Cancer-related fatigue and depression: a monocentric, prospective, cross-sectional study in advanced solid tumors.

BACKGROUND: Cancer-related fatigue (CRF) is common in patients with advanced solid tumors and several risk factors are described. The possible role of depression is reported by clinicians despite the association with CRF being unclear. MATERIAL AND METHODS: In this monocentric, cross-sectional, prospective study we recruited patients with advanced solid tumors who were hospitalized at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. The primary objective was to assess the correlation between CRF and depression. Secondary objectives were the estimation of CRF and depression prevalence and the identification of associated clinical risk factors. CRF and depression were evaluated through the Functional Assessment of Cancer Therapy-Fatigue subscale and the Zung Self Depression Scale (ZSDS) questionnaires. The Cochran-Armitage trend test was used to demonstrate the primary hypothesis. Univariate and multivariate logistic regression models were used to investigate the impact of clinical variables. RESULTS: A total of 136 patients were enrolled. The primary analysis found a linear correlation (P < 0.0001) between CRF and depression. The prevalence of CRF and of moderate to severe depressive symptoms was 43.5% and 29.2%, respectively. In univariate analysis, patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), anemia, distress, pain, and receiving oncological treatment were at a significantly higher risk for CRF, whereas poor ECOG PS, pain, and distress were risk factors for depression. In multivariate analysis, high levels of ZSDS were confirmed to be correlated to CRF: odds ratio of 3.86 [95% confidence interval (CI) 0.98-15.20) and 11.20 (95% CI 2.35-53.36) for ZSDS of 50-59 and 60-100, respectively (P value for trend 0.002). Moreover, the ECOG PS score was confirmed to be significantly associated with CRF (OR 7.20; 95% CI 1.73-29.96; P = 0.007). CONCLUSIONS: Our data suggest a strong correlation between CRF and depression in patients with advanced solid tumors. Further investigations are needed to better understand this relationship and if depressive disorder therapeutic strategies could also impact on CRF.

Circulating adhesion molecules and arterial stiffness.

AIM: VCAM-1 and ICAM-1 are two important members of the immunoglobulin gene superfamily of adhesion molecules, and their potential role as biomarkers of diagnosis, severity and prognosis of cardiovascular disease has been investigated in a number of clinical studies. The aim of the present study was to determine the relationship between circulating ICAM-1 and VCAM-1 levels and aortic stiffness in patients referred for echocardiographic examination. METHODS: Aortic distensibility was determined by echocardiography using systolic and diastolic aortic diameters in 63 consecutive patients referred for echocardiography. Venous samples were collected in the morning after a 12-hour overnight fast, and serum concentrations of ICAM-1 and VCAM-1 were measured using commercial enzyme immunoassay kits. RESULTS: Data of a total of 63 participants (mean age 55.6 ± 10.5 years, 31 male) were included in the study. Circulating levels of adhesion molecules were VCAM-1: 12.604 ± 3.904 ng/ml and ICAM-1: 45.417 ± 31.429 ng/ml. We were unable to demonstrate any correlation between indices of aortic stiffness and VCAM-1 and ICAM-1 levels. CONCLUSION: The role of soluble adhesion molecules in cardiovascular disease has not been fully established and clinical studies show inconsistent results. Our results indicate that levels of circulating adhesion molecules cannot be used as markers of aortic stiffness in patients.

Contraction velocity influence the magnitude and etiology of neuromuscular fatigue during repeated maximal contractions.

This study aimed to compare the magnitude and etiology of neuromuscular fatigue during maximal repeated contractions performed in two contraction modes (concentric vs isometric) and at two contraction velocities (30/s vs 240°/s). Eleven lower limb-trained males performed 20 sets of maximal contractions at three different angular velocities: 0°/s (KE0), 30/s (KE30), and 240°/s (KE240). Cumulated work, number of contraction, duty cycle, and contraction time were controlled. Torque, superimposed and resting twitches, as well as gas exchange, were analyzed. Increasing contraction velocity was associated with greater maximal voluntary torque loss (KE0: -9.8 ± 3.9%; KE30: -16.4 ± 8.5%; KE240: -32.6 ± 6.3%; P < 0.05). Interestingly, the torque decrease was similar for a given cumulated work. Compared with KE0, KE240 generated a greater evoked torque loss (Db100: -24.3 ± 5.3% vs -5.9 ± 6.9%; P < 0.001), a higher O2 consumption (23.7 ± 6.4 mL/min/kg vs 15.7 ± 3.8 mL/min/kg; P < 0.001), but a lower voluntary activation (VA) loss (-4.3 ± 1.6% vs -11.2 ± 4.9%; P < 0.001). The neuromuscular perturbations were intermediate for KE30 (Db100: -10.0 ± 6.8%; VA: -7.2 ± 2.8%). Although the amount of mechanical work cumulated strongly determined the magnitude of torque decrease, the contraction velocity and mode influenced the origin of the neuromuscular fatigue. The metabolic stress and peripheral fatigue increased but reduction of VA is attenuated when the contraction velocity increased from 0°/s to 240°/s.

Late-Onset Glycogen Storage Disease Type 2.

Glycogenosis II (GSDII) is an autosomal recessive lysosomal storage disorder resulting from acid alpha-glucosidase (GAA) deficiency, subsequent lysosomal accumulation of glycogen in muscles, impairment of autophagic processes and progressive cardiac, motor and respiratory failure. The infantile form usually appears in the first month of life, progresses rapidly and presents with severe cardiac involvement and complete deficiency of alpha-glucosidase activity (< 1% of normal controls). The late-onset form is characterized by great variability of the phenotypical spectrum. Main findings are muscle weakness and severe respiratory insufficiency while cardiac involvement may be completely absent. Residual GAA enzyme activity may correlate with severity of phenotype but many adult patients sharing the same mutations present with a wide variability in residual enzyme activity, age of onset and rate of disease progression, thus supporting a role for other factors, i.e., post-translational modifications and modifier genes, in modulating disease presentation. Enzyme replacement therapy (ERT) with alglucosidase alfa stabilizes the disease or improves muscle and/or respiratory function. However, efficacy of ERT may be influenced by several factors including age when ERT begins, extent of muscle damage, degree of defective autophagy, diversity in muscle fiber composition, difficulties in delivery of the therapeutic agent and antibody production. Further studies should be warranted to investigate factors determining the differences in clinical expression and therapeutic response in order to achieve better clinical and therapeutic management of these patients.

Cryptosporidium in pet snakes from Italy: molecular characterization and zoonotic implications.

To provide information on the occurrence of Cryptosporidium species and genotypes in captive snakes from Italy, faecal specimens from 120 snakes belonging to 13 different genera of the families Boidae, Colubridae and Pythonidae were collected. Faecal samples were taken from the ground of the terrarium when available; otherwise cloacal cotton swabs were used. No clinical signs of cryptosporidiosis were observed in any animal at the time of sampling. Samples were examined for the presence of Cryptosporidium by using a direct immunofluorescence antibody test (IFAT) and two-step nested PCR at the small subunit (SSU) rRNA locus. PCR-positive samples were genotyped by restriction fragment length polymorphism (RFLP) analysis with the endonucleases SspI and VspI. By IFAT, 42 out of 120 snakes (35.0%) were found to be shedding Cryptosporidium oocysts. A significant higher percentage of positive ophidians were detected by using faecal specimens obtained from the terrarium (55.5%) than by cloacal cotton swabs (29.0%). SSU rRNA gene products were obtained from 25 isolates. Twenty samples tested positive to both microscopy and molecular techniques. Our data reveal a wide extent of cryptosporidial infections in snake-food animals since most of the identified isolates belonged to Cryptosporidium species, some of them with zoonotic potential, considered specific for rodents and resulting from ingestion of infected preys. The reptilian-specific species Cryptosporidium serpentis was identified in only one isolate. The common presence of reptile non-specific and, in some cases, zoonotic Cryptosporidium oocysts in snake faeces should to be taken into consideration in order to avoid the misidentification of the protozoan as well as the possible public health implications.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Investigation of cartilage degradation in patients with spinal cord injury by CTX-II.

STUDY DESIGN: Clinical cross-sectional study. OBJECTIVES: To investigate the cartilage degradation by turnover of C-telopeptide fragments of collagen type-II (CTX-II), a molecule specific for articular cartilage in spinal cord injured patients with respect to clinical functional status. SETTING: Physical Medicine and Rehabilitation Clinics, hospital settings. METHODS: In 68 patients with spinal cord injury (SCI) level and severity of lesion, duration of disease, American Spinal Injury Association Impairment Scale (AIS), motor and sensory score, presence of spasticity, functional ambulation score (FAS) and duration of daily ambulation were evaluated. Cartilage degradation was demonstrated by urinary CTX-II (uCTX-II) measured by enzyme-linked immunosorbent assay. T test, analysis of variance and Pearson correlation analysis were used for statistical calculations. RESULTS: uCTX-II level was significantly higher in patients with AIS grade A, non-functional ambulators or in patients who did not ambulate at all (P<0.05). Although AIS grade, lower extremity motor score, FAS score and duration of daily ambulation were found to be correlated (P<0.05) with uCTX-II, duration of disease, level of neurological lesion, presence of spasticity were not. CONCLUSION: This is the first study providing evidence that cartilage degradation is associated with elevated uCTX-II levels in non-ambulating or non-functional ambulating SCI patients. AIS grade A, FAS zero score and no time for daily ambulation were found to cause significant differences in CTX-II level. It may be important to initiate therapeutic programs as soon as possible after SCI to prevent cartilage atrophy.

Cytokine levels in patients with Epstein-Barr virus associated laryngeal carcinoma.

OBJECTIVE: Some researchers have suggested that Epstein-Barr virus may play a role in the pathogenesis of laryngeal malignancies. In order to clarify the role of cytokines in this disease context, the current study aimed to determine the serum levels of cytokines in Epstein-Barr virus DNA positive patients with laryngeal carcinoma. SUBJECTS: The study included 10 patients with diagnosed laryngeal carcinoma and Epstein-Barr virus DNA positive tumour tissue samples. The control group comprised 10 Epstein-Barr virus DNA negative patients diagnosed with laryngeal carcinoma, 10 patients with acute Epstein-Barr virus infection and 10 healthy individuals. METHOD: Serum cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: The Epstein-Barr virus DNA positive and negative laryngeal carcinoma patients showed no differences regarding serum levels of the following cytokines: interleukins 1beta, 2, 6 and 12, tumour necrosis factor alpha, and interferon gamma. However, serum levels of interleukin 10 and transforming growth factor beta1 were significantly higher in Epstein-Barr virus DNA positive laryngeal carcinoma patients compared with Epstein-Barr virus DNA negative laryngeal carcinoma patients (p < 0.05). CONCLUSION: Our results suggest that the cytokines interleukin 10 and transforming growth factor beta1 may act as growth factors in Epstein-Barr virus related laryngeal carcinoma. These cytokines may thus represent potential targets for molecular therapeutic treatment for laryngeal carcinoma; they may also be useful as indicators of disease prognosis.

Ultrasonographic and biochemical evaluation of visceral obesity in obese women with non-alcoholic fatty liver disease.

OBJECTIVE: Identification of specific origin of lipid accumulation in the liver of patients with non-alcoholic fatty liver disease (NAFLD) is the most important step in preventing this condition. Because liver steatosis, in the obese patients without any systemic disease, can be graded easily by ultrasonography (US), we aimed to demonstrate the degree of liver steatosis and abdominal fat distribution by US, furthermore evaluate biochemical, anthropometrical measurements, and define the possible relationship between these parameters in obese women with different grades of liver steatosis. METHODS: In this controlled clinical study, according to US evaluation of liver steatosis, the patients were divided into four groups: control (no steatosis), mild, moderate and severe steatosis groups. Demographic, biochemical and anthropometric measurements were done. Insulin resistance was determined by using homeostasis model assessment (HOMA-IR). Liver steatosis and abdominal fat distributions were evaluated by US. RESULTS: The subcutaneous and preperitoneal fat layer measurements did not show any significant difference between the groups. The visceral fat layer thickness was significantly higher in severe liver steatosis group compared to the control and steatosis groups. The highest serum fasting insulin, uric acid levels and HOMA-IR index were observed in the severe liver steatosis group. Visceral fat thickness was positively correlated with serum UA levels and HOMA-IR CONCLUSIONS: This study suggests that visceral adipose tissue, HOMA-IR and serum uric acid levels are the main determinants of NAFLD in obese patients.

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis.

Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing-remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.

Mycobacterium tuberculosis complex DNA does not exist in atheromatous plaques.

The possible potential role of several infectious agents in atherosclerosis has been shown. Several infectious agents DNA in atheromatous plaques have been displayed by PCR. In patients with atheromas antibody levels against Hsp65 were higher. Vaccination of mice with recombinant Hsp65 and Hsp65-rich M. tuberculosis resulted in formation of atheromatous plaques. We attempted to detect M. tuberculosis DNA in atherosclerotic plaque samples by PCR. In endarterectomy tissue samples obtained from patients during coronary artery bypass graft surgery DNA was prepared by proteinase-K digestion, phenol/chloroform extraction and ethanol precipitation. After amplification with M.tuberculosis complex IS6110 region specific primers, the products were analyzed on electrophoresis. M. tuberculosis DNA was negative in all tissue samples. More data on etiological studies with mycobacteriaceae will be yield information on atherosclerosis pathogenesis.

[Hemolytic uremic syndrome]. / La sindrome emolitico uremica.

Hemolytic uremic syndrome (HUS) is a disease characterized by non immune hemolytic anemia, low platelet count and renal impairment. In children, the disease is most commonly triggered by Shiga-like toxin (Stx)-producing Escherichia coli (Stx-E. Coli): however, renal function recovers in up to 70% of patients. Plasma infusion or exchange reduces mortality and the risk of end-stage renal disease (ESRD) in adult patients. Non-Shiga toxin-associated HUS (non-Stx-HUS), accounting for only 5-10% of all disease cases, can be sporadic or familial. Collectively, non-Stx-HUS forms have a poor outcome. Up to 50% of cases progress to ESRD or have irreversible brain damage, and 25% can die during the acute phase of the disease. Genetic studies have recently documented that the familial form is associated with genetic abnormalities of complement regulatory proteins, and evidence is now emerging that similar genetic alterations can predispose to sporadic cases of non-Stx-HUS as well. Mutations of genes encoding for factor H, a glycoprotein that plays an important role in the regulation of the alternative pathway of complement and for MCP, a widely expressed transmembrane glycoprotein with an inhibitory role of activated C3, are reported in familial HUS. These mutations are more likely to predispose rather than to cause the disease directly.

Assessment of human papilloma viral load of archival cervical intraepithelial neoplasia by real-time polymerase chain reaction in a Turkish population.

The purpose of this study was to determine the existence, and viral load of human papilloma virus (HPV) subtypes 16 and 18 in paraffinized cervical intraepithelial neoplasia (CIN) samples by real-time polymerase chain reaction (RT-PCR). Overall 94 women were included. Of these patients 47 (50%) had CIN I, 27 (28.8%) had CIN II, and 20 (21.2%) had CIN III. HPV positivity for these three groups were 4.2%, 14.8% and 45%, respectively. HPV positivity in CIN III patients was significantly higher than CIN I (OR = 18.41, 95% CI 3.00-145.73; p < 0.001), and CIN II patients (OR = 4.70, 95% CI 1.00-23.76; p = 0.05). The difference between CIN I and II was not significant (p = 0.18). Viral loads were 10(2), and 10(4) copy/ml for two CIN I patients; 10(2), 10(3), and 10(5) for three CIN II patients; and 10(2), 10(3), 10(4), 10(4), 10(5), 10(5), and 10(6) copy/ml for eight patients with CIN III. Viral load of the remaining one patient could not be assessed. No significant variance was noted among the groups with respect to viral load (p = 0.73). RT-PCR had important advantages of detecting, typing, and quantifying at the same time. Although HPV positivity was increased significantly by the degree of lesions, this relation was not observed for viral load.

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).

Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A phase II study of the Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD).

BACKGROUND: To evaluate the safety and efficacy of the novel raltitrexed/oxaliplatin combination (TOMOX) as first-line chemotherapy for patients with advanced colorectal cancer. MATERIALS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 3 mg/m2 plus oxaliplatin 100 mg/m2, both intravenously, on day 1 every 3 weeks. Patients were re-evaluated after every third cycle and chemotherapy was continued up to tolerance or disease progression. RESULTS: Fifty-eight patients from 13 Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD) centers were accrued from September 1999 to November 2000. According to the intention-to-treat analysis from 58 patients, the overall response rate was 50% [95% confidence interval (CI) 38% to 62%], with three complete responses and 26 partial responses. The median overall survival (44 patients currently alive) was >9 months and the median time to disease progression was 6.5 months (range 1-15 months). The main hematological toxicity was grade III/IV neutropenia, which occurred in 17% of patients, while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were transient transaminitis (17% of patients); asthenia (16% of patients); neurotoxicity (10% of patients) and diarrhea (7% of patients). No toxic death was observed, one patient with grade IV asthenia after the first cycle refused chemotherapy. CONCLUSIONS: The results of this study suggest that the TOMOX combination is an effective and well tolerated regimen for the treatment of advanced colorectal cancer. Its ease of administration and patient tolerance warrant further investigation as an alternative to fluoropyrimidine-based regimens with repeated and prolonged fluorouracil infusions.

Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study.

PURPOSE: Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS: All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS: We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION: The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.

Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors often affect women of childbearing age and the prognosis is outstanding. Given the young age of several patients and the good prognosis, fertility-sparing surgery is considered adequate for stage I tumors. However, women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique. METHODS: From 1981 to 1997, 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospectively. After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter. Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor. RESULTS: With a median follow-up of 71, months 28 women treated with fertility-sparing surgery (28/164 = 17%) had either recurrence of borderline tumor (23) or recurrence with carcinoma. Complete details of follow-up procedures are available for 24 women and they represent the study population. An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor. One patient had diagnosis due to persistent free fluid. All five women with invasive carcinoma had diagnosis of a complex adnexal mass. Gynecologic examination was suspicious (palpable mass) in 7 cases and obviously abnormal (large mass or nodules) in another 7. CA 125 serum levels were elevated in 8 cases. CONCLUSION: Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor.

Early-stage epithelial ovarian cancer: an overview.

The clinical treatment of malignant epithelial ovarian cancer limited to the gonad(s) involves many problems that have given rise to analyses in recent literature and to different approaches: i. intensive anatomo-radio-surgical staging, evaluation and clinical incidence of prognostic risk factors; ii. re-staging of patients after inadequate and incomplete surgery; iii. indications, role and topicality of second-look surgery; iv. conservative surgery in patients of a fertile age wishing to have children and retain activity of the gonads; v. laparoscopic surgery for treatment, staging, re-staging and surveillance; vi. the lymph node issue; vii. adjuvant therapy: indications, options, type of drugs, doses and length; viii. quality and frequency of surveillance; ix. malignant epithelial ovarian cancer limited to the gonads in pregnancy. The clinical handling of these tumours entails many complex problems causing emotional involvement since it is most frequent at a fertile age.