Metastatic adeno or undifferentiated carcinoma from an unknown primary site--natural history and guidelines for identification of treatable subsets

Two hundred and eighty-six patients presenting with metastatic adenocarcinoma or undifferentiated carcinoma whose primary site was not identified by clinical history, physical examination and chest radiograph have been studied. Median survival from presentation was 22 weeks. Factors independently predicting improved survival were lymph node presentations, good performance status and body weight loss of less than 10 per cent. In 88 (31 per cent) patients the primary tumour site was subsequently identified, in 58 (20 per cent) during life. Lung cancer was the most frequently identified primary tumour, and in only 32 (11 per cent) of the patients was a 'treatable' primary tumour (i.e. germ cell, breast, ovarian, prostate, thyroid cancer or lymphoma) identified. Among the treatable primary tumours were those in eight out of 16 female patients presenting with axillary metastases who were subsequently shown to have primary breast cancer and four of 13 females presenting with ascites who were found to have primary ovarian cancer. Prostatic cancer was confirmed in five out of 13 men with raised serum acid phosphatase. Of 22 patients with elevated serum alphafoetoprotein (AFP) or beta-human chorionic gonadotrophin levels (beta HCG) 18 had some features of the 'atypical teratoma syndrome'. Of the total of 32 patients with treatable tumour types, 29 (90 per cent) were identified during life. Median survival for patients with treatable tumour types identified during life was 104 weeks, compared with 22 weeks for the group as a whole. Retrospective immunocytochemical staining of the original biopsy showed that prostatic specific antigen and antibodies to beta HCG and AFP were diagnostically useful, but a series of organ site non-specific markers of histogenesis or cellular differentiation (carcinoembryonic antigen, secretory component for IgA, peanut lectin binding, epithelial membrane antigen and keratin) showed no significant correlations with identified primary sites, responsiveness to empirical chemotherapy or survival. Metastatic undifferentiated carcinoma or adenocarcinoma from an unknown primary site represents 6.5 per cent of all referrals to the medical oncology unit, Royal Prince Alfred Hospital, Sydney. We offer guidelines for the rapid identification of the limited number of primary sites for which effective and specific forms of systemic treatment are available.     

Metastatic Adeno or Undifferentiated Carcinoma from an Unknown Primary Site Natural History and Guidelines for Identification of Treatable Subsets

Two hundred and eighty-six patients presenting with metastaticadenocarcinoma or undifferentiated carcinoma whose primary sitewas not identified by clinical history, physical examinationand chest radiograph have been studied. Median survival frompresentation was 22 weeks. Factors independently predictingimproved survival were lymph node presentations, good performancestatus and body weight loss of less than 10 per cent. In 88(31 per cent) patients the primary tumour site was subsequentlyidentified, in 58 (20 per cent) during life. Lung cancer wasthe most frequently identified primary tumour, and in only 32(11 per cent) of the patients was a ‘treatable’primary tumour (i.e. germ cell, breast, ovarian, prostate, thyroidcancer or lymphoma) identified. Among the treatable primarytumours were those in eight out of 16 female patients presentingwith axillary metastases who were subsequently shown to haveprimary breast cancer and four of 13 females presenting withascites who were found to have primary ovarian cancer. Prostaticcancer was confirmed in five out of 13 men with raised serumacid phosphatase.Of 22 patients with elevated serum alphafoetoprotein(AFP) or ß-human chorionic gonadotrophin levels (ßHCG)18 had some features of the ‘atypical teratoma syndrome’.Of the total of 32 patients with treatable tumour types, 29(90 per cent) were identified during life. Median survival forpatients with treatable tumour types identified during lifewas 104 weeks, compared with 22 weeks for the group as a whole. Retrospective immunocytochemical staining of the original biopsyshowed that prostatic specific antigen and antibodies to ßHCGand AFP were diagnostically useful, but a series of organ sitenon-specific markers of histogenesis or cellular differentiation(carcinoembryonic antigen, secretory component for IgA, peanutlectin binding, epithelial membrane antigen and keratin) showedno significant correlations with identified primary sites, responsivenessto empirical chemotherapy or survival. Metastatic undifferentiated carcinoma or adenocarcinoma froman unknown primary site represents 6.5 per cent of all referralsto the medical oncology unit, Royal Prince Alfred Hospital,Sydney. We offer guidelines for the rapid identification ofthe limited number of primary sites for which effective andspecific forms of systemic treatment are available. Present address: Catholic Medical College, St Pauls Hospital,Seoul, Korea.     

Recombinant interferon alpha-2A in the treatment of HIV-associated Kaposi sarcoma. Long-term results

47 HIV-positive male patients with cutaneous Kaposi's sarcoma (KS) were treated with recombinant interferon alpha-2A (IFN) in an open, prospective study. 45 patients received 18 million I.U. IFN s.c. daily for the first three months. From the fourth month, the patients received 18 million I.U. IFN s.c. three times weekly. Four of the 45 patients withdrew from therapy because of side effects during the first weeks (weeks 2 to 6) of treatment. The remaining 41 patients were treated for a minimum period of two years or until their death. Two further patients received 36 million I.U. IFN daily for three months. After three months of IFN therapy we observed complete remission (CR) in five of the 41 patients (12%), partial remission (PR) in seven patients (17%), stable disease in seven patients (17%) and progressive disease (PD) in 22 patients (54%). The mean survival time from the beginning of IFN therapy to date is 26 months for the 19 responders (patients with CR, PR or SD; six are still alive) and nine months for the 22 non-responders (patients with PD; all died). Recurrence of tumor progression occurred in 15 of the 19 responders after an average of ten months of continuous IFN therapy. The longest time of survival in this group is 54 months up to now. Of the four remaining patients, all in the CR group, two died after 24 and 26 months of IFN therapy, without any recurrence of KS growth (causes of death: Burkitt's lymphoma and unknown). The two other patients, both still alive, have not suffered any recurrence of tumor progression after 40 and 41 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone metastasis as the first manifestation of lung cancer

Bone metastasis usually occurs late in the course of the disease, but in some patients it is the first manifestation of lung cancer. To evaluate the characteristics of patients with bone metastasis as a first manifestation of lung cancer, the medical records of 1063 patients with lung cancer between 1976 and 2001 were reviewed retrospectively. Twenty-four (2.3%) lung cancer patients presented symptoms of bone metastasis as a first manifestation; 11 patients had bone metastasis as the only site of spread in lung cancer; 16 had adenocarcinoma; five had a primary lesion <30 mm, and nine had N0-1 disease. Patients with sole bone metastasis did not have a more favourable survival rate than patients with bone and other systemic metastases (p=0.2938). Whether metastasis is the first manifestation of lung cancer or not, the occurrence of bone metastasis generally means a poor prognosis.     

急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨

背景：急性肝衰竭行急诊肝移植患者围手术期治疗的病情复杂,风险大,并发症多,死亡率高,与普通肝脏移植有着明显不同。目的：总结急诊肝移植治疗急性肝功能衰竭的围手术期治疗经验,以提高急性肝功能衰竭的治疗成功率。方法：回顾性分析38例因急性肝功能衰竭行急诊肝移植患者的临床资料,男21例,女17例,年龄15-69岁。其中乙型肝炎病毒性肝炎23例（其中乙型合并丁型肝炎2例）,Wilsons病7例,3例为毒蕈中毒,2例不明原因药物肝脏损害,1例雷公藤多甙中毒,1例为外伤行肝脏部分切除后失代偿,1例尸体肝移植后患者。结果与结论：38例患者生存时间为13-1740d,中位生存时间为634d。患者的围手术期存活率为76%,1年存活率为63%,2年存活率为58%。9例围手术期死亡原因包括脑水肿及颅内高压、肾功能衰竭、严重肺部感染、多脏器功能衰竭、凝血功能障碍（颅内出血、上消化道出血等）、急性成人呼吸窘迫综合征、移植物原发性无功能。目前急诊肝移植仍是治疗急性肝功能衰竭最有效的方法,出血、感染、排异反应是死亡的主要原因,肝移植围手术期间每一环节的处理,对于肝移植的成功和患者长期存活具有重要意义。     

培美曲塞治疗老年肺腺癌临床观察

目的观察培美曲塞单药一线治疗老年肺腺癌的临床疗效和不良反应。方法给予17例老年腺癌患者培美曲塞二钠500 mg/m~2,第1天静脉滴注,每3周为1个周期,2个周期进行疗效评价。结果 17例患者完全缓解(CR)0例,部分缓解(PR)7例,稳定(SD)7例,进展(PD)3例,有效率为41.2%,中位疾病进展时间为4.4个月,中位总生存期为5.3个月。主要不良反应为骨髓抑制。结论培美曲塞治疗老年肺腺癌具有较好的疗效,且不良反应轻,患者耐受性好。     

The impact of bisphosphonate therapy on the survival time of patients undergoing radiotherapy for bone metastases

Background. Bisphosphonates are form of medical therapy for bone metastases. Morbidity from bone metastases including hypercalcemia episodes, pain, pathological fractures and appearance of new metastases in skeletal system is decreased by bisphosphonate therapy. The aim of this article is to determine the influence of bisphosphonate therapy on survival time of patients irradiated due to bone metastases.
Material and methods. 305 patients irradiated due to bone metastases were assessed in this retrospective study. 94 of them were additional treated by bisphosphonates. Median survival time counted from the end of radiotherapy to the death of patients was assessed. Using U Mann Whitney test the influence of bisphosphonates therapy on survival time was determined. The significance level of p = 0,05 was accepted.
Results. The median survival time of patients irradiated due to bone metastases and treated by bisphosphonates was 8,1 month and 5,24 month in the group treated only by radiotherapy. Median survival time of pts with breast cancer and with unknown primary site of cancer who were treated by radiotherapy and bisphosphonates was significantly longer (respectively p = 0,001 and p = 0,016) as compared with the group with irradiated bone metastases only.
Conclusions. 1. Bisphosphonates therapy improved the median survival time in the whole group of patients irradiated due to bone metastases. 2. Statisticaly significant prolonged survival time was observed in groups of patients with breast cancer and with unknown primary site of cancer. Median survival time was prolonged in these groups about 5 months and 3,5 months respectively.     

Breast cancer: metastatic patterns and their prognosis

From 1969 to 1977, metastatic disease developed in 145 of the 558 patients treated for breast cancer at the University of Maryland Medical System. The most common first site of distant spread was bone (51%), followed by lung (17%), brain (16%), and liver (6%). The remaining 10% of patients had multiple metastatic sites. Fewer than 10% of the entire group received adjuvant chemotherapy after primary treatment. When metastatic disease appeared, most patients had palliative systemic chemotherapy and/or irradiation. In general, patients with initially negative axillary nodes had a longer median time until relapse (development of metastatic disease) and a longer survival time after diagnosis of metastases than patients with initially positive nodes. Liver was the least common initial metastatic site; while liver metastasis was seen only in patients with positive axillary nodes, it carried the worst prognosis. The overall median survival time after metastasis was 12 months for bone and lung lesions, three months for brain lesions, and only one month for liver metastasis. The median survival of patients with multiple metastatic sites was 7.5 months. No correlation was found between time until relapse and survival after metastasis. Patients in whom distant metastases developed relatively soon after the initial diagnosis had the same postmetastatic prognosis as patients whose disease metastasized later. No correlation was found between age at initial diagnosis and metastasis-free interval or survival after metastasis.     

Renal cell carcinoma metastatic to the pancreas: clinical and radiological features

OBJECTIVE: To review the clinical features, computed tomographic (CT) appearance, and treatment outcomes in a case series of patients with renal cell carcinoma (RCC) metastatic to the pancreas. PATIENTS AND METHODS: We retrospectively reviewed the records of 23 patients (15 men and 8 women) with RCC metastatic to the pancreas, detected by CT examination between 1986 and 1996. All patients had undergone a previous nephrectomy for RCC. RESULTS: Isolated mild elevation in liver function test results (in 5 patients) or in serum amylase level (in 8 patients) was observed. New-onset diabetes was detected in 3 patients. The CT characteristics of the pancreatic metastases generally resembled those of primary RCC with well-defined margins and greater enhancement than normal pancreas with a central area of low attenuation. The mean interval between resection of the primary RCC and detection of the pancreatic metastases was 116 months (range, 1-295 months). In 18 patients (78%), the pancreatic metastases were diagnosed more than 5 years after nephrectomy. The pancreas was the initial metastatic site in 12 patients (52%). Survival was shortened with higher tumor grade (mean survival time of 41 months and 10 months in patients with grade 2 and 3, respectively). Surgical resection was carried out in 11 patients (7 distal and 3 total pancreatectomies and 1 distal pancreatectomy followed 4 years later by total pancreatectomy), with 8 patients alive at a mean follow-up of 4 years, 6 of whom remained free of recurrence. Overall, 12 patients (52%) were alive at a mean of 42 months after diagnosis of metastatic disease. CONCLUSIONS: The appearance of metastatic RCC lesions in the pancreas closely resembles the appearance of primary RCC on CT images. Pancreatic metastases from RCC are frequently detected many years after nephrectomy. Patient survival correlates with tumor grade. Histologic analysis of pancreatic masses in patients with a history of resected primary RCC is important since the prognosis for RCC metastatic to the pancreas is much better than that for primary pancreatic adenocarcinoma.     

Therapy of 'high risk' myelodysplastic syndromes with an association of low-dose Ara-C, retinoic acid and 1,25-dihydroxyvitamin D3.

Forty-four patients with high risk primary myelodysplastic syndromes and an excess of marrow blasts were treated with a combination of low-dose Ara-C, retinoic acid and vitamin D3. Morphological subtypes were refractory anemia with excess of blasts (RAEB) in 16, RAEB in transformation (RAEB-T) in 20 and chronic myelomonocytic leukemia (CMML) in eight patients. The therapy was continued in responders until relapse or death. The results were compared to those of a matched control of 44 patients given a supportive therapy only. In the treated group the overall response rate was 50% (75% in RAEB, 50% in RAEB-T and 0% in CMML) and the survival was significantly better than in the control group (P < 0.025). Comparing separately each FAB subgroup gave statistical evidence that the treatment prolonged the survival in the RAEB-T subgroup only (P < 0.002). The median duration of response was 15 months and the survival in responders was statistically better than in non-responders (P < 0.0001). Myelosuppression has been the most important side effect, however, no death related to the treatment was observed. Our study suggests that patients with RAEB-T, who are not suitable candidates for aggressive chemotherapy, could benefit from our treatment schedule. The long duration of therapy seems to be of value for patients achieving a response in order to prolong the survival. The toxicity is acceptable and the therapy can be given on an outpatient basis.     

Systemic chemotherapy with epirubicin for treatment of advanced or multifocal hepatocellular carcinoma

BACKGROUND: The purpose of this retrospective study was to determine the response rate and effect on survival of chemotherapy with epirubicin in non-resectable advanced hepatocellular carcinoma (HCC). METHODS: Fifty-two patients with non-resectable disease were treated with epirubicin. A treatment cycle consisted of 20 mg/m(2) i.v. on days 1, 8 and 15 and was repeated every 4 weeks to a maximum dose of 1,000 mg/m(2). Forty-four patients were eligible for analysis. RESULTS: Out of 44 patients, 1 (2.3%) achieved a complete response, 3 (6.8%) had partial responses and 16 (36%) had stable disease (SD). For patients with successful disease control (complete and partial responders and patients with SD), the median survival was 16.2 months; for non-responders, it was 6.1 months (p < 0.003). Eight (88.9%) of 9 patients with alpha-fetoprotein (AFP) levels <50 microg/l achieved successful disease control compared to 12 (34.9%) out of 35 patients with initially elevated AFP (p < 0.0001). CONCLUSION: Epirubicin appears to be an active therapeutic option for patients with non-resectable HCC. Especially the subgroup of patients with low levels of AFP may benefit from this treatment.     

Total body irradiation as an alternative to systemic chemotherapy in small-cell anaplastic lung cancer

The effectiveness of total body irradiation (TBI) plus local radiotherapy in the treatment of small-cell lung cancer was studied in 13 patients, using 4,000 cGy in 15 fractions over three weeks to the local site and 150 cGy in ten fractions over two weeks to the whole body. The mean survival for 12 patients was 31 weeks, with a median survival of 32 weeks. One patient received six courses of combination chemotherapy for recurrent disease four months after TBI without marrow depression and survived 72 weeks, the longest survivor in this series. Brain metastases occurred in only one patient, the most common site of metastases being the liver. All patients tolerated TBI well without nausea, vomiting or hair loss. When bone marrow suppression occurred it was asymptomatic, requiring no treatment and resolving within eight weeks.     

Morphine responsiveness,efficacy and tolerability in patients with chronic non-tumor associated pain - results of a double-blind placebo-controlled trial (MONTAS)

Efficacy, long-term effectiveness and safety of opioids in chronic non-tumor associated pain syndromes (NTAS) are still under debate. The study (MONTAS) was performed by physicians and psychologists as a multicenter prospective, randomized, double-blind placebo-controlled crossover trial, followed by an open long-term study. Patients were enrolled only when pain relief from specific defined pretreatment was insufficient. Patients were randomly assigned to group I receiving sustained-release morphine (doses: 20mg/d titrated appropriately to a maximum of 180mg/d) in the first week, placebo in the second week or group II receiving study medication in reverse order. The primary endpoint was defined as: (i) adequate pain relief (pain intensity of less than 50% of pretreatment intensity or less than 5 on a 11 point Numerical Rating Scale) and (ii) pain rated as tolerable and (iii) adverse effects rated as tolerable. Full responders (all criteria fulfilled under morphine) and partial responders (less pain relief, but tolerable side effects) were offered continuation of treatment with oral morphine in an open long-term study (LAMONTAS), to be published later. Forty-nine patients of 997 patients screened fulfilled the inclusion criteria for MONTAS and were enrolled. Mean pain intensity in all patients was reduced by morphine from 7.8 to 5.2 (NNT: 2.2); in 17 (35.4%) responders from 7.4 to 2.9, in 17 (35.4%) partial responders from 7.8 to 5.6 and in 14 (29.2%) non-responders from 8.2 to 7.7. Pain reduction correlated with improvement of physical function. Pain disability, depression score, mood and exercise endurance improved, particularly in responders. Gastrointestinal complaints increased, central nervous system-related complaints were reduced. Efficacy and safety of morphine in NTAS were demonstrated in this randomized-controlled trial. Pretreatment failure was the indication for trying morphine treatment; predictive factors for responsiveness could not be identified.     

Electron microscopy in determining origin of metastatic adenocarcinomas

Light microscopy has limited value in predicting where the primary site of a metastatic adenocarcinoma might be located. In our series, electron microscopy was useful in determining the primary site in approximately 85% of patients with a metastatic adenocarcinoma of unknown origin. This study is based on the ultrastructural examination of more than 100 such cases. In the remaining 15% of the cases, electron microscopy usually provided assistance in reducing the differential diagnosis to a minimum, usually to two possible primary sites. The majority of the metastatic adenocarcinomas showed rather specific ultrastructural features to suggest the site of origin. This application of electron microscopy has never been fully explored and has considerable clinical importance and economic impact in health care systems. An extensive work-up to determine the primary site, with its inconvenience to patient and family, as well as delay in adequate treatment, can be avoided with early diagnosis of the primary site.     

紫杉醇、顺铂、卡培他滨联合治疗晚期胃腺癌的疗效分析

目的：评价紫杉醇、顺铂、卡培他滨三药联合一线治疗晚期胃腺癌的疗效和安全性。方法：回顾分析46例经病理学确诊并经影像学和（或）手术明确分期的、未经化疗的晚期胃腺癌患者经紫杉醇、顺铂、卡培他滨三药联合一线化疗的临床资料。结果：46例患者中42例可评价疗效,所有患者可评价不良反应。完全缓解率为2.4%（2/42）,部分缓解率为42.9%（18/42）,中位治疗至进展时间为6.2个月,中位生存时间为11.1个月,1年生存率为40.5%（17/42）,生活质量的改善率为38.1%（16/42）。主要不良反应Ⅲ~Ⅳ度中性粒细胞减少发生率为26.1%（12/46）。结论：紫杉醇、顺铂、卡培他滨三药联合一线治疗晚期胃腺癌的疗效和安全性均好。     

膀胱腺癌的诊治:附12例报告

目的:探讨膀胱腺癌的诊治方法。方法:回顾性分析1996—2005年诊治12例膀胱腺癌患者的临床资料。结果:12例患者中男性7例,女性5例;年龄38～78岁;11例因血尿、尿频等尿路症状就诊,1例因其他疾病就诊时发现。B超检查均提示膀胱内占位;膀胱镜检发现肿瘤直径1.0～8.5 cm。5例首次就诊即行根治性全膀胱切除术;5例行膀胱部分切除术,4例术后复发,其中2例行根治性全膀胱切除术,2例再次行扩大膀胱部份切除术;2例患者行经尿道膀胱肿瘤电切术,其中1例术后1个月原位复发,行CT检查证实为脐尿管癌,行扩大膀胱部份切除,脐尿管切除术;1例首次术后病理提示膀胱移行细胞癌,术后3次复发,第3次手术后病理提示膀胱印戒细胞癌。10例患者获得随访,随访2～8年。2年生存率60%(6/10),5年生存率33%(2/6)。首次行全膀胱切除患者2年生存率75%(3/4),5年生存率67%(2/3);首次行膀胱部份切除患者2年生存率50%(2/4),5年生存率33%(1/3);首次行经尿道膀胱肿瘤电切术患者2例,其中脐尿管癌1例术后随访4年存活,未复发;移行细胞癌多次复发转变为印戒细胞癌1例术后随访2年存活。结论:膀胱腺癌是一种高度恶性肿瘤,预后差,早期积极的综合治疗对延长患者生存时间有重要意义。     

Surgery for non-colorectal and non-neuroendocrine liver metastases

INTRODUCTION: Hepatic resection has been shown to prolong survival in selected patients with colorectal liver metastases. Due to slow tumor growth patients with neuroendocrine liver metastases tend to have a good prognosis and benefit from chemo-embolisation and symptomatic treatment. The role of surgery in treating non-neuroendocrine and non-colorectal liver metastases is discussed controversially, due to the limited knowledge on this subject. The aim of our study was, therefore, to evaluate our own experiences with hepatic surgery for non-neuroendocrine, non-colorectal liver metastases. METHODS: A retrospective review of 72 patients (median age 60.9 years) who underwent 73 hepatic resections for non-neuroendocrine, non-colorectal liver metastases between 1980 and 2000 at a single tertial referral center was carried out. RESULTS: Hepatic resection was combined with surgery for the primary tumor in 30 cases (41.1%). Hospital mortality was 4.2%. 35 patients (47.9%) developed complications. The mean hospital stay was 17.5 days. In 64.4% of the cases a potentially curative resection was reached. Overall actuarial survival was 52.1% at 1 year, 25.3% at 3 years and 9.9% at 5 years. The respective median overall survival times were 7.1 months (gastric cancer metastases; n = 15), 4.9 months (cholangiocellular cancer metastases; n = 9), 5.6 months (gall bladder, bile duct cancer metastases; n = 8), 35.4 months (kidney cancer metastases; n = 8), 14.4 months (breast cancer metastases; n = 4), 15.3 months (pancreas and other adenocarcinoma metastases; n = 11), 49.9 months (sarcoma metastases; n = 10) and 32.9 months (other metastases; n = 7). CONCLUSIONS: In isolated hepatic metastases originating from sarcoma and hypernephroma radical resection can prolong survival. However, surgery cannot improve the prognosis in patients with liver metastases originating from the pancreas, gallbladder and the biliary tract. In selected patients with liver metastases from gastric and breast cancer long term survival seems possible after resection.     

Treatment of advanced ovarian cancer as an interdisciplinary task: surgery, histopathology, radiotherapy, and chemotherapy

From February 1977 to February 1981 we treated 55 patients with ovarian cancer (45 stage III and 10 stage IV) with simultaneous radio-chemotherapy; 34 of these patients underwent a therapeutic second-look operation. The overall response rate was 94%, comprising 63% complete and 31% partial remissions. In the group with residual tumours exceeding 2 cm in diameter after primary operation 52% complete remissions were observed. In the stage III group there were 74% complete and 26% partial remissions. Cytoreductive surgery to less than 2 cm was achieved by means of an early second-look operation in 74% of these cases. These patients have as good a prognosis as those with an equivalent residual tumour after primary resection. Unlike the cases with tumour spread to the retroperitoneal area, macroscopic tumour spread to the surface of the liver or diaphragm indicated a worse prognosis. The survival time of patients who prove to be tumour-free at the time of the diagnostic operation is significantly longer than of those with residual tumours. Neither the age of the patients nor the histological findings after primary operation have any significant influence on survival time. Late intestinal complications made us change the therapeutic strategy employed since March 1981 to sequential radio-chemotherapy. Possible cure for stage III patients can be achieved only by way of interdisciplinary cooperation. In stage IV patients the prognosis is so bad that local therapy is possible only in selected cases.     

Monoethylglycinexylide kinetics and galactose elimination capacity during treatment with interferon-alfa for hepatitis C virus infection: Possible predictors of response?

Background: Evidence shows that interferon (IFN) depresses the hepatic drug metabolizing activity (DMA) in the liver.Objectives: We studied the influence of long-term IFN treatment on liver function as assessed by monoethylglycinexylide (MEGX) kinetics as an index of DMA and galactose elimination capacity (GEC), which quantifies the functioning liver mass. We also investigated whether the monitoring of such tests during IFN therapy might predict treatment outcome.Methods: Outpatients with biopsy-proven chronic hepatitis and/or cirrhosis received IFN-alfa-2b for 1 year. MEGX kinetics, including the 45-minute sample and the area under the curve (AUC), and GEC were measured before, during, and 6 to 12 months after treatment in primary responders (those with normalization of alanine aminotransferase [ALT] levels with or without disappearance of hepatitis C virus RNA) and nonresponders (those without normalization of ALT levels). Another liver biopsy was performed 1 year after IFN withdrawal in sustained responders.Results: Of the 25 outpatients included in the study, 16 (64%) had biopsy-proven chronic hepatitis and 9 (36%) had cirrhosis. Eleven of 25 (44%) patients were considered primary responders; 4 (36.4%) of these patients were sustained responders. Baseline 45-minute MEGX levels (mean [SEM]) were significantly higher in patients with chronic hepatitis (68.5 [5.3] ng/mL) than in patients with cirrhosis (46.8 [10.1] ng/mL; P < 0.01). Pretreatment 45-minute MEGX levels were 54.1 (4.6) ng/mL in nonresponders and 66.9 (6.8) ng/mL in primary responders. During treatment, these levels were 63.3 (6.8) ng/mL in nonresponders and 72.7 (8.6) ng/mL in primary responders at month 4 and 76.7 (5.6) ng/mL in primary responders at month 12. In sustained responders, these levels were 71.5 (13.2) at entry, 80.1 (12.2) and 87.6 (6.9) after 4 and 12 months of IFN therapy, respectively, and these patients also showed a significant decrease of hepatic inflammation (P < 0.05). MEGX further increased in sustained responders and relapsers after IFN withdrawal, although not significantly so. The changes of MEGX AUCs paralleled those of the 45-minute concentrations. Baseline GEC was similar in primary responders and nonresponders and changed little during and after therapy.Conclusions: Based on the present study, DMA is not depressed during long-term IFN therapy, and pretreatment MEGX assessment does not help identify patients likely to respond to treatment. GEC has no value in predicting treatment outcome.     

Treatment of unresectable pancreatic carcinoma by intraluminal brachytherapy in the duct of Wirsung

BACKGROUND AND STUDY AIMS: Our aim was to evaluate the feasibility and clinical outcome of intraluminal brachytherapy (ILBT) in the duct of Wirsung in patients with unresectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Nine patients (eight men, one woman; mean age 72.4 +/- 9.1, range 52 - 80) with unresectable pancreatic adenocarcinoma of the head or body underwent ERCP for biliary and/or pancreatic stent placement and placement of a nasopancreatic drain with/without nasobiliary drain. The ILBT dose administered was 30 - 50 Gy calculated at 1 cm from the iridium-192 wire axis. Seven patients received ILBT from the duct of Wirsung whereas two patients received dual-duct ILBT (duct of Wirsung and the common bile duct). Three patients received combined-modality treatment (ILBT with external beam radiotherapy and 5-fluorouracil). The patients were prospectively followed up. RESULTS: No endoscopy-related complications occurred. No radiation-related toxicity occurred in patients treated with ILBT alone. One patient undergoing combined-modality treatment developed gastric bleeding. Intraluminal source dislodgement occurred in three patients. Obvious tumor mass reduction of greater than 50 % was seen in three patients at 8 weeks after brachytherapy. Median survival was 11 months (range 6 - 37 months) and the 1-year and 3-year actuarial survival rates were 44 % and 15 %, respectively. CONCLUSION: Intraluminal brachytherapy in the duct of Wirsung in patients with unresectable pancreatic carcinoma is safe and feasible. Further clinical trials are warranted.