Proteolysis-inducing factor (PIF), a novel cachectic factor, is detectable in the urine of cancer patients experiencing weight loss. We report the expression of PIF in gastrointestinal cancers, and a correlation between PIF expression in tumours, its detection in urine and weight-loss. These data provide the first direct evidence that tumours are the source of PIF in humans. © 2001 Cancer Research Campaign http://www.bjcancer.com
proteolysis-inducing factor; tumour expression; weight-loss; humans
Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, −2 and −3, with a long half-life. Tivozanib has demonstrated clinical activity and acceptable tolerability in renal cell carcinoma (RCC). This phase Ib study determined the recommended phase II dose (RP2D) and evaluated the safety and clinical activity of tivozanib plus temsirolimus, a mammalian target of rapamycin inhibitor.
Patients and methods
Patients with advanced RCC were administered open-label tivozanib 0.5, 1.0 or 1.5 mg/d orally (3 weeks on/1 week off) and temsirolimus 15 or 25 mg/week intravenously in a 3 + 3 dose–escalation design and subsequent expansion cohort.
Of 27 patients treated, 20 patients had received ≥1 prior VEGF-targeted therapy. No dose-limiting toxicities occurred; the RP2D was determined to be tivozanib 1.5 mg/d plus temsirolimus 25 mg/week. Combination of tivozanib plus temsirolimus demonstrated acceptable tolerability and suggested no synergistic toxicity. The most common grade ≥3 adverse events were fatigue and thrombocytopenia (15% each). One patient each required dose reduction of tivozanib or temsirolimus due to an adverse event. Confirmed partial responses and stable disease were achieved at 23% and 68%, respectively. Pharmacokinetic analyses may suggest lack of an interaction between tivozanib and temsirolimus.
In this small phase Ib study, tivozanib and temsirolimus were safely combined at the fully recommended dose and schedule of both agents. The observed clinical activity and manageable toxicity profile of this combination warrant further exploration in patients with RCC.
Dose escalation; Maximum tolerated dose; Pharmacokinetics; Renal cell carcinoma; Tivozanib; Temsirolimus
Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
Hepatoceullular carcinoma; Cholangiocarcinoma; Bi-phenotypic tumors; Computed tomography, Magnetic resonance imaging
Cleidocranial dysplasia (CCD) is an autosomal dominant disease with a wide range of expression, characterized by clavicular hypoplasia, retarded cranial ossification, delayed bone and teeth development, supernumerary teeth, stomatognathic, craniofacial and skeletal abnormalities. This paper presents a case of CCD in a female with brachycephalic skull, depressed frontal bone and nasal bridge, hypoplastic middle one-third of face with mandibular prognathism and hyper mobility of both shoulders with associated radiographic features. Odontologist is often the first professional who patient of CCD approaches, since there is a delay in the eruption or absence of permanent teeth. The premature diagnosis allows a scope for proper treatment modalities, offering a better life quality for patient.
Clavicle; Cleidocranial dysplasia; Genetic disorder; Supernumerary teeth
Petroleum products play a major role in fueling the economy of the world but the pollution they create has become a critical issue. Understanding the diversity present in pipeline muck will help with the exploration of new microbial strains with better hydrocarbon degrading capacities for bioremediation of polluted sites. This study provides an analysis of petroleum muck using next generation sequencing.
We provide the first report on the metagenomic approach for unveiling the microbial diversity in the saline desert of Kutch. High-throughput metagenomic sequencing of environmental DNA isolated from soil collected from seven locations in Kutch was performed on an Ion Torrent platform.
The purpose of this pictorial review is to understand the embryological basis of the development of congenital hepatic vascular shunts and to review the multimodality imaging appearances of congenital and acquired hepatic vascular shunts. Hepatic vascular shunts are commonly seen in imaging. Familiarity with their characteristic appearances is important in order to accurately characterise these shunts and diagnose the underlying disorders.
Background: Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of esophageal and gastric carcinomas. Although previous studies have examined tyrosine kinase inhibitors of EGFR, there remains limited data regarding the role of EGFR-directed monoclonal antibody therapy in these malignancies. We carried out a multi-institutional phase II study of cetuximab, a monoclonal antibody against EGFR, in patients with unresectable or metastatic esophageal or gastric adenocarcinoma.
Patients and Methods: Thirty-five patients with previously treated metastatic esophageal or gastric adenocarcinoma were treated with weekly cetuximab, at an initial dose of 400 mg/m2 followed by weekly infusions at 250 mg/m2. Patients were followed for toxicity, treatment response, and survival.
Results: Treatment with cetuximab was well tolerated; no patients were taken off study due to drug-related adverse events. One (3%) partial treatment response was noted. Two (6%) patients had stable disease after 2 months of treatment. Median progression-free survival and overall survival were 1.6 and 3.1 months, respectively.
Conclusion: Although well tolerated, cetuximab administered as a single agent had minimal clinical activity in patients with metastatic esophageal and gastric adenocarcinoma. Ongoing studies of EGFR inhibitors in combination with other agents may define a role for these agents in the treatment of esophageal and gastric cancer.
cetuximab; esophageal adenocarcinoma; gastric adenocarcinoma
Brachial plexus injuries represent devastating injuries with a poor prognosis. Neurolysis, nerve repair, nerve grafts, nerve transfer, functioning free-muscle transfer and pedicle muscle transfer are the main surgical procedures for treating these injuries. Among these, nerve transfer or neurotization is mainly indicated in root avulsion injury.
Materials and Methods:
We analysed the results of various neurotization techniques in 20 patients (age group 20-41 years, mean 25.7 years) in terms of denervation time, recovery time and functional results. The inclusion criteria for the study included irreparable injuries to the upper roots of brachial plexus (C5, C6 and C7 roots in various combinations), surgery within 10 months of injury and a minimum follow-up period of 18 months. The average denervation period was 4.2 months. Shoulder functions were restored by transfer of spinal accessory nerve to suprascapular nerve (19 patients), and phrenic nerve to suprascapular nerve (1 patient). In 11 patients, axillary nerve was also neurotized using different donors - radial nerve branch to the long head triceps (7 patients), intercostal nerves (2 patients), and phrenic nerve with nerve graft (2 patients). Elbow flexion was restored by transfer of ulnar nerve motor fascicle to the motor branch of biceps (4 patients), both ulnar and median nerve motor fascicles to the biceps and brachialis motor nerves (10 patients), spinal accessory nerve to musculocutaneous nerve with an intervening sural nerve graft (1 patient), intercostal nerves (3rd, 4th and 5th) to musculocutaneous nerve (4 patients) and phrenic nerve to musculocutaneous nerve with an intervening graft (1 patient).
Motor and sensory recovery was assessed according to Medical Research Council (MRC) Scoring system. In shoulder abduction, five patients scored M4 and three patients M3+. Fair results were obtained in remaining 12 patients. The achieved abduction averaged 95 degrees (range, 50 - 170 degrees). Eight patients scored M4 power in elbow flexion and assessed as excellent results. Good results (M3+) were obtained in seven patients. Five patients had fair results (M2+ to M3).
Nerve transfers; root avulsions; upper brachial plexus injury
Arteriovenous malformations (AVMs) are uncommon errors of vascular morphogenesis; haemodynamically, they are high-flow lesions. Approximately 50% of AVMs are located in the craniofacial region. Subtotal excision or proximal ligation of the feeding vessel frequently results in rapid progression of the AVMs. Hence, the correct treatment consists of highly selective embolisation (super-selective) followed by complete resection 24–48 hours later. We treated 20 patients with facial arteriovenous malformation by using this method. Most of the lesions (80%) were located within the cheek and lip. There were no procedure related complications and cosmetic results were excellent.
Arteriovenous malformation; super-selective embolisation; resection
Extra-articular fractures of lower end radius are conventionally immobilized in palmar flexion and ulnar deviation. In view of poor functional results, the conventional method of immobilization is giving way to dorsiflexed-immobilized method. The aim of our study is to evaluate and compare the radiological and functional outcome in extra-articular fractures of lower end radius treated conservatively with respect to its position of immobilization.
Materials and Methods:
Sixty-four patients, all above 20 years of age with closed extra-articular fractures of lower end radius who were treated conservatively by close reduction and below elbow cast application constitute the clinical material. Irrespective of fracture geometry the patients were randomly allocated to dorsal or palmar flexed immobilized position of wrist. Patients were followed up for a minimum six-month period. The radial tilt, palmar tilt and ulnar variance are measured at prereduction, postreduction and at 6 month followup. The results were scored by Demerit Scoring System of Saito.
All fractures united. Individual movement of dorsiflexion, palmar flexion, supination, pronation and radial-ulnar deviation were all significantly better in the dorsiflexed-immobilized group as compared with the palmar flexed immobilized group. Grip strength recovery with subjective assessment was better in the dorsiflexed group (77%) as compared to the palmar flexed group (23%). Radiological parameters were markedly better in the dorsiflexed group. Ninety-one per cent of patients in the dorsiflexed group had excellent to good results as compared to 66% in the palmar flexed group.
Functional results of extra-articular fractures of lower end radius are superior if the fractures after reduction are immobilized in dorsiflexion of wrist rather than in conventional palmar flexion position.
Cast immobilization; dorsiflexion; extra-articular fracture of lower end radius; palmar flexion
The principal objectives of arthroplasty are relief of pain and enhancement of range of motion. Currently, postoperative pain and functional capacity are assessed largely on the basis of subjective evaluation scores. Because of the lack of control inherent in this method it is often difficult to interpret data presented by different observers in the critical evaluation of surgical method, new components and modes of rehabilitation. Gait analysis is a rapid, simple and reliable method to assess functional outcome. This study was undertaken in an effort to evaluate the gait characteristics of patients who underwent arthroplasty, using an Ultraflex gait analyzer.
Materials and Methods:
The study was based on the assessment of gait and weight-bearing pattern of both hips in patients who underwent total hip replacement and its comparison with an age and sex-matched control group. Twenty subjects of total arthroplasty group having unilateral involvement, operated by posterior approach at our institution with a minimum six-month postoperative period were selected. Control group was age and sex-matched, randomly selected from the general population. Gait analysis was done using Ultraflex gait analyzer. Gait parameters and vertical ground reaction forces assessment was done by measuring the gait cycle properties, step time parameters and VGRF variables. Data of affected limb was compared with unaffected limb as well as control group to assess the weight-bearing pattern. Statistical analysis was done by‘t’ test.
Frequency is reduced and gait cycle duration increased in total arthroplasty group as compared with control. Step time parameters including Step time, Stance time and Single support time are significantly reduced (P value <.05) while Double support time and Single swing time are significantly increased (P value <.05) in the THR group. Forces over each sensor are increased more on the unaffected limb of the THR group as compared to the control group. Vertical ground reaction force variables are also altered.
Significant changes (P value <.05) in gait parameters and vertical ground reaction forces show that gait pattern is not normalized after THR and weight-bearing is not equally shared by both hips. Patient walks with residual antalgic gait even after surgery, which results in abnormal loading around hip joints and the integrity of the prosthesis fixation could be compromised.
Gait parameters; total hip replacement; vertical ground reaction forces
Ten cultures of Pseudomonas spp. were established from soil samples collected in and around a lake in Antarctica. Based on their morphology, biochemical and physiological characteristics, and moles percent G + C of their DNA, they were identified as P. fluorescens, P. putida, and P. syringae. This is the first report on the identification of Pseudomonas spp. from continental Antarctica.