Head and neck squamous cell carcinoma: evaluation of iodine overlay maps and low-energy virtual mono-energetic images acquired with spectral detector CT.

AIM: To evaluate the diagnostic value of spectral detector computed tomography (SDCT)-derived iodine overlay maps and low-energy virtual mono-energetic images (VMI) for the initial locoregional assessment of primary, therapy-naive head and neck cancer. MATERIALS AND METHODS: Fifty-six patients with histologically confirmed untreated squamous cell carcinoma of the head and neck who underwent SDCT of the neck for staging purposes were included in this retrospective study. Attenuation, image noise as well as signal- and contrast-to-noise ratios (S-/CNR) in VMI40-70keV were obtained from region of interest (ROI)-based measurements in the tumour and important anatomical landmarks (sternocleidomastoid muscle, subcutaneous fat, thyroid gland, submandibular gland, carotid artery, and jugular vein). Tumour conspicuity and delineation, as well as subjective image quality, were rated for conventional images, VMI40-70keV, and iodine overlay maps using five-point Likert scales. RESULTS: The CNR of the tumour versus the floor of the mouth and the CNR of the tumour versus the sternocleidomastoid muscle was significantly higher in VMI40keV in comparison to conventional images (10.0 ± 7.3 versus 3.8 ± 3.3 and 11.3 ± 7.6 versus 3.6 ± 2.8; p<0.05 each). This was supported by qualitative results, as tumour conspicuity and delineation received superior ratings in iodine overlay maps and VMI40keV compared to conventional images (5 [3-5] and 5 [4-5] versus 3 [2-5]; 5 [2-5] and 5 [3-5] versus 3 [2-4], respectively, all p<0.05). VMI40keV yielded the highest score among all included image reconstructions for overall image quality (p<0.05 all). CONCLUSION: Iodine overlay maps and low-energy VMI derived from SDCT improve initial assessment of primary squamous cell carcinoma of the head and neck compared to conventional images.

[Intraosseous foreign body or osteoma : Challenging differential diagnosis after open radius fracture]. / Intraossärer Fremdkörper oder Osteom : Anspruchsvolle Differenzialdiagnose nach offener Radiusfraktur.

Presentation of a 16-year-old male patient due to a cycling accident while mountain biking 14 days after primary treatment after open epiphyseal injury. Metaphyseal intraosseous stones within the anatomically reduced distal radius fracture were misinterpreted as an incidental osteoma.

Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer.

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.

A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer.

BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.

Comparison of clinical outcome of single-incision laparoscopic surgery using a simplified access system with conventional laparoscopic surgery for malignant colorectal disease.

AIM: Instrument crowding is encountered in single-incision laparoscopic surgery (SILS). Our aim was to compare the results of SILS with those of conventional laparoscopic surgery (CLS) for malignant colorectal disease. METHODS: The records of 27 patients who received SILS for the treatment of malignant disease using a home-made multiple-port system were compared with those of 68 patients who received CLS performed in a standard manner using four to five trocar sites. RESULTS: There were no significant differences in age, gender, disease stage, tumour location or tumour size between the SILS and CLS groups. The most common surgery was high anterior resection in both groups (SILS, 63.0%vs CLS, 58.8%). There were no significant differences between the groups in types of surgery performed, length of bowel resected, resection margin, blood loss, duration of surgery or postoperative complications. Postoperative pain scores were significantly higher in the SILS group than in the CLS group (3.07 ± 1.14 vs 2.41 ± 0.63, respectively, P < 0.001). CONCLUSIONS: SILS is as effective as CLS, and is not associated with increased duration of surgery, blood loss or complications.

Cost-effectiveness of biological therapy in remission induction of moderate to severe plaque psoriasis.

BACKGROUND: The introduction of biological agents has considerably changed the treatment of moderate to severe psoriasis. So far only limited data on their cost-effectiveness exist. OBJECTIVE: Determination of the cost-effectiveness of biologicals from a German third payer's perspective, assessed over a 12-week period. METHODS: Efficacies of the biologicals were determined by a literature review. Treatment modalities were taken from the European S3 psoriasis guideline. Costs were calculated on the basis of the German physicians' fee schedule. Cost-effectiveness was determined and a sensitivity analysis performed. RESULTS: Infliximab at a dose of 3 mg/kg was the most cost-effective agent, directly followed by adalimumab, infliximab 5 mg/kg and ustekinumab. The least cost-effective agent was etanercept 2 × 50 mg/week. Sensitivity analysis showed considerable overlap of the cost-effectiveness ratios. CONCLUSION: Under the conditions of the German health care system, biological agents for psoriasis differ in their cost-effectiveness ratios. Differences are small, however. A major limitation of the study is the short time horizon of 12 weeks.

Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia.

Previous reports have demonstrated that small- to medium-diameter dorsal root ganglia (DRG) cells in rats can be subgrouped into individual cell types by patterns of voltage-activated currents. These cell types have consistent responses to algesic compounds and maintain characteristic histochemical phenotypes. Using immunocytochemical methods, we have now examined expression of TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related acid sensitive K+ (TASK) channels, TASK-1, TASK-2 and TASK-3, in nine electrophysiologically identified small- to medium-diameter DRG cell types. The immunoreactivity in DRG cells was diverse, with all nine cell types expressing one to all three TASK channels. Some cells expressed TASK-1 (types 1, 4, 6 and 9), some TASK-2 (types 2, 4, 5, 6, 7 and 9), and some TASK-3 (types 1, 2, 3, 4, 5, 6 and 8). The co-expression of TASK-1 and TASK-3 in cell types 1, 4 and 6 suggests that these sensory afferents might contain functional heterodimeric channels. In peripheral sensory afferents, TASK channels have been implicated in the pain sensory transduction pathway, and can be modulated by anesthetics and neuroprotective agents. This study seeks to identify TASK channel populations in electrophysiologically characterized populations of putative nociceptive afferents.

Mutant Bik expression mediated by the enhanced minimal topoisomerase IIalpha promoter selectively suppressed breast tumors in an animal model.

To ensure the success of systemic gene therapy, it is critical to enhance the tumor specificity and activity of the promoter. In the current study, we determined that topoisomerase IIalpha promoter is selectively activated in breast cancer cells. An element containing an inverted CCAAT box (ICB) was shown to be responsible for the breast cancer specificity. When the ICB-harboring topoisomerase IIalpha minimal promoter was linked with an enhancer sequence from the cytomegalovirus immediate early gene promoter (CMV promoter), this composite promoter, CT90, exhibited activity comparable to or higher than the CMV promoter in breast cancer cells in vitro and in vivo, yet expresses much lower activity in normal cell lines and normal organs than the CMV promoter. A CT90-driven construct expressing BikDD, a potent proapoptotic gene, was shown to selectively kill breast cancer cells in vitro, and to suppress mammary tumor development in an animal model of intravenously administrated, liposome-delivered gene therapy. Expression of BikDD was readily detectable in the tumors but not in the normal organs (such as heart) of CT90-BikDD-treated animals. The results indicate that liposomal CT90-BikDD is an effective systemic breast cancer-targeting gene therapy.

The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers.

Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usually are effective in prevention and treatment. However, the emergence of resistance is common, especially for locally advanced tumors and metastatic tumors, in which case resistance is predictable. The phenotypes of these resistant tumors include receptor-positive, ligand-dependent; receptor-positive, ligand-independent; and receptor-negative, ligand-independent. The underlying mechanisms of these phenotypes are complicated, involving not only sex hormones and sex hormone receptors, but also several growth factors and growth factor receptors, with different signaling pathways existing alone or together, and with each pathway possibly linking to one another. In this review, we will discuss the potential mechanisms of antihormone-therapy resistance in breast and prostate cancers, especially focusing on the similarities and differences of these two cancers. We will also discuss novel agents that have been applied in clinical practice or with clinical potential in the future.

Characterization and function of TWIK-related acid sensing K+ channels in a rat nociceptive cell.

We examined the properties of a proton sensitive current in acutely dissociated, capsaicin insensitive nociceptive neurons from rat dorsal root ganglion (DRG). The current had features consistent with K(+) leak currents of the KCNK family (TASK-1, TASK-3; TWIK-related acid sensing K(+)). Acidity and alkalinity induced inward and outward shifts in the holding current accompanied by increased and decreased whole cell resistance consistent with a K(+) current. We used alkaline solutions to open the channel and examine its properties. Alkaline evoked currents (AECs; pH 10.0-10.75), reversed near the K(+) equilibrium potential (-74 mV), and were suppressed 85% in 0 mM K(+). AECs were insensitive to Cs(+) (1 mM) and anandamide (1 microM), but blocked by Ba(++) (1 mM), quinidine (100 microM) or Ruthenium Red (10 microM). This pharmacology was identical to that of rat TASK-3 and inconsistent with that of TASK-1 or TASK-2. The TASK-like AEC was not modulated by PKA (forskolin, kappa opioid agonists U69593 and GR8696, somatostatin) but was inhibited by PKC activator phorbol-12-myristate-13 acetate (PMA). When acidic solutions were used, we were able to isolate a Ba(++) and Ruthenium Red insensitive current that was inhibited by Zn(++). This Zn(++) sensitive component of the proton sensitive current was consistent with TASK-1. In current clamp studies, acidic pH produced sensitive changes in resting membrane potential but did not influence excitability (pH 7.2-6.8). In contrast, Zn(++) produced substantial changes in excitability at physiological pH. Alkaline solutions produced hyperpolarization followed by proportional burst discharges (pH 10.75-11.5) and increased excitability (at pH 7.4). In conclusion, multiple TASK currents were present in a DRG nociceptor and differentially contributed to distinct discharge mechanisms.

Distribution of P2X1, P2X2, and P2X3 receptor subunits in rat primary afferents: relation to population markers and specific cell types.

We determined the co-expression of immunoreactivity (IR) for ATP-receptor subunits (P2X1, P2X2, and P2X3), neuropeptides, neurofilament (NF), and binding of the isolectin B(4) from Griffonia simplicifolia type one (GS-I-B(4)) in adult dorsal root ganglion neurons. P2X1-IR was expressed primarily in small DRG neurons. Most P2X1-IR neurons expressed neuropeptides and/or GS-I-B(4)-binding, but lacked NF-IR. P2X1-IR overlapped with P2X3-IR, though each was also found alone. P2X2-IR was expressed in many P2X3-IR small neurons, as well as a group of medium to large neurons that lacked either P2X3-IR or GS-I-B(4)-binding. A novel visible four-channel fluorescence technique revealed a unique population of P2X2/3-IR neurons that lacked GS-I-B(4)-binding but expressed NF-IR. Co-expression of P2X1, and P2X3 in individual neurons was also demonstrated. We examined P2X subunit-IR on individual recorded neurons that had been classified by current signature in vitro. Types 1, 2, 4 5, and 7 expressed distinct patterns of P2X-IR that corresponded to patterns identified in DRG sections, and had distinct responses to ATP. Types with rapid ATP currents (types 2, 5, and 7) displayed P2X3-IR and/or P2X1-IR. Types with slow ATP currents (types 1 and 4) displayed P2X2/3-IR. Type 1 neurons also displayed P2X1-IR. This study demonstrates that the correlation between physiological responses to ATP and the expression of particular P2X receptor subunits derived from expression systems is also present in native neurons, and also suggests that novel functional subunit combinations likely exist.

Successful surgical treatment of solitary adrenal metastases from non-small cell lung cancer: case report.

Lung cancer is one of the most common types of maligancies and has been one of the leading causes death due to cancer for a long time. Although surgery is the treatment of choice for patients with non-N2 localized disease, most of the lung cancer patients are found to have metastatic lesions at the same time as initial diagnosis. The median survival of patients with metastatic lung cancer is less than one year even when systemic chemotherapy is given. We present a patient with non-small cell lung cancer with no initial evidence of metastasis. He underwent curative resection of the primary tumor followed by local radiotherapy. Adrenal gland metastasis was found fours years after the first surgery. After surgical resection of this metastatic lesion, followed by adjuvant chemotherapy, this patient's survival was prolonged with no evidence of disease recurrence until now. The prolonged survival of this patient may be due to a slow rate of progression of the primary tumor.

Treatment of upper lip wrinkles: a comparison of the 950 microsec dwell time carbon dioxide laser to manual tumescent dermabrasion.

BACKGROUND: High-energy pulsed or computer-scanned continuous-wave carbon dioxide (CO2) laser resurfacing has gained popularity as a wrinkle treatment because of its minimal thermal injury and precise control of tissue vaporization depth. Manual tumescent dermabrasion has also been effective for treating facial wrinkles. This is, to our knowledge, the first study comparing the use of CO2 laser to manual tumescent dermabrasion for the treatment of wrinkles on the upper lip. OBJECTIVE: To compare prospectively the clinical efficacy of the 950 microsec dwell time CO2 laser to that of manual tumescent dermabrasion in the treatment of upper lip wrinkles. METHODS: Twenty female subjects with moderate to severe upper lip wrinkles were randomly treated with the 950 microsec dwell time CO2 laser on one side of the upper lip and manual tumescent dermabrasion on the other. RESULTS: The average upper lip laser-treated wrinkle score (0 = none to 5 = severe) decreased from 4.3 +/- 0.2 before treatment to 1.8 +/- 0.3 at 6 months after treatment. The average upper lip dermabrasion-treated wrinkle score decreased from 4.4 +/- 0.2 to 1.5 +/- 0.3. The degree to which the wrinkle score improved after laser treatment compared with that after dermabrasion was not statistically significant (P =.216). CONCLUSION: Manual tumescent dermabrasion and 950 microsec dwell time CO2 laser resurfacing are equally effective for the treatment of upper lip wrinkles.

Treatment of upper lip wrinkles: a comparison of 950 microsec dwell time carbon dioxide laser with unoccluded Baker's phenol chemical peel.

BACKGROUND: The high energy, pulsed, or computer-scanned continuous wave carbon dioxide laser (CO2 laser) has gained popularity as a wrinkle treatment because of its minimal thermal injury and precise control of tissue vaporization depth. Chemical peels such as phenol have also been effective in treating facial wrinkles. This is, to our knowledge, the first study comparing the use of CO2 laser to phenol for treatment of wrinkles on the upper lip. OBJECTIVE: To compare the effectiveness and side effect profile of the 950 microsec dwell time CO2 laser to that of unoccluded Baker's phenol chemical peel in the treatment of upper lip wrinkles. METHODS: Twenty female subjects with moderate to severe upper lip wrinkles were randomly treated with Baker's phenol on one side of the upper lip and the 950 microsec dwell time CO2 laser on the other side. RESULTS: The average upper lip laser-treated wrinkle score (0 = none to 5 = severe) decreased from 4.30+/-0.20 before treatment to 1.11+/-0.28 at 6 months after treatment. The average upper lip phenol-treated wrinkle score decreased from 4.20+/-0.20 to 0.47+/-0.12. The degree in which the wrinkle score improved after phenol treatment compared with that after laser treatment was statistically significant (p<0.03). CONCLUSION: Treatment of upper lip wrinkles with Baker's phenol resulted in greater improvement than treatment with the 950 microsec dwell time CO2 laser.

Prognosis of the adenocarcinoma of the cervix uteri: a comparative study.

The different prognoses for patients with adenocarcinomas and squamous cell carcinomas of the cervix uteri were proved by matched-pair analysis. One hundred forty-four patients with adenocarcinoma treated in 1964-1985 were compared in a ratio of 1:2 with 268 patients with squamous cell carcinoma comparable in age, stage, and treatment modality. In both groups 45% of patients were in stage I, 38% in stage II, 15% in stage III, and 2% in stage IV. Five- and 10-year survivals of patients with adenocarcinoma were significantly lower than for those with squamous cell carcinoma (53% resp. 42% vs 68% vs 58%, P = 0.006). In an analyses of patients' prognosis according to clinical stage there was no significant difference between both groups in stages III and IV treated exclusively by radiotherapy. No significant differences were found in stage I and II patients treated by radical surgery. However, the most significant difference in prognosis was seen in stage I and II patients treated by radiotherapy. Five-year survival was 58.6% in stage I adenocarcinomas compared with 85.0% in squamous cell carcinomas. It can be concluded from these results that a discussion of the problem of FIGO staging is more necessary than a discussion of the different radiosensitivities of these two histological types. Surgical treatment must have the same priority as radical surgery or staging laparotomy for exact histologic staging in adenocarcinomas of the cervix uteri.