Routine Use of Contrast Swallow After Total Gastrectomy and Esophagectomy: Is it Justified?

BACKGROUND: After gastrectomy or esophagectomy, esophagogastrostomy and esophagojejunostomy are commonly used for reconstruction. Water-soluble contrast swallow is often used as a routine screening to exclude anastomotic leakage during the first postoperative week. In this retrospective study, the sensitivity and specificity of oral water-soluble contrast swallow for the detection of anastomotic leakage and its clinical symptoms were analysed. MATERIAL/METHODS: Records of 104 consecutive total gastrectomies and distal esophagectomies were analysed. In all cases, upper gastrointestinal contrast swallow with the use of a water-soluble contrast agent was performed on the 5th postoperative day. Extravasation of the contrast agent was defined as anastomotic leakage. When anastomotic insufficiency was suspected but no extravasation was present, a computed tomography (CT) scan and upper endoscopy were performed. RESULTS: Oral contrast swallow detected 7 anastomotic leaks. Based on CT-scans and upper endoscopy, the true number of anastomotic leakage was 15. The findings of the oral contrast swallow were falsely positive in 4 and falsely negative in 12 patients, respectively. The sensitivity and specificity of the oral contrast swallow was 20% and 96%, respectively. CONCLUSIONS: Routine radiological contrast swallow following total gastrectomy or distal esophagectomy cannot be recommended. When symptoms of anastomotic leakage are present, a CT-scan and endoscopy are currently the methods of choice.

Free latissimus dorsi myocutaneous flap for pelvic floor reconstruction following pelvic exenteration.

INTRODUCTION: Pelvic floor defects following pelvic exenteration constitute a challenge to the reconstructive surgeon. Whenever the common reconstruction options such as the gluteus maximus myocutaneous flap (GLM) and the vertical rectus abdominis myocutaneous flap (VRAM) are not feasible, free tissue transfer will be the only remaining option. Being one of the most reliable and versatile flaps used for microsurgical reconstruction, the free latissimus dorsi (LD) muscle flap provides an adequate solution to this problem. PATIENTS AND METHODS: We describe our experience with 12 consecutive patients who underwent the free transfer of LD free flap for secondary reconstruction of the pelvic floor and perineum following pelvic exenteration for management of locally advanced pelvic malignancies in Klinikum Oldenburg from 2007 to 2014. RESULTS: Recurrent cancer of the anal canal was the most common pathology necessitating the performance of pelvic exenteration. Thrombosis of the vascular anastomosis was reported in two cases and ended with total flap loss in one of them. Functional limitations arose in two patients postoperatively. The mean hospital stay was 25 days. CONCLUSION: Free LD myocutaneous flap provides an adequate solution for reconstruction of pelvic defects resulting from radical oncological resections in cases where the use of locoregional flaps, such as the gluteus maximus flap and the vertical rectus abdominis flap, is not feasible because of an extensive defect, disruption of the vascular pedicle, or due to planning for bilateral stomas placement.

Laparoscopic versus conventional ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy (LapConPouch Trial)-a randomized controlled trial.

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). While minimal invasive techniques have been applied increasingly, clear evidence of superiority for laparoscopic pouch procedures is not yet available. The aim of the LapConPouch Trial was to compare the effectiveness of laparoscopic (LAP) versus conventional (CON) ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy. METHODS: The trial was designed as a single-centre, pre-operatively randomized, controlled trial using a two-group parallel superiority design. Eligible for participation were patients scheduled for restorative proctocolectomy either for FAP or for UC. Patients and outcome assessors were blinded to group assignment. The primary endpoint was defined as the amount of blood loss. Statistical analyses were explorative since the trial had to be stopped prematurely. RESULTS: A total of 42 patients (21 LAP (50.0 %); 21 CON (50.0 %)) were randomized. The trial had to be stopped prematurely due to insufficient patient recruitment. There was no difference in the amount of blood loss between both groups: LAP 261.5 ± 195.4 ml, CON 228.1 ± 119.5 ml. Secondary endpoints differ in both groups. Laparoscopic surgery was superior regarding the length of skin incision; in contrast, the conventional approach was superior in duration of operation. There were no discrepancies in length of hospital stay, postoperative pain, bowel function, and quality of life between both approaches. The conversion rate from LAP to CON approach was 23.8 %. CONCLUSION: There was no difference with respect to blood loss between the LAP and the CON group. The LAP approach is feasible for restorative proctocolectomy, and IPAA seems at least as safe as CON surgery. The most obvious advantage of the minimal invasive technique is the improved cosmesis.

Evaluation of bowel peristalsis by dynamic cine MRI: detection of relevant functional disturbances--initial experience.

PURPOSE: To investigate the diagnostic performance of a cine magnetic resonance imaging (MRI) sequence in the visualization and detection of impaired bowel peristalsis. MATERIALS AND METHODS: In all, 91 consecutive patients (mean age 45 years) were prospectively examined on a 1.5 T system and stratified into a surgery group (n = 22) and a nonsurgery group (n = 69). A coronal fast imaging with steady-state precession (TrueFISP) sequence with 30 acquisitions per slice covered the abdomen in 10-15 slices each 7-12 mm thick (temporal resolution: 6-8 sec per frame). Image evaluation for reduced bowel peristalsis and relevant bowel stenosis was compared to surgical findings or clinical follow-up. RESULTS: Cine MRI reached 96% accuracy (94% sensitivity; 100% specificity) in detecting a relevant reduction in bowel peristalsis and 85% of relevant stenosis was identified in the surgery group. Twenty of 69 patients of the nonsurgery group showed reduced peristalsis on cine MR which was attributed to underlying disease; 49/69 patients in this group had no findings on cine MR and were uneventfully followed up. CONCLUSION: Cine MRI of the bowel provides functional information of bowel passage. The visualization of a reduction in peristalsis may improve the assessment of the functional impact of suspected bowel adhesions or stenosis. Standard bowel MR protocols can be easily complemented by cine MR, extending scan time by <4 minutes.

Restoration of intestinal continuity after Hartmann's procedure--not a benign operation. Are there predictors for morbidity?

BACKGROUND: Restoration of intestinal continuity is usually the second step after Hartmann's procedure and an established procedure in abdominal surgery, particularly for complicated diverticular disease. This descriptive study aimed to examine the morbidity and mortality associated with the procedure and to define potential risk factors. PATIENTS AND METHODS: Data from 161 consecutive patients (median age 62 years, median BMI 25.2) undergoing elective surgery with restoration of bowel continuity between October 2001 and November 2008 at the Department of Surgery, University of Heidelberg, were included in this study. The association of potential prognostic variables with postoperative morbidity and mortality were examined by univariate and multivariate analyses. RESULTS: The median time between the initial operation and the restoration of bowel continuity was 7 months. The median operation time was 185 min with a blood loss of 150 ml and median postoperative hospital stay of 9 days. Fifty-one percent of the patients had an uneventful recovery, whereas 49% had a postoperative complication. Surgical infections occurred in 18% of patients, 3.8% suffered from anastomotic leakage, and surgical re-exploration was necessary in 11.2%. Medical complications occurred in 21.1% of the patients, with pneumonia in 2.5% and urinary tract infections in 1.3%. One patient died 17 days after surgery. Univariate analysis showed that patients taking immunosuppressant drugs had significantly more wound infections and, interestingly, protective ileostomy was associated with postoperative anastomotic stenosis in our cohort. The administration of PRBC and a prolonged hospital were significantly associated with increased postoperative morbidity in the multivariate analysis. CONCLUSIONS: Restoration of bowel continuity is a surgical procedure with high overall morbidity. The high morbidity confirmed in our study and various other papers justify a randomized clinical study to investigate the one-stage concept with primary anastomosis against the Hartmann's procedure and its reversal.

A randomised controlled trial to evaluate and optimize the use of antiplatelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007).

BACKGROUND: Due to the increase of cardiovascular diseases acetylsalicylic acid (ASA) has become one of the most frequently prescribed drugs these days. Despite the rising number of patients with ASA medication presenting for elective general and abdominal surgery and the potentially increased risk of hemorrhage in these patients, there are no clear, evidence-based guidelines for the perioperative use of antiplatelet agents. The present randomised controlled trial was designed to evaluate the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. METHODS/DESIGN: This is a two-arm, monocenter randomised controlled trial. Patients scheduled for elective surgical treatment (i.e. inguinal hernia repair, cholecystectomy and colorectal resections) with ASA as a permanent medication are randomised equally to perioperative continuation or discontinuation of ASA. Patients who are randomised in the discontinuation group stop the administration of ASA five days prior to surgical treatment and start intake of ASA on postoperative day 5. Fifty-two patients will be enrolled in this trial. The primary outcome is the incidence of postoperative bleeding and cardiovascular events at 30 days after surgery. In addition a set of general as well as surgical variables are analysed. DISCUSSION: This is a randomised controlled two-group parallel trial designed to assess the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. The results of this pilot study build the basis for a confirmative randomised controlled trial that may help to clarify the use and potential risk/benefits of perioperative ASA medication in patients undergoing elective surgery. TRIAL REGISTRATION: The trial is registered with Current Controlled Trials ISRCTN45810007.

Heterogeneous detection of circulating tumor cells in patients with colorectal cancer by immunomagnetic enrichment using different EpCAM-specific antibodies.

BACKGROUND: Circulating tumor cells (CTC) and disseminated tumor cells (DTC) are thought to be responsible for metastasis, so the detection of CTC may serve as individual prognostic factor in patients suffering from colorectal cancer. Therefore, a series of immunomagnetic enrichment methods for CTC have been developed using a variety of monoclonal antibodies against the Epithelial Cell Adhesion Molecule (EpCAM). However, it remains unclear whether all commercially available EpCAM antibodies show the same sensitivity and specificity. Furthermore, it remains unclear which method of sample preparation and cell extraction is most suitable for immunomagnetic enrichment and detection of CTC. In this study, we aimed to investigate whether the detection of CTC by a cytokeratin 20 reverse transcriptase-polymerase chain reaction (CK20 RT-PCR) may be influenced by the use of various Epithelial Cell Adhesion Molecule (EpCAM) antibodies for immunomagnetic isolation of CTC. RESULTS: Using both EpCAM antibodies (mAb BerEP4 and mAb KS1/4) for immunomagnetic enrichment in blood samples of 39 patients with colorectal cancer we found heterogenous results in each patient with regard to tumor cell detection. In the tumor cell spiking experiments with whole blood samples the sensitivity of the CK 20 RT-PCR assay was higher using immunomagnetic beads coated with mAb KS1/4 compared to precoated mAb BerEP4 Dynabeads. Extraction of MNC fraction with Ficoll gradient centrifugation prior to immunomagnetic enrichment resulted in a higher sensitivity of the CK 20 RT-PCR assay. CONCLUSIONS: We concluded that isolation and detection of CTC with immunomagnetic enrichment methods is critically dependent on the used EpCAM clone. Further studies with a larger number of patients should clarify if the enrichment protocol influences the prognostic value of the tumor cell detection protocol.

Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling.

Balanced expression of proteases and their inhibitors is one prerequisite of tissue homeostasis. Metastatic spread of tumor cells through the organism depends on proteolytic activity and is the death determinant for cancer patients. Paradoxically, increased expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural inhibitor of several endometalloproteinases, including matrix metalloproteinases and a disintegrin and metalloproteinase-10 (ADAM-10), in cancer patients is negatively correlated with their survival, although TIMP-1 itself inhibits invasion of some tumor cells. Here, we show that elevated stromal expression of TIMP-1 promotes liver metastasis in two independent tumor models by inducing the hepatocyte growth factor (HGF) signaling pathway and expression of several metastasis-associated genes, including HGF and HGF-activating proteases, in the liver. We also found in an in vitro assay that suppression of ADAM-10 is in principle able to prevent shedding of cMet, which may be one explanation for the increase of cell-associated HGF receptor cMet in livers with elevated TIMP-1. Similar TIMP-1-associated changes in gene expression were detected in livers of patients with metastatic colorectal cancer. The newly identified role of TIMP-1 to create a prometastatic niche may also explain the TIMP-1 paradoxon.

A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression.

High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM, claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer (n = 104), liver metastasis (n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6 complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However, claudin-7-associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation.

Ischemic colitis: analysis of risk factors for postoperative mortality.

BACKGROUND: Ischemic colitis is a disease with high postoperative mortality when surgery is necessary. The definition of risk factors for perioperative mortality, which is currently lacking in the literature, could be helpful in clinical decision making and in optimizing perioperative treatment. MATERIALS AND METHODS: Based on a prospective database, 85 consecutive patients undergoing surgery for ischemic colitis between November 04, 2001 and October, 26, 2004 at the Department of Surgery, University of Heidelberg, were included in this study. The influence of different known factors on perioperative mortality such as age, type of operation, blood loss, comorbidities, hospital course, and complications was tested by univariate and multivariate analysis. RESULTS: Sixty-seven percent of patients were operated as emergency cases (within 24 h after surgical evaluation). About half of the patients underwent subtotal or total colectomy and 80% had stoma creation. Twenty-two percent of patients developed surgical complications and 47% of patients died in the further postoperative course. Univariate analysis showed underlying cardiovascular diseases, American Society of Anesthesiologists (ASA) status, emergency surgery, total colectomy, elevated intraoperative blood loss and intraoperative allogeneic blood transfusion or transfusion of fresh frozen plasma to be associated with an increased postoperative mortality. Multivariate analysis confirmed ASA status > III, emergency surgery, and blood loss to be independently associated with postoperative mortality in ischemic colitis. CONCLUSIONS: The mortality of patients requiring surgery for ischemic colitis will remain high as the majority of afflicted patients are patients with significant comorbidities in a reduced general condition. But earlier diagnosis and measures to reduce blood loss may contribute to improving the overall outcome.

Hepaticojejunostomy--analysis of risk factors for postoperative bile leaks and surgical complications.

Anastomoses between the jejunum and the bile duct are an important component of many surgical procedures; however, risk factors for clinically relevant bile leaks have not yet been adequately defined. The objective of this study was to describe the incidence of bile leaks after hepaticojejunostomy and to define predictive factors associated with this risk and with surgical morbidity. Between October 2001 and April 2004, hepaticojejunostomies were performed in 519 patients in a standardized way. Patient- and treatment-related data were documented prospectively. A bile leak was defined as bilirubin concentration in the drains exceeding serum bilirubin with a consecutive change of clinical management or occurrence of a bilioma necessitating drainage. Surgical morbidity occurred in 15% of patients, the incidence of a bile leak was 5.6%. Multivariate analysis confirmed preoperative radiochemotherapy, preoperative low cholinesterase levels, biliary complications after liver transplantation necessitating a hepaticojejunostomy, and simultaneous liver resection as risk factors for bile leakages, whereas biliary complications after liver transplantation necessitating hepaticojejunostomy, simultaneous liver resection, and diabetes mellitus were significantly associated with postoperative surgical morbidity. Our results demonstrate that hepaticojejunostomy is a safe procedure if performed in a standardized fashion. The above found factors may help to better predict the risk for complications after hepaticojejunostomy.

Totally laparoscopic versus conventional ileoanal pouch procedure--design of a single-centre, expertise based randomised controlled trial to compare the laparoscopic and conventional surgical approach in patients undergoing primary elective restorative proctocolectomy--LapConPouch-Trial.

BACKGROUND: Restorative proctocolectomy is increasingly being performed minimal invasively but a totally laparoscopic technique has not yet been compared to the standard open technique in a randomized study. METHODS/DESIGN: This is a two armed, single centre, expertise based, preoperatively randomized, patient blinded study. It is designed as a two-group parallel superiority study. Power calculation revealed 80 patients per group in order to recruit the 65 patients to be analysed for the primary endpoint. The primary objective is to investigate intra-operative blood loss and the need for blood transfusions. We hypothesise that intra-operative blood loss and the need for peri-operative blood transfusions are significantly higher in the conventional group. Additionally a set of surgical and non-surgical parameters related to the operation will be analysed as secondary objectives. These will include operative time, complications, postoperative pain, lung function, postoperative length of hospital stay, a cosmetic score and pre-and postoperative quality of life. DISCUSSION: The trial will answer the question whether there is indeed an advantage in the laparoscopic group in regard to blood loss and the need for blood transfusions. Moreover, it will generate data on the safety and potential advantages and disadvantages of the minimally invasive approach.

Intraoperative Fluid Excess Is a Risk Factor for Pancreatic Fistula after Partial Pancreaticoduodenectomy.

Background. After pancreaticoduodenectomy (PD), pancreatic fistulas (PF) are a frequent complication. Infusions may compromise anastomotic integrity. This retrospective analysis evaluated associations between intraoperative fluid excess and PF. Methods. Data on perioperative parameters including age, sex, laboratory findings, histology, infusions, surgery time, and occurrence of grade B/C PF was collected from all PD with pancreaticojejunostomy (PJ) performed in our department from 12/2011 till 02/2015. The glomerular filtration rate (GFR), infusion rate, and the ratio of both and its association with PF were calculated. ROC analysis was employed to identify a threshold. Results. Complete datasets were available for 83 of 86 consecutive cases. Median age was 66 years (34-84; 60% male), GFR was 93 mL/min (IQR 78-113), and surgery time was 259 min (IQR 217-307). Intraoperatively, 13.6 mL/min (7-31) was infused. In total, n = 18 (21%) PF occurred. When the infusion : GFR ratio exceeded 0.15, PF increased from 11% to 34% (p = 0.0157). No significant association was detected for any of the other parameters. Conclusions. This analysis demonstrates for the first time an association between intraoperative fluid excess and PF after PD with PJ even in patients with normal renal function. A carefully patient-adopted fluid management with due regard to renal function may help to prevent postoperative PF.

Transsphincteric tumor resection in case of a pararectal solitary fibrous tumor.

Transsphincteric resection of rectal tumors was first described about 120 years ago. Nowadays, this approach faded into obscurity due to standardized guidelines and practice in surgical oncology including lymphadenectomy, mesorectal excision and radical dissection of veins. However, transsphincteric resection seems reasonable in some cases, especially if an abdominal approach can be avoided. In the following, we will present and describe the technique of the transsphincteric approach with its variations in rectal surgery in the case of a rare pararectal tumor.

Incidence of Metachronous Distant Metastasis and ypN Classification Influence Patient Survival in Endosonographically Confirmed uT3 Rectal Cancer after Neoadjuvant Therapy and R0 Resection: A Historical Cohort Analysis.

BACKGROUND: Tumor response after neoadjuvant radiochemotherapy (NRC) prior to surgery and other parameters are likely to have an influence on the survival rate of patients suffering from T3 rectal cancer. METHODS: 51 patients (17 female, 34 male; 59.0 years; Apache < 9 points: 95.1%; ASA I-II 88.3% and ASA III 11.8%) were treated with NRC (50.4 Gy; 5-fluorouracil/folinic acid) 4-6 weeks prior to surgery because of uT3 rectal cancer (G2: 96%; adenocarcinoma 86.3%; cUICC II 62.7%). NRC led to a tumor response (TR) (ypT0-ypT2) in 45.1% (ypT0N0M0 7.8%). RESULTS: Neither the age of patients nor Apache/ASA score, histology, UICC staging, ypTNM, Dukes staging, infiltration of vessels, surgical procedure, local recurrence nor TR had a significant influence on the patients' survival time. Patients with metachronous distant metastasis (MDM) during the follow-up period (mean: 8.2 years; 1 month to 14.5 years) and patients with ypN1-ypN2 had a significantly shorter survival time. CONCLUSIONS: NRC prior to surgery leads to a remarkable TR rate but has no significant impact of TR on the patients' survival time. Occurrence of MDM during the follow-up period and ypN1/N2 status do have a greater influence. It is necessary to investigate larger cohorts of patients in the future to obtain more conclusive results and to define factors with influence on survival.

Short description of an alternative simplified method for screening recombinant clones within the "AdEasy-System" by Duplex-PCR.

BACKGROUND: Recombinant adenoviral vectors are highly efficient for in vitro and in vivo gene delivery. They can easily be produced in large numbers, transduce a wide variety of cell types and generate high levels of transgene expression. The AdEasy system is a widely used system for generating recombinant adenoviral vectors, which are created with a minimum of enzymatic manipulations and by employing homologous recombination in E. coli. In this paper we describe an alternative simplified method for screening recombinant DNA within the AdEasy system. This Duplex-PCR-method is independent of the transgene or insert and can be used for the complete AdEasy system. It is characterized by a simple standard protocol and the results can be obtained within a few hours. The PCR is run with two different primer sets. The primers KanaFor and KanaRev hybridizise with the Kanamycin resistence gene and AdFor and AdRev detect the adenoviral backbone. In case of recombinant clones, two diagnostic fragments with a size of 384 bp and 768 bp are generated. RESULTS: The practicability of this method was verified with three different transgenes: Cytosin Deaminase (AdCD), p53 (Adp53) and Granulocyte Macrophage Colony Stimulating Factor (AdGM-CSF). Recombinant clones are indicated by two diagnostic fragments and are then suitable for further processing. CONCLUSION: In summary, the presented protocol allows fast detection of recombinants with an easy technique by minimizing the amount of necessary steps for generating a recombinant adenovirus. This method is time sparing and cost-effective.

Is the lateral lymph node compartment relevant?

Lateral pelvic lymphadenectomy is routinely performed in advanced lower rectal cancers by Japanese surgeons, whereas in the western world it has not progressed to a frequently performed technique. Claimed benefit for this extensive surgery is an improved locoregional control; on the other hand, low positive lateral lymph node yields, questionable prognostic significance, and high morbidity (urinary and sexual dysfunction) are main reasons against this procedure. Clinical results published on lateral lymphadenectomy in the literature are conflicting. Due to major improvements in local control and survival of rectal cancer patients mainly based on preoperative radiotherapy and total mesorectal excision (TME), only a few patients may profit from lateral lymph node dissection. This article gives an overview of the current status and the clinical relevance of the lateral lymph node compartment in rectal cancer surgery.

The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines.

AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS: Human pancreatic cancer cell lines Capan-1(p53mut), Capan-2(p53wt), FAMPAC(p53mut), PANC1(p53mut), and rat pancreatic cancer cell lines AS(p53wt) and DSL6A(p53null) were used for in vitro studies. Following infection with different ratios of Ad-p53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size, apoptosis (TUNEL) and survival were determined. RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

Gastric Metastasis of Malignant Melanoma: Report of a Case and Review of Available Literature.

BACKGROUND: Malignant melanoma is a tumor with common lymphogenic or hematogenic metastasis. Metastasis to the gastric mucosa is uncommon. CASE REPORT: We present the case of a 43-year-old female patient with metastases of a malignant melanoma to the lesser curvature of the stomach. The primary malignant melanoma of the right breast was resected 2 years previously. CONCLUSION: Metastases to the gastric mucosa are rarely seen. Esophagogastroduodenoscopy should be performed in symptomatic patients to rule out metastatic disease. When R0 resection can be achieved, it should be undertaken in order to increase the overall prognosis of the patient.

Simultaneous cholecystectomy during gastric and oesophageal resection: a retrospective analysis and critical review of literature.

The higher incidence of gallstone formation after gastrectomy for cancer has been reported as a common complication in many studies but the management strategies are still controversial and need further evaluation. We retrospectivaly analysed between 2007 and 2013, 206 patients who underwent gastric and or oesophageal resection. In 29/93 patients receiving an oesophagectomy a simultaneous cholecystectomy was performed, respectively 31 from 111 patients who underwent a gastrectomy received an incidental cholecystectomy. In 2 patients with an extended gastrectomy, the gallblader removing was performed simultaneously in one case. A subsequent cholecystectomy was performed in 11 cases. The increased surgical mortality was significant higher correlated with an intervention at a later stage point. That suggest that the prohylactic cholecystectomy can be safely performed during a major intervention in order to reduce complication and a reoperation.