Formulation of ciprofloxacin-loaded oral self-emulsifying drug delivery system to improve the pharmacokinetics and antibacterial activity.

This study aims to increase the aqueous solubility of ciprofloxacin (CPN) to improve oral bioavailability. This was carried out by formulating a stable formulation of the Self-Emulsifying Drug Delivery System (SEDDS) using various ratios of lipid/oil, surfactant, and co-surfactant. A pseudo-ternary phase diagram was designed to find an area of emulsification. Eight formulations (F1-CPN-F8-CPN) containing oleic acid oil, silicone oil, olive oil, castor oil, sunflower oil, myglol oil, polysorbate-80, polysorbate-20, PEO-200, PEO-400, PEO-600, and PG were formulated. The resultant SEDDS were subjected to thermodynamic study, size, and surface charge studies to improve preparation. Improved composition of SEDDS F5-CPN containing 40% oil, 60% polysorbate-80, and propylene glycol (Smix ratio 6: 1) were thermodynamically stable emulsions having droplet size 202.6 nm, charge surface -13.9 mV, and 0.226 polydispersity index (PDI). Fourier transform infra-red (FT-IR) studies revealed that the optimized formulation and drug showed no interactions. Scanning electron microscope tests showed the droplets have an even surface and spherical shape. It was observed that within 5 h, the concentration of released CPN from optimized formulations F5-CPN was 93%. F5-CPN also showed a higher antibacterial action against S. aurous than free CPN. It shows that F5-CPN is a better formulation with a good release and high antibacterial activity.

Surgical Outcome Of Intradural Spinal Tumours.

BACKGROUND: This study was conducted to determine the short-term outcome of surgical procedure in patients having spinal intradural tumours. METHODS: This cross-sectional study was conducted from 26 April 2016 to 25 March 2019 on 56 patients after approval from hospitals ethical and research committee. MRI spine were studied in detail for all patients to know about the site, size, shape, extent and nature of the tumour. History, examination, pre-operative MRI findings, post-operative findings were documented in patient's pro forma. Short term as well as long term post-operative results were documented after surgery, during stay at hospital and followup visits till 6 months. RESULTS: In this study, 56 patients with spinal intradural tumours were observed. Male to female ratio was 1.33:1. Age ranged from 5-65 years (32.5±14.6). Paraparesis, hypesthesia, sphincter dysfunction were the presenting symptoms in most of the patients. 47% (21) patients improved according to MRC Grading system 46% (20) patients remained static 7% (3) patients deteriorated. Wound infection was found in 7 (12.5%) patients, followed by Neurological Deficit in 5 (8.9%) cases, Meningitis was found in 2 (3.57%), CSF leak was noted in 4 (7.14%) patients and mortality in 1 (1.7%) of the case. CONCLUSIONS: Surgery of the intradural spinal tumours carry good neurological outcome with acceptable complication rates.

City tumour board Karachi: an innovative step in multidisciplinary consensus meeting and its two years audit.

Management of cancer patients is a team work which usually comprises of surgeons, oncologists, radiologists, pathologists, psychiatrist, nutritionist and a nurse. Any patient who is suffering from any tumour needs a multimodality meeting as cancer treatment is not a single persons job. Most of the time, it is difficult to get the whole team together for a plan discussion due to their busy schedule. This problem was overcome by starting a tumour board meeting early morning of Sunday in Karachi which was named "City Tumour Board (CTB) Karachi". Its first meeting was held on Sunday March 28, 2010 and since then it takes place regularly fortnightly. Till March 2012, 44 sessions were conducted and total 264 cases were discussed. Here we present an audit of these two years. On average, in 60% of cases, tumour was up (36%) or down staged (12%) while in 52% of cases the stage remained unchanged. In 70% of cases (inclusive of above 60%), initial treatment plan was changed after discussion in the tumour board. This data signifies the importance of tumour board especially in a Pakistani setup where patient and even referring persons are not well aware of this disease and its outcome. It is advisable that every case should be discussed in tumour board before embarking on any treatment so that the best treatment plan can be given. It is also important that all relevant specialists should be present in the tumour board when planning for any treatment.

Prognostic sub-grouping of diffuse large B-cell lymphomas into germinal centre and post germinal centre groups by immunohistochemistry after 6 cycles of chemotherapy.

INTRODUCTION: Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment. OBJECTIVE: To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy. SUBJECTS AND METHODS: In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression. RESULTS: The mean age was 54.2 ± 15. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant. CONCLUSION: GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.

Aneurysmal bone cyst of the occipital bone.

A 13 years boy presented with a painless hard and fixed swelling in occipital region for the last three months. Plain X-ray, CT scan and MRI showed an expansile multi loculated cystic lesion in occipital bone. Histopathological examination revealed it to be an aneurysmal bone cyst. Treatment of choice is surgery. However, radiotherapy may be helpful in incompletely excised lesions.

Omental caking: a rare manifestation of malignant peripheral nerve sheath tumour.

Malignant peripheral nerve sheath tumour (MPNST) is a very rare tumour with an incidence of one per 100,000 and constitutes between 3 to 10% of all soft tissue sarcomas. Most of the sarcoma involve the extremities and retroperitoneal regions. However, this case presented with mass in left inguinal region and then spread rapidly to omentum, assuming the appearance of an omental cake. Mass responded well to chemotherapy comprising of Ifosfamide and Doxorubicin.

Long-term survivor of brain metastases from malignant melanoma.

Malignant melanoma is notorious for distant metastases. Median survival for stage IV melanoma is 6-10 months and 5 year survival is less than 5%. Median survival for melanoma with brain metastases is even lower i.e. 2 to 9 months. Here a case is reported who was treated for melanoma of sole of left foot with ipsilateral inguinal adenopathy and brain metastases in 2001 and is still surviving disease-free after a lapse of 8 years.

Gliosarcoma: a rare variant of glioblastoma multiforme.

Gliosarcoma is a rare variant of Glioblastoma Multiforme (GBM). It is a very aggressive tumour and usually managed like GBM. Treatment of choice is surgery with good surgical margins followed by radiotherapy (60 Gy). Median survival is seven months. Here we present a case report of 55 years old male who was diagnosed as brain tumour in left temporoparietal region. It turned out to be gliosarcoma after surgical resection and histopathological evaluation.

Porocarcinoma: a rare sweat gland malignancy.

Eccrine Porocarcinoma (ECP) is a malignant tumour arising from the intraepithelial ductal parts of the sweat gland. It has also been described as malignant hidroacanthoma simplex, sweat gland carcinoma, malignant intra-epidermal eccrine poroma, eccrine poroepithelioma, dysplastic poroma, malignant syringo acanthoma and porocarcinoma. Treatment with wide local excision but metastatic lesions can be treated with chemotherapy. Here, we present a case report of 52 years old male who presented with a fungating growth on left pre-auricular region that came out to be a case of ECP on histopathological examination.

Hepatic and skeletal metastases from primary intracranial atypical meningioma.

Meningioma constitutes 27% of primary CNS tumours. It rarely metastasizes to distant sites (< 0.1%). Here, we present a case report of primary atypical intracranial meningioma metastasizing to liver and bone after 4 years of surgery and postoperative radiotherapy presenting with multiple episodes of hypoglycemia.

Therapeutic effects of 20 gray radiotherapy over a week in the management of brain metastases.

OBJECTIVE: To determine the therapeutic effects of 20 Gy over a week in the management of multiple brain metastases. Secondly to determine the toxicity profile and survival at 6th month in patients treated with the above-mentioned protocol. METHODS: This was a single arm interventional study, conducted at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from May 8, 2006 to May 31, 2007. Thirty patients with multiple brain metastases were inducted in this study. Mean age was 52 +/- 11 years. Fifty Four percent were females and 46% males. After initial workup, all were planned for whole brain radiotherapy. 20 Gy was given to whole brain by two parallel opposed, equally weighted lateral fields in five consecutive daily fractions. Dose per fraction was four Gy. All were followed up for six months for survival. Treatment response was categorized in four different categories i.e., > 50%, approximately 50%, < 50% and no response. RESULTS: It revealed that there was significant effect of treatment with 20 Gy radiotherapy as 76% of the patients during and 80% on the last day of therapy showed > 50% response (p < 0.05). Secondly, median survival of the patients after radiotherapy was two months (p < 0.05). No serious toxicity was noted during this therapy. CONCLUSION: Twenty Gy over a week is highly effective in palliation of symptoms due to multiple brain metastases. In comparison with other studies, this protocol had no significant difference in overall survival and acute toxicity.

Correlation of perfusion and contractility of left ventricle myocardium on gated myocardial perfusion scintigraphy.

BACKGROUND: Gated Single Photon Emission Computerized Tomography (SPECT) is a modality which is helpful in the detection of wall motion, thickening and ejection fraction of left ventricle. The purpose of this study was to correlate the ungated and gated SPECT in evaluation of left ventricle dysfunction. METHOD: It was a prospective study done at Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, in 2001/02. 76 patients (47 male and 29 female) with an average age of 52+/-11 years were inducted in this study. All patients underwent two days stress-rest Tc-99m MIBI (Methoxy Isobutyl Isonitrile) gated SPECT scan where 1110 MBq (30 mCi) was injected intravenously. Eight frames gating technique (variable fixed temporal resolution) of ECG was used to gate the cardiac cycle and whole acquisition was completed in 30 minutes. RESULTS: This technique very well evaluated the perfusion as well as wall motion/thickening (W/M/T) status of left ventricle. Out of 76 scans, 30% were normal, 22% transmural infarct, 25% partial thickness infarct, and 22% reversible ischemia. By doing the 20 segmental analyses, total 1520 segments were analyzed that revealed good concordance of perfusion with W/M/T in 78% of segments while 22% segments showed poor concordance. Out of these 22%, 12% were having more wall motion abnormalities than that of perfusion, while in 10%, it was vise versa. CONCLUSION: Results of this study shows good correlation between gated and ungated SPECT for evaluation of left ventricle dysfunction (r = 0.73, p< or =0.01).

Outcome of chemoradiation in treating carcinoma esophagus.

OBJECTIVE: To observe the role of chemoradiation in treating carcinoma of esophagus, its complications and outcome of disease. DESIGN: Analytical descriptive study. PLACE AND DURATION OF STUDY: Conducted at IRNUM in collaboration with Hayatabad Medical Complex (HMC), Peshawar, for one year. PATIENTS AND METHODS: A total of 47 males and 53 females with an average age of 53 +/- 13 years were inducted in this study. Patients having upper end carcinoma or esophageal surgery were excluded from this study. They were treated with radio as well as chemotherapy. Those patients who had completed radiation six months before were planned for repeat endoscopies. Response evaluation was categorized as no evidence of disease, residual disease or stricture formation simulating carcinoma. Seventy percent of endoscoped patients were disease free and 30% were having residual disease. Of these 30%, 10% were having growth while rest of the 20% showed stricture formation due to radiation. RESULTS: Out of 100 patients, 70% were palliated maximally and no evidence of disease was found on endoscopy done after 1-6 months. Only 30% came up again with dysphagia. Out of these 30%, 20% were having esophageal stricture, which on dilatation improved the quality of life. Rest of the 10% were having stricture hiding the residual disease. Giving 1-2 cycles of chemotherapy before the start of radiation reduced the disease burden and predicted response to radiation by improving dysphagia. CONCLUSION: In spite of certain complications like neutropenia, emesis and stricture formation, chemoradiation is still the best treatment option available. It is because of its safety, well-tolerability and cost effectiveness. It is equally good for patients who refuse surgery and those with advanced disease.

Recurrent rectal carcinoma treated with high dose rate intraluminal brachytherapy.

A 65 years old man with recurrent rectal cancer was treated with remote afterloading High Dose Rate Intraluminal Brachytherapy (HDRILB). After eight weeks of HDRILB there was complete regression of the tumor. Bleeding per rectum and pain in the perineum were greatly improved. He died of myocardial infarction after 41 months of treatment with HDRILB. The treated lesions were incomplete remission at the time of death. The procedure was well tolerated. The only treatment-associated toxicity was grade 2 proctitis, which was treated conservatively. HDRILB can be used as one of the treatment options in patients with recurrent rectal cancers who have undergone previous abdominal surgery and external beam irradiation, as exhibited in our limited experience.

High dose rate intraluminal brachytherapy in combination with external beam radiotherapy for palliative treatment of cancer rectum.

OBJECTIVE: To evaluate the feasibility, efficacy and toxicity of High Dose Rate Intraluminal Brachytherapy (HDRILB) in combination with External Beam Radiotherapy (EBR) used in the palliative treatment of selected patients of adenocarcinoma rectum. DESIGN: A prospective pilot study. PLACE AND DURATION OF STUDY: The study was conducted at the Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar. The study started in April 1996 and the patients accrual was completed in June 1997. PATIENTS AND METHODS: The patients with adenocarcinoma rectum, who refused surgery, had contraindications for surgery or had advanced and/or metastatic disease were treated with HDRILB in combination with external beam radiotherapy (EBR). The apparatus used for HDRILB was Ralstron 20B remote afterloading unit with 60Co stepping source. Indigenously designed rectal applicators were used. The EBR was delivered through Pheonix 60Co teletherapy machine (Theratron AECL). The data for symptom burden and symptomatic relief was analyzed by applying Likert's method of summated scales. RESULTS: Data was analyzed after one week and at the end of the treatment. After one week of treatment, the relief in pain and bleeding per rectum (P/R) was 97%. Excellent palliation was achieved at the end of the treatment when perineal pain and bleeding P/R were relieved in 100%, discharge P/R in 87% and tenesmus in 93% of the cases. CONCLUSION: The use of HDRILB in combination with EBR can provide quick relief of symptoms in selected patients of adenocarcinoma rectum. This combination has an excellent palliative value because of its effectiveness, acceptable toxicity and overall short treatment duration.