Measurement Of Serum Tumor Markers Research Articles

Modeling strategies to analyse longitudinal biomarker data: An illustration on predicting immunotherapy non-response in non-small cell lung cancer

Serum tumor markers acquired through a blood draw are known to reflect tumor activity. Their non-invasive nature allows for more frequent testing compared to traditional imaging methods used for response evaluations. Our study aims to compare nine prediction methods to accurately, and with a low false positive rate, predict progressive disease despite treatment (i.e. non-response) using longitudinal tumor biomarker data. Bi-weekly measurements of CYFRA, CA-125, CEA, NSE, and SCC were available from a cohort of 412 advanced stage non-small cell lung cancer (NSCLC) patients treated up to two years with immune checkpoint inhibitors. Serum tumor marker measurements from the first six weeks after treatment initiation were used to predict treatment response at 6 months. Nine models with varying complexity were evaluated in this study, showing how longitudinal biomarker data can be used to predict non-response to immunotherapy in NSCLC patients.

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers.

BackgroundAlthough simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown.MethodsA retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients.FindingsAmong the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme.InterpretationThe models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.

Long-term outcomes after biliary diversion operation for pancreaticobiliary maljunction in adult patients.

AimPancreaticobiliary maljunction (PBM) with or without congenital biliary dilatation (CBD) is a risk factor for biliary tract cancer. We investigated long‐term outcomes after biliary diversion operation with special reference to types of CBD.MethodsSubjects comprised 40 adult patients who underwent biliary diversion operation for PBM without biliary tract cancer. Group A comprised 20 patients with type Ia or Ic CBD, or non‐dilated bile ducts, while group B comprised 20 patients with type IV‐A CBD. The clinical findings and postoperative outcomes were compared between groups.ResultsOf 40 patients, nine patients suffered from repeated cholangitis and eight of these nine patients suffered from hepatolithiasis after biliary diversion operation. Biliary tract cancer or pancreatic cancer was detected in four patients at 3 years and 2 months to 24 years after the operation. In three of these four patients, the serum concentration of carbohydrate antigen 19‐9 increased before detection of carcinoma. One patient died of hepatic failure due to repeated cholangitis. The proportions of patients with repeated cholangitis, hepatolithiasis, and re‐operation, and patients who died of biliary tract cancer, pancreatic cancer, or hepatic failure, were significantly higher in group B than in group A. The survival rate was significantly worse in group B than in group A.ConclusionsCareful long‐term follow‐up with measurement of serum tumor markers is necessary after biliary diversion operation for PBM, especially in patients with type IV‐A CBD or repeated cholangitis.

An open-label, single-group, phase 2 study of brentuximab vedotin as salvage therapy for males with relapsed germ-cell tumors (GCT): Results at the end of first stage (FM12GCT01).

480 Background: Prognosis of patients (pts) failing multiple chemotherapy (CT) regimens is quite dismal. CD30 is expressed and prognostic in embryonal carcinoma, hence it is a rational target for treatment. Brentuximab Vedotin (BV) is an antibody-drug conjugate consisting of the chimeric anti-CD30 antibody SGN-30 conjugated to an antitubulin synthetic analog (MMAE). A phase 2 trial is ongoing in GCT (NCT01851200). Methods: 24 pts with biopsy-proven CD30+ GCT will receive BV 1.8 mg/Kg IV q3 weeks until disease progression or onset of unacceptable toxicity. Eligibility will include failure of 2 or 3 platinum-based CT (including HDCT). All pts will undergo measurement of serum tumor markers (STM), a computed tomography and a PET scan q6 weeks. An optimal Simon’s 2-stage design will be applied. The primary endpoint is the objective response-rate (ORR; H0: ≤ 5%, H1: ≥ 25%, α and β = 10%). In stage 1, 9 evaluable patients will be accrued. Sequential peripheral blood samples are being collected for immune profiling by flow cytometry of immune cell subsets. Results: From 07/13 to 04/15, 9 pts have been treated, 3 in third-line, and 6 beyond the third-line. 5 had received HDCT. STM decline was obtained in 7 pts (77.8%) after the first dose and in 4 pts (44.4%) after 2 doses (with normalized [1] or still positive [3] STM). ORR was 22.2% (1 CR+1 PR) according to RECIST v1.1, and there were 3 metabolic PR. 3-month PFS was 11.1% (95%CI: 0.6-38.8), 6-month OS was 85.7% (95%CI: 33.4-97.9). 1 case of reversible G3 hyperglycemia was recorded. No BV discontinuation due to toxicity occurred. In 7 evaluable pts, a trend to increasing expression of activation (HLA-DR), proliferation (Ki67), and functional differentiation (Granzyme B) markers in CD4 and CD8 T cells was observed during BV. In CR patient, an increased frequency of naive and central memory T cells was observed after the first cycle of BV, as well as a reduction in the fraction of PD1+/CD8+ T cells. Conclusions: Brentuximab is endowed with potent antitumor activity and meaningful immunomodulatory effects in GCT. The rapid development of resistance is a concern. ORR is pending confirmation in the whole sample size. Clinical trial information: NCT01851200.

Design of a Phase 2 STudy of Brentuximab Vedotin (SGN-35) as Salvage Therapy for Males with Chemoresistant Germ-Cell Tumors (GCT)

ABSTRACT Background Complete responses with third-line or later salvage chemotherapy (CT) for GCT range from 5% to 10%, and nearly all patients (pts) progressing after high-dose CT will ultimately die. CD30 is expressed by embryonal carcinoma (ECA) thus lending support to a rationale for a targeted approach. SGN-35 is an antibody-drug conjugate consisting of the chimeric anti-CD30 antibody SGN-30 chemically conjugated to an antitubulin synthetic analog. The primary objective of the study will be the activity of SGN35 in refractory GCT. Trial design 24 pts with biopsy-proven CD30+ GCT will receive intravenous SGN35 at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity. Further eligibility requirements will include failure of 2 or 3 platinum-based CT (including HDCT). All pts will undergo measurement of serum tumor markers, a computed tomography and a PET scan q6 weeks. An optimal Simon's 2-stage design will be applied. The primary endpoint is the objective response-rate (ORR). An ORR of 5% is not promising, while a 25% rate will be promising. In stage 1, 9 evaluable patients will be accrued. If ≥1 patient will be responding, enrollment will be extended to the 2nd stage for further 15. If, over the total of 24 stage 1 plus stage 2 pts, 3 at least will be responding, treatment will be declared worthy for further investigations. The type I and II error are set both at 0.1 (power = 90%). We will test the hypothesis that brentuximab can promote anti-tumor immunity, which might contribute to the clinical efficacy. We will use multiparametric flow cytometry to assess whether SGN-35 can: a) impact on frequency and absolute counts of all main cellular subsets; b) shift the TH1/TH2 balance, in favor of a TH1-type of response; c) reduce the frequency of circulating CD30+ regulatory T cells and CD30+ TH2 memory T cells; d) promote an increase in circulating CD161+TH17 T cells; d) reverse the condition of immune dysfunction, by assessing the expression of negative co-signaling molecules (PD-1, CTLA-4, CD160, CD244, CD57, TIM-3, LAG-3) and of activation/proliferation markers (Ki67, GranzymeB, CD69) on main T cell subsets. As of July 2014, 6 pts have been enrolled (NCT01851200). Disclosure All authors have declared no conflicts of interest.

Pazopanib in chemoresistant patients with germ cell tumors (GCT): Updated results of the open-label, single-group, phase 2 Pazotest-01 trial.

e15529 Background: Patients (pts) with GCT who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. We updated the initial results of the ongoing open-label, single-group, phase 2 study which is sponsored by INT Milano. Methods: Patients failing at least 2 platinum-based CT (including high-dose CT) received PZP 800 mg/day orally until disease progression (PD) or evidence of unacceptable toxicity/side effects. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after 1 month and q2 months thereafter. In a Simon’s 2-stage design, the primary endpoint is 3-month progression-free survival (PFS). In stage 1, 18 evaluable patients will be accrued. If ≥ 3 pts will be progression-free at 3 months, enrolment will be extended to the 2ndstage. Results: From 06 to 12...

Activity of pazopanib in chemo-resistant patients with germ cell tumors (GCT): First results of the open-label, single-group, phase II PAZOTEST-01 trial.

376 Background: Patients (pts) with germ cell tumors (GCT) who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. Here we report the initial results of the ongoing open-label, single-group, phase II study which is sponsored by INT Milano (ClinicalTrials.gov NCT01743482). Methods: Pts with refractory GCT received pazopanib 800 mg/day orally until disease progression or evidence of unacceptable toxicity/side effects. Eligibility requirements included failure of at least two platinum-based CT, including high-dose CT. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after one month of treatment and q2 months thereafter. Results: From May 2013 to July 2013, five pts were enrolled, three in fourth, and two in fifth-line. Median age was 39 (IQR: 33 to 48). Three out of five had failed high-dose chemotherapy (HDCT), two had an extragonadal primary, all pts had at least one elevated STM at baseline, the sole parameter in one patient, two had liver metastases, four pts had a retroperitoneal relapse. Four had elevation of alfafetoprotein (AFP), one of human choriogonadotropin (HCG). Four were nonseminomas, one a pure seminoma. After the first month of treatment, four out of five pts had a decrease in marker levels, one patient had disease progression (PD). Two of the responding pts had a necrotic evolution of disease at computed tomography corresponding to a RECIST and metabolic (PET/CT) progression, two had a stable disease. Two-month follow up is available for three out of four responders: one interrupted PZP for toxicity and had a marker PD, another an increase to baseline levels and the last one a further reduction (pure seminoma, one out of five confirmed response at two months). There were two cases of hepatic toxicities (one G2 and one G3-4 with dose interruption). Conclusions: PZP is endowed with preliminary activity in extensively pretreated patients with GCT. The unique availability of STM in interpreting densitometric and metabolic response might provide insights into response assessment of solid tumors under antiangiogenic therapy. Clinical trial information: NCT01743482.

Surveillance After Initial Surgery for Pediatric and Adolescent Girls With Stage I Ovarian Germ Cell Tumors: Report From the Children's Oncology Group

To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults.

Assessment of Treatment Response after Chemoradiation of Head and Neck Cancer

Accurate early diagnosis and staging is an essential step in the management of recurrent head and neck cancer. Nevertheless, the diagnosis and staging of recurrent head and neck cancer previously treated by radiation therapy often combined with chemotherapy, remains a challenge. The differentiation between radiation induced reaction and recurrent cancer is a difficult clinical and radiological problem. It is clear that timely diagnosis in case of residual or recurrent tumor is of great importance to increase the possibility of cure. A variety of interventions such as office clinical examinations, blood tests, serum tumor marker measurements, imaging studies and endoscopies are being used to follow-up these patients. No single intervention proved to be absolute or complete in being simultaneously sensitive, specific, inexpensive, safe and efficient at detecting suspected recurrence of head and neck cancer, particularly after chemoradiation. In addition to that, there is no clear evidence of what surveillance regimen or frequency is considered the most adequate or effective in this setting. In this article, we analyze the diagnostic difficulties of tumor recurrence after combined treatment with chemotherapy plus radiation therapy and review the role of clinical, endoscopic and imaging techniques in the follow-up of these patients.

The prognostic values of CA125, CA19.9, NSE, AND SCC for stage I NSCLC are limited

Amongst the current detections of tumor markers, measurement of serum tumor markers is the most convenient and the safest way. However, there are few promising serum tumor markers with confirmed prognostic value in NSCLC (non-small-cell lung cancer, NSCLC). Therefore, scientists only grafted the useful tumor markers, such as CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 which have been found in other solid tumors. However, previous reports about this issue remain controversial. This study is to analyze the prognostic values of these 6 markers in stage I NSCLC. One hundred and sixty four patients with stage I NSCLC who underwent operation by single-surgery-team in Department I of Thoracic Surgery, Peking University Cancer Hospital between March 2000 and March 2011 were included. These patients had measurement of CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 using electrochemiluminescence immunoassay one week before operation. The relationship between the level of these 6 tumor markers and long term survival rate was analyzed. The positive rate for CA125, CA19.9, NSE, SCC, CEA and CYFRA 21.1 in the 121 adenocarcinoma patients was 5.7%, 5.7%, 18.3%, 5.3%, 18.3%, and 20.7% respectively; whereas 3.1%, 2.6%, 23.8%, 26.8%, 14.0%, and 42.9% in 43 non-adenocarcinoma patients, respectively. In univariate analysis, the overall 5 year survival rate of patients with elevated CYFRA21.1 level was lower than that of patients with normal level in ADC subgroup (54.5% vs. 83.8%, p < 0.05) and in all 164 cases (49.5% vs. 76.4%, p < 0.05). In multivariate analysis, the level of CYFRA21.1 was an independent prognostic factor. But the other 5 markers didn't show significant prognostic value. We found that the prognostic values of CA125, CA19.9, NSE, and SCC for stage I NSCLC are limited. CYFRA21.1 might be a hopeful prognostic serum tumor marker for stage I NSCLC.

Utility of serum tumor markers during surveillance for stage I seminoma

The serum tumor markers α-fetoprotein (AFP), β-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse. Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x-rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow-up until the time of relapse. Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow-up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n = 64) or physical examination (n = 1), for which the treatment and outcome were not affected. Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of serum tumor markers can be discontinued safely in seminoma surveillance schedules.

Management and follow-up of pediatric asymptomatic testicular microlithiasis: are we doing it well?

To define timing and methods for a balanced follow-up of testicular microlithiasis (TM) in pediatric age. We retrospectively reviewed medical records of 21 pediatric asymptomatic patients (42 testicular units) diagnosed with TM and without associated risk factors. Microliths were found bilaterally on ultrasonography in all the patients. Distribution of microliths (focal or diffuse) inside the parenchyma was evaluated as well as its eventual variation over time. Every six months, each patient underwent clinical and ultrasonography evaluation, as well as serum chemistry markers (α-fetoprotein and β-human chorionic gonadotropin) measurement to detect potential malignancy. In the interval between the follow-ups, parents and/or patients themselves were asked to control eventual enlargement of the gonads or scrotal swelling. Testicular biopsy was not performed in any of our subjects. Of 21 patients, 6 had unilateral undescended testis, 4 varicocele, and 1 patent processus vaginalis with scrotal swelling while 10 patients did not show associated anomalies. The distribution pattern of microliths on ultrasonography remained unchanged in all follow-ups in every patient, showing a predominance of diffuse pattern in the undescended testis series. Tumor markers remained within normal limits. In no subject, we observed a shift toward a malignant condition. In the pediatric population with an incidentally diagnosed TM and without any associated risk factor, a slight follow-up is suggested, consisting of clinical evaluation every 6 months, without any justifiable recommendation to perform a testis biopsy and a measurement of serum tumor markers.

Regression of metastatic seminoma in a patient referred for carcinoma of unknown primary origin

A 63-year-old man presented to an emergency department with abdominal and back pain. A 5 x 3 x 2 cm para-aortic mass was found adjacent to the left kidney, but the location of the primary tumor could not be identified. He was referred to a tertiary center with a diagnosis of retroperitoneal carcinoma of unknown primary origin. Atrophy of the left testicle was noted. Review of the biopsy material obtained at the first presentation showed histology characteristic of seminoma, and imaging revealed the presence of small intratesticular lesions. Repeat CT showed complete resolution of the metastatic para-aortic mass. The patient underwent left orchiectomy and adjuvant radiation therapy, and showed no signs of disease 6 months later. CT of the chest, abdomen and pelvis, measurement of serum tumor markers, upper gastrointestinal endoscopy, colonoscopy, PET-CT and percutaneous needle biopsy of the para-aortic mass at the first presentation; physical examination, review of biopsy specimen with immunohistochemical staining for tumor markers, testicular ultrasonography and repeat CT of the chest, abdomen and pelvis at the second presentation. Metastatic seminoma with spontaneous regression of the metastatic lesion. Radical orchiectomy and adjuvant radiation therapy.

Value of (18)F-FDG imaging and serum tumor markers in the diagnosis of recurrent endometrial carcinoma

Both (18)F-fluorodeoxyglucose (FDG) imaging and serum tumor marker measurements can be used in the post-therapy surveillance of recurrent endometrial carcinoma, but the relationship between those two methods has not been demonstrated yet. The purpose of this study was to compare the diagnostic efficiency of (18)F-FDG imaging and serum tumor marker measurements in the diagnosis of recurrent endometrial carcinoma, as well as to analyze the correlation between those two methods. Thirty-five patients with histopathologically confirmed endometrial carcinoma and suspected to have recurrent disease during post-therapy surveillance were included in this study. (18)F-FDG images from the thorax to the pelvis were obtained in all patients by using GE-Millennium VG Hawkeye system, and the abnormal FDG uptake was judged as tumor recurrence. Serum CA-125 and CP-2 were also measured for each patient by enzyme-linked immunoassay, and a cutoff value of 35 U/ml was taken as the criteria for predicting tumor recurrence. Based on the final clinical diagnosis, the efficiency of tumor markers (CA-125, CP-2) and (18)F-FDG imaging in the diagnosis of recurrent tumor was evaluated. According to the histopathological diagnosis or follow-up examinations, tumor recurrence was confirmed in 13 of the 35 patients. Elevated serum level of CA-125 was found in 7 patients, serum CP-2 was increased in 9, and (18)F-FDG imaging was positive in 15. The diagnostic sensitivity, specificity and accuracy were 53.8%, 100% and 82.9% for the serum CA-125; 38.5%, 81.0% and 65.7% for the serum CP-2, and 100%, 90.9% and 94.3% for the (18)F-FDG imaging, respectively. The diagnostic coincidence rate between the (18)F-FDG imaging and serum CA-125 was 77.1% (Kappa = 0.50, P = 0.001), but no significant correlation was found between the (18)F-FDG imaging and serum CP-2. In the patients with true positive (18)F-FDG imaging, a positive correlation between the tumor volume and the serum CA-125 value was found (r = 0.89, P < 0.001), but no correlation was found between the tumor uptake and the serum CA-125 values. For the post-therapy surveillance of patients with endometrial carcinoma, serum CA-125 is a high specific tumor marker for diagnosing recurrent disease and better than CP-2, but (18)F-FDG imaging is better than CA-125, and there is a positive correlation between tumor volume and serum CA-125 value.

Hepatocellular Carcinoma in Keio Affiliated Hospitals — Diagnosis, Treatment, and Prognosis of this Disease —

We have retrospectively investigated patients with hepatocellular carcinoma (HCC) (912 cases) treated in the Affiliated Hospitals of Keio University (the Keio Association for the Study of Liver Diseases: KASLD) and here we review the recent diagnosis and treatment of HCC. HCC is a major cause of death in Japan and a major etiology of this disease is chronic viral infection such as hepatitis C virus (HCV) and hepatitis B virus (HBV). Screening of HCC by imaging studies and measurement of serum tumor markers successfully prolonged survival of the patients in Japan. The prognosis of this disease has been determined by both tumor factors and degree of liver function, and its staging is usually established with a recent system such as Japan Integrated Staging Score (JIS). The 5-year survival rate of JIS stage 0, 1, 2 and 3 were 68.3%, 51.9%, 25.8% and 16.6%, respectively in our cohort. Multivariate analysis using Cox proportional hazard models showed that age (>65) , HCV infection, tumor number, TB (>1.0), AFP (>20) and PIVKA-II (>40) were significant factors affecting survival among the entire patients. Major treatment strategies are hepatic resection, radio frequency ablation and transarterial chemo-embolization, but alternative treatments such as radiation, chemotherapy, and their combination have been used to reduce tumor sizes resulting prolongation of the survival or maintenance of patients' quality of life, while liver transplantation has not been popular in Japan. However, the overall survival continues to decrease from year to year, and does not show a plateau phase in Kaplan-Mayer curve. These results suggest that the best way to improve survival can be achieved by prevention of the disease. Antiviral therapies have decreased the incidence of HCC, indicating that treatment for chronic hepatitis is the best way to prevent HCC development at present.

A case of synchronous bilateral testicular seminoma

A previously healthy 51-year-old man with two children sustained a minor testicular trauma and subsequently sought medical care for persistent discomfort. Physical examination, scrotal ultrasonography, Doppler ultrasound evaluation of testicular blood flow, scrotal MRI, measurement of serum tumor markers and testosterone levels, CT of the chest, abdomen and pelvis, intraoperative frozen section analysis and final pathologic analysis. Bilateral testicular seminoma (clinical stage I). The patient initially underwent radical left orchiectomy with intraoperative frozen section analysis, which returned equivocal results. Final pathologic analysis revealed a 2.5 cm left testicular seminoma without vascular invasion. After careful discussion, he ultimately underwent radical right orchiectomy; pathologic analysis revealed a 2.7 cm right seminoma with vascular invasion. Testosterone replacement therapy was initiated. After further discussion, the patient elected to undergo adjuvant abdominal radiotherapy to a total of 25 Gy. The patient showed no evidence of disease over a post-treatment follow-up period of 24 months.

A paraneoplastic case of palmar fasciitis and polyarthritis syndrome

A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.

Direct evidence that PTHrP expression promotes prostate cancer progression in bone

Parathyroid hormone-related protein (PTHrP) is an oncoprotein that is expressed in many malignancies as well as normal tissues. At essentially every site of expression, PTHrP regulates cell growth and proliferation. We and other investigators have previously reported that PTHrP is widely expressed by prostate cancer. For this tumor, there are substantial in vitro and correlative data that PTHrP expression regulates the progression of the tumor, especially in bone, but little direct data. We studied the effects of PTHrP expression on prostate cancer behavior directly in a mouse model of human prostate cancer cells that were transfected to express different forms of the polypeptide and then injected intraskeletally. Skeletal progression of the prostate cancer cells was evaluated radiologically and by measurement of serum tumor markers. PTHrP transfection converted a non-invasive cell line into one that progressed in the skeleton: Injection of the PTHrP transfected cells resulted in greater tumor progression in bone when compared to non-transfected cells, and this effect was also influenced by non-amino terminal peptides of PTHrP. Serum measurements of PTHrP, IL-6, IL-8, and calcium reflected tumor burden. Our experiments provide direct in vivo evidence that PTHrP expression results in the skeletal progression of prostate cancer cells.

Monitoring of skeletal progression of prostate cancer by GFP imaging, X-ray, and serum OPG and PTHrP.

Prostate cancers (PCas) produce factors that can serve as biomarkers for tumor metastasis and bone progression. Transduced GFP expression by cancer cells can be imaged to monitor therapy. We exploited both concepts by developing a GFP-expressing PCa cell line that expresses PTHrP and studying it in an animal model of malignancy with methods that assess the skeletal progression of this tumor. We developed a GFP-producing PCa cell line by stable transduction of PC-3 PCa cells. This PC-3 variant was used to study tumor progression in an immunocompromised mouse model. Skeletal progression of the PCa cells and the effects of pamidronate administration were evaluated radiologically, fluorometrically, and by measurement of serum tumor markers. The PC-3 cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3 cells could be monitored by GFP optical imaging, X-ray, and by measurements of tumor products in serum, notably PTHrP and OPG. Pamidronate treatment reduced tumor burden as assessed at autopsy by imaging and biomarkers. Pamidronate treatment exhibited anti-tumor effects that were reflected by decreases in serum PTHrP, OPG, and by GFP and radiological imaging procedures. Imaging of GFP expression enables real-time monitoring of tumor growth in the bone. PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas.

Ovarian masses in adolescent girls.

Ovarian masses are the most frequent gynecological pathology seen in adolescent girls. Functional or organic tumors of the ovary are usually benign and the incidence rises with age. Most cysts are functional and adnexal torsion is the main complication, but a malignant etiology must nevertheless always be eliminated. The clinical presentation is quite variable. Ultrasonography is the investigation of choice: the sonogram will reveal a strictly fluid, benign functional cyst, suggest an adnexal torsion, and provide evidence of a heterogeneous mass. Emergency surgery is indicated only in the case of suspected ovarian torsion, in order to perform detorsion. In all other cases, serum tumor marker measurements will orient the diagnosis and MRI is an essential complement to imaging of tumors with heterogeneous solid components. Surgery and histopathological examination then determine the stage and the benign or malignant nature of the mass. Ovarian tumors are classified by the World Health Organization based on the cell of origin into epithelial tumors, germ cell tumors and sex cord-stromal tumors. Surgery should always follow oncological standards and be as conservative as possible to preserve future fertility.