ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

Purpose

To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status.

Materials and Methods

One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2×, 1×, and 5× drug concentrations, and the CI values were compared.

Results

CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin.

Conclusion

Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.     

Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies

Purpose

Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1.

Materials and Methods

We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number.

Results

An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis.

Conclusion

We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis".     

Cervical Arthroplasty for Moderate to Severe Disc Degeneration: Clinical and Radiological Assessments after a Minimum Follow-Up of 18 Months: Pfirrmann Grade and Cervical Arthroplasty

Purpose

Clinical outcomes and radiologic results after cervical arthroplasty have been reported in many articles, yet relatively few studies after cervical arthroplasty have been conducted in severe degenerative cervical disc disease.

Materials and Methods

Sixty patients who underwent cervical arthroplasty (Mobi-C®) between April 2006 and November 2011 with a minimum follow-up of 18 months were enrolled in this study. Patients were divided into two groups according to Pfirrmann classification on preoperative cervical MR images: group A (Pfirrmann disc grade III, n=38) and group B (Pfirrmann disc grades IV or V, n=22). Visual analogue scale (VAS) scores of neck and arm pain, modified Oswestry Disability Index (mODI) score, and radiological results including cervical range of motion (ROM) were assessed before and after surgery.

Results

VAS and mean mODI scores decreased after surgery from 5.1 and 57.6 to 2.7 and 31.5 in group A and from 6.1 and 59.9 to 3.7 and 38.4 in group B, respectively. In both groups, VAS and mODI scores significantly improved postoperatively (p<0.001), although no significant intergroup differences were found. Also, cervical dynamic ROM was preserved or gradually improved up to 18 months after cervical arthroplasty in both groups. Global, segmental and adjacent ROM was similar for both groups during follow-up. No cases of device subsidence or extrusion were recorded.

Conclusion

Clinical and radiological results following cervical arthroplasty in patients with severe degenerative cervical disc disease were no different from those in patients with mild degenerative cervical disc disease after 18 months of follow-up.     

Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

Purpose

Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements.

Materials and Methods

We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure.

Results

Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.

Conclusion

CCBs inhibit the antiplatelet activity of clopidogrel.     

Clinical Characteristics of Asthma Combined with COPD Feature

Purpose

In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD). The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.

Materials and Methods

A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV₁) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled. Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV₁/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up. We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data. All of the tests mentioned above were performed within one week.

Results

The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV₁/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV₁/FVC <70). The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group. Significantly lower FEV₁ and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group. Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.

Conclusion

Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function.     

Early Feeding Is Feasible after Emergency Gastrointestinal Surgery

Purpose

This study was undertaken to assess the feasibility of early feeding in patients that have undergone emergency gastrointestinal (GI) surgery.

Materials and Methods

The authors retrospectively reviewed 84 patients that underwent emergency bowel resection and/or anastomosis from March 2008 to December 2011. Patients with severe shock, intestinal ischemia, sustained bowel perforation, or short bowel syndrome were excluded. Patients were divided into the early (group E; n=44) or late (group L; n=40) group according to the time of feeding commencement. Early feeding was defined as enteral feeding that started within 48 hours after surgery. Early and late feeding groups were compared with respect to clinical data and surgical outcomes.

Results

The most common cause of operation was bowel perforation, and the small bowel was the most commonly involved site. No significant intergroup differences were found for causes, sites, or types of operation. However, length of stay (LOS) in the intensive care unit (1 day vs. 2 days, p=0.038) and LOS in the hospital after surgery were significantly greater (9 days vs. 12 days, p=0.012) in group L than group E; pulmonary complications were also significantly more common (13.6% vs. 47.5%, p=0.001) in group L than group E.

Conclusion

After emergency GI surgery, early feeding may be feasible in patients without severe shock or bowel anastomosis instability.