Limb sparing surgery in soft tissue sarcoma of extremities: an Indian perspective.

This is a retrospective study of 57 patients with extremity soft tissue sarcomas treated at Gujarat Cancer Research Institute, Gujarat, India from January 2005 to December 2007. It aims to review the feasibility of limb sparing surgery for extremity soft tissue sarcoma in Indian population. Twenty-eight percent (28%) of tumors were located in the upper limbs and 72% in the lower extremities. The goal of treatment was limb salvage if feasible. The treatment consisted of amputation in 17 (30%) and local wide excision i.e. limb salvage surgery (LSS) in 40 (70%) patients. The most common histology was pleomorphic sarcoma (21%). Sixty-four percent (64%) of the patients were treated with surgery alone, 32% with surgery plus radiation and 4% with surgery plus systemic chemotherapy. Inadequate margins were present in 12% of the patients. All the patients were followed up for at least 2 years. Recurrence in the form of local and distant occurred in 39% of the patients. Local recurrence occurred in 18% of the patients who underwent LSS and in 35% of those who underwent amputation. Pulmonary metastasis was detected in 16% of patients. The 2 year mortality was 10.5% with the most common etiology being lung metastasis and the most common histology being leiomyosarcoma. We concluded that limb salvage surgery for soft tissue sarcoma is feasible in the Indian population (70%) although the rate is lower than that of world literature at 90%.

Comparison of esophagectomy with and without thoracotomy in a low-resource tertiary care center in a developing country.

Esophageal cancer surgery is traditionally performed by a number of open surgical approaches. Open approaches require thoracotomy and laparotomy. Developments in instrumentation and optics have allowed the use of minimally invasive approaches to esophageal cancer, which had been traditionally managed by open operation. Minimally invasive surgery (MIS) avoids thoracotomy and laparotomy and results in quicker return to normal functions and less morbidity. In this prospective study, we compared the immediate surgical and oncologic outcomes of patients who have undergone MIS with those who have had open surgery. From November 1, 2003 to March 30, 2006, 62 cases of carcinoma esophagus were operated in Surgical unit 3 (MIS unit) in the institute. Out of the 62 patients, 34 (54.8%) underwent minimally invasive esophagectomy (MIE), and the remaining 28 patients (45.2%) underwent open surgery. Both operations were done by the same team of surgeons. The groups were compared in terms of perioperative outcomes, morbidity, mortality, and adequacy of oncologic excision. The average duration for MIS was 312.35 min (60-480 min), which was more than that of open group surgery whose average duration was 261.96 min (60-360 min). This difference was found to be not significant (P < 0.110). The average blood loss was 275.74 mL (200-500 mL) in minimally invasive group compared with 312.50 (200-500 mL) in open group (P-value 0.33). Four patients (11.76%) in MIS group had been converted to open surgery. Average duration of hospitalization was 11.9 (4-24) days in MIS group compared with 12.19 (5-24) days in open group (P-value 0.282). Nine (26.47%) patients in MIS group had developed major or minor morbidity. Similarly, eight (28.57%) patients in open group had morbidity. One patient each expired in each group. The morbidity and mortality rates were not statistically significant. There were four leaks (11.76%) in MIS group and three leaks (10.71%) in open group (P-value 0.85). Regarding the extent of nodal clearance, an average number of 9.5 (0-19) nodes were removed in MIS group compared with an average of 7.26 (0-12) nodes in open group (P-value 0.05). Better visibility and magnification enabled more number of lymph nodes to be removed in MIS group. MIE is oncologically safe compared with open surgery. It has almost similar postoperative course, morbidity pattern, and duration of hospital stay as open surgery. Increased duration of procedure compared with open surgery is a disadvantage of MIS, especially in the early part of learning curve.

Laparoscopic salvage total pelvic exenteration: Is it possible post-chemo-radiotherapy?

Indications for total pelvic exenteration in a male (removal of the bladder, prostate and rectum) and in a woman (removal bladder, uterus, vagina, ovaries and rectum) are rare. The advanced stage generally dictates that the patient has some form of chemotherapy or radiotherapy, or a combination of two to shrink/debulk the tumour. We report the first two cases of a salvage laparoscopic total pelvic exenteration in a male for rectal adenocarcinoma invading into the bladder and prostate, post-chemo-radiotherapy and in a woman for squamous cell carcinoma of cervix invading the bladder and rectum post-chemo-radiotherapy. Salvage surgery is often difficult and has been noted to have high morbidity. Applying a laparoscopic approach to this group may have advantages for the patient and the surgeon, i.e. less pain, early recovery and magnified views. As we have technically shown it to be possible, perhaps laparoscopic approaches should be discussed if the teams in these centres are of advanced laparoscopic surgeons working in multi-skilled groups.

Body-mass index, waist-size, waist-hip ratio and cardiovascular risk factors in urban subejcts.

BACKGROUND AND OBJECTIVE: Influence of obesity as determinant of cardiovascular risk factors has not been well studied. To determine association of obesity, measured by body-mass index (BMI), waist-size or waist-hip ratio (WHR), with multiple risk factors in an urban Indian population we performed an epidemiological study. METHODS: Randomly selected adults > or = 20 years were studied using stratified sampling. Target sample was 1800 (men 960, women 840). 1123 subjects (response 62.4%) were evaluated and blood samples were available in 532 men and 559 women (n=1091, response 60.6%). Measurement of anthropometric variables, blood pressure, fasting blood glucose and lipids was performed. Atherosclerosis risk factors were determined using current guidelines. Pearson's correlation coefficients (r) of BMI, waist and WHR with various risk factors were determined. BMI was categorized into five groups: <20.0 Kg/m2, 20.0-22.9, 23.0-24.9, 25.0-29.9, and > or = 30 Kg/m2; waist size was divided into five groups and WHR into six groups in both men and women. Prevalence of cardiovascular risk factors, smoking, hypertension, diabetes, metabolic syndrome and dyslipidaemias was determined in each group and trends analyzed using least-squares regression. RESULTS: There is a significant positive correlation of BMI, waist-size and WHR with systolic BP (r= 0.46 to 0.13), diastolic BP (0.42 to 0.16), fasting glucose (0.15 to 0.26), and LDL cholesterol (0.16 to 0.03) and negative correlation with physical activity and HDL cholesterol (-0.22 to -0.08) in both men and women (p<0.01). With increasing BMI, waist-size and WHR, prevalence of hypertension, diabetes, and metabolic syndrome increased significantly (p for trend <0.05). WHR increase also correlated significantly with prevalence of high total and LDL cholesterol and triglycerides (p <0.05). CONCLUSIONS: There is a continuous positive relationship of all markers of obesity (body-mass index, waist size and waist hip ratio) with major coronary risk factors- hypertension, diabetes and metabolic syndrome while WHR also correlates with lipid abnormalities.

99mTcN complexes of tert-butyl dithiocarbamate and methoxyisobutyl dithiocarbamate as myocardial and brain imaging agents.

OBJECTIVE: Two ligands viz. tert-butyl dithiocarbamate (TBDTC) and methoxyisobutyl dithiocarbamate (MIBDTC), which are analogous to the tert-butyl isonitrile (TBI) and sestamibi (MIBI) ligands, were synthesized and labelled with the [99mTcN] core to evaluate their potential as myocardial agents. As these complexes have low molecular weights, and are neutral and lipophilic in nature, they have a tendency to cross the blood-brain barrier and thus deserve evaluation as potential brain perfusion imaging agents. METHODS: The dithiocarbamate ligands were synthesized from their respective amines, i.e., tert-butylamine and methoxyisobutylamine, by reacting with carbon disulfide in dry ether in the presence of crushed sodium hydroxide. The ligands were characterized by elemental analyses. The 99mTc-nitrido intermediate was prepared from 99mTcO(-)4 using commercially available nitrido kits. The complexation was carried out by mixing the freshly prepared 99mTc-nitrido intermediate and the ligand followed by incubation at room temperature for 10 min. These complexes were characterized by high-performance liquid chromatography (HPLC) using a C-18 reversed phase column with acetonitrile:water as the mobile phase, and by paper electrophoresis. Biodistribution studies were carried out in normal Swiss mice. RESULTS: The ligands were synthesized in near quantitative yields. They were radiolabelled in > 95% yields using the 99mTc-nitrido core, at low ligand concentrations of 0.01 mg . ml(-1) (5.8 x 10(-5) M) for TBDTC and 1 mg . ml(-1) (4.8 x 10(-3) M) for MIBDTC, respectively. Both the complexes were found to be neutral and eluted out as single species in HPLC. Both the complexes showed myocardial as well as brain uptake. The 99mTcN(TBDTC)2 complex showed a better heart/blood and heart/lung ratio when compared to 99mTcN(NOEt)2, an agent in phase III clinical trials proposed for myocardial imaging. This complex also showed brain uptake (3.74%ID/g) at 10 min post-injection (p.i.) with brain/blood ratios better than that of the standard agent 99mTc-D,L-HMPAO at all time points studied. 99mTcN(MIBDTC)2 showed myocardial uptake of 6.41%ID/g at 5 min p.i., which decreased to 1.76%ID/g, 60 min p.i. 99mTcN(MIBDTC)2 also showed good brain uptake (3.21%ID/g at 5 min p.i.) but relatively fast washout (1.33%ID/g at 60 min p.i.) from the target organ. CONCLUSION: Both the complexes under study showed myocardial as well as brain uptake. The results obtained with 99mTcN(TBDTC)2 shows promise towards its development as a potential brain imaging agent.

Construction and evaluation of cDNA libraries for large-scale expressed sequence tag sequencing in wheat (Triticum aestivum L.).

A total of 37 original cDNA libraries and 9 derivative libraries enriched for rare sequences were produced from Chinese Spring wheat (Triticum aestivum L.), five other hexaploid wheat genotypes (Cheyenne, Brevor, TAM W101, BH1146, Butte 86), tetraploid durum wheat (T. turgidum L.), diploid wheat (T. monococcum L.), and two other diploid members of the grass tribe Triticeae (Aegilops speltoides Tausch and Secale cereale L.). The emphasis in the choice of plant materials for library construction was reproductive development subjected to environmental factors that ultimately affect grain quality and yield, but roots and other tissues were also included. Partial cDNA expressed sequence tags (ESTs) were examined by various measures to assess the quality of these libraries. All ESTs were processed to remove cloning system sequences and contaminants and then assembled using CAP3. Following these processing steps, this assembly yielded 101,107 sequences derived from 89,043 clones, which defined 16,740 contigs and 33,213 singletons, a total of 49,953 "unigenes." Analysis of the distribution of these unigenes among the libraries led to the conclusion that the enrichment methods were effective in reducing the most abundant unigenes and to the observation that the most diverse libraries were from tissues exposed to environmental stresses including heat, drought, salinity, or low temperature.

Syntheses, in vitro and in vivo characterization of a 99mTc-(I)-tricarbonyl-benzylamino-dihydroxymethyl phosphine (NP(2)) chelate.

Studies were performed to study the complexation chemistry of 99mTc(CO)(+)(3) with a new tridentate amino-dihydroxymethyl phosphine (NP(2)) ligand with the 99mTc(CO)(3)(OH(2))(+)(3) synthon at tracer levels. A single, well-defined 99mTc(CO)(3)NP(2) complex is formed at pH 7.5 within 10 min at 60 degrees C that exhibits high in vitro and in vivo stability.

188Re-labeled hydroxyapatite particles for radiation synovectomy.

A new procedure for labeling hydroxyapatite (HA) particles with 188Re for radiation synovectomy is described and standardized. The particles were labeled with 188Re in high yields (99%) in acidic medium. HA particle size remained unaffected by reaction conditions as checked by laser diffraction particle analyzer. 188Re-HA was found to be stable retaining 99% radiochemical purity after 4 days when stored in ascorbic acid solution (10mg/ml, pH 5). Intra-articular injection in rats revealed approximately 98% retention of 188Re-HA in the knee after 48-h pi.

Synthesis and characterization of (99m)Tc- and (188)Re-complexes with a diamido-dihydroxymethylenephosphine-based bifunctional chelating agent (N(2)P(2)-BFCA).

A diamido-dihydroxymethylenephosphine (N(2)P(2)) bifunction chelating agent (BFCA) was shown to form well-defined (99m)Tc- and (188)Re-chelate structures. The 4, 4-bis [bis-hydroxymethyl-phosphonyl-propylcarbonmoyl]-butyric acid bifunctional chelating agent (N(2)P(2)-BFCA) formed stable complexes with (99m)Tc and (188)Re in >95% yield with high radiochemical purity (RCP). The biodistribution of the (99m)Tc- and (188)Re-N(2)P(2)-BFCAs after intravenous injection studied in normal mice showed the activity was excreted primarily via renal-urinary pathway indicating their use for labeling peptides with (99m)Tc and (188)Re.

Rupture of a radial keratotomy incision after 11 years during clear corneal phacoemulsification.

We report a case of rupture of a radial keratotomy (RK) incision that occurred during clear corneal phacoemulsification 11 years after the initial surgery. The RK was done in both eyes for correction of high myopia (>8.0 diopters). This was followed by 2 enhancement procedures at 6 month intervals. The patient presented with diminished vision in both eyes. The diagnosis was nuclear cataract in the right eye, and clear corneal phacoemulsification was done. The intraoperative and postoperative courses were uneventful. Nine months later, clear corneal temporal phacoemulsification was done in the left eye. During surgery, 1 of the radial incisions opened to one third its length. The wound was sutured, and the procedure was completed uneventfully. One month later, best corrected visual acuity was 20/20.

186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation.

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x 10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous chloride. The complex was found to be stable for 6 days with RC purity remaining approximately 97%. The complex was characterized by paper chromatography in saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively. Biodistribution studies of the complex were performed in male Wistar rats. Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the injected activity in skeleton) at 3 h post injection remained almost constant up to 48 h. Minimum activity was observed in blood and other soft tissues. The complex showed major renal clearance. Scintigraphic images in rabbits after injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were observed to be superior to 186Re-HEDP, prepared by a procedure standardized by us. Insignificant activity was observed in other vital organs. The results suggest the suitability of the complex for further evaluation in higher animals for bone pain palliation.

Prognostic significance of DNA aneuploidy and p21 ras oncoprotein expression in colorectal cancer and their role in the determination of treatment modalities.

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21 ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21 raspositive and p21 ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21 ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.

Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models.

The syntheses of four alpha-aminomethyl phosphonates and their complexation studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography. The (99m)Tc complexes were stable for more than 4 h, while the (186/188)Re complexes were stable for 3-8 days when stored at 4 degrees C. Biodistribution of these complexes in Wistar rats were carried out, and the uptake in bone and other soft tissue are detailed. Bone uptake of the (99m)Tc complexes varied from 40-60% at 30 min postinjection depending on the ligands. The uptake in soft tissue was minimum with all the complexes. A comparison of the biodistribution studies of the (99m)Tc complexes with that of the well-established radiopharmaceutical (99m)Tc-MDP was carried out for the purpose of evaluating the efficacy of the radiopharmaceutical preparation with the complexes of these ligands. The bone uptake of the (186/188)Re complexes varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The residual activity in both (99m)Tc and (186/188)Re complexes showed renal clearance.

Anterior capsular staining with trypan blue for capsulorhexis in mature and hypermature cataracts. A preliminary study.

PURPOSE: To study the efficacy and safety of 0.1% Trypan Blue dye to stain the anterior capsule for capsulorhexis in mature and hypermature cataracts. METHODS: This preliminary study included 25 eyes of 25 patients with a unilateral mature or hypermature cataract, including one case of traumatic mature cataract. In all these cases 0.2 ml of 0.1% trypan blue dye was used to stain the anterior capsule. The efficacy and safety of the dye was evaluated on the basis of intraoperative and postoperative observations. RESULTS: In all 25 eyes the capsulorhexis was completed. There was peripheral extension of the capsulorhexis in the eye with traumatic cataract and the stained edge of the anterior capsule helped identification and redirection of the capsulorhexis. Successful phacoemulsification with intraocular lens implantation was performed in all eyes. Adverse reactions related to the dye such as raised intraocular pressure, anterior chamber inflammation and endothelial damage were not observed in the immediate postoperative period or at the end of mean follow-up of 3 months. CONCLUSION: Trypan blue dye staining of the anterior capsule appears to be a very useful and safe technique that simplifies capsulorhexis in mature and hypermature cataracts.

High-performance implementation and analysis of the Linkmap program.

Linkage analysis uses information from family pedigrees to map genes and locate disease genes on particular chromosomes. A recombination fraction denoted as theta is estimated as a measure of crossing over between two loci. Genetic linkage calculations are very time-consuming particularly for large family pedigrees, a large number of theta values, and an increased number of markers. This paper reports the implementation of a dynamic master-slave scheme for the parallelization of the Linkmap program on a high-performance cluster such as the Origin 2000 (O2K) consisting of 56 R12000 processors. The Linkmap program is one of four programs in the LINKAGE/FASTLINK legacy package widely used by the medical research community. Implementations issues are addressed and results are compared with previous results on a cluster of DEC Alphas, and with the sequential execution on the O2K machine.

Prevalence of coronary risk factors among Indian physicians.

BACKGROUND AND OBJECTIVES: Prevalence of coronary risk factors has not been well studied in Indian physicians, therefore, to determine prevalence of selected lifestyle and biochemical coronary risk factors we performed this study. METHODS: Physicians attending a national conference were invited to participate. Of the 1000 questionnaires circulated 256 physicians (221 males, 35 females) responded and were examined for presence of smoking, obesity, truncal obesity, hypertension and ECG abnormalities. Two hundred and thirty four physicians (91.4%, 203 males, 31 females) underwent a fasting blood examination for determination of glucose and lipid profile. Subjects were divided into three age groups: Group I aged < 40 years; Group II 40-49 years; and Group III > or = 50 years. RESULTS: Mean age of the study population was 41.7 +/- 9.3 years (range 26-70). There was no significant difference in the distribution of height, weight, body-mass index (BMI), waist and hip circumference and waist-hip ratio (WHR) in different age-groups. Systolic blood pressure (BP) and fasting glucose and triglyceride levels increased with age in both males and females, while diastolic BP, total - LDL and HDL cholesterol levels did not change. Smoking or tobacco use was seen in five males (2.3%). Prevalence of obesity (BMI > or = 25.0 kg/m2) was in 104 (48.6%) males and 18 (51.4%) females. Truncal obesity diagnosed by WHR > 0.9 in males and > 0.8 in females was in 160 (72.4%) males and 23 (65.7%) females and a large waist circumference, > or = 100 cm in males and > or = 90 cm in females, was in 58 (26.2%) males and 7 (20.0%) females. Hypertension (> or = 140/90) was in 74 (33.5%) males and 7 (20%) females. A high prevalence of diabetes diagnosed using fasting blood glucose > or = 126 mg/dl or previous history was noted in males 19 (9.4%), females 4 (12.9%). Prevalence of high total cholesterol levels > or = 200 mg/dl was in 91 (44.8%) males and 10 (32.3%) females. High LDL cholesterol level (> or = 100 mg/dl) was in 144 (70.9%) males and 22 (70.9%) females and LDL levels > or = 130 mg/dl in 70 (34.5%) males and 9 (29.0%) female physicians. High triglyceride levels (> or = 200 mg/dl) were in 38 (18.7%) males and 4 (12.9%) females. Electrocardiographic abnormalities were present in seven subjects: Q-waves in two males and one female and ST-T changes in three males and one female. BMI correlated significantly (p < 0.05) with systolic BP, fasting glucose, and triglycerides and WHR with systolic BP, diastolic BP, fasting glucose, cholesterol and triglyceride levels. CONCLUSIONS: There is a high prevalence of obesity, truncal obesity, hypertension and hypercholesterolaemia in Indian physicians while smoking, low HDL cholesterol and hypertriglyceridemia is low. The overall coronary risk is lower among Indian physicians as compared to previous Indian population studies.

Mullerian adenosarcoma of the uterine cervix.

Sarcomas in the uterine cervix are rare, the incidence being 0.5% to 1% of all cervical malignancies. This is a report of cervical mullerian adenosarcoma, which was encountered in a hysterectomy performed for prolapse. The tumor was composed of benign glandular elements and malignant stromal component, thus justifying its nomenclature. We wish to emphasize the distinctive morphological features of this rare cervical tumor.