Assessing inter and intrafraction uncertainties in adult brain cancer patients using 2D/3D kV and CBCT imaging.

METHOD: 2D/3D kV imaging and CBCT data using 6 degrees of freedom (6DoF) were compared to evaluate inter and intrafraction motion. RESULTS: Results showed that intrafraction errors were low and interfraction levels were within institutional protocols. CONCLUSION: Confidence was given to use low dose 2D/3D kV imaging to confirm daily patient set up errors, and to use pre-treatment CBCT only once weekly for additional imaging information. IMPLICATIONS FOR PRACTICE: Further research is necessary to assess other uncertainties, to enable the calculation of a margin and determining the feasibility of further reduction of this.

Surgical Treatment of Cardiac Tumors: a 17-year Experience at Department of Cardiac Surgery, NICVD, Dhaka.

Cardiac Myxoma is the most common benign intra-cardiac tumor of heart. We studied its incidence, clinical presentations, short term outcome, morbidity and mortality following surgery over a period of 17 years. The retrospective observational study was performed in the Department of Cardiac Surgery, National Institute of Cardiovascular Diseases (NICVD) Dhaka, Bangladesh from 2000 to 2016. NICVD is the tertiary hospital for cardiovascular surgery in the Government sector. One hundred twenty nine (129) patients were of cardiac myxoma among 11,923 open heart surgery was done in this study period of 17 years. As a result, cardiac myxoma patients represent 1.08% of all open heart surgery. Pre-operative diagnosis was done on clinical presentations and 2D echocardiography, which is the most important tool for its diagnosis. Most of the patients presented at 4th to 5th decade of life. The patients presented with triad of valve obstructive features, embolic symptoms and constitutional symptoms alone or in combination. Among all myxoma patients, majority (86.6%) had left atrial myxoma. Cardiac myxoma forms a very small percentage of all cardiac diseases requiring surgical treatment. Immediate surgical excision is indicated in all patients to avoid life-threatening complications. Outcome of surgical treatment was excellent.

Rapid advances in auto-segmentation of organs at risk and target volumes in head and neck cancer.

Advances in technical radiotherapy have resulted in significant sparing of organs at risk (OARs), reducing radiation-related toxicities for patients with cancer of the head and neck (HNC). Accurate delineation of target volumes (TVs) and OARs is critical for maximising tumour control and minimising radiation toxicities. When performed manually, variability in TV and OAR delineation has been shown to have significant dosimetric impacts for patients on treatment. Auto-segmentation (AS) techniques have shown promise in reducing both inter-practitioner variability and the time taken in TV and OAR delineation in HNC. Ultimately, this may reduce treatment planning and clinical waiting times for patients. Adaptation of radiation treatment for biological or anatomical changes during therapy will also require rapid re-planning; indeed, the time taken for manual delineation currently prevents adaptive radiotherapy from being implemented optimally. We are therefore standing on the threshold of a transformation of routine radiotherapy planning via the use of artificial intelligence. In this article, we outline the current state-of-the-art for AS for HNC radiotherapy in order to predict how this will rapidly change with the introduction of artificial intelligence. We specifically focus on delineation accuracy and time saving. We argue that, if such technologies are implemented correctly, AS should result in better standardisation of treatment for patients and significantly reduce the time taken to plan radiotherapy.

Surgical Management of a Critical Ischemic Mitral Regurgitation Patient.

Functional ischemic mitral regurgitation is strongly associated with poor outcomes in patient with coronary artery disease. The best management for mitral regurgitation at the time of coronary revascularization remains controversial. We report, a case of 58 years-old men admitted to GKNM hospital, Coimbatore, Tamil Nadu, India with chest pain and respiratory distress for last 6 hours during my fellowship training in that hospital. ECG showed acute antero-septal MI. The transthoracic echocardiogram revealed severe left ventricular dysfunction with moderate mitral regurgitation. Coronary angiogram revealed triple vessels disease. We planned for early CABG. But the patient suddenly developed severe respiratory distress with ventricular tachycardia. Patient managed with the support of invasive ventilation and IABP. After that, CABG along with mitral valve repair was done under cardiopulmonary bypass. The patient showed excellent symptomatic improvement during his early post-operative period. Mitral valve repair along with CABG may be a preferable treatment option for patient with Ischemic heart disease with moderate mitral regurgitation.

Application of anti-leukocyte common antigen and anti-cytokeratin antibodies to the biopsy diagnosis of gastric large cell lymphoma.

Definitive diagnosis of gastric large cell lymphoma and its distinction from anaplastic carcinoma in endoscopic biopsy material may be problematic. To assess the utility of immunohistochemical studies in routinely processed, paraffin-embedded tissue in this situation, we applied immunostaining for leukocyte common antigen (LCA) and cytokeratin in 17 cases diagnosed on biopsy as undifferentiated malignant tumor but proved on resection to be primary gastric large cell lymphoma. Clinical and endoscopic features failed to distinguish lymphoma from carcinoma in these cases. Immunoreactivity for LCA occurred in 15 cases (88 per cent) and was correctly and readily interpreted on blinded evaluation. Open review increased the yield to 16 cases (94 per cent). Tumor cells were uniformly negative for cytokeratin; however, staining of adjacent epithelium for cytokeratin provided additional confirmation of the lymphoid nature of the tumor. The one case in which excessive background staining precluded interpretation consisted of a single biopsy specimen of necrotic tumor. We conclude that antibodies to LCA and cytokeratin are sensitive, specific, and reliable diagnostic adjuncts that are useful in the definitive biopsy diagnosis of gastric large cell lymphoma.

Intraepithelial neoplasia of the anal canal in hemorrhoidal tissue: a study of 19 cases.

The investigators report the clinical and pathologic features of 19 cases of intraepithelial neoplasia occurring in the anal canal mucosa of routinely excised hemorrhoidal tissue, a condition that has been infrequently described. The patients were 12 women and seven men having an age range of 21 to 74 years (mean, 48 years). Two patients had coexistent anogenital condylomata acuminata. Leukoplakia of the hemorrhoidal surface was noted in two patients. Intraepithelial neoplasia arose in the transition zone of the anal canal of 11 cases, in the squamous zone of three cases, and in both sites of five cases. All were high-grade intraepithelial neoplasms; one was classified moderate to severe dysplasia, 17 exhibited severe dysplasia/carcinoma in situ, and one contained microinvasive carcinoma. Both keratinizing and cloacogenic type neoplasms were observed. Associated koilocytotic atypia was identified in 16 cases (84%). In situ hybridization for human papillomavirus (HPV) messenger RNA demonstrated HPV RNA sequences in seven of nine neoplasms (78%) studied by that technique (five HPV type 16, one HPV type 18, and one coinfection with HPV types 6 and 18). Eighteen patients had no clinically evident recurrent or progressive disease at mean follow-up of 6.6 years. Residual/recurrent intraepithelial neoplasia was noted in one patient at 1, 2, 5, and 49 months posthemorrhoidectomy. Our data indicate that incidentally discovered high-grade intraepithelial neoplasia present in hemorroidal tissue is a clinically nonaggressive lesion frequently associated with HPV infection. Hemorrhoidectomy alone is curative in most cases.

Cytologic and immunohistochemical diagnosis of neuroendocrine (Merkel cell) carcinoma in cerebrospinal fluid.

Neuroendocrine (Merkel cell) carcinoma of the skin is a rare entity. Often locally aggressive, this lesion may also metastasize to organ systems, including bone, liver, and brain. The authors report a case of a 64-year-old male who presented with hoarseness and dysphagia 17 months after resection of a primary Merkel cell carcinoma of the nose. Additional studies revealed bilateral vocal cord paralysis secondary to central nervous system dysfunction. Cytologic evaluation of the cerebrospinal fluid revealed malignant tumor cells consistent with metastatic Merkel cell carcinoma. Presented are the cytologic and immunohistochemical findings in a case of metastatic Merkel cell carcinoma involving the central nervous system.

The role of aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis.

The experience at one institution concerning the diagnosis of pulmonary tuberculosis by aspiration biopsy is reviewed. Twelve cases in which acid-fast bacilli were identified in pulmonary aspiration material are reported. The cytologic findings were confirmed by microbiologic culture in nine cases. The advantages of using aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis are discussed. In our experience we conclude that the use of aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis is not only accurate, but also offers several advantages that are important in patient care.

Value of urine cytology versus bladder washing in bladder cancer.

A prospective study compared the diagnostic outcome of paired urine cytology and bladder washings in 26 patients as well as the diagnostic accuracy of cytologic reading of voided urine in 43 patients, all with documented bladder cancer. We demonstrate the superiority of bladder washing over voided urine cytology and recommend its routine use in spite of the additional cost and patient discomfort.

Study of cerebrospinal fluid flow dynamics in TGF-beta 1 induced chronic hydrocephalic mice.

In a previous study, we found that the CSF level of transforming growth factor beta 1 (TGF-beta 1) is elevated following subarachnoid hemorrhage (SAH) in patients who later develop communicating hydrocephalus, while in mice, an intrathecal injection of TGF-beta 1 can induce communicating hydrocephalus. Recently, histopathological changes in the leptomeninges were studied using the above TGF-beta 1 induced mice model of hydrocephalus. In the present study, in order to further clarify the ventricular dilatation mechanism, we examined cerebrospinal fluid (CSF) flow dynamics in TGF-beta 1 induced hydrocephalic mice. To assess CSF flow, Indian ink was injected into the passage pathway and the time taken for the ink to pass from the parietal intrameningeal CSF space to cervical lymph nodes was determined. The ink study revealed a significant lengthening of the ink passage time due to altered CSF flow dynamics, while a histological examination showed ink stasis in the altered leptomeningeal CSF space compared to PBS injected control mice. TGF-beta 1 induced increased cellularity in the leptomeninx and fibrosis, and a subsequent narrowing of the intrameningeal CSF space. This narrowing causes a disturbance in CSF flow, thus generating a mild pressure gradient, which ultimately leads to the development of slowly progressive ventricular dilatation. After SAH, elevated TGF-beta 1 in the CSF may play a similar role, in concert with other factors, in the development of communicating hydrocephalus in human.

Aspiration biopsy of primary neoplasms of bone.

Aspiration biopsy of bone is a simple and relatively safe diagnostic tool that had a diagnostic accuracy of 72 per cent in thirty-one patients who had a primary bone tumor that was suspected of being malignant and of 83 per cent in twelve patients who had a suspected giant-cell tumor. However, twenty-six primary lesions of bone that were thought likely to be benign were not as easily and definitively diagnosed (an accuracy rate of 23 per cent), and for these lesions, multiple needle-aspiration samples or open biopsy provides greater diagnostic accuracy.

Fine needle aspiration cytology of an ectopic parathyroid adenoma: a case report.

BACKGROUND: Surgical exploration in the region of the neck identifies a majority of parathyroid adenomas; however, in individuals in whom surgical exploration has failed, fine needle aspiration (FNA) biopsy can be useful. Ectopic parathyroid adenomas can be rapidly diagnosed by the cytologic appearance of aspirate smears with the identification of stromal and intracellular lipid on oil red O-stained smears. CASE: A 59-year-old male presented with hyperparathyroidism; surgical exploration of the neck in the region of the thyroid gland failed to identify any parathyroid abnormality. Subsequent imaging with (99m)technetium and (201)thallium showed a mass in the left supraclavicular region that, on FNA biopsy, was confirmed as an ectopic adenoma. Removal of the adenoma resulted in normal serum calcium levels. CONCLUSION: FNA can be successfully utilized in the localization of ectopic parathyroid tissue.

Endodermal sinus tumor of the mediastinum. Cytologic diagnosis on a pleural effusion.

A primary mediastinal endodermal sinus tumor in a young man was diagnosed by cytologic examination of a pleural effusion. Subsequent evaluation revealed a greatly elevated serum alphafetoprotein (AFP); computed tomographic scan of the chest showed a large anterior mediastinal mass. Routine examination of the smears and cell block preparations revealed clusters of tumor cells with a few intracytoplasmic hyaline droplets. Immunohistochemical stains for AFP, alpha-1-antitrypsin and cytokeratin were positive in the tumor cells while stains for carcinoembryonic antigen and the beta subunit of human chorionic gonadotropin were negative. This supported the diagnosis of endodermal sinus tumor, a rare primary tumor within the mediastinum.

Fine needle aspiration cytology of liposarcoma of the breast. A case report.

Aspiration cytology has become an accepted procedure in the evaluation of breast abnormalities. Encountering unusual findings in cytologic material, therefore, may become more frequent. We describe a primary liposarcoma of the breast diagnosed by fine needle aspiration cytology and review the cytologic features of liposarcoma in general. The differential diagnosis is considered, and the previous literature regarding liposarcomas of the breast is reviewed.

Maximum tolerable dose of cyclophosphamide and azathioprine in Pakistani patients with primary renal disease.

OBJECTIVE: The immunosuppressive regimens, at present, mainly rely on western guidelines that were derived from studies conducted in western populations. No such study exists for South Asian population, which is home to almost two billion people different in both genetics and environment from west. Locally derived thresholds for side effects markedly different from western figures may warrant re-adjustment of current local immunosuppressive regimens that are at present based largely on western guidelines. In order to define optimum dose for Cyclophosphamide (CYC) and Azathioprine (AZA) based immunosuppressive therapy, we conducted this study to find out maximum tolerable doses of azathioprine (AZA) and cyclophosphamide (CYC) beyond which neutropenia and thrombocytepenia are most likely to occur in patients with primary renal pathology. METHOD: Patients with systemic vasculitis and idiopathic glomerulonephritis who were on CYC and AZA were identified through review of medical records at a tertiary care hospital in Pakistan (The Aga Khan University Hospital, Karachi). Patients were categorized under three principal diagnosis i.e. systemic lupus erythematosus (SLE), primary (idiopathic) glomerulonephritis (GN) and Wegener's granulomatosis (WG). The Receiver Operating Curve (ROC) was used to calculate the maximum tolerable dose for both CYC and AZA. RESULTS: We identified 94 patients aged 6-82 years (median 44.5 years) with primary renal disease (Wegener's granulomatosis n=13, Systemic lupus erythematosis n=62 and idiopathic glomerulonephritis n=19) who received CYC or AZA. Of these 94 patients, 36.2% (n=34) received CYC and 63.8% (n=60) received AZA. The mean dose of CYC was 1.54 +/- 0.50 mg/kg of body weight (range: 0.77-2.93). The mean dose of AZA was 1.64 +/- 0.59 mg/kg of body weight (range: 0.47-2.97). The maximum tolerable doses calculated for CYC and AZA were 1.25 mg/kg and 1.30 mg/kg of body weight respectively. The maximum tolerable dose for CYC and AZA among males could not be calculated, because of insufficient number of patients who developed neutropenia and thrombocytopenia. The maximum tolerable doses for CYC and AZA among females were 1.34 mg/kg and 1.03 mg/kg of body weight respectively. Also we found out that AZA was relatively more likely to cause neutropenia and thrombocytopenia (p=0.07). CONCLUSION: We thereby recommend that CYC should be initiated at a dose no more than 1 mg/kg of body weight and AZA at an initial dose of 0.75-1.0 mg/kg of body weight. The dose may be adjusted later on the basis of clinical response and laboratory reports.

Mediastinal needle biopsy. A 15-year experience with 139 cases.

BACKGROUND: Radiologically guided needle biopsy and cytologic evaluation provide a reliable method of diagnosis for planning definitive therapy of patients with mediastinal lesions. MATERIALS AND METHODS: In this retrospective study of one of the largest series from a single institution, 141 consecutive mediastinal needle biopsies from 139 patients were reviewed during a 15-year period. RESULTS: Adequate material was obtained with a diagnosis achieved in 128 cases (92%). Of these, 33 cases (26%) had benign diagnoses; the remaining 95 (74%) had malignant diagnoses, including 81 carcinomas, 3 sarcomas, 8 lymphoproliferative lesions, 2 malignant germ cell tumors, and 1 malignant thymoma. All benign cases were diagnostically confirmed, and 94 of 95 malignant cases were classified correctly. The only discrepancy that occurred involved a malignant lymphoma diagnosed as a malignant germ cell tumor. Of the 13 inadequate samples, the major category included a nodular sclerosis variant of Hodgkin's disease (4 cases), 1 case of thymoma, 1 case of tuberculous lymphadenitis, and 7 cases for which no follow-up data were available. CONCLUSION: Needle biopsy is reaffirmed as a reliable and sensitive diagnostic tool for mediastinal lesions, with an overall cytologic diagnostic accuracy of 99% with adequate material. Sclerotic lesions may pose a limitation to this technique and require generous sampling before a more invasive diagnostic procedure is undertaken.

Urothelial carcinoma after cyclophosphamide therapy.

We report a case of transitional cell carcinoma of the bladder after cyclophosphamide therapy for chronic lymphocytic leukemia. Urologic evaluation and histologic confirmation occurred only after low grade tumor cells were identified in multiple urine samples. Malignant cells can be distinguished from drug effect in urinary specimens from patients treated with cyclophosphamide and all such cases should include regular cytologic evaluations.

Mediastinal needle biopsy.

A review of 52 consecutive needle biopsies of the mediastinum is presented. The aspirated material yielded cytologic and/or histologic diagnosis in 50 needle biopsies; two needle biopsies failed to yield adequate cellular material for diagnosis. All but two of the 50 patients had confirmation of the biopsy diagnosis by surgical, autopsy, or clinical correlation. In 32 patients, a 20-gauge needle was used for the biopsy. A larger-bore (17-gauge) needle with a cutting device was used in 20 cases to obtain more tissue for histologic diagnosis of benign or unusual malignant lesions. Despite the larger size of the needle, the rate of complications remained low.

Aspiration biopsy of the kidney. Simultaneous collection of cytologic and histologic specimens.

Aspiration biopsy of mass lesions of the kidney is a diagnostic procedure whose potential benefit to patients with equivocal radiologic findings, suspected metastases, palpable flank masses, nonfunctioning kidneys and even cortical cysts has not been fully explored. Over the past 7 years 163 renal aspiration specimens from 152 patients have been examined. Diagnostic yield was enhanced by use of modified "fine" needles with notched tips so that tissue fragments for histology as well as smears for cytology were obtained in 89% of solid tumors. The availability of aspirated tissue contributed significantly to pathologic classification and often spared patients additional surgery for confirmation of the cytologic diagnosis. Among the 152 cases, there were 35 with renal cell carcinomas, a sufficient number for detailed semiquantitative evaluation of their cytologic features. The remaining cases comprised metastatic carcinomas, lymphomas, transitional cell carcinomas, oncocytomas, cortical cysts, and miscellaneous conditions, e.g., abscesses, nonfunctioning kidneys, and hematomas. Overall, the aspiration biopsy determined the nature of the renal mass in 141 cases (93%). False-negative interpretations were due to insufficient diagnostic material in all but one instance. There was one false-positive result.

Flow cytometry versus urinary cytology in the evaluation of patients with bladder cancer.

We compared the roles of urinary cytology and flow cytometry in the evaluation of patients with bladder cancer in clinical practice situations at a large general hospital. Specimens included 105 bladder washings from patients being followed for urothelial carcinomas and 28 control washings from individuals undergoing cytoscopy for other reasons. Flow cytometry and cytology were performed on aliquots of the same specimen in all bladder cancer samples. When carcinoma was present at the time of specimen collection it was detected by positive cytology in 75 per cent and deoxyribonucleic acid aneuploidy in 78 per cent of the cases. Combination of flow cytometry and urinary cytology increased the diagnostic yield to 95 per cent. Flow cytometry was slightly more sensitive than urinary cytology for detection of abnormalities in specimens from noninvasive and untreated tumors but the only statistically significant difference between the 2 procedures occurred among specimens from treated invasive cancers in which flow cytometry was a less sensitive method than cytology. Abnormal deoxyribonucleic acid ploidy was documented in a few specimens from noncancer-bearing patients having diseases associated with high urothelial cell turnover rates but the concomitant urinary cytology was negative for neoplasia. When used in conjunction with urinary cytology, flow cytometry was a valuable procedure in the followup of patients with bladder cancer. The diagnostic yield with this combination was such that flow cytometry and cytology may be used to reduce the frequency of cystoscopy and biopsy during clinical management in selected situations.