Survival Benefit of Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer: A Multi-institutional Case Control Study

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study.

Methods

The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors.

Results

From June 1997–July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors.

Conclusion

When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results.     

Pharmacokinetics of Oxaliplatin During Open Versus Laparoscopically Assisted Heated Intraoperative Intraperitoneal Chemotherapy (HIPEC): An Experimental Study

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The technical feasibility of the laparoscopic approach for HIPEC has been demonstrated in a previous study. An experimental study on the porcine model was carried out to compare oxaliplatin pharmacokinetics during a laparoscopic-assisted procedure versus the coliseum technique for HIPEC.

Methods

Adult pigs received an HIPEC procedure that was based on 460 mg/m² of oxaliplatin over 30 minutes with a perfusate heated at 41°C to 43°C. The HIPEC drains were placed in the upper and lower quadrants of the abdomen. Peritoneal fluid and blood samples were collected every 10 minutes during the procedure, and the pharmacokinetics of oxaliplatin was studied.

Results

Two groups of 10 adult pigs were studied. All the procedures were successfully completed with an adequate intra-abdominal temperature and distribution. No major technical problems were encountered. At the end of the HIPEC, 41.5% of the molecule was absorbed in the laparoscopic group compared with 33.4% in the laparotomy group (P = .0543). Peritoneal oxaliplatin half-life (T_½) was significantly faster in the laparoscopic procedure (median, 37.5 vs. 59.3 minutes, P = .02). The area under the curve ratio of peritoneal to plasma reflects a more important oxaliplatin crossing through the peritoneal barrier in the laparoscopic procedure (ratio, 16.4 in the closed procedure vs. 28.1 in the open one; P = .03).

Conclusions

This study confirms the technical feasibility and reliability of the laparoscopic approach for HIPEC, and it extends knowledge concerning peritoneal drug absorption. Oxaliplatin absorption is far higher with laparoscopy in terms of time course in peritoneal perfusion. Clinical application in selected patients may be expected after further experimental investigation designed to define the adequate drug dosage.

     

Impact of young age on platinum response in women with epithelial ovarian cancer: Results of a large single-institution registry

ObjectiveIn young women, EOC is a rare disease with an uncertain genetic and biological substrate.MethodsWe report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures.ResultsEOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11–288 months). No genetic abnormalities were found.ConclusionsYoung EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.     

Determination of the learning curve for ultrasound-guided jugular central venous catheter placement

Purpose

Use of ultrasound (US) when introducing central venous catheters (CVC) may improve success rates, reduce the number of needle punctures, and decrease complication rates, but has been hampered by supposed difficulty in learning how to perform the technique. This study describes the learning curve for US-guided jugular CVC placement after a training program.

Methods

After an initial slide presentation and a video, intensivists who had not previously used US for CVC placement were evaluated qualitatively for US set up (score S1) and technical skills (score S2). Quantitative measures included durations of different components of the procedure (T ₁, time from entry of the US into the patient’s room to sterile dressing of the intensivist; T ₂, time needed for sterile drapes, venous line preparation, and sterile sheath placement; T ₃, time from skin puncture to venous flashback; T ₄, time from guide insertion to dressing; T _tot, total duration of the procedure); number of skin punctures; and a difficulty score allocated by the intensivist.

Results

We performed 150 evaluations of 30 intensivists: 50 % had no prior experience of CVC placement and 50 % no prior US experience. Maximal S1 and S2 scores were obtained with the fourth and eighth placement procedures, respectively. T ₁ and T ₂ did not change with ongoing training (5 and 8 min, respectively), but T ₃ and T ₄ decreased, from 5 min (first procedure) to less than 1 min (seventh procedure), and from 10 min (first procedure) to 7 min (sixth procedure), respectively. T _tot decreased from 34 to 21 min at the eighth procedure. The number of skin punctures and the difficulty score decreased rapidly with the number of evaluations.

Conclusions

Our study demonstrates that skills in US-guided CVC placement can easily be acquired with training.     

Risk factors analysis for Pneumocystis jiroveci pneumonia (PCP) in patients with haematological malignancies and pneumonia

A retrospective matched case-control investigation was conducted to assess risk factors suggesting Pneumocystis jiroveci pneumonia (PCP) when pneumonia occurs in adult patients with haematological malignancies. Cases and controls included were HIV-negative, presented with pneumonia and had benefited from a bronchoalveolar lavage (BAL). The presence of Pneumocystis jiroveci cysts was systematically investigated by cytochemical staining and/or immunofluorescence. Cases were patients with Pneumocystis jiroveci cysts isolated on BAL fluid (n = 31, mean age 51+/-14 y; range 20-73 y). Controls were patients without Pneumocystis jiroveci cysts (n = 62, mean age 54+/-13 y; range 25-75 y) and were matched to case patients by age and y of pneumonia diagnosis. Statistical analysis indicated that the following factors were associated with PCP: vincristine (p = 0.009, odds ratio (OR) =2.11, 95% confidence interval (CI): 1.19-3.72), a daily corticosteroid therapy for more than 1 month (p = 0.05) during the past y, and a lymphocyte count less than 0.5 x 10(9)/l on the d of pneumonia diagnosis (p = 0.04). Clinicians should be aware, in order to evoke this diagnosis when pneumonia occurs in patients with these risk factors. The goal of this exploratory study was to identify risk factors that could eventually be further investigated by a larger prospective multicentre study.     

Gas exchange measurements within a magnetic environment: validation of a new system

Although simultaneous measurements of pulmonary oxygen uptake (VO2) and Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is attractive to investigate muscular metabolism during exercise, the superconducting magnet requires the design of specific gas exchange analyser (GEA). Thus, this study aimed to assess the validity of a commercial GEA system (ZAN600) compatible with (31)P MRS measurements. Using nonmagnetic pneumotachograph and prolonged sampling line (from 2m, control condition, to 6.5m) did not alter the proper synchronisation between flow and gas concentration signals. Also, end-expiratory fraction of O2 (FETO2) and CO(2) (FETCO2), and finally the values of steady-state ventilation (V(E)), carbon dioxide production (VCO2) and VO2 kinetics during moderate knee-extension exercise were not significantly different between 2m and 6.5m conditions and between 6.5m condition inside and outside the magnet. These results showed that a prolonged sampling line used inside the superconducting magnet did not affect the accuracy of VO2 measurements of a commercial GEA system; the latter appears suitable for simultaneous measurements of VO2 and (31)P MRS.     

Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features

The green lineage is reportedly 1,500 million years old, evolving shortly after the endosymbiosis event that gave rise to early photosynthetic eukaryotes. In this study, we unveil the complete genome sequence of an ancient member of this lineage, the unicellular green alga Ostreococcus tauri (Prasinophyceae). This cosmopolitan marine primary producer is the world's smallest free-living eukaryote known to date. Features likely reflecting optimization of environmentally relevant pathways, including resource acquisition, unusual photosynthesis apparatus, and genes potentially involved in C(4) photosynthesis, were observed, as was downsizing of many gene families. Overall, the 12.56-Mb nuclear genome has an extremely high gene density, in part because of extensive reduction of intergenic regions and other forms of compaction such as gene fusion. However, the genome is structurally complex. It exhibits previously unobserved levels of heterogeneity for a eukaryote. Two chromosomes differ structurally from the other eighteen. Both have a significantly biased G+C content, and, remarkably, they contain the majority of transposable elements. Many chromosome 2 genes also have unique codon usage and splicing, but phylogenetic analysis and composition do not support alien gene origin. In contrast, most chromosome 19 genes show no similarity to green lineage genes and a large number of them are specialized in cell surface processes. Taken together, the complete genome sequence, unusual features, and downsized gene families, make O. tauri an ideal model system for research on eukaryotic genome evolution, including chromosome specialization and green lineage ancestry.     

Three-dimensional contrast-enhanced hepatic MR imaging: comparison between a centric technique and a linear approach with partial Fourier along both slice and phase directions

Purpose

To compare the image quality of two variants of a three‐dimensional (3D) gradient echo sequence (GRE) for hepatic MRI.

Materials and Methods

Thirty‐nine patients underwent hepatic MRI on a 3.0 Tesla (T) magnet (Intera Achieva; Philips Medical Systems). The clinical protocol included two variants of a 3D GRE with fat suppression: (i) a “centric” approach, with elliptical centric k‐space ordering and (ii) an “enhanced” approach using linear sampling and partial Fourier in both the slice and phase encoding direction. “Centric” and “Enhanced” 3D GRE images were obtained both precontrast (n = 32) and after gadoxetic acid injection (n = 39). Two reviewers jointly reviewed MR images for anatomic sharpness, overall contrast, homogeneity, and absence of artifacts. The liver‐to‐lesion signal difference ratio (SDR) was measured. Paired sample Wilcoxon test and paired t‐tests were used.

Results

Enhanced 3D GRE images performed better than centric 3D GRE images with respect to anatomic sharpness (P = 0.0156), overall contrast (P = 0.0195), homogeneity (P < 0.0001), and absence of artifacts (P = 0.0003) on precontrast images. For postcontrast MRI, enhanced 3D GRE images showed better quality in terms of overall contrast (P = 0.0195), homogeneity (P < 0.0001), and absence of artifacts (P = 0.009). Liver‐to‐lesion SDR on enhanced 3D GRE images (0.48 ± 0.13) was significantly higher than that of conventional 3D GRE images (0.40 ± 0.19, P = 0.0004) on postcontrast images, but not on precontrast images.

Conclusion

The enhanced 3D GRE sequence available on our scanner provided better hepatic image quality than the centric variant, without compromising lesion contrast. J. Magn. Reson. Imaging 2011;33:160–166. © 2010 Wiley‐Liss, Inc.