In vitro analysis of biopolymer coating with glycidoxypropyltrimethoxysilane on hernia meshes.

Certain coatings may improve the biocompatibility of hernia meshes. The coating with self-assembled monolayers, such as glycidoxypropyltrimethoxysilane (GOPS) can also improve the materials characteristics of implants. This approach was not yet explored in hernia meshes. It was the aim of this work to clarify if and how hernia meshes with their three-dimensional structure can be coated with GOPS and with which technique this coating can be best characterized. Commercially available meshes made from polypropylene (PP), polyester (PE), and expanded polytetrafluorethylene (ePTFE) have been coated with GOPS. The coatings were analyzed via X-ray photoelectron spectroscopy (XPS), confocal laser scanning microscopy (CLSM), and cell proliferation test (mouse fibroblasts). Cell viability and cytotoxicity were tested by MTT test. With the GOPS surface modification, the adherence of mouse fibroblasts on polyester meshes and the proliferation on ePTFE meshes were increased compared to noncoated meshes. Both XPS and CLSM are limited in their applicability and validity due to the three-dimensional mesh structure while CLSM was overall more suitable. In the MTT test, no negative effects of the GOPS coating on the cells were detected after 24 h. The present results show that GOPS coating of hernia meshes is feasible and effective. GOPS coating can be achieved in a fast and cost-efficient way. Further investigations are necessary with respect to coating quality and adverse effects before such a coating may be used in the clinical routine. In conclusion, GOPS is a promising material that warrants further research as coating of medical implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1083-1090, 2017.

Microbiology of the infected recurrent sacrococcygeal pilonidal sinus.

The aim of the present retrospective single centre study was to define the changes in the microbiological flora of the recurring sacrococcygeal pilonidal sinus (PS). Microbiological findings of swab samples of abscess-forming PS from 2000 to 2010 were evaluated. Within this time span, 73 swab samples were taken from primary sacrococcygeal pilonidal sinus (pPS) and 23 swab samples of patients with recurring sacrococcygeal pilonidal sinus (rPS). Our results show a statistically significant shift of the bacterial flora towards the gram-positive range (P = 0·029) and a shift with tendency towards the aerobic range (P = 0·090). Pathogens of pPS are not always solely anaerobic or gram-negative, and those of rPS not always aerobic or gram-positive. Therefore, antibiosis preceding microbiological examination should cover both the aerobic and anaerobic bacteria as well as the gram-positive and the gram-negative spectrum.

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features.

Gastric cancer is one of the most common malignancies worldwide. The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved. A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome. With this intention, first steps have been made in the research of growth factor signaling. Regarding morphogens, cell cycle and nuclear factor-κB signaling, a remarkable count of target-specific agents have been developed, nevertheless the transfer into the field of clinical routine is still at the beginning. The potential utility of epigenetic targets and the further evaluation of microRNA signaling seem to have potential for the development of novel treatment strategies in the future.

Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival.

Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.

Predictive factors for survival and recurrence rate in patients with node-negative gastric cancer--a European single-centre experience.

PURPOSE: Gastric cancer is a common disease with poor prognosis. Lymph node involvement is the strongest prognostic factor regarding survival in curatively (R0) resected patients. The aim of this study was to determine if a subgroup with higher risk for tumour recurrence exists in patients with node-negative gastric cancer. Furthermore, we aimed to identify prognostic factors and recurrence patterns for this subgroup. METHODS: We collected demographical, clinical, pathohistological and follow-up data from 1,074 patients with gastric cancer in a prospectively maintained database. In 228 cases, R0 resections for node-negative gastric cancer were performed. The median follow-up period was 59 months. Statistical analysis was performed using SPSS 19.0. RESULTS: The 5- , 10- and 15-year overall survival was 83, 75.5 and 73 %, respectively, with a disease-free survival of 78, 73 and 73 %. Tumour recurrence was observed in 18.9 % (43 cases), 14 % of which were diagnosed after more than 5 years. Gender, T-category , lymphangioinvasion, tumour differentiation, serosal infiltration, histological growth pattern, tumour size and classification according to Lauren were significant prognostic factors for overall survival in univariate analysis. Multivariate analysis showed tumour size and female sex to be independent prognostic factors. Non-exophytic tumour growth was a relevant factor for the development of local recurrence. Diffuse type gastric cancers as well as signet ring cells were significantly associated with the development of peritoneal carcinomatosis, and male gender with hematogenous metastases. CONCLUSIONS: Multimodal treatment and individual follow-up might be beneficial in patients with higher risk of recurrence after R0 resection of node-negative gastric cancer.

Suture granuloma mimicking a recurrent sacro-coccygeal pilonidal sinus after Limberg flap.

Sacro-coccygeal pilonidal sinus disease is classified as an asymptomatic, acutely abscess-forming or chronic subcutaneous inflammation in the sacro-coccygeal region featuring characteristic pits in the bottom cleft. Due to high rates of recurrence, two flap techniques have been established in the course of the past three decades. One of them is the Karydakis operation, the other option is a rotation flap named Limberg procedure. We report about a case of suture granuloma in the area of a Limberg flap after recurrent pilonidal sinus with extrusion of the suture material, thus mimicking recurrence. In case of recurrent pilonidal sinus following plastic coverage or primary closure, respectively, the differential diagnosis of suture granuloma should be considered.

Clinical symptoms and sonographic follow-up after surgical treatment of nonparasitic liver cysts.

BACKGROUND: The optimal treatment of nonparasitic liver cysts is still a topic of debate. Only symptomatic cysts are being considered as requiring treatment. Aim of this study is to evaluate our experience with this disease over the past ten years with a structured follow-up program. METHODS: From January 2000 to August 2010, 56 consecutive patients with nonparasitic liver cysts were treated at our institution. We assessed morbidity, recurrence and complication rates, quality of life as well as pre- and post-operative sonographic status of the cysts and course of clinical symptoms. RESULTS: In 84% of the patients surgery was started as a laparoscopic procedure. Conversion rate was 6.4%. Average diameter of deroofed cysts was 12 cm. Overall complication rate was 16% and overall recurrence rate 28.3% (8.7% recurrences at the surgical site, 19.6% new or enlarged cysts). One half of the patients were symptom-free after surgery and the other half had at least one persisting symptom post-operatively. In one half of these patients with persisting symptoms, symptoms were ameliorated by surgery. In the other half of patients the number of symptoms increased after surgery. Two thirds of the overall patients reported their post-operative health as being good or very good. CONCLUSIONS: Surgical deroofing is the most effective treatment option for symptomatic liver cysts. Half of our patient population retained at least one symptom from a group of more than ten abdominal symptoms.Only the minority of these cases may be attributed to true recurrence, de-novo cysts or growing pre-existing cysts. The analysis of our cases suggests that the persistent symptoms in our patients may in part be due to the fact that the association between clinical complaints and the liver cysts was not sufficiently established. A more rigid patient selection should be implemented in order to achieve better results from the treatment of cysts. Because even large cysts are frequently asymptomatic, patient selection should not primarily be based on the cyst size only. The decision should be based strictly on the correlation between cyst / cyst location and symptoms / clinical complaints. In our opinion, further diagnostic procedures may be necessary in individual cases to clarify such a correlation.

Waiting time, not donor-risk-index, is a major determinant for beneficial outcome after liver transplantation in high-MELD patients.

BACKGROUND: Due to the increasing donor shortage, patients undergo liver transplantation actually mostly with high MELD-scores. In this study, we analyze high-MELD patients who underwent liver transplantation at a german single center. MATERIAL AND METHODS: Since implementation of the MELD-score within the Eurotransplant region (December 2006) up to May 2011, 45 patients with a lab-MELD-score ≥ 36 underwent liver transplantation at our center. We correlated the 1-year-survival with donor data (especially the donor risk index, DRI), the time interval from reaching a lab-MELD-score ≥ 36 up to liver transplantation and the recipient's state prior transplantation. RESULTS: The overall 1-year-survival in our cohort is 68,8%. Waiting time of survivors was significantly shorter compared to non-survivors (MedianSurvivors: 2 days vs. MedianNon-survivors: 4 days; p=0.049). DRI showed no significant differences between both groups. Furthermore, the recipient's state prior transplantation (dialysis, mechanical ventilation, catecholamines) showed no significant association with the outcome. CONCLUSIONS: The outcome after liver transplantation in high-MELD patients is worse compared to that of patients with a marked lower MELD-score. Especially the time interval between reaching a lab-MELD score ≥ 36 to the transplantation is a major determinant for survival. Since the DRI is not associated with a worsened outcome, transplantation centers should accept even marginal organs for high-MELD patients to keep the waiting time as short as possible.

Liver transplantation for hilar cholangiocarcinoma--a single-centre experience.

BACKGROUND: Cholangiocarcinoma is an infrequent malignancy, often unresectable at the time of diagnosis. Liver transplantation may offer a chance for cure, but results in the past have been disappointing, prompting transplant centres to adopt multimodal treatment protocols and extreme patient selection. PURPOSE: This study was designed to evaluate the outcome of patients with irresectable hilar cholangiocarcinoma undergoing liver transplantation in order to determine criteria for patient selection. METHODS: We reviewed our prospective cancer registry for patients with hilar cholangiocarcinoma treated by transplantation since 1997. Data were evaluated regarding tumour location, stage, overall survival, recurrence rates and prognostic factors. RESULTS: Liver transplantation with lymphadenectomy was realised in 16 patients with hilar cholangiocarcinoma. Seven patients received a living donor graft. Lymph node metastases were found in eight patients with a median of 13 harvested nodes and had a statistically significant negative impact on overall survival irrespective of tumour size. Only one patient underwent neoadjuvant brachytherapy and developed fatal septic complications; 3- and 5-year survival rates were 63 and 50 % in lymph node-negative patients without neoadjuvant treatment. CONCLUSIONS: Acceptable survival rates can be achieved by transplantation for hilar cholangiocarcinoma with lymph node metastases as the only exclusion criterion. We recommend staging laparotomy with lymphadenectomy along the common hepatic artery prior to liver transplantation.

Long-term results and prognostic factors after resection of hepatic and pulmonary metastases of colorectal cancer.

BACKGROUND: Resection of colorectal liver or lung metastases is an established therapeutical concept at present. However, an affection of both these organs is frequently still regarded as incurable. METHODS: All cancer patients are documented in our prospective cancer registry since 1995. Data of patients who underwent liver and lung resection for colorectal metastases were extracted and analysed. RESULTS: Sixty-five patients underwent surgery for liver and lung metastases. In 33 cases, the first distant metastasis was diagnosed synchronously to the primary tumour. For the remaining patients, median time interval between primary tumour and first distant metastasis was 18 months (5-69 months). Complete resection was achieved in 51 patients (79 %) and was less likely in patients with synchronous disease (p = 0.017). Negative margins (p = 0.002), the absence of pulmonary involvement in synchronous metastases (p = 0.0003) and single metastases in both organs (p = 0.036) were associated with a better prognosis. Five- and 10-year survival rates for all patients are 57 and 15 % from diagnosis of the primary tumour, 37 and 14 % from resection of the first metastasis and 20 and 15 % from resection of the second metastasis. After complete resection, 5- and 10-year survival rates increased to 61 and 18 %, 43 and 17 % as well as 25 and 19 %, respectively. Long-term survivors (≥10 years) were seen only after complete resection of both metastases. CONCLUSIONS: Patients with resectable liver and lung metastases of the colorectal primary should be considered for surgery after multidisciplinary evaluation regardless of the number or size of the metastases or the disease-free intervals. Clear resection margins are the strongest prognostic parameter.

New methods for clinical pathways-Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM).

PURPOSE: Clinical pathways (CP) are nowadays used in numerous institutions, but their real impact is still a matter of debate. The optimal design of a clinical pathway remains unclear and is mainly determined by the expectations of the individual institution. The purpose of the here described pilot project was the development of two CP (colon and rectum carcinoma) according to Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM). METHODS: BPMN is an established standard for business process modelling in industry and economy. It is, in the broadest sense, a computer programme which enables the description and a relatively easy graphical imaging of complex processes. t.BPM is a modular construction system of the BPMN symbols which enables the creation of an outline or raw model, e.g. by placing the symbols on a spread-out paper sheet. The thus created outline can then be transferred to the computer and further modified as required. CP for the treatment of colon and rectal cancer have been developed with support of an external IT coach. RESULTS: The pathway was developed in an interdisciplinary and interprofessional manner (55 man-days over 15 working days). During this time, necessary interviews with medical, nursing and administrative staffs were conducted as well. Both pathways were developed parallel. Subsequent analysis was focussed on feasibility, expenditure, clarity and suitability for daily clinical practice. The familiarization with BPMN was relatively quick and intuitive. The use of t.BPM enabled the pragmatic, effective and results-directed creation of outlines for the CP. The development of both CP was finished from the diagnostic evaluation to the adjuvant/neoadjuvant therapy and rehabilitation phase. The integration of checklists, guidelines and important medical or other documents is easily accomplished. A direct integration into the hospital computer system is currently not possible for technical reasons. CONCLUSION: BPMN and t.BPM are sufficiently suitable for the planned modelling and imaging of CP. The application in medicine is new, and transfer from the industrial process management is in principle possible. BPMN-CP may be used for teaching and training, patient information and quality management. The graphical image is clearly structured and appealing. Even though the efficiency in the creation of BPMN-CP increases markedly after the training phase, high amounts of manpower and time are required. The most sensible and consequent application of a BPMN-CP would be the direct integration into the hospital computer system. The integration of a modelling language, such as BPMN, into the hospital computer systems could be a very sensible approach for the development of new hospital information systems in the future.

Non-curative gastric resection for patients with stage 4 gastric cancer--a single center experience and current review of literature.

PURPOSE: The majority of patients with gastric cancer present with an advanced stage and, therefore, may not be eligible for curative treatment. The role of non-curative gastric resection in situations other than emergency treatment for life threatening tumor-related complications is still under discussion. METHODS: Data from 290 consecutive patients with advanced gastric cancer who were treated in our hospital were analyzed. A total of 48 patients underwent primary non-curative gastric resection. RESULTS: The overall survival in the non-curatively resected group was 15 months and 6 months for non-resected patients, respectively (p < 0.001). The incidence of tumor-related complications which required intervention was 63% in non-resected patients as compared to 12% in patients who underwent primary non-curative resection. Younger age, less than three tumor locations, and chemotherapy have been identified as prognostic factors for improved survival by univariate analysis. D3 lymph node involvement and chemotherapy were independent prognostic factors in the multivariate analysis. Peritoneal carcinosis did not significantly influence survival in resected patients. Non-curative resection in combination with chemotherapy resulted in longer overall survival than resection alone. CONCLUSIONS: Primary non-curative gastric resection can reduce the incidence of severe tumor-related complications and can prolong overall survival in selected subgroups. In particular, younger patients with no more than two tumor locations should be considered for this procedure.

Stent migration to the ileum: a potentially lethal complication after Montgomery salivary bypass tube placement for hypopharyngeal stenosis after laryngectomy.

BACKGROUND: Montgomery salivary bypass tubes (MSBTs) have been used for decades in the treatment of stenoses and fistulae of the hypopharynx and the cervical esophagus. Generally, MSBT use is not associated with serious complications. Only a small number of cases with severe MSBT-associated complications have been reported in the literature. METHODS AND RESULTS: We report for the first time an MSBT migration to the ileum in a laryngectomized patient who underwent surgical pharyngocutaneous fistula closure with MSBT placement. The MSBT was removed surgically via laparotomy. The patient died 15 days later due to sepsis associated with peritonitis. CONCLUSION: To avoid potentially lethal complications associated with MSBT migration into the intestinal tract, we recommend secure fixation of the MSBT to a nasogastric tube.

Resection of liver metastases is beneficial in patients with gastric cancer: report on 15 cases and review of literature.

BACKGROUND: Although up to 9% of patients with gastric cancer develop liver metastases, liver resection is rarely performed because of co-existing non-curative factors. Furthermore, the benefit of liver resection is still controversially discussed. Our goal was to investigate the outcome of patients who underwent liver resection or radiofrequency ablation (RFA) for hepatic metastasized gastric cancer. METHODS: Retrospectively collected data from a prospectively maintained database were analyzed from 15 patients who underwent liver resection or RFA for liver metastases from gastric cancer. RESULTS: Overall 5-year survival and median survival were 27% and 48 months for resected/RFA patients. The peri-operative complication rate was low. One patient has been tumor-free for 90 months now. CONCLUSIONS: Liver resection in patients with hepatic metastasized gastric cancer is beneficial and safe if an R0 situation can be achieved. RFA might be a useful alternative in those patients where surgery is not feasible.

Impact of clinical and pathohistological characteristics on the incidence of recurrence and survival in elderly patients with gastric cancer.

BACKGROUND: Gastric cancer is one of the most frequent malignant tumors worldwide. Despite improvements in diagnostic procedures, as well as the introduction of multimodal treatment strategies, the overall prognosis remains poor. The role of gastric resection in elderly patients with gastric cancer has not been clearly defined as yet. The goal of the present study was to assess whether specific pathohistological features result in different outcomes for younger patients and elderly patients. METHODS: A total of 272 patients with advanced gastric cancer treated surgically in our hospital between 1998 and 2009 were included in the study. Data were analyzed from a prospectively maintained database. RESULTS: Median overall survival was 84 months in the younger subgroup and 37 months in the elderly subgroup (P = 0.038), whereas local recurrence occurred more frequently in younger patients (33% vs. 23%). We identified positive lymph nodes at the contralateral curvature, perilymphonodular tumor cells, and positive lymph node conglomerates as strong negative prognostic factors. There were few pathohistological characteristics that affected survival and the incidence of tumor recurrence differently in elderly and younger patients. Although only a few elderly patients underwent chemotherapy plus gastric resection (7% vs. 28% of the younger patients), there was a trend toward longer survival for those who received multimodal treatment. CONCLUSIONS: Our results suggest that there is no tumor-related prognostic difference between young and elderly patients that would preclude radical surgery in elderly patients, as long as they are generally fit for surgery.

Predictors of long-term survival in patients with colorectal liver metastases: a single center study and review of the literature.

PURPOSE: Prognosis after resection of liver metastases of colorectal cancer is influenced by a variety of clinical factors. For more than 20 years, efforts have been made to restructure and simplify prognostic parameters into clinical scores. We evaluated the influence of various clinical and pathological factors on survival and recurrence and developed a simple model for risk stratification. METHODS: We have analyzed a total of 13 prognostic factors in 382 consecutive and prospectively enrolled R0-resected patients and applied our data set to ten published prognostic scoring systems. Prognostic factors that influenced disease-specific and disease-free survival were included into a model clinical risk score. RESULTS: The 5- and 10-year observed survival rates were 43% and 28%, respectively, for all 382 patients. The disease-specific 5- and 10-year survival rates were 49% and 37%, respectively; the 5- and 10-year recurrence rates were 68% and 70%, respectively. For patients with synchronous liver metastases, survival was not affected by the timing of liver resection. The prognosis after treatment of any recurrence was best after the accomplishment of a repeated R0 situation, independent of the location of the recurrence. In the multivariate analysis, the disease-specific survival and recurrence rates were statistically significantly influenced by more than three lymph node metastases of the primary tumor, more than two lesions within the liver, and the presence of extrahepatic tumor. CONCLUSIONS: From these data, we have developed a simple score for the risk stratification which may be useful for future studies on interdisciplinary management of colorectal liver metastases.

Relationship between degree of chromosomal aberration and survival in intestinal-type gastric cancer - a preliminary report based on three cases of hepatic metastasized gastric cancer with long-time survival.

BACKGROUND: Gastric cancer is one of the most frequent malignancies worldwide. More than 50% of all patients present with advanced stage of disease, with long-time survival of less than 5%. In selected subgroups, palliative gastric resection seems to be beneficial for survival and improved quality of the remaining life time, but is still controversially discussed. PATIENTS AND METHODS: We report 3 cases of patients with intestinal-type advanced gastric cancer. All patients presented preoperatively with stage IV disease with liver metastases. The patients underwent palliative gastric resection and subsequent palliative chemotherapy. We performed a genome-wide DNA analysis of 9 gastric cancer tissue specimens using the DNA microchip array technique. RESULTS: 4 and 6 years after palliative surgery and chemotherapy, 2 of the patients show no signs of recurrence, while the third patient shows stable disease under third-line chemotherapy 4 years after the initial diagnosis. Comparative genetic analysis of 9 gastric cancer tissue specimens suggested that the degree of chromosomal aberration was closely related to survival for intestinal-type gastric cancers. CONCLUSIONS: Palliative gastric resection is beneficial for survival and quality of life in selected patients. Determination of the degree of chromosomal aberrations might be helpful in predicting the response on multimodal treatment in intestinal-type gastric cancer. A better understanding of molecular biology is needed to define prognosis markers and molecular targets.

Thrombin-mediated hepatocellular carcinoma cell migration: cooperative action via proteinase-activated receptors 1 and 4.

Proteinase-activated receptor-1 (PAR(1)), a thrombin receptor and the prototype of a newly discovered G-protein-coupled receptor subfamily, plays an important role in tumor development and progression. In this study, we documented the expression of the thrombin receptors PAR(1), PAR(3), and PAR(4) in permanent hepatocellular carcinoma (HCC) cell lines and primary HCC cell cultures. Stimulation of HCC cells with thrombin and the PAR(1)-selective activating peptide, TFLLRN-NH(2), increased transmembrane migration across a collagen barrier. This effect was blocked by the PAR(1) antagonist SCH 79797, confirming that the PAR(1) thrombin receptor subtype is involved in regulating hepatoma cell migration. In addition, the PAR(4)-selective agonist, AYPGKF-NH(2), also stimulated HCC cell migration whilst the PAR(4) antagonist, trans-cinnamoyl-YPGKF-NH(2), attenuated the effect of thrombin on HCC cell migration. PAR(1)- and PAR(4)-triggered HCC cell migration was blocked by inhibiting a number of key mediators of signal transduction, including G proteins of the G(i)/G(o) family, matrix metalloproteinases, ERK/MAPKinase, cyclic AMP-dependent protein kinase, Src tyrosine kinase, and the EGF receptor kinase. Our data point to a cooperative PAR(1)/PAR(4) signaling network that contributes to thrombin-mediated tumor cell migration. We suggest that a combined inhibition of coagulation cascade serine proteinases, the two PARs and their complex signaling pathways may provide a new strategy for treating hepatocellular carcinoma.