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1.  Pyloric gland adenoma of the cystic duct with malignant transformation: report of a case with a review of the literature 
BMC Cancer  2012;12:570.
Pyloric gland adenoma consists of closely packed pyloric-type glands lined by mucus-secreting cells. To date, approximately 230 cases have been reported, mostly of gastric localization with a tumour size up to 3.5 cm and a mean age of occurrence around 70 years. Adenocarcinoma develops in about 40% of cases and may be difficult to detect due to relatively mild nuclear atypia.
Case presentation
We present the first case of a pyloric gland adenoma of the cystic duct in a 62-year-old male patient and demonstrate the clinicopathologic characteristics, including radiographic, molecular, and cytogenetic findings. The 2 cm-tumour developed in the cystic duct and protruded into the hepatic and common bile duct. On microscopic examination, it displayed closely packed pyloric-type glands, and focal architectural distortion with mild nuclear atypia. Immunohistochemically, it expressed MUC1, MUC5AC, MUC6 and p53, but not MUC2 and CD10. The Ki67-proliferation index was 25%. Furthermore, high-grade intraepithelial neoplasia was observed in the surrounding bile duct. We detected chromosomal gains at 7p, 7q11q21, 15q, 16p, 20, losses at 6p23pter, 6q, 18, and amplifications at 1q and 6p21p22 in the pyloric gland adenoma by comparative genomic hybridization. A KRAS codon 12 mutation (c.35G>T; p.G12V) was detected in the pyloric gland adenoma and in the adjacent dysplasia by sequencing analysis. The diagnosis of pyloric gland adenoma was established with transition into well-differentiated adenocarcinoma and high-grade biliary intraepithelial neoplasia.
Pyloric gland adenoma evolving in the cystic duct is a rare differential diagnosis of obstructive bile duct tumours. Other premalignant bile duct lesions may be associated. Due to the risk of developing adenocarcinoma, surgical resection should be performed.
PMCID: PMC3532145  PMID: 23206236
Pyloric gland adenoma; Adenocarcinoma; Cystic duct; Comparative genomic hybridization (CGH); KRAS mutation
2.  Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model 
BMC Surgery  2012;12:3.
Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model.
100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%.
At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93).
Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels.
PMCID: PMC3305372  PMID: 22361346
3.  Thymidylate Synthase as a Prognostic Biomarker for Locally Advanced Rectal Cancer after multimodal Treatment 
Annals of Surgical Oncology  2011;18(9):2442-2452.
For years, 5-fluorouracil (5-FU) has been the backbone of radiochemotherapy (RCT) of locally advanced rectal cancer. Its main target, thymidylate synthase (TS), is speculated to be an important biomarker for response prediction and long-term prognosis. In this study, we analyzed TS expression in the rectal cancer tissue of 208 patients to evaluate its predictive/prognostic potential.
All patients included were diagnosed with locally advanced adenocarcinoma of the rectum (UICC II and III) and were treated within randomized clinical trials of the German Rectal Cancer Study Group. Preoperative RCT (50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin) was administered in 167 patients followed by surgical resection with total mesorectal excision (TME). Another 41 patients received postoperative RCT. TS levels and further clinicopathological parameters were assessed in univariate and multivariate analyses. Additionally, a TS gene polymorphism was analyzed with respect to the intratumoral protein levels.
Low TS expression in pretreatment biopsies correlated with impaired patient survival (p = 0.015). Analysis of a 28-bp repeat revealed a correlation between the *3/*3 genotype and high TS expression in pretherapeutic biopsies. In this study, a correlation of TS expression and grade of RCT-induced tumor regression was not found. Histopathological examination confirmed a complete tumor remission in 16 patients (9.6%).
Analyses of the resection specimen indicated an unfavorable prognosis for patients with low intratumoral TS expression in case of detected lymph node metastases (p = 0.04).
TS can serve as a prognostic biomarker indicating an unfavorable prognosis for patients with low TS expression.
Electronic supplementary material
The online version of this article (doi:10.1245/s10434-011-1608-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3162628  PMID: 21347782
4.  Multimodal treatment options for bilobar colorectal liver metastases 
Langenbeck's Archives of Surgery  2010;395(6):633-641.
We evaluated individualized multimodal oncological strategies in patients with bilobular colorectal liver metastases (biCRC-LM) as well as their effect on R0 resection rates, disease-free survival (DFS), and overall survival (OS).
Between January 2001 and December 2008, 64 patients were assigned to straightforward or two-stage liver resection ± preoperative 5-fluorouracil (5FU)-based chemotherapy (CTx). Postoperative strategy after R0-resection was either “wait and see” or “adjuvant” therapy (3 cycles of CTx or anti-carcinoembryonic antigen (CEA)-radioimmunotherapy with 131I-labetuzumab in a dose of 40–50 mCi/m2).
Forty-three initially unresectable patients received preoperative CTx for downsizing of their biCRC-LM. Straightforward or two-stage liver resection was intended in 40 and 24 patients, respectively. Histopathologically confirmed R0-liver resection could be achieved in 47 patients. Surgical morbidity and mortality rates were 33% and 1.5%, respectively. Postoperatively, 26 patients received anti-cancer therapy (5 × CTx, 21 × anti-CEA-radioimmunotherapy). After R0-liver resection, median OS was significantly better compared to R1/R2 resections followed by palliative 5FU-CTx (38 versus 19 months, p = 0.035). There was no significant difference in DFS (p = 0.650) and OS (p = 0.435) between straightforward and two-stage liver resection. Compared to “wait and see” strategy, the application of postoperative therapy in adjuvant intent was associated with a better OS (p = 0.048).
Extensive liver resection within multimodal treatment concepts is justified in patients with biCRC-LM when complete resection of all metastases seems to be achievable.
PMCID: PMC2908753  PMID: 20213463
Multimodal treatment; Two-stage hepatectomy; Portal vein ligation; Oncological strategy; Adjuvant therapy
5.  Preoperative Chemoradiotherapy Does Not Necessarily Reduce Lymph Node Retrieval in Rectal Cancer Specimens—Results from a Prospective Evaluation with Extensive Pathological Work-up 
Preoperative chemoradiotherapy (CRT) is supposed not only to reduce lymph node metastases but also lymph node recovery in rectal cancer specimens. The objective of this prospective study was to determine the effects of chemoradiation on mesorectal lymph node retrieval under terms of a meticulous histopathological evaluation.
Specimens from 64 consecutive patients with stage II/III rectal cancer receiving preoperative 5-FU-based CRT were investigated. All patients were treated within the German Rectal Cancer Trial CAO/ARO/AIO-04. After surgery (including quality assessed total mesorectal excision), extensive pathological diagnostics was performed with embedding and microscopic evaluation of the whole mesorectal soft tissue compartment.
A total number of 2,021 lymph nodes were recovered (31.6 per specimen) within pathological work-up. There was no significant correlation between the number of retrieved nodes and patient- as well as tumor-dependent parameters. Lymph node size constantly amounted for less than 0.5 cm. Twenty patients (31.3%) had persistent nodal metastases. A considerable incidence of residual micrometastatic involvement in lymph nodes <0.3 cm (in 9.4% of all patients) was detected by extensive pathologic work-up.
Reliable nodal staging with high numbers of detected nodes was feasible after neoadjuvant CRT. Micrometastases frequently occur in small lymph nodes detected by microscopic evaluation.
PMCID: PMC2793396  PMID: 19830503
Locally advanced rectal cancer; Preoperative chemoradiotherapy; Total mesorectal excision; Pathologic diagnostics

Results 1-5 (5)