Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy.

PURPOSE: Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. METHODS: Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. RESULTS: 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH. CONCLUSION: Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups.

PURPOSE: Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created. METHODS: Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS. RESULTS: 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]). CONCLUSION: DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival.

Treatment of Giant Fibroadenoma in Young Women: Results after Tumor Excision without Reconstructive Surgery.

Introduction: Giant fibroadenoma (GFA) of the breast is defined as fibroadenoma larger than 5 cm, usually presenting unilaterally and manifesting as breast asymmetry or deformity of the breast. Material and Methods: A retrospective database search was done of all patients with giant fibroadenoma who underwent surgery for GFA in the breast center of Hanover Medical School between 2007 and 2014; all patients with GFA were followed up. Data were analyzed with regard to tumor and patient characteristics and esthetic outcome. Results: A total of 13 patients with symptomatic GFA underwent surgery between 2007 and 2014. Mean patient age was 21.2 years (range 14-31 years). In 8 of 13 patients the tumor had resulted in breast deformity and/or breast asymmetry. Average size of the mass was 10.2 cm (range 8.5-12 cm) and average weight was 203.6 g (range 151.2-323.5 g). Initial clinical suspicion of GFA was confirmed by ultrasound examination. Preoperative core biopsy revealed fibroadenoma in 8/13 cases, cellular fibroepithelial lesions with a differential diagnosis of benign phyllodes tumor in 3 cases and unspecific histological findings in the remaining 2 cases. Conclusion: Excision was done using an inframammary or periareolar approach without reconstructive plasty. The cosmetic results were good, as were the outcomes on follow-up. We therefore favor this surgical technique to treat giant fibroadenoma of similar size to those described above.

SPECT/CT for SLN dissection in vulvar cancer: Improved SLN detection and dissection by preoperative three-dimensional anatomical localisation.

OBJECTIVE: In this study, we assessed the feasibility and clinical advantages of single photon emission computed tomography with CT (SPECT/CT) for sentinel lymph node (SLN) detection in vulvar cancer. METHODS: This is a unicentric prospective trial. Vulvar cancer patients underwent preoperative SLN marking (10MBq Technetium (TC)-99m-nanocolloid) and subsequent planar lymphoscintigraphy (LSG) and SPECT/CT for SLN visualization. Directly before surgery, a patent blue dye was injected. We assessed detection rates of SPECT/CT and those of planar LSG and intraoperative detection. We analyzed the sensitivity, negative predictive value and false negative rate. RESULTS: At Hannover Medical School, 40 vulvar cancer patients underwent SLN dissection after preoperative LSG and SPECT/CT. The mean diameter of all tumors in final histology was 2.23 (0.1-10.5) cm with a mean tissue infiltration of 3.93 (0.25-11) mm. In preoperative imaging, SPECT/CT identified significantly more SLNs (mean 8.7 (1-35) LNs per patient) compared to LSG (mean 5.9 (0-22) LNs, p<0.01). In addition, SPECT/CT led to a high spatial resolution and anatomical localization of SLNs. Thus, SPECT/CT identified aberrant lymphatic drainage in 7/40 (17.5%) patients. There were no significant differences, but significant correlation was found between SPECT/CT and intraoperative SLN identification. Regarding inguino-femoral LNs, for all patients who underwent complete groin dissection, sensitivity was 100%, NPV was 100% and false negative rate was 0%. CONCLUSION: SPECT/CT leads to higher SLN identification compared to LSG in vulvar cancer. Due to its higher spatial resolution and three-dimensional anatomical localisation of SLNs, SPECT/CT provides the surgeon with important additional information, facilitates intraoperative SLN detection and predicts aberrant lymphatic drainage.

Breast reconstruction and revision surgery for implant-associated breast deformities using porcine acellular dermal matrix: a multicenter study of 156 cases.

BACKGROUND: Acellular dermal matrix is increasingly used as caudolateral coverage for breast implants in immediate breast reconstruction after skin-sparing mastectomy or in the correction of implant-associated breast deformities. Matrices of human, bovine, and porcine origin are available. The purpose of this retrospective multicenter study was to report experiences with porcine acellular dermal matrices, as only limited data can be found in the literature. METHODS: In the hospital databases of five institutions, 127 patients were identified who underwent breast reconstructions in 156 breasts using an acellular porcine dermal matrix. Medical records were reviewed. Patients were divided into three groups: immediate expander-implant or direct to implant reconstructions (n = 98), delayed expander-implant reconstructions (n = 14), and revision surgery for implant-associated breast deformities (n = 44). RESULTS: With a mean follow-up of 19.6 months, total major complication rate was 7.1 %: implant loss (3.2 %), skin flap necrosis (2.6 %), delayed skin healing (2.6 %), hematoma (1.9 %), seroma (1.3 %), infection (0.6 %), and capsular contracture (0.6 %). Total minor complication rate was 22.9 %, with seroma being the most frequent complication (19.2 %). In the group of immediate breast reconstructions, 20.4 % of the breasts had received radiotherapy in the past. These patients exhibited a significantly higher rate of seroma than patients without prior radiotherapy (35.0 vs. 14.9 %, p = 0.031). CONCLUSIONS: Complication rates using porcine acellular dermal matrix in breast reconstruction are comparable to complication rates reported in studies using human acellular dermal matrices. Thus, porcine acellular dermal matrices can safely be applied in breast reconstructive surgery.

Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.

OBJECTIVE: We evaluated the clinical feasibility of a new injection technique for sentinel detection in endometrial carcinoma (EC), transcervical subepithelial injection into the isthmocervical region of the myometrium. We compared detection of sentinel lymph nodes (SLN) by single photon emission computed tomography with CT (SPECT/CT) with planar lymphoscintigraphy. METHODS: This is a unicentric prospective study. In all patients, transcervical injection of 10 MBq Technetium-99m-nanocolloid was performed into the isthmocervical myometrium without anaesthesia. After 40 (30-60) min, lymphoscintigraphy and SPECT/CT were performed. Patent blue was administered before surgery. The number and localisation of SLN detected in SPECT/CT and lymphoscintigraphy were recorded and compared to the SLN and non-SLN dissected intra-operatively. RESULTS: Between August 2008 and March 2012, 31 patients with EC were enrolled. The new transcervical injection of labelling substances led to high intra-operative (90.3%) detection rates, pelvic bilateral (57%), para-aortic (25%). SPECT/CT significantly identified more SLN than lymphoscintigraphy (mean 2.2 (1-8) to 1.3 (1-7)) in more patients (29/31 (93.5%) to 21/31 (68%), p<0.01). If SLN were identified in one hemi-pelvis, the histological evaluation of the SLN correctly predicted lymph node (LN) metastases for this basin which led to sensitivity 100%, negative predictive value (NPV) 100%, and false negative results 0%. CONCLUSION: Transcervical SLN marking in combination with SPECT/CT is easily applicable and leads to high physiologic detection rates in pelvic and para-aortic lymphatic drainage areas. Non-affected SLN truly predicted a non-affected LN basin. Combining both methods SLN dissection may be a safe and feasible staging technique for clinical routine in EC.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

Vitamin D status and per-oral vitamin D supplementation in patients suffering from chronic pancreatitis and pancreatic cancer disease.

UNLABELLED: Exocrine pancreatic insufficiency due to chronic pancreatitis may result--depending on the degree of insufficiency--, in a decrease in serum 25-hydroxyvitamin D (25(OH)D) level. However, the data in the literature concerning the rate and extent of vitamin D deficiency in pancreatic cancer with or without previous pancreas resection, are very rare, in particular regarding the question how to supplement these patients with vitamin D. In recent years, vitamin D is increasingly being discussed as one factor involved not only in musculo-skeletal diseases but also in cardiovascular and autoimmune diseases, cancer development, diabetes mellitus and overall mortality. PATIENTS AND METHODS: In all, 248 ambulatory patients (n=140 patients suffering from exocrine pancreatic insufficiency due to chronic pancreatitis, pancreatic cancer with/without previous resections of the pancreas n=108 patients without pancreatic disease), we measured the serum 25(OH)D concentrations by the chemoluminescence method. In addition, in 91 of these patients (n=65 pancreatic patients, n=26 controls), we started supplementation with oral vitamin D in combination with dietary advice and adequate substitution with pancreatic enzyme preparations, followed by subsequent serum 25(OH)D determinations. The oral vitamin D doses varied from 1000 IU per day over 1× 20,000 IU per week, or 2-3 times 20,000 IU per week up to 20,000 IU per day in single patients, depending on the underlying disease and the estimated degree of maldigestion/malassimilation. In addition, in a pilot trial vitamins A and E were measured in the serum from 121 and 105 of these patients respectively (resp.) (HPLC method). RESULTS: Serum 25(OH)D concentrations were <30 ng/ml in 93% of the patients with pancreatic diseases,<20 ng/ml in 77.9%, <10 ng/ml in 32.1% and <4 ng/ml in 9.3%. The results were comparable to those in patients suffering from chronic pancreatitis and those with pancreatic tumor disease, with or without a previous tumor resection (n=51 Whipple procedure, n=11 left resection, n=9 total duodeno-pancreatectomy). Similar data were also found in the controls, only slightly higher. In contrast to the vitamin D data, however, determination of vitamins A and E in the serum resulted in values within the normal range for the majority of the patients of both groups, suggesting a diminished vitamin D uptake as being at least one reason to explain the low serum vitamin D concentrations in the patients with pancreatic diseases. Individual supplementation with oral vitamin D in all patients studied (n=91) resulted in an increase of the serum 25(OH)D concentrations into the normal range (14.2±5.8 up to 42.3±12 in controls, 11.9±7.4 up to 46.6±15.7 in patients with pancreatic diseases). The data of a subgroup of patients with continuous long-term supplementation, however, suggest that some patients with pancreatic diseases may need a significantly higher vitamin D supplementation, up to 20000 IU per day in single patients, compared to the controls. CONCLUSION: The results demonstrate that vitamin D deficiency is a common problem in patients suffering from exocrine pancreatic insufficiency from various reasons as well as in our controls. Apart from insufficient sun exposure, exocrine pancreatic insufficiency, as well as a too low vitamin D uptake with food seem to represent the main causes of low serum 25(OH)D. In nearly all patients, the serum 25(OH)D concentrations could be normalized by oral supplementation of vitamin D in the case of individual therapy based on routine serum controls.

Combination therapy with gemcitabine (GEM) and erlotinib (E) in exocrine pancreatic cancer under special reference to RASH and the tumour marker CA19-9.

We report on the results of a prospective treatment of 30 proven metastatic pancreatic cancer patients with the recently described combination of gemcitabine and erlotinib (GEM+E) (24× 1st line therapy, 8× 2nd line therapy). Eight of these patients received GEM+E for treatment of metastastic tumour recurrence after previous resective surgery, followed by adjuvant chemotherapy with gemcitabine. In 2 patients GEM+E was given as 1st line treatment and later, after complete response which was followed by a new recurrence, also as a second line therapy. The evaluation of RASH severity grades, the course of the serum tumour marker CA19-9 were determined every 14 days and the evaluation of the imaging methods CT or MRT, evaluated every 6-8 weeks, revealed the following results: there was a tendency for RASH grades to correlate with the tumour response, however, with observed exceptions. The decision for interruption or maintenance of GEM+E, therefore, should not be based on the RASH phenomenon, but on a detailed follow-up with imaging methods and the relevant tumour markers as in the follow-up before erlotinib introduction into pancreatic cancer therapy. As known from previous studies tumour markers represent more sensitive parameters compared to the imaging methods. GEM+E was active in the whole group of patients, mainly given as 1st line therapy (34% PD, 29% SD, 47% MR, PR, CR), but also in the 2 subgroups: in the patients with GEM+E as 2nd line therapy, as well as in patients after previous adjuvant gemcitabine therapy after tumour resection. In the 2 patients with transient-CR after 1st line therapy with GEM+E the 2nd line therapy also resulted in a CR with long lasting remission. These data should motivate clinicians to focus their interest not only to 1st line therapy regimens with erlotinib, but also to 2nd and 3rd line strategies within the previously published concept of an efficacy-orientated sequential polychemotherapy or multimodal-therapy for pancreatic cancer.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

CA19-9 serum concentrations--analysis of the serum kinetics during first-line therapy of pancreatic cancer in relation to overall survival.

In order to investigate the use of CA19-9 serum concentration kinetics during first-line chemotherapy of pancreatic cancer as a potential predictive prognostic factor for overall survival, we retrospectively analysed the data of 47 patients suffering from proven exocrine pancreatic cancer. The patients were treated following our concept of efficacy-orientated sequential palliative chemotherapy (EOSPC), on the basis of a short-term follow-up including CA19-9 determinations at least monthly and imaging methods CT and/or MR every 2 months. The results are in agreement with our previous reports suggesting an increase of survival of pancreatic cancer patients in relation to the number of effective treatment regimens applied. However, apart from a weak correlation between the lowest CA19-9 levels induced by the first-line therapy (as a % of the initial pretherapeutical CA19-9 levels) and progression-free survival there was no correlation between the various parameters of serum kinetics of CA19-9 in the course of the first-line therapy and overall survival of the patients. A potential correlation as reported by others seems to be confirmed in our patient group by the potential antitumoral and life-prolonging effects of the second- and third-line therapies.

Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

Reflections on treatment strategies for palliative chemotherapy of pancreatic cancer.

Following our concept of efficacy-orientated sequential polychemotherapy, we report on the results of palliative chemotherapy in 69 patients suffering from exocrine pancreatic cancer, admitted to our unit in 2004. Evaluation of tumor response was mainly based on the serum courses of the tumor markers CA 19-9 and CEA; in addition, the modern imaging methods CT or MRT, including MRCP and MR-angiography, were performed bi-monthly. The median survival of the 69 patients (65% metastasized stages) was 16 months. The median survival increased with the number of effective treatment sequences, for the whole group from 5 to 10 and 23 months in relation to 0, 1 and > 1 effective sequences respectively. The results support our concept of EOSPC in pancreatic cancer patients, compared to clinical studies following protocols with only 1 treatment sequence and median survival rates of no more than 6-9 months. Compared to the efficacy-orientated sequential polychemotherapy (EOSPC) concept, which does not exclude but also allows the inclusion of clinical trials for further evaluation of new drugs or drug combinations, the common practice looking for survival in studies following protocols with only 1 treatment sequence might represent a negative predictive factor with respect to overall survival, as can be demonstrated by a comparison of our data with relevant recent literature. Our results further indicate that the interest of the clinicians and companies should not be focused only on first-line therapies, but also on 2nd- and 3rd-line strategies, as in our patients a second- and third-line therapy could be started in 73% and 68% of the patients respectively.

Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use.

The aim of this article is to present updated guidelines for the use of serum, tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of CRC. For patients with stage II or stage III CRC who may be candidates for either liver resection or systemic treatment should recurrence develop, CEA should be measured every 2-3 months for at least 3 years after diagnosis. Insufficient evidence exists to recommend routine use of tissue factors such as thymidylate synthase, microsatellite instability (MSI), p53, K-ras and deleted in colon cancer (DCC) for either determining prognosis or predicting response to therapy in patients with CRC. Microsatellite instability, however, may be used as a pre-screen for patients with suspected hereditary non-polyposis colorectal cancer. Faecal occult blood testing but not faecal DNA markers may be used to screen asymptomatic subjects 50 years or older for early CRC.

Further evidence for prolongation of survival of pancreatic cancer patients by efficacy orientated sequential polychemotherapy (EOSPC) based on serial tumor marker determinations (CA 19-9/CEA).

The results of palliative chemotherapy in 55 patients suffering from exocrine pancreatic cancer are reported, following our concept of efficacy orientated sequential polychemotherapy (EOSPC). Tumor answer/regression was mainly analyzed on the basis of the serum courses of the tumor markers CA 19-9 and CEA. Up to four different treatment trials were tried in the individual patients. The results confirm previously published data: a prolongation of survival in relation to the number of effective treatments (CR/PR/MR/SD vs. PD). The median survival of the whole group of patients (n=55, including n=39 patients with distant metastasis) was 12 months. The results support our concept of EOSPC in pancreatic cancer patients in order to improve survival. Furthermore, the data should stimulate attention not only on new and potentially more effective 1st- line regimens, but also to effective 2nd- and/or 3rd-line treatments. Moreover, the results should encourage clinicians to rediscuss the actual concepts of prospective therapeutical trails mainly based on analyzing the effects of single agents or drug combinations on survival. Furthermore, a comparison of 1st-line treatments with gemcitabine as monotherapy, and in combination with mitomycin-C, confirms that the combination of gemcitabine + mitomycin-C seems to be more active than gemcitabine monotherapy and that this combination might also be of value as 2nd-line therapy after gemcitabine monotherapy.

Sequential polychemotherapy in exocrine pancreatic cancer.

The results of palliative chemotherapy in 162 patients suffering from exocrine pancreatic cancer are presented. They are mainly discussed with respect to the possibility of improving survival of exocrine pancreatic cancer patients by an efficacy-orientated sequential polychemotherapy (EOSP). In about 40% of the patients treated between 1998 and 2001, sequential chemotherapy induced more than one effective treatment in the case that SD after a progressive prephase as well as MR, PR and CR are considered as antitumoral efficacy. Sequential polychemotherapy seems to be able to prolong the survival of these patients. The whole group of patients showed a 1-year survival of 56% and a 2-year survival of 16%. Especially in the case of metastasized tumor disease (M1), sequential polychemotherapy seems to be able to prolong survival: 45% of the metastasized tumor patients survived more than 1 year, 12% more than 2 years. The median survival for the whole group of locally advanced tumors was 15 months and the median survival for the whole group of metastasized tumors was 8 months. The results should stimulate clinicians to try palliative chemotherapy for pancreatic cancer more actively than before and to rediscuss the actual concepts of prospective therapeutical trials mainly based on analysing the effects of single agents or drug combinations on survival.

Atypical courses of serum tumor markers--4 case reports.

We report on 4 cancer patients with transient unspecific elevations of the serum tumor markers CA 19-9, CEA, CA 125 and CA 72-4, respectively. In one patient cholangitis due to biliary obstruction induced a significant transient increase of CA 19-9, in another patient HUS, probably as a severe complication after Mitomycin-C + Gemcitabine therapy resulted in a significant increase of serum CA 125. One patient demonstrated an extensively elevated and inexplicable serum CA 19-9 concentration (9450 u/ml) during a period of abdominal pain with continuous decrease and finally normalization within the following 5 years. Also inexplicable is an unexpected remittent increase of serum CA 72-4 in the course of chemotherapy after gastrectomy for gastric carcinoma. The presented data underline the necessity of interpreting serum courses of tumor markers only in the light of all available clinical data, imaging data and other laboratory tests in order to avoid misinterpretations.

Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.

Improved sensitivity of fuzzy logic based tumor marker profiles for diagnosis of pancreatic carcinoma versus benign pancreatic disease.

BACKGROUND: The definite diagnosis of pancreatic tumors of unknown origin remains a clinical challenge. Imaging techniques may fail to differentiate malignant tumors from inflammation, especially in chronic pancreatitis. In a considerable number of cases, the definitive diagnosis needs laparotomy. Single tumor markers as CA 19-9 or CEA are of limited value in these cases because of their limited sensitivity and specificity. This study was performed to find out, whether a classification method based on fuzzy logic analysis of tumor marker profiles is feasible in patients with pancreatic carcinoma and benign pancreatic disease. PATIENTS AND METHODS: Tumor markers and other clinical and laboratory parameters of 74 consecutive patients, either with histologically proved pancreatic carcinoma (n = 43) or presumed benign pancreatic disease (n = 31) assessed by ultrasound, endoscopic retrograde pancreatography, or computed tomography were analysed in order to detect their diagnostic value in the multi-dimensional approach of fuzzy logic analysis. RESULTS: Given a specificity of 95%, sensitivity was considerably increased by the fuzzy logic method (83%) compared with the best single tumor marker CA 19-9 (65%). CA 19-9, CYFRA 21-1 and CA 15-3 gave the most considerable contributions to the classification system, whereas CEA, CA 125, CA 72-4, AFP, liver enzymes, lipase, amylase, bilirubin, and ferritin were of no or little value. CONCLUSIONS: Tumor marker profiles analysed with the fuzzy logic method may have an improved sensitivity compared with single standard tumor markers. The diagnostic efficacy should be proved in patients with pancreatic tumors of unknown origin.

Irinotecan(Campto R): efficacy as third/forth line therapy in advanced pancreatic cancer.

Following the concept that the actual survival of pancreatic cancer patients can only be significantly improved by sequential poly-chemotherapy (EOSPC) in order to add one or two further progression free-survival times (PFST), in addition to the potential antitumoral effects of a first- or second-line therapy we studied the therapeutic efficacy of a third- or fourth-line chemotherapy with irinotecan alone, or in combination with oxaliplatin and high dose 5-FU/FA respectively, in a pilot study in 17 patients. Follow-up was performed on the basis of clinical investigations, imaging methods and the course of tumor markers, mainly CT and CA 19-9. The overall response rate in these cases of third/fourth-line therapies was 1 PR, 4 MR, 6 SD in the imaging methods compared to 5 PR, 2 MR and 5 SD on the basis of the tumor marker courses in the serum. The median PFST amounted to 4 months. Side effects could be seen as reported in the literature. Only in 1 patient did treatment have to be stopped due to irinotecan-induced gastrointestinal symptoms. Our data might suggest that combinations are more effective than irinotecan alone. However, further studies have to demonstrate whether irinotecan alone or in combination with e.g. oxaliplatin and 5-FU/FA will be more effective. The results suggested that irinotecan alone or in combination might also be used as third- and fourth-line therapeutical trials in exocrine pancreatic cancer in order to improve the survival time of these patients based on efficacy orientated sequential poly-chemotherapy (EOSPC).