Elevated Serum Tumor Markers Research Articles

Long‐term results of first‐line sequential high‐dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.

Tomografía de emisión de positrones con fluordesoxiglucosa-F 18 en el seguimiento del cáncer de endometrio

Objective To assess the utility of FDG-PET in the follow-up of patients treated for endometrial cancer and with suspicion of recurrence according to conventional imaging methods (CT, MRI) and/or elevation of serum tumour markers. Materials and methods Between April 2002 and December 2005, eleven patients underwent 17 FDG-PET studies (six with 2 studies); mean age was 63.4 yrs (range, 52-69 yrs) and time since diagnosis ranged from 11 months to 12 yrs (mean of 56 months). Initially, seven patients were in stage I, three in stage III and one in stage IV (FIGO classification). Histologically, they corresponded to 8 endometrioid carcinomas and 3 non endometrioid carcinomas. Results FDG-PET showed infradiaphragmatic uptake in 3 patients and disseminated disease in 7 cases. FDG-PET showed no uptake in one patient. CT (n = 7) or MRI (n = 7) detected infradiaphragmatic lesions in 5 patients and visceral lesions in 2. In 11 patients, tumour markers were elevated (CA125, n = 9; CA19.9, n = 2; CA15.3, n = 2). In 7 patients, FDG-PET modified the information yielded by conventional imaging techniques and in 4 patients, the FDG-PET contributed no additional information. In 2 patients, histologic confirmation of the lesions was obtained and in 9 patients, there were clinical follow-up (from 3 to 20 months, mean of 8.7 months) and imaging studies. Conclusions FDG-PET is superior to CT and MRI for detecting recurrences in the follow-up of patients with endometrial cancer.

Three cycles of etoposide and cisplatin chemotherapy in clinical stage IS nonseminomatous testicular cancer

To assess the efficacy of three cycles of etoposide and cisplatin (EP) chemotherapy in the patients with serological disease only after orchiectomy. Fifteen patients with nonseminomatous germ cell tumors of the testis and elevated serum tumor markers as the only evidence of persistent disease following radical orchiectomy (clinical stage IS cancer), were treated at our institution from March 1995 to February 2003. All patients received three cycles of EP chemotherapy. The toxicity was compared with that in control group consisting of 93 patients treated with three standard cycles of cisplatin, etoposide and bleomycin for good-prognosis metastatic diseases. The markers normalized in all patients after one (in 11 cases) or two (in 4 cases) cycles. One patient required subsequent surgery for recurrent retroperitoneal mature teratoma. All patients remained disease-free during the median follow-up period of 85 months (range: 33-128). In patients receiving EP chemotherapy less number of treatment cycles was associated with grade IV leukopenia compared to control group (p=0.04). A treatment program that consists of three cycles of EP caused complete disease control in all patients. The applied regimen may be considered as a therapeutic option with reduced toxicity in clinical stage IS nonseminomatous testicular cancer patients. More evidence, however, needs to be accumulated.

The role of FDG‐PET/CT in suspected recurrence of breast cancer

Early diagnosis of recurrent breast cancer is crucial to selection of the most appropriate therapy. The current study evaluated the role of FDG-PET/CT in the assessment of suspected recurrent breast cancer in patients who presented with elevated serum tumor markers. Forty-seven consecutive FDG-PET/CT studies of 46 women (aged 32-79 years; mean, 59.9 years) with a history of breast cancer presented with elevated serum tumor markers 1-21 years (mean = 6.2 years) after their initial diagnosis and were retrospectively evaluated. PET/CT results were confirmed by pathology (n = 11), further imaging, and follow-up (mean = 17.2 months; n = 36). Changes in further management based on PET/CT were recorded. Thirty (65%) patients had tumor recurrence, and 16 (35%) patients showed no further evidence of disease. Thirty-one patients had 32 abnormal PET/CT studies, and 15 patients had normal studies with an overall sensitivity, specificity, and accuracy of 90%, 71%, and 83%, respectively. In 37 patients, PET/CT was compared with contrast-enhanced CT and had a higher sensitivity (85% vs 70%), specificity (76% vs 47%), and accuracy (81% vs 59%). PET/CT had an impact on the management of 24 (5l%) patients. Of these, chemotherapy or radiotherapy was started in 16 patients, treatment was modified in 2 patients, and 6 patients were referred to biopsy, followed by referral to surgery for 2 patients. In patients with breast cancer and rising tumor markers, FDG-PET/CT had high performance indices and was superior to CT for diagnosis of tumor recurrence, which led to changes in the subsequent clinical management of 51% of these patients.

Clinical outcome of patients managed for late relapse of germ cell tumor

4550 Background: The significance of late relapse (LR) of germ cell tumor (GCT) and its association with poor survival is becoming increasingly recognized. Methods: Between 1990 and 2004, 75 patients (pts) were managed for LR of GCT at MSKCC. Using our prospective databases and following IRB approval, clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method and Cox-proportional hazards model was used to assess for predictors of outcome. Results: Clinical stage (CS) at initial presentation was I in 15 (21%), II in 32 (44%), and III in 26 (36%) of pts. Management prior to LR included surveillance in 10 (13%) pts, RPLND only in 8 (11%) pts, chemotherapy only in 19 (25%) pts, and both chemotherapy (induction or adjuvant) and RPLND in 38 (51%) pts. The median time to LR was 6.8 (2.1–37.7) years. Overall, 56/75 (75%) of pts had LR in the retroperitoneum (RP), including 25 of 27 (93%) initially managed without RPLND prior to LR. At LR, 45/75 (60%) of pts were symptomatic and 46/75 (61%) pts had elevated serum tumor markers (STM) (78% AFP and 39% βHCG). Overall 5 year cancer-specific survival (CSS) was 59% (95% CI 47%–72%). Pts who underwent complete resection (with or without salvage chemotherapy) at time of LR (n = 44) had a 5 year CSS of 77% (95% CI 62%–92%). In contrast, 5 year CSS for patients treated without complete surgical resection (n = 31) was 39% (95% CI 21%–57%) (p = 0.0001). The pathology of 69 pts at LR revealed viable GCT in 39 (57%), only teratoma in 13 (19%), malignant transformation in 14 (20%), and fibrosis in 3 (4%). A multivariable analysis of pretreatment parameters showed that at time of LR, a solitary site of metastasis (HR 2.6, 95% CI 1.1–6.2, p = 0.03) and no prior chemotherapy (HR 4.2, 95% CI 1.2–14.2, p = 0.02) were predictive of improved cancer-specific survival. Elevated STM and presence of symptoms did not impact survival independently in this model. Conclusions: Although LR of GCT is associated with poor survival, pts who are chemotherapy naïve and have a solitary metastatic site at LR experience improved survival. The data suggest that meticulous control of the RP is critical to prevent LR in the RP. Survival is greatly improved if complete surgical excision of disease at LR is attained, highlighting the critical role for surgery in these patients. No significant financial relationships to disclose.

Outcome Analysis for Patients With Elevated Serum Tumor Markers at Postchemotherapy Retroperitoneal Lymph Node Dissection

To evaluate the therapeutic benefit of postchemotherapy retroperitoneal lymph node dissection (PCRPLND) in patients with persistently elevated serum tumor markers. One hundred fourteen patients with metastatic germ cell cancer with elevated serum tumor markers after first-line (50 patients) or second-line chemotherapy (64 patients) who underwent PCRPLND between 1977 and 2000 with a minimum follow-up of 2-years were included in this retrospective study. The 5-year overall survival was 53.9%. Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months. Fifty-three patients died of disease, with a medium time to death of 8.0 months. Mean preoperative serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betaHCG) levels were 483 ng/mL and 555 mU/mL, respectively, with no difference in 5-year survival (P = .2). Retroperitoneal pathology revealed germ cell cancer in 53.5% of patients, teratoma in 34.2% of patients, and fibrosis in 12.2% of patients, with 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P < .0001). Predictors of retroperitoneal pathology included an increasing serum AFP or betaHCG, betaHCG more than 100 ng/mL, redo retroperitoneal lymph node dissection (RPLND), and second-line chemotherapy. Poor prognostic variables by multivariable analysis included betaHCG status, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. A subset of patients with elevated serum tumor markers after chemotherapy is curable with surgery. The prognostic factors predictive of outcome in this analysis include an increasing betaHCG, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. These factors, along with clinical and surgical experience, should aid in determining the appropriate integration of surgery and chemotherapy in this population.

A tumor in the medulla oblongata producing beta-HCG and AFP

A 23 year-old woman presented with dysarthria, hoarseness, dysphasia, ataxia and dyspnoea. MRI showed a mass of heterogeneous intensity at the dorsal medulla oblongata. Laboratory studies revealed high serum alpha-fetoprotein (AFP) and beta-subunit human chorionic gonadotropin (beta-HCG) levels. No other tumours were found on systemic investigation. An intracranial non-germinomatous germ cell tumour (NGGCT) was strongly suspected. The patient received combination chemotherapy using ifosfamide, cisplatin, and etoposide and local irradiation to a total of 52 Gy. Serum AFP and beta-HCG levels normalized after four cycles of chemotherapy and she became asymptomatic apart from mild postural hypotension. A follow-up MRI showed only a tiny residual lesion in the medulla oblongata, which has been stable for more than three years. Surgical resection should be carefully considered in patients with brainstem tumours with elevation of serum tumour markers as chemo- and radiotherapy may be effective for brainstem NGGCT.

Retroperitoneal Lymph Node Dissection for Nonseminomatous Germ Cell Testicular Cancer: Impact of Patient Selection Factors on Outcome

To investigate the impact of patient selection criteria on the outcome of patients with nonseminomatous germ cell testicular cancer (NSGCT) treated by primary retroperitoneal lymph node dissection (RPLND). Since 1999, our criteria have excluded patients with persistent postorchiectomy elevation of serum tumor markers (STM) or clinical stage (CS) IIB disease from RPLND. Between 1989 and 2002, 453 patients underwent primary RPLND at our institution for CS I to IIB NSGCT. Patient information was obtained from a prospective database. Retroperitoneal pathology and relapse rates were compared for patients treated before and after application of the current selection criteria in 1999. By excluding patients with elevated STM or CS IIB disease after 1999, the proportion of pathologic stage II patients with low-volume (pN1) retroperitoneal disease increased significantly (40% before 1999 v 64% after 1999; P = .01), without significantly affecting the rate of retroperitoneal teratoma (21% v 22%, respectively; P = .89) or pathologic stage I disease (56% v 67%, respectively; P = .06). For patients who did not receive adjuvant chemotherapy, the 4-year progression-free probability improved significantly from 83% before 1999 (95% CI, 79% to 88%) to 96% after 1999 (95% CI, 91% to 100%; P = .005). Elevated postorchiectomy STM (P < .0001), clinical stage (P = .0002), and pre-1999 RPLND (P = .05) were independent pretreatment predictors of progression. Excluding patients with CS IIB disease or elevated postorchiectomy STM from primary RPLND has had a favorable impact on the extent of retroperitoneal disease and has significantly reduced the risk of relapse after RPLND. For patients with normal STM and CS I to IIA disease, the low rate of systemic progression and 22% incidence of retroperitoneal teratoma supports RPLND as the preferred primary intervention.

Primary retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ-cell tumor (NSGCT): Impact of trends in patient selection on retroperitoneal pathology and outcome

4523 Background: Elevated pre-RPLND serum tumor markers (STM) is prognostic for relapse for clinical stage (CS) IS and pathologic stage (PS) N1 patients, and for persistence of disease for PS N2–3 patients. Since 1999, we have recommended that patients with elevated STM and/or CS IIB receive induction chemotherapy. We examined the impact of these selection criteria on outcome after primary RPLND. Methods: Since 1989, 453 patients with NSGCT have undergone primary RPLND (345 pre-1999, 108 post-1999). Data was obtained from a prospective database. A level of AFP or BhCG that was elevated and not declining according to half-life pre-RPLND was considered elevated. The median follow-up was 68 and 25 months for patients treated pre- and post-1999, respectively. Results: Pre-1999, 28 (8%) patients had elevated STM and 23 (7%) had CS IIB. Post-1999, all patients had normal STM and 1 (1%) had CS IIB. Patients treated since 1999 trended toward a lower rate of PS II (44% pre- vs. 33% post-1999, P=0.06). Among patients with PS II, those treated since 1999 were more likely to have low-volume (PN1) retroperitoneal disease at RPLND (64% vs. 40%, P=0.01), even when excluding patients with elevated STM and CS IIB (63% vs. 52%, P=0.02). Patients treated since 1999 have had lower rates of relapse after RPLND (4-year relapse-free survival 97% vs. 90%, P=0.04), even when excluding those receiving adjuvant chemotherapy (96% vs. 88%, P=0.049). In multivariate analysis, elevated STM (P=0.001) was the only significant pre-RPLND predictor of relapse when accounting for the use of adjuvant chemotherapy. Although not statistically significant, embryonal carcinoma predominance (P=0.06), treatment year (P=0.07) and clinical stage (P=0.09) may also be important predictors of relapse. Conclusions: As a result of excluding patients with elevated STM and/or CS IIB, proportionately more PS II patients have low-volume retroperitoneal disease and are likely to be cured by RPLND alone. Patients treated since 1999 may have a favorable prognosis independent of STM status and clinical stage. No significant financial relationships to disclose.

Primary retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ-cell tumor (NSGCT): Impact of trends in patient selection on retroperitoneal pathology and outcome

4523 Background: Elevated pre-RPLND serum tumor markers (STM) is prognostic for relapse for clinical stage (CS) IS and pathologic stage (PS) N1 patients, and for persistence of disease for PS N2–3 patients. Since 1999, we have recommended that patients with elevated STM and/or CS IIB receive induction chemotherapy. We examined the impact of these selection criteria on outcome after primary RPLND. Methods: Since 1989, 453 patients with NSGCT have undergone primary RPLND (345 pre-1999, 108 post-1999). Data was obtained from a prospective database. A level of AFP or BhCG that was elevated and not declining according to half-life pre-RPLND was considered elevated. The median follow-up was 68 and 25 months for patients treated pre- and post-1999, respectively. Results: Pre-1999, 28 (8%) patients had elevated STM and 23 (7%) had CS IIB. Post-1999, all patients had normal STM and 1 (1%) had CS IIB. Patients treated since 1999 trended toward a lower rate of PS II (44% pre- vs. 33% post-1999, P=0.06). Among patients with PS II, those treated since 1999 were more likely to have low-volume (PN1) retroperitoneal disease at RPLND (64% vs. 40%, P=0.01), even when excluding patients with elevated STM and CS IIB (63% vs. 52%, P=0.02). Patients treated since 1999 have had lower rates of relapse after RPLND (4-year relapse-free survival 97% vs. 90%, P=0.04), even when excluding those receiving adjuvant chemotherapy (96% vs. 88%, P=0.049). In multivariate analysis, elevated STM (P=0.001) was the only significant pre-RPLND predictor of relapse when accounting for the use of adjuvant chemotherapy. Although not statistically significant, embryonal carcinoma predominance (P=0.06), treatment year (P=0.07) and clinical stage (P=0.09) may also be important predictors of relapse. Conclusions: As a result of excluding patients with elevated STM and/or CS IIB, proportionately more PS II patients have low-volume retroperitoneal disease and are likely to be cured by RPLND alone. Patients treated since 1999 may have a favorable prognosis independent of STM status and clinical stage. No significant financial relationships to disclose.

Surgical “salvage” therapy for intrathoracic chemorefractory metastases from non-seminomatous germ cell cancer of testicular origin: An institutional retrospective review

4528 Background: Cisplatin-based chemotherapy (CTx) followed by surgical extirpation of residual disease represents the usual sequence of curative therapy for metastatic non-seminomatous germ cell cancer of testicular origin (NSGCT). Occasionally residual disease is chemorefractory in the form of either persistent NSGCT or degeneration into non-germ cell cancer (NGCC). This retrospective review evaluated patients (pts) undergoing “salvage” surgery to remove chemorefractory cancer metastatic to the thorax. Methods: From 1981–2001, 438 pts with NSGCT had surgery to remove residual intrathoracic disease after CTx at Indiana University Hospital. A subset of 134 pts who underwent 186 thoracic surgical procedures to remove chemorefractory cancer is the basis of this review. Eighty-one (60.4%) pts underwent second line CTx prior to surgery and 72 (53.7%) had elevated serum tumor markers at the time of surgery. The mean age was 27 yrs. Eighty-four pts had removal of pulmonary metastases, 74 mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 pts with persistent NSGCT, 38 with NGCC, and 12 had both malignant pathologic categories. Sixty-eight pts with persistent NSGCT received CTx after surgery. Results: There were 4 (2.1%) operative deaths. The median survival was 67 months in operative survivors with 55 (41%) pts alive and well after a mean follow-up of 49 months. Twenty-seven variables were analyzed using Cox regression. Of these, older age (p<0.01) and pulmonary (vs. mediastinal) metastases (p=0.01) were significantly predictive of poorer long-term survival. Log rank analysis additionally identified preoperative BHCG≥1,000ng/ml (p<0.04) and ≥ 4 metastases (p<0.01) as negative predictors for survival. Conclusions: Aggressive “salvage” surgical therapy to remove chemorefractory cancer metastatic to the thorax can result in long-term survival. We have identified variables which appear to influence survival for this subset of NSGCT pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline

Surgical “salvage” therapy for intrathoracic chemorefractory metastases from non-seminomatous germ cell cancer of testicular origin: An institutional retrospective review

4528 Background: Cisplatin-based chemotherapy (CTx) followed by surgical extirpation of residual disease represents the usual sequence of curative therapy for metastatic non-seminomatous germ cell cancer of testicular origin (NSGCT). Occasionally residual disease is chemorefractory in the form of either persistent NSGCT or degeneration into non-germ cell cancer (NGCC). This retrospective review evaluated patients (pts) undergoing “salvage” surgery to remove chemorefractory cancer metastatic to the thorax. Methods: From 1981–2001, 438 pts with NSGCT had surgery to remove residual intrathoracic disease after CTx at Indiana University Hospital. A subset of 134 pts who underwent 186 thoracic surgical procedures to remove chemorefractory cancer is the basis of this review. Eighty-one (60.4%) pts underwent second line CTx prior to surgery and 72 (53.7%) had elevated serum tumor markers at the time of surgery. The mean age was 27 yrs. Eighty-four pts had removal of pulmonary metastases, 74 mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 pts with persistent NSGCT, 38 with NGCC, and 12 had both malignant pathologic categories. Sixty-eight pts with persistent NSGCT received CTx after surgery. Results: There were 4 (2.1%) operative deaths. The median survival was 67 months in operative survivors with 55 (41%) pts alive and well after a mean follow-up of 49 months. Twenty-seven variables were analyzed using Cox regression. Of these, older age (p<0.01) and pulmonary (vs. mediastinal) metastases (p=0.01) were significantly predictive of poorer long-term survival. Log rank analysis additionally identified preoperative BHCG≥1,000ng/ml (p<0.04) and ≥ 4 metastases (p<0.01) as negative predictors for survival. Conclusions: Aggressive “salvage” surgical therapy to remove chemorefractory cancer metastatic to the thorax can result in long-term survival. We have identified variables which appear to influence survival for this subset of NSGCT pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline

Management of primary malignant germ cell tumor of the mediastinum.

Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear. Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile. Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had non-seminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%. Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine the indications for further chemotherapy.

Outcome of patients with residual germ cell or non-germ cell malignancy after resection of primary mediastinal nonseminomatous germ cell cancer.

To identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer. Forty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed. At diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively. The presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.

Mucinous cystadenoma of the pancreas 17 years after excision of gallbladder because of a choledochal cyst

A 56-year-old woman who had undergone excision of the gallbladder because of a choledochal cyst had a tumorous lesion of the pancreas identified by upper abdominal ultrasonography, but an operation was not carried out, because there was no apparent increase in the cystic mass and no elevation of serum tumor markers. In October 2001, she was admitted to our hospital to check for malignancy because of elevated levels of the tumor marker Dupan-2. Abdominal enhanced computed tomography and upper abdominal ultrasonography revealed a large multilocular cystic mass in the body to tail of the pancreas. Endoscopic retrograde cholangiopancreatography showed elongation of the common duct that communicates with the common bile duct and the main pancreatic duct, indicating an anomalous arrangement of the biliary and pancreatic duct system. No apparent communications between the cystic mass and the main pancreatic duct were observed. In January 2002, the patient underwent a spleen-preserving distal pancreatectomy, and histopathological and immunohistochemical examinations led to the diagnosis of pancreatic mucinous cystadenoma with ovarian-like stroma. The mucinous cystadenoma was detected 17 years after the operation for the choledochal cyst. To the best of our knowledge, no documented case reports of mucinous cystadenoma of the pancreas associated with a choledocal cyst have been reported to date. We present here the first case report of pancreatic mucinous cystadenoma occurring in the body to tail of the pancreas, associated with a choledocal cyst.

PET-CT in recurrent ovarian cancer: initial observations.

Noninvasive diagnosis of early recurrence of ovarian cancer is challenging due to the small size of peritoneal metastases. Small-volume disease may not be evident at anatomic imaging in patients with elevated serum tumor markers. Functional imaging in the form of positron emission tomography (PET) can help identify patients with recurrent tumor. However, lesion localization for possible surgical treatment is difficult with PET alone. Combined functional-anatomic imaging with fused PET and computed tomographic (CT) scans is feasible and may improve disease detection by increasing radiologic sensitivity and specificity. PET and PET-CT have a potential role in evaluating patients for recurrent ovarian cancer, particularly those with negative CT or magnetic resonance imaging findings and rising tumor marker levels. Fused PET-CT scans obtained with combined scanners can help localize pathologic activity and differentiate this activity from physiologic radiotracer uptake. Combined functional-anatomic imaging can also increase diagnostic confidence at CT. Further study is needed to determine the possible benefits of lesion conspicuity at PET and anatomic localization at CT on fused PET-CT scans.

Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma

Objectives Autoimmune pancreatitis (AIP) is a newly described entity with characteristic clinical, histologic, and morphologic changes, in which autoimmune mechanisms are involved in pathogenesis. However, difficulties can arise in the differentiation of AIP from pancreatic carcinoma. The aims of this study were to clarify clinical and radiologic features of AIP to elucidate areas of diagnostic confusion. Methods Clinical, serologic, and radiologic findings were evaluated in 17 patients with AIP . Results All 17 patients were initially suspected to have pancreatic carcinoma. The patients were predominantly elderly men who frequently presented with jaundice but without features of acute pancreatitis. Elevation of serum γ-globulin and IgG along with the presence of autoantibodies were usually evident, whereas serum tumor markers were elevated in 54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct were radiologically characteristic; however, segmental swelling and narrowing were detected in seven and two patients, respectively. In segmental cases, neither atrophy of the distal pancreas nor marked upstream dilation of the distal main pancreatic duct was observed. Angiographic abnormalities occurred in 54% of cases. Serologic and radiologic abnormalities showed considerable improvement with steroid therapy. Conclusions Frequent stenosis of the bile duct, elevation of serum tumor markers, segmental pancreatic enlargement or narrowing of the main pancreatic duct, and angiographic abnormalities can cause confusion in the differential diagnosis of AIP and pancreatic carcinoma.

Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma.

Autoimmune pancreatitis (AIP) is a newly described entity with characteristic clinical, histologic, and morphologic changes, in which autoimmune mechanisms are involved in pathogenesis. However, difficulties can arise in the differentiation of AIP from pancreatic carcinoma. The aims of this study were to clarify clinical and radiologic features of AIP to elucidate areas of diagnostic confusion. Clinical, serologic, and radiologic findings were evaluated in 17 patients with AIP. All 17 patients were initially suspected to have pancreatic carcinoma. The patients were predominantly elderly men who frequently presented with jaundice but without features of acute pancreatitis. Elevation of serum gamma-globulin and IgG along with the presence of autoantibodies were usually evident, whereas serum tumor markers were elevated in 54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct were radiologically characteristic; however, segmental swelling and narrowing were detected in seven and two patients, respectively. In segmental cases, neither atrophy of the distal pancreas nor marked upstream dilation of the distal main pancreatic duct was observed. Angiographic abnormalities occurred in 54% of cases. Serologic and radiologic abnormalities showed considerable improvement with steroid therapy. Frequent stenosis of the bile duct, elevation of serum tumor markers, segmental pancreatic enlargement or narrowing of the main pancreatic duct, and angiographic abnormalities can cause confusion in the differential diagnosis of AIP and pancreatic carcinoma.

The growing teratoma syndrome

Growing teratoma syndrome is defined as enlarging masses of mature teratoma following chemotherapy for malignant nonseminomatous germ-cell tumors. Typically, there is associated normalization of initially elevated serum tumor markers. We describe clinical and imaging findings in a case of growing teratoma syndrome originating from immature teratoma of the ovary in a 12-year-old girl. Familiarity with this unusual entity is important to avoid confusion with advancing malignancy.

Elevated serum tumor markers in niacin induced cholestatic jaundice

Niacin is a commonly used vitamin that can cause potentially serious liver abnormalities. We present the case of a 70 year-old man who had cholestatic jaundice secondary to Niacin, that was associated with raised levels of serum tumor markers CA 19–9, and CEA. Though there have been previous case reports of Niacin induced cholestatic jaundice, to our knowledge, this is the first case where elevated serum tumor marker levels were also found. This case also illustrates the importance of obtaining a detailed history, and interpreting diagnostic tests appropriately in patients with deranged liver function tests. A 70 year-old white man presented with significant weight loss, malaise, and fatigue for three months. A questionnaire filled by the patient listed aspirin and vitamins as his medications. Physical exam was unremarkable except for marked scleral icterus. Laboratory data showed Conjugated Hyperbilirubinemia. CA 19–9 was 241u/ml, and CEA was 22.8 ng/ml. A abdominal CT scan and ERCP were normal. On a subsequent office visit the patient was advised to bring all his medicines with him, and it was found that the patient was taking Niacin-2 grams per day in divided doses, which had been listed as vitamins. He was advised to stop the Niacin, and his liver function tests, and CA 19–9 and CEA levels returned to normal levels. Niacin, used to treat hypercholestrolemia, may cause a wide range of liver problems. These side effects are seen more often with the Sustained Release form rather than the Immediate Release form. Many patients report this as a vitamin, and if a more detailed history is not obtained this very important cause of liver abnormality may be missed. CA 19–9 and CEA are used as serum tumor markers especially for GI and Hepato-biliary malignancies. Levels are usually higher in malignancies compared to benign conditions, but because of the poor sensitivity and specificity, these markers are not recommended for screening for malignancies, and are usually used for confirming diagnoses and monitoring response to therapy. In patients with deranged liver function tests a detailed history should be obtained to exclude potentially hepatotoxic over-the-counter medications. Patients should be encouraged to bring their pill bottles to the office at the time of initial consultation. Serum tumor markers should be ordered selectively, and should be interpreted appropriately to avoid expensive, and potentially harmful invasive procedures.