Philipp Schüler

Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial

BACKGROUND Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. METHODS This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. FINDINGS Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598; OR 0·91, 95% CI 0·66-1·25; p=0·64). Serious adverse events also did not differ between the groups-146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). INTERPRETATION Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. FUNDING Johnson & Johnson Medical Limited.

Gastrointestinal stromal tumors

IntroductionThe gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the intestinal tract, known to be refractory to conventional chemotherapy or radiation. Its pathogenesis is defined by mutations within the KIT and PDGFRA gene, which constitutively activate KIT and PDGFRA oncoproteins, and serve as crucial diagnostic and therapeutic targets.DiscussionBesides surgery, therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. Still, the only curative option for GIST is given after complete surgical removal even in a metastatic setting, but recurrence is common, and the risk can be defined by surgical factors like incomplete resection, intraperitoneal rupture, or bleeding and tumor associated factors like tumor size, mitotic index, or localization.ConclusionConsequently, adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors is recommended for high-risk patients after complete resection. For unresectable and advanced GIST, a partial response or stable disease can be achieved in about 80% of patients with imatinib mesylate.

Enrichment of CD133-expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival

The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as Prominin or PROM1) has been described as a potential stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study, CD133 expression was evaluated in pre‐RCT tumor biopsies and the corresponding post‐RCT surgical specimens from patients with locally advanced rectal adenocarcinoma, and expression levels were correlated with histopathologic features and clinical follow‐up.

Common Genomic Aberrations in Basaloid Squamous Cell Carcinoma and Carcinosarcoma of the Esophagus Detected by CGH and Array CGH

Basaloid squamous cell carcinoma (BSCC) and carcinosarcoma of the esophagus are rare entities, making up fewer than 2% of esophageal malignancies. Comparative genomic hybridization (CGH) in 1 case of BSCC and 2 cases of carcinosarcoma and subsequent array CGH in 1 case each of BSCC and carcinosarcoma revealed common chromosomal gains at 2p25.3-2p12, 7q21.3-7q22.3, and 11q13.2-11q13.4. Chromosomal losses at 13q31qter were observed in both carcinosarcomas. In addition, progression of genomic instability from in situ to invasive carcinosarcoma could be demonstrated by using array CGH. Our observations suggest a common genetic origin of BSCC and carcinosarcoma.

Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival.

In gastrointestinal stromal tumors (GISTs), the occurrence of an epithelioid/mixed phenotype has been correlated to PDGFRA mutations, gastric localization and favorable outcome. On the other hand, the prognostic significance of an epithelioid/mixed growth pattern occasionally observed in GISTs with KIT mutation is unclear. The aim of this study was to evaluate the prognostic significance of an epithelioid/mixed phenotype in correlation to anatomical localization, genotype, and expression of cell-cycle markers in a series of 116 primary GISTs with KIT mutation on a tissue microarray. Independent of their anatomical localization, the majority of KIT-mutated GISTs displayed a pure spindled phenotype (72%), with the remaining tumors showing an epithelioid/mixed growth pattern. In KIT-mutated GISTs from the stomach, the occurrence of an epithelioid/mixed growth pattern was significantly correlated with larger tumor diameters (P=0.005), higher mitotic counts (P=0.0001), high-risk category (P=0.001), higher expression of the G2-phase cell-cycle marker cyclin B1 (P=0.04), higher expression of the G1 to M-phase proliferation marker Ki67 (P=0.02) and a significantly shorter disease-free survival (P=0.003) compared with tumors with pure spindled morphology. In contrast, there were no significant differences between pure spindled and epithelioid/mixed GISTs from the small/large bowel. Our findings indicate that the epithelioid/mixed phenotype in KIT-mutant gastric GISTs represents a secondary tumor growth pattern associated with tumor progression and adverse outcome, probably through accelerated G1/S-phase restriction point passage.

Emergency Repair of Giant Inguinoscrotal Hernia in a Septic Patient

IntroductionGiant inguinoscrotal hernias are rare but still exist even in developed countries. Although accompanied by a higher perioperative mortality, an elective surgical approach should be undertaken. In critically ill patients, however, the surgical intervention requires specific demands.MethodsWe report a case of a 45-year-old man who was referred to the hospital after perforation of the hernia with concomitant peritonitis and sepsis.ResultsAfter initial stabilization of the patient, a subtotal colectomy and a partial small bowl resection was performed. In a second step after stabilization of organ functions, the hernia sac was resected, and the abdominal cavity was reconstructed. The patient was discharged and is doing well until today but still refuses any plastic surgery.ConclusionResection of giant inguinoscrotal hernia is feasible even in patients being administered in an emergency setting. Especially in case of an intra-abdominal infection, intestinal resection is the therapy of choice to allow the reconstruction of the abdominal cavity. A two-step approach should be considered to allow a successful recovery.

High chromosomal instability in adenocarcinoma of the ileum arising from multifocal gastric heterotopia with gastritis cystica profunda.

Adenocarcinoma of the small intestine arising from heterotopic gastric mucosa is extremely rare. In this report, we present the case of a 68-year-old woman who complained of abdominal pain, weight loss and subileus. Gross examination of resected small bowel revealed multiple flat polypous lesions with cysts in the ileal submucosa, one of which containing an ulcerated, stenosing tumour. On microscopic examination, an adenocarcinoma of the ileum arising from multifocal gastric heterotopia with secondary gastritis cystica profunda was diagnosed. Comparative genomic hybridization of the adenocarcinoma revealed chromosomal gains at 1q, 3q, 5p, 8q, 11p, 12p, 13q and losses at Xp, 4q, 8p, 10p, 14q, 17p, 20p, compatible with a high degree of genomic instability.

Effect of laparotomy and CO2 pneumoperitoneum on tumor growth of human colon carcinoma and expression pattern of tumor-associated proteins in the SCID mouse

Background and aimsThe impact of laparoscopy on tumor progression is still unclear. This study investigated the effect of CO2 pneumoperitoneum on the intra-abdominal growth of human colon carcinoma independently of the effect of the immune system.MethodsSCID mice underwent either median laparotomy or laparoscopy. Human colon carcinoma cells were implanted into the upper abdomen. The control group was not operated on following cell injection. Tumor growth and the protein expression pattern of proliferation marker Ki67, cell-cell adhesion molecules E-cadherin, α- and β-catenin, and cell-extracellular matrix adhesion molecules CD44 v5 and v6 in tumor tissue were analyzed on postoperative day 14.ResultsTotal tumor volume in the laparoscopy group significantly exceeded that in the laparotomy group. Immunohistochemistry revealed reduced expression of α-catenin and elevated expression on β-catenin and CD44 v5 in the tumor tissue of the laparoscopy group.ConclusionThe expression pattern of proteins associated with tumor progression and the increase in tumor growth suggest an increased risk of laparoscopy at least for the growth of advanced human colon carcinoma.

Neoadjuvant Therapy in Rectal Cancer - Biobanking of Preoperative Tumor Biopsies

Translational research relies on high-quality biospecimens. In patients with rectal cancer treated preoperatively with radiochemotherapy tissue based analyses are challenging. To assess quality challenges we analyzed tissue samples taken over the last years in a multicenter setting. We retrospectively evaluated overall 197 patients of the CAO/ARO/AIO-94- and 04-trial with locally advanced rectal cancer that were biopsied preoperatively at the University Medical Center Goettingen as well as in 10 cooperating hospitals in Germany. The cellular content of tumor, mucosa, stroma, necrosis and the amount of isolated DNA and RNA as well as the RNA integrity number (RIN) as quality parameters were evaluated. A high RNA yield (p = 2.75e–07) and the content of tumor (p = 0.004) is significantly associated to high RIN-values, whereas a high content of mucosa (p = 0.07) shows a trend and a high amount of necrosis (p = 0.01) is significantly associated with RNA of poor quality. Correlating biopsies from Goettingen and the cooperating centers showed comparable tumor content results. By taking small sized biopsies we could assess a clear correlation between a good RNA quality and a high amount of RNA and tumor cells. These results also indicate that specimens collected at different centers are of comparable quality.

Individual endoscopic management of anastomotic insufficiency after esophagectomy for esophageal squamous cell carcinoma and creation of a neostomach

A 57-year-old patient with a T3, cN0, G2, M0 esophageal squamous cell cancer received neoadjuvant radiochemotherapy according to the CROSS trial. After successful esophagectomy and consecutive gastroesophageal anastomosis, the patient recovered appropriately. Unfortunately, the patient developed circular anastomotic insufficiency with two cavities at Day 7 (▶Fig. 1). One of the cavities arose from the circular insufficiency (2×2 cm), and the other was formed by a stapler insufficiency of the stomach (3×2 cm). The final tumor stage was histologically proven to be ypT0, N0, cM0, L0, V0, R0. We started repetitive endoluminal vacuum therapy (Endo-Sponge; B. Braun, Melsungen, Germany) for a treatment period of 2 months (▶Video1). Owing to the remarkable dimension of the cavities, we decided initially to place two devices per insufficiency (▶Fig. 2), and in total, 11 device replacements were performed. After 2 weeks of treatment, the use of one Endo-Sponge appeared to be sufficient to cover all areas of insufficiency. A negative intracavital pressure was applied (15–20mmHg) in order to avoid the development of pulmonary fistula. Antibiotic and antifungal treatment was also administered during the first 2 weeks of the vacuum therapy. The patient received parenteral nutrition but was allowed to drink liquids during the treatment period (▶Fig. 3). Unfortunately, despite appropriate endoscopic procedures and frequent Endo-Sponge exchange, the insufficiencies failed to heal and the cavities persisted. Therefore, a more aggressive endoscopic therapeutic approach was initiated (▶Video1). We utilized cytological brushes and argon plasma coagulation at the edges of cavital insufficiencies in order to induce vascular spreading and wound granulation (▶Fig. 4). Fibrotic tissue and surgical staple sutures were endoscopically removed using cutting devices and graspers. Mucosal bridges were cut by needle-knife incision, leading to development of a neostomach and esophagogastric continuity. In addition, epithelial mucosa spreading occurred, evolving from the upper esophageal tissue. After 2 months of endoscopic treatment, neither fistula nor anastomotic insufficiencies were detectable. In addition, a neostomach had been created, consisting of mediastinal parietal pleura, the distal esophagus, and the remnant stomE-Videos