0.76 in the original study. CONCLUSION: Although this study is small, the results are encouraging and suggest the nomogram is a useful tool to estimate the likelihood of positive axillary non-SLN. However, variations in pathological assessment between centres are the major impediment to widespread application of BCN. If SLN positive patients decline the standard recommendation of CAD or entry into clinical trials evaluating the significance of CAD then the BCN could help in decision making.

Alendronate-induced chemical laryngitis.

Alendronate is a bisphosphonate used in treating osteoporosis. Its recognized side-effects include oesophageal irritation and ulceration. The authors describe a case of laryngitis induced by transient contact of this medication with the laryngeal mucosa. Successful management of this case is also detailed.

Management of serum calcium levels in post-thyroidectomy patients.

Otolaryngologists are increasingly performing thyroid surgery and are responsible for optimising parathyroid function postoperatively. The aim of this study was to establish an evidence-based algorithm for the management of postoperative calcium levels and to try and answer some relevant postoperative management issues. These include the following: (1) What is the risk of hypocalcaemia both temporary and permanent? (2) When should calcium replacement be commenced and in what form? (3) What is the best method for calcium replacement without suppressing a recovering parathyroid? (4) How to identify recovering parathyroid function if the patient is already on calcium replacement? A systematic review of the literature was carried out supported by a retrospective analysis of postoperative calcium levels obtained from clinical records of patients undergoing thyroidectomy under our care (n = 167). We present an evidence based, user-friendly algorithm for the management of the serum calcium in patients undergoing thyroid surgery.

A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK.

Epidemiology data on multiple myeloma (MM) occurrence and outcome is inconsistent whilst a major limitation of randomized controlled trials is selection bias. We present a population-based analysis of patients diagnosed with MM in the South Thames area, which comprises 5.4 million adult inhabitants. A total of 855 cases of MM were ascertained between 1999 and 2000 in a collaborative project involving haematologists and the Thames Cancer Registry. The age-standardized rate was 3.29 per 100 000 and 4.82 cases per 100 000 (World Standard and European Population respectively). The median age was 73 years. The median survival for the whole group was 24 months whist it was 42 and 18 months in those aged less than 65 years and greater than 65 years respectively (P < 0.001). This population study has shown a higher incidence than previously reported in the UK and Europe and provides a benchmark for future studies. If survival is to be improved, future clinical trials and health care planning should consider patients over 65 years of age.

Infiltrating lobular carcinoma--a comparison of diagnosis, management and outcome with infiltrating duct carcinoma.

The treatment and outcomes for 182 patients with lobular carcinoma were compared with 1612 patients with infiltrating ductal carcinoma managed concurrently at The Strathfield Breast Centre. The lobular carcinomas were larger (P < 0.0001) but of lower grade (P < 0.0001). Diagnosis with mammography and FNA was less sensitive in ILC (mammography P = 0.0002, FNA P < 0.0001). Although similar numbers of patients underwent initial attempted conservation, patients with ILC were more likely to have positive margins at attempted breast conservation surgery and the final mastectomy rate was higher (58.2% ILC versus 47% IDC, P = 0.0041). Of the patients who had successful conservation, the local recurrence rates for ILC (3.9%) were equivalent to the patients with IDC (5.3%). There was no significant difference in overall survival (90% ILC, 87% IDC, median follow-up 3.6 years ILC, 4.3 years IDC) or disease free survival (87.9% ILC, 81.6% IDC). Although mastectomy is more likely to be necessary to obtain clear margins, breast conservation therapy is reasonable in patients with infiltrating lobular carcinoma where clear margins can be obtained.