Evaluation of the POSSUM score in surgical treatment of cholangiocarcinoma.

BACKGROUND/AIMS: The surgical treatment for cholangiocarcinoma (CCC) is still a challenge. The aim of this study was to evaluate the POSSUM scoring system for preoperative physiological risk adjustment and for the operative risk of postoperative morbidity and mortality. METHODOLOGY: The operative notes and hospital files of 171 patients with CCC were analyzed retrospectively. The POSSUM scoring system was used to predict morbidity and mortality rates after surgery. The physiological sub score and the operative sub score of the POSSUM score were analyzed with regard to their ability to predict major postoperative complications. RESULTS: The overall complication rate was 40.9% and the mortality was 11.2%. The morbidity predicted by POSSUM was 63.5% and the prediction for postoperative mortality was 23.7%. Both rates are much higher than the observed morbidity and mortality. High operative severity sub scores correlate with the occurrence of major complications. CONCLUSION: The POSSUM scoring system over predicts morbidity and mortality in surgery for CCC. Operative severity and intraoperative parameters have a greater influence on postoperative mortality and morbidity rates than the physiological parameters represented in the POSSUM physiological score. Prospective studies will have to show whether POSSUM can be modified or whether it is necessary to develop a new score for assessing morbidity and mortality in surgery for CCC.

Impact of the site of anastomosis after oncologic esophagectomy on quality of life--a prospective, longitudinal outcome study.

BACKGROUND: For patients undergoing oncologic surgery, the quality of life (QoL) is generally accepted as an important outcome parameter in addition to long-term survival, mortality, and complication rates. Our study focused on outcome in terms of QoL in patients with esophageal cancer, comparing the sites of anastomosis (cervical versus thoracic anastomosis). METHODS: In a prospective longitudinal single-center study from 1998 to 2005, 105 patients underwent surgery for esophageal cancer. To assess QoL the EORTC-QLQ-C-30 and a tumor-specific module were administered before surgery, at discharge, and three, six, 12, and 24 months after surgery. Clinical data were collected prospectively and follow-up was performed every six months. RESULTS: The histological type was squamous cell carcinoma in 51.4% of the cases, adenocarcinoma in 41.9%, and some other type in 6.7%. There was no significant difference between cervical and thoracic anastomosis with regard to morbidity, mortality, and survival rates (30% five-year survival rate), whereas tumor stage was a significant (p < 0.001) prognostic factor. Most QoL scores dropped significantly below baseline in the early postoperative period. Even though they recovered slowly during the follow-up period, they never reached preoperative levels again. There was no statistically significant difference in any of the QoL scales between patients with a cervical or a thoracic anastomosis. CONCLUSIONS: Esophageal resections are associated with significant deterioration of QoL, which persists during the follow-up period. The surgical technique and position of the esophagogastrostomy did not affect QoL deterioration.

Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease.

BACKGROUND: Genetic susceptibility contributes to the aetiology of gallbladder diseases as shown by multiple epidemiological studies. A major gallstone susceptibility locus (Lith6) was identified in 2003 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in apolipoprotein B mRNA-editing protein (APOBEC1) and peroxisome proliferator-activated receptor gamma (PPARG) are located in this interval. AIMS: To investigate APOBEC1 and PPARG as candidate genes for common symptomatic gallstone disease in humans. PATIENTS AND METHODS: Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset 50) were compared with 718 sex-matched control individuals. An independent additional sample included 368 gallstone patients and 368 controls. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms were genotyped for PPARG (N=32) and APOBEC1 (N=11). RESULTS: The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.45. No evidence of association of the two genes in the single-point tagging markers, coding variants and in the sliding window haplotype analysis was detected (all nominal single point P-values >0.04). A logistic regression analysis including age, sex and BMI as covariates was also negative (nominal P-values > or =0.08). CONCLUSIONS: In the investigated German samples, no evidence of association of APOBEC1 and PPARG with gallstone susceptibility was detected. Systematic fine mapping of the complete Lith6 region is required to identify the causative genetic variants for gallstone in mice and humans.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

Impact of preoperative physiological risk profile on postoperative morbidity and mortality after emergency operation of complicated peptic ulcer disease.

AIM: The aim of this study was to evaluate the preoperative physiological risk profile for postoperative morbidity and mortality after emergency treatment of complicated peptic ulcer disease (PUD). METHODS: Operative notes and hospital files of 261 patients--111 female, 150 male; median age 67 years (range 17-100 years)--undergoing an emergency operation from 1993 to 2005 were analyzed retrospectively. The physiologic subscore of the POSSUM score (POSSUM-phys) was analyzed with regard to predicting postoperative complications. Follow-up was obtained from questionnaires sent to family practitioners or by patient interviews. RESULTS: The overall complication rate was 44%, and mortality was 24%. Among risk factors studied (e.g., sex, patient's age, duration of symptoms, type of surgery), a high POSSUM-phys score was the strongest predictor for postoperative sepsis, anastomotic/suture dehiscence, postoperative bleeding, and mortality. Cut points for patients at risk could be calculated. Surgical procedures (organ-preserving versus resection) had no influence when matched for POSSUM-phys score. Nevertheless, organ resections were associated with higher scores. Recurrent PUD was a rare event (7.6%). CONCLUSION: The preoperative physiologic POSSUM score is a promising instrument for identifying patients at increased risk to develop major postoperative complications after emergency surgery for complicated PUD. Prospective studies are needed to prove its applicability for adjusting treatment to individual patients.

Small bowel cancer: single-centre results over a period of 12 years.

BACKGROUND/AIMS: Tumors of the small bowel are rare, accounting for about 3-6% of all gastrointestinal neoplasms. However, diagnosis and treatment are difficult and an ongoing challenge. METHODOLOGY: Follow-up and clinical data of 43 patients with small bowel cancer who underwent surgery at our hospital. RESULTS: Subgroups consisted of adenocarcinoma (n=16; 37.2%), neuroendocrine tumors (n=12; 27.9%), gastrointestinal stroma tumor (GIST) (n=10; 23.3%), lymphoma (n=3; 7%) and desmoid tumor (n=2; 4.6%). Tumor localizations were within duodenum (46.5%), jejunum (16.3%) and ileum (37.2%). Thirty patients were curatively operated, 13 for palliative treatment or diagnostic purpose. Adenocarcinoma patients showed preponderance of advanced tumor stages: stage I/II in 5 pts, III/IV in 11 patients. Stage distribution for patients with neuroendocrine tumors was 3 each for I and II and 6 for III. Localization was predominantly within the ileum (n=7). Overall survival after five/ten years was 48/37%. Patients with neuroendocrine tumors showed best survival results (75/57%), GIST patients 60/35% and adenocarcinoma (27% each). There was a strong trend towards better survival at early tumor stages in patients with adenocarcinoma and neuroendocrine tumors. CONCLUSIONS: Early diagnosis is essential for prognosis of small bowel malignancies. Cure is unlikely if lymph node or distant metastases have already developed.

Elastofibroma dorsi as differential diagnosis in tumors of the thoracic wall.

We report the case of a 73-year-old woman who presented with a soft tissue tumor located between the scapula and the rib cage. Magnetic resonance imaging showed an inhomogeneous tumor on the right dorsolateral thoracic wall that measured 7 x 4 x 7 cm with contrast enhancement. The findings were suggestive of partial infiltration of intercostal muscles and were suspicious of a malignant tumor. After local excision at a district hospital had failed to render definitive diagnosis, the patient underwent complete resection of the tumor at our institution. Histology from the specimen was consistent with elastofibroma dorsi with free resection margins.

Benign abdominal and pulmonary metastasizing leiomyoma of the uterus.

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. METHODS: We report of a 42-year-old African woman with a BML in the abdomen and lung who had undergone a hysterectomy for uterine leiomyoma 10 years ago. She was admitted to our hospital for investigation of a huge tumor mass in the pelvis consisting of multiple nodules in the abdomen and left lung. Assuming an advanced intraperitoneal malignancy was present, a 'palliative' limited tumor debulking and due to a tumor compressing the sigmoid a Hartmann's procedure was performed. RESULTS: The histopathologic examination showed a leiomyoma positive for estrogen receptor. Treatment was started with GnRH analoga. In the presence of a stable disease after 12 months, the patient underwent a re-laparotomy with a reanastomosis of the colon. Treatment was continued with GnRH analoga and the residual nodules have not increased in size during 36 months of follow-up. CONCLUSIONS: The review of the literature supports the concept that the primary tumor of BML is located in the uterus and that leiomyomas in the uterus can metastasize leading via hematogenous spread to BML. However, the origin of the tumor remains controversial.

A modified random oligonucleotide-based combination therapy for adjuvant treatment of pancreatic ductal adenocarcinoma.

Anti-cancer therapy in pancreatic ductal adenocarcinoma (PDAC) is mostly based on surgical removal or palliative therapy using antimetabolites, like 5'-fluorouracil or gemcitabine. Adjuvant treatment using these chemotherapeutics has recently proven a beneficial concept, though general survival rates are still poor. Most recently, combination therapy of gemcitabine with other targeted drugs was evaluated in clinical trials. We present here a study performed in a mouse orthotopic xenotransplant model of PDAC, using an oligo-nucleotide-based approach. We have shown previously that antisense oligonucleotides against p53 reduce the weight of orthotopic pancreatic tumours in immune-deficient mice. We further characterised terminal modifications of phosphorothioate oligonucleotides in vitro and found a random, unrelated control sequence carrying a D,L-alpha-tocopherol modification at the 5' and 3' ends to be most efficient in induction of cell death in PancTu-1 cells. Modified random oligonucleotide (MRON) were thus further tested in vivo. MRON showed a reduction of tumour weight in established primary orthotopic tumours in SCID/bg mice. In a surgically adapted pre-clinical model, where primary tumours were resected and animals received adjuvant treatment, MRON was very efficient in suppression of relapse and metastasis, when combined with gemcitabine. While the exact molecular mechanism of MRON activity still needs to be elucidated, the compound showed a remarkable preference for uptake into tumour cells in vivo.

Adjuvant treatment of pancreatic carcinoma in a clinically adapted mouse resection model.

BACKGROUND: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model. METHODS: Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated. RESULTS: All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events. CONCLUSION: Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.

Feasibility and early results of interstitial intensity-modulated HDR/PDR brachytherapy (IMBT) with/without complementary external-beam radiotherapy and extended surgery in recurrent pelvic colorectal cancer.

BACKGROUND: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. PATIENTS AND METHODS: 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. RESULTS: Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. CONCLUSION: The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.

Sigmoid perforation by compressed carbon dioxide.

Self-induced injuries of the bowel have various accidental mechanisms. This is a report of a 35-year-old patient with disruption of the recto-sigmoid junction caused by carbon dioxide (CO2) originating from a bottle of sparkling wine, which was introduced transanally for sexual stimulation. The patient underwent resection of the recto-sigmoid junction and primary anastomosis. The postoperative course was uneventful except for wound infection. The patient was discharged 12 days later. The physical backgrounds, the pathological pathways for perforation and diagnostic modalities including diagnostic pitfalls are critically discussed.

Laparoscopic appendicectomy is associated with a lower complication rate even during the introductory phase.

BACKGROUND: The benefit of laparoscopic appendicectomy is under debate. To study the beneficial clinical effects of laparoscopic appendicectomy during the introductory phase we analysed, retrospectively, 493 patients from one district general hospital. PATIENTS AND METHODS: During a period of 3 years 250 patients were operated on prospectively by open appendicectomy, and 243 patients were operated on laparoscopically. Both groups were compared with regard to their demographic data, operation time, body mass index and complication rate. RESULTS: The conversion rate was 4.5%. The distribution of histological stages of inflammation was comparable in both groups. The median operating time was significantly longer for the open (40 min) than for the laparoscopic procedure (35 min, P=0.002). The body mass index in the laparoscopic group was significant higher (23.7 kg/m(2) vs 22.6 kg/m(2), P=0.009). Perioperative white blood cell count, C-reactive protein and body temperature were equal in both groups. There was no significant difference with regard to the analgesia required postoperatively between the open and the laparoscopic group. Nevertheless, the specific complication rate after open appendicectomy (18.4%) was significantly higher than that following laparoscopic appendicectomy (10.8%, P=0.03). CONCLUSION: Even during the introductory phase, laparoscopic appendicectomy is a safe and clinically beneficial operating procedure.

Prospective evaluation of diagnostic modalities in suspected acute appendicitis.

BACKGROUND: The aim of this prospective study was to evaluate different diagnostic modalities routinely employed in a district hospital. METHOD: Four hundred subsequent patients presenting with acute abdominal pain were included over a period of 18 months. Patient characteristics, diagnostic work-up, intraoperative findings, histology and clinical outcome were documented. Rectal temperature, white cell count (WCC), C-reactive protein (CRP), ultrasonography (US) and Ohmann score were analysed with relation to diagnostic value. RESULTS: Negative appendicectomy rate and negative laparotomy rate on the day of admission were 22% and 21%, respectively. Sensitivity was highest for WCC and CRP (0.82 and 0.85) but US showed highest values for specificity (0.92), accuracy (0.85) and odds ratio (13.06). No patient with an Ohmann score below 6.5 suffered from acute appendicitis. With regard to different levels of training in US, experienced surgeons and radiologists had best values for specificity (1.00 and 0.98) and accuracy (0.90 and 0.94). Surprisingly, less-experienced sonographers also achieved good results with regard to specificity (up to 0.96) and positive predictive value (up to 0.89). CONCLUSION: Diagnostic accuracy of acute appendicitis remains insufficient, with an unacceptable high rate of unnecessary operations. Only the promotion of routine ultrasonography might contribute to an improvement in the near future.