A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50–99% regression) sustained for ⩾28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options

Diagnosis, staging and treatment of hepatocellular carcinoma

Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies

Reversing hepatocellular carcinoma progression by using networked biological therapies

The liver is distinguished from other tissues by (a) its detoxifying function, (b) its resistance to apoptosis, and (c) its regenerative response to damage. Hepatocellular carcinoma arises when chronic insults, such as hepatitis or iron overload, constitutively activate this regenerative program. Here, we propose that the proliferative response of the liver to damage underlies the resistance of hepatocellular carcinoma to cytotoxic therapy, and that hepatocellular carcinoma growth should therefore be more readily controlled by using a networked combination of noncytotoxic interventions to interrupt the damage-inducible regenerative pathway. To this end, hepatocellular carcinoma boasts a wealth of potential drug targets, including viral replication, the antiapoptotic immunosuppressant alpha-fetoprotein, hepatic iron overload, inflammatory signaling, extracellular proteases, and growth factors. By blocking these positive feedback loops in parallel, and so returning the host environment to a more normal state, epigenetic repression of tumor-suppressor gene function may be reversed and tumor dormancy restored. Noncytotoxic maneuvers that short circuit damage resistance loops may thus represent an indirect form of gene therapy meriting incorporation into hepatocellular carcinoma clinical trials.link_to_subscribed_fulltex

Analysis of Differentially Expressed Genes in Hepatocellular Carcinoma with Hepatitis C Virus by Suppression Subtractive Hybridization

Hepatitis C virus (HCV) infection is associated with pathogenesis of hepatocellular carcinoma (HCC). We carried out suppression subtractive hybridization to identify variable expression of genes linked to HCC with HCV infection. RNA from both tumorous (tester) and nontumorous (driver) liver tissues was isolated. The cDNA clones were subjected to MegaBACE PCR sequencing to identify those that hybridized to the subtracted library with preference. Nucleic acid sequences generated were searched against the human UniGene database. Among 576 clones screened in the tumorous liver tissue, we identified 30 genes and 28 expressed sequence tags (ESTs). Among 30 genes detected, 23 were with known functions and 7 with unknown functions. The known genes identified had diversified functions and could be divided into 10 functional categories. Twenty percent of these genes were previously known to be tumor related and those most frequently appearing were haptoglobin alpha(2FS)-beta precursor, haptoglobin related protein, and alpha-2-macroglobulin. Four out of 30 known genes (immunoglobulin lambda light chain, kappa immunoglobulin, spliceosomal protein, and X-ray repair cross-complementing protein) were related to chromosome translocation and nucleotide repair. These four genes may contribute to carcinogenesis caused by DNA-damaged agents and to the efficiency of anticancer therapy. The genes with unknown function, which were most frequently detected, were PRO2760 and PRO2955; both encode proteins that express in fetal liver. Twenty-one known and six novel genes were discovered in the nontumorous liver tissue. Apparently, these 27 genes were lost in the tumorous liver tissues. Therefore, using suppression subtractive hybridization, we have identified a number of genes associated with HCC with HCV infection. Most of these genes have not been reported in HCC. Further characterization of these differentially expressed known and unknown genes will provide useful information in understanding the genes responsible for the development of HCC.link_to_subscribed_fulltex

Protocol driven assessment programme effectively shortens new case waiting time

Service Priorities and Programmes Free Papers: SPP4.6 Quality and Safety in Healthcare 1Conference Theme: Consolidating Health Care - 固本培員, 健行不息Introduction: The waiting time for new cases in endocrine clinic has been rising due to increasing demand. The average waiting time has increased to 26.3 ± 5.5 weeks in February 2012. To improve the situation, a protocol driven assessment (PDA) programme has been established and incorporated into the triage pathway starting from April 2012. Objectives: (1) To shorten the waiting time of new case at the Endocrine Clinic; and (2) to enhance efficient work flow of triage system and improve patient care. Methodology: Protocols for endocrine diseases including obesity, hyperprolactinaemia, hypercalcaemia, hypopituitarism and hypogonadism were developed. Patients referred for such conditions were triaged to the PDA programme in which history taking, assessments, investigations and early interventions were carried out according to the protocols set by an endocrine nurse and subsequently followed by endocrinologists. Results: 225 referrals were screened from May 2012 to December 2012. 64 patients were triaged to the programme. The referralto-nurse and referral-to-endocrinologist times for the programme were 5.9 ± 4.9 and 9.8 ± 5.3 weeks respectively. This showed a significant improvement when compared with their original referral-to-endocrinologist time (26.6 ± 5.7 weeks, p<0.05). Referral-to-endocrinologist time for patients not recruited into the programme also showed significant improvement (10.3 ± 9.0 vs. 26.2 ± 5.4 weeks, p< 0.05) and the PDA programme was one of the measures that contributed to this success. Early intervention has been initiated during the initial nursing assessment of the programme. 18 obese patients received prompt referrals to relevant allied health disciplines before assessments by specialists. Four patients, referred for hyperprolactinaemia, had normal serum prolactin level after re-checked by endocrine nurse under a controlled non-stressed condition. They could be discharged from clinic at the first specialist assessment. More urgent conditions, such as visual field defects and high blood pressure, had also been detected early in the nursing assessment stage and resulted in prompt treatment action. The establishment of PDA programme, conducted by an experienced nurse, not only shortens waiting time but also provides patients with a more streamlined, timely and efficient model of care