Antibiotic treatment after appendectomy for acute complicated appendicitis to prevent intrabdominal abscess and wound infections.

INTRODUCTION: The purpose of this analysis was to investigate the most appropriate duration of postoperative antibiotic treatment to minimize the incidence of intraabdominal abscesses and wound infections in patients with complicated appendicitis. MATERIALS AND METHODS: In this retrospective study, which included 396 adult patients who underwent appendectomy for complicated appendicitis between January 2010 and December 2020 at the University Hospital Erlangen, patients were classified into two groups based on the duration of their postoperative antibiotic intake: ≤ 3 postoperative days (group 1) vs. ≥ 4 postoperative days (group 2). The incidence of postoperative intraabdominal abscesses and wound infections were compared between the groups. Additionally, multivariate risk factor analysis for the occurrence of intraabdominal abscesses and wound infections was performed. RESULTS: The two groups contained 226 and 170 patients, respectively. The incidence of postoperative intraabdominal abscesses (2% vs. 3%, p = 0.507) and wound infections (3% vs. 6%, p = 0.080) did not differ significantly between the groups. Multivariate analysis revealed that an additional cecum resection (OR 5.5 (95% CI 1.4-21.5), p = 0.014) was an independent risk factor for intraabdominal abscesses. A higher BMI (OR 5.9 (95% CI 1.2-29.2), p = 0.030) and conversion to an open procedure (OR 5.2 (95% CI 1.4-20.0), p = 0.016) were identified as independent risk factors for wound infections. CONCLUSION: The duration of postoperative antibiotic therapy does not appear to influence the incidence of postoperative intraabdominal abscesses and wound infections. Therefore, short-term postoperative antibiotic treatment should be preferred.

Surgical and oncological outcome after extended lymph node dissection for carcinoma of the stomach and the esophagogastric junction: a retrospective analysis from an experienced single center.

Introduction: Gastric cancer remains the fourth leading cause of cancer-related death in Europe, while the proportion of adenocarcinomas of the esophagogastric junction has risen by more than one third over recent years. In 2018, 14,700 new cases of gastric cancer were estimated in Germany, while the 5-year relative survival rate is reported to be 33% for women and 30% for men; in the USA almost the same rate was reported, with 31% 5-year survival. Material and methods: Between 2001 and 2014, 590 patients with a diagnosis of gastric cancer underwent surgery in our institution, including 120 Siewert type II/III carcinomas of the esophagogastric junction. All patients underwent distal resection of the stomach, gastrectomy or total gastrectomy combined with transhiatal distal esophageal resection. All operations included D2-D3 lymph node dissection (LND). Data were recorded by the cancer registry of the department of surgery and analyzed retrospectively. Results: The patients were classified according to the TNM (UICC 2010) and Lauren classification. 29% of the patients underwent primary surgery and 31% received neoadjuvant therapy. The median number of harvested lymph nodes was 33 for patients diagnosed with gastric cancer, and 29 for esophagogastric adenocarcinomas, respectively. The anastomotic leak rate was 3%. In this study, the 5-year overall survival rate was 51% concerning gastric carcinomas, 44% for Siewert type II and 47% for Siewert III cancers of the esophagogastric junction. Conclusions: Increased survival with low complication rates were achieved after individualized and multimodal treatment concepts combined with consistently applied extended lymphadenectomy.

The role of intraoperative swab during appendectomy in patients with uncomplicated and complicated appendicitis.

INTRODUCTION: Bacteria play an important role not only in pathogenesis of appendicitis but also in the postoperative course of patients. However, the usefulness of an intraoperative swab during appendectomy is controversial. The primary aim of this study was to investigate the impact of intraoperative swab during appendectomy on the postoperative outcome in patients with uncomplicated and complicated appendicitis. METHODS: A retrospective analysis was conducted on a consecutive series of 1570 adult patients who underwent appendectomy for acute appendicitis at the University Hospital Erlangen between 2010 and 2020. Data regarding the intraoperative swab were collected and analyzed for the entire cohort as well as for patients with uncomplicated and complicated appendicitis. RESULTS: An intraoperative swab was taken in 29% of the cohort. The bacterial isolation rate in the obtained intraoperative swabs was 51%, with a significantly higher rate observed in patients with complicated appendicitis compared to those with uncomplicated appendicitis (79% vs. 35%, p < 0.001). The presence of a positive swab was significantly associated with worse postoperative outcomes, including higher morbidity, increased need for re-surgery, and longer hospital stay, when compared to patients without a swab or with a negative swab. A positive swab was an independent risk factor for postoperative morbidity (OR 9.9 (95% CI 1.2-81.9), p = 0.034) and the need for adjustment of postoperative antibiotic therapy (OR 8.8 (95% CI 1.1-72.5), p = 0.043). However, a positive swab resulted in postoperative antibiotic therapy adjustment in only 8% of the patients with bacterial isolation in the swab. CONCLUSION: The analysis of swab samples obtained during appendectomy for acute appendicitis can help identify patients at a higher risk of a worse postoperative outcome. However, the frequency of antibiotic regime changes based on the swab analysis is low.

Risk Factors for Conversion from Laparoscopic to Open Appendectomy.

(1) Background: Since its introduction in the 1990s, laparoscopic appendectomy has become established over the years and is today considered the standard therapy for acute appendicitis. In some cases, however, a conversion to the open approach is still necessary. The primary aim of this study was to identify risk factors for the need to convert from the laparoscopic to an open approach during appendectomy for acute appendicitis. (2) Methods: A retrospective analysis of 1220 adult patients who underwent laparoscopic appendectomy for acute appendicitis from 2010 to 2020 at the University Hospital Erlangen was performed. Data, including patient demographics and pre-, intra-, and postoperative findings, were collected and compared between patients with and without conversion. (3) Results: The conversion rate in our cohort was 5.5%. A higher preoperative WBC count and CRP (OR 1.9, p = 0.042, and OR 2.3, p = 0.019, respectively), as well as the presence of intraoperative perforation, necrosis or gangrene, perityphlitic abscess and peritonitis (OR 3.2, p = 0.001; OR 2.3, p = 0.023; OR 2.6, p = 0.006 and OR 2.0, p = 0.025, respectively) were identified as independent risk factors for conversion from the laparoscopic to the open approach. Conversion was again independently associated with higher morbidity (OR 2.2, p = 0.043). (4) Conclusion: The laparoscopic approach is feasible and safe in the majority of patients with acute appendicitis. Only increased inflammatory blood markers could be detected as the preoperative risk factors potentially influencing the choice of surgical approach but only with low specificity and sensitivity. For the decision to convert, intraoperative findings are additionally crucial. However, patients with conversion should receive special attention in the postoperative course, as these have an increased risk of developing complications.

Risk factors for postoperative morbidity, prolonged length of stay and hospital readmission after appendectomy for acute appendicitis.

PURPOSE: The aim of the present study was to identify risk factors associated with postoperative morbidity and major morbidity, with a prolonged length of hospital stay and with the need of readmission in patients undergoing appendectomy due to acute appendicitis. METHODS: We performed a retrospective analysis of 1638 adult patients who underwent emergency appendectomy for preoperatively suspected acute appendicitis from 2010 to 2020 at the University Hospital Erlangen. Data including patient demographics, pre-, intra-, and postoperative findings were collected and compared between different outcome groups (morbidity, major morbidity, prolonged length of postoperative hospital stay (LOS) and readmission) from those patients with verified acute appendicitis (n = 1570). RESULTS: Rate of negative appendectomies was 4%. In patients with verified acute appendicitis, morbidity, major morbidity and readmission occurred in 6%, 3% and 2%, respectively. Mean LOS was 3.9 days. Independent risk factors for morbidity were higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, longer time to surgery and longer duration of surgery. As independent risk factors for major morbidity could be identified higher age, higher preoperative CRP, lower preoperative hemoglobin and longer time to surgery. Eight parameters were independent risk factors for a prolonged LOS: higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, need for conversion, longer surgery duration, presence of intraoperative complicated appendicitis and of postoperative morbidity. Presence of malignancy and higher preoperative WBC-count were independent risk factors for readmission. CONCLUSION: Among patients undergoing appendectomy for acute appendicitis, there are relevant risk factors predicting postoperative complications, prolonged hospital stays and readmission. Patients with the presence of the identified risk factors should receive special attention in the postoperative course and may benefit from a more individualized therapy.

[Pylorus-Preserving Pancreaticoduodenectomy (PPPD) with Segmental Portal Vein Resection]. / Pyloruserhaltende partielle Pankreatoduodenektomie mit segmentaler Pfortaderresektion.

INTRODUCTION: Pylorus-preserving partial pancreatoduodenectomy is a complex visceral operation, especially when simultaneous resection and reconstruction of the portal venous axis is necessary. Pancreatic anastomosis plays a decisive role in this procedure, since postoperative pancreatic fistula (POPF) is a frequent complication, with serious consequences (morbidity and mortality) for the affected patient. Various techniques are available for anastomosing the residual pancreas: the duct-to-mucosa pancreaticojejunostomy, invaginating pancreatojejunostomy, Blumgart anastomosis and pancreatogastrostomy. INDICATION: Adenocarcinoma of the pancreatic head with portal vein infiltration. PROCEDURE: Pylorus-preserving pancreaticoduodenectomy (PPPD) with portal vein resection. CONCLUSION: A standardised and structured approach to pylorus-preserving partial pancreatoduodenectomy helps the surgeon to perform this procedure safely. Performing a simultaneous portal vein resection increases the complexity of the procedure, but nonetheless, if infiltration of the portal venous axis is suspected, the indication for en-bloc resection should be given generously, as intraoperatively it is not possible to differentiate reliably between inflammatory adherence and tumour infiltration and portal vein/V.-mesenterica-superior-resection does not increase morbidity and mortality. The choice of the surgical technique for anastomosing the residual pancreas should be made by the surgeon on the basis of his expertise and, if necessary, adapted to the patient's situs, since the most important pancreatic anastomosis techniques appear to be equivalent according to the current evidence.

[Pancreatic cancer]. / Pankreaskarzinom.

Pancreatic cancer Abstract. Pancreatic cancer is the second most common cancer in the GI tract in Europe and North America and it is associated with a poor prognosis due to its aggressive tumor biology. Each year the number of deaths from pancreatic cancer is almost the same as the number of new cases diagnosed. Most of the pancreatic cancers develop from exocrine cells, while endocrine pancreatic cancers (i. e., neuroendocrine tumors or islet cell tumors) are uncommon. The term "pancreatic cancer" is typically used to refer to pancreatic adenocarcinoma, which will be the focus of this paper. Despite the introduction of multimodal therapy concepts, advanced surgical techniques, and increasing surgical specialization, overall survival in pancreatic cancer has not significantly improved. Early and complete surgical tumor resection remains the only curative option; however, this is rarely achieved, mainly due to the advanced stage at diagnosis. Adjuvant chemotherapy has become the gold standard after upfront resection. Neoadjuvant chemotherapy regimens, such as FOLFIRINOX, represent a valid option in order to achieve complete surgical tumor resection in more advanced cases. However, the overall uptake of this promising concept is very low.

[Economic impact of the COVID-19 pandemic in general and visceral surgery : A comparison of performance and revenue data from two departments of hospitals with different levels of referral]. / Ökonomische Auswirkung der COVID-19-Pandemie in der Allgemein- und Viszeralchirurgie : Ein Vergleich von Leistungs- und Erlösdaten zweier Kliniken aus Krankenhäusern unterschiedlicher Versorgungsstufen.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, German hospitals were required to limit the capacity for elective surgery to prevent the healthcare system from general overload. In March 2020, the German government passed the COVID-19 Hospital Relief Act that guaranteed compensation payments for these limitations. In this study the regional impact of this intervention were analyzed. MATERIAL AND METHODS: The performance data and revenue figures for the departments of general and visceral surgery of the University Hospital of Erlangen (UKER) and the District Hospital St. Anna Höchstadt/Aisch (KKH) during the period from 1 April to 30 June 2019 were compared with the respective period in 2020. RESULTS: There was a significant decrease in bed occupancy rates and case numbers of inpatient treatment. The latter declined by 20.06% in the UKER and 60.76% in the KKH. Nononcological elective surgery was reduced by 33.04% in the UKER and 60.87% in the KKH. The number of emergency procedures remained unchanged in the UKER, while they decreased by 51.58% in the KKH. The revenues from diagnosis-related groups (DRG) decreased by 22.12% (UKER) and 54% (KKH), respectively. After taking compensation payments and savings from variable material costs into account, the UKER recorded a loss of -3.87%, while there was a positive revenue effect of 6.5% in the KKH. DISCUSSION: The nonselective restriction of elective surgery had a significant impact on patient care and revenue figures at both locations. With respect to the increase of intensive care capacities, such untargeted measures do not appear to be efficient. In addition, the fixed rate of compensation payments led to an unbalanced distribution of the financial aid between the two departments.

Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis.

PURPOSE: Non-operative management of acute uncomplicated appendicitis has shown promising results but might carry the risk of delayed diagnosis of premalignant or malignant appendiceal tumors found by chance in 0.7-2.5% of appendiceal specimen after appendectomy. Purpose of this study was to analyze whether appendiceal tumors are associated with a complicated appendicitis and to determine risk factors for appendiceal neoplasm and malignancy in patients with acute appendicitis. METHODS: We performed a retrospective analysis of 1033 adult patients, who underwent appendectomy for acute appendicitis from 2010 to 2016 at the University hospital Erlangen. Data included patients' demographics; comorbidities; pre-, intra- and postoperative findings; and histopathological results. Complicated appendicitis was defined in the presence of perforation or abscess. RESULTS: Appendiceal neoplasm respectively malignancy rate was 2.8% respectively 1.5%. Using univariate analysis, we identified seven risk factors at least for appendiceal neoplasm or malignancy: age, ASA, C-reactive protein, appendiceal diameter, perforation, intraoperative perithyphilitic abscess, and complicated appendicitis. Risk for appendiceal neoplasm or malignancy was 4.4% respectively 2.7% in complicated acute appendicitis compared to 2.0% respectively 1.0% in uncomplicated appendicitis (p = 0.043 respectively p = 0.060). In multivariate analysis, age ≥ 50 years and a diameter of the appendix in the sonography ≥ 13 mm were independent risk factors predicting the presence of appendiceal neoplasm and malignancy. CONCLUSION: Among patients with appendicitis, there are relevant risk factors predicting appendiceal tumors, especially age and appendiceal diameter in sonography. But the identified risk factors have a low sensitivity and specificity, so obtaining a confident preoperative diagnosis is challenging.

[Laparoscopic Right Hemicolectomy with Complete Mesocolic Excision (CME)]. / Laparoskopische Hemikolektomie rechts mit kompletter mesokolischer Exzision (CME).

INTRODUCTION: Complete mesocolic excision (CME) is considered as good clinical practice according to the German S3 Guideline for colorectal cancer. This recommendation is based on evidence showing improved histopathological quality criteria of specimens taken and better oncological outcomes following CME surgery compared to conventional colon resections. However, CME surgery, especially of the right colon, is more complex - due to the high variability of the vascular structures (e.g. Truncus Henle) and the anatomical proximity to the stomach, duodenum and pancreas. To increase safety of laparoscopic right hemicolectomy with CME and to improve surgical education of this procedure, a German expert group has developed a standardised procedure with critical safety assessment. This video shows the technique of laparoscopic right hemicolectomy with complete mesocolic excision (CME), according to the concept first described by the German expert group on Lap-CME. INDICATION: Carcinoma of the ascending colon. PROCEDURE: Laparoscopic right hemicolectomy with complete mesocolic excision (CME). CONCLUSION: The proposed standardisation of laparoscopic right hemicolectomy with complete mesocolic excision accommodates the increased complexity of the right colon and structures it into well-defined steps with critical safety assessments, which may result in minimised intraoperative complications and increased patient safety and should improve training.

Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis.

BACKGROUND: Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets. METHODS: We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets. FINDINGS: We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF+/-) mice revealed neuronal enrichment of nNOS to be a consequence of BDNF loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre;Atg5fl/fl) against the hypersecretion/cerulein-induced, painful CP mouse model, we show that a similar nNOS enrichment is present in the painful cerulein-CP model, but absent in painless genetic models. Consequently, mice afflicted with painful cerulein-induced CP could be significantly relieved upon treatment with the specific nNOS inhibitor NPLA. INTERPRETATION: We propose nNOS inhibition as a novel strategy to treat the unbearable pain in CP. FUND: Deutsche Forschungsgemeinschaft/DFG (DE2428/3-1 and 3-2).

Laparoscopic right hemicolectomy with CME: standardization using the "critical view" concept.

BACKGROUND: Complete mesocolic excision is gradually becoming an established oncologic surgical principle for right hemicolectomy. However, the procedure is technically demanding and carries the risk of serious complications, especially when performed laparoscopically. A standardized procedure that minimizes technical hazards and facilitates teaching is, therefore, highly desirable. METHODS: An expert group of surgeons and one anatomist met three times. The initial aim was to achieve consensus about the surgical anatomy before agreeing on a sequence for dissection in laparoscopic CME. This proposal was evaluated and discussed in an anatomy workshop using post-mortem body donors along with videos of process-informed procedures, leading to a definite consensus. RESULTS: In order to provide a clear picture of the surgical anatomy, the "open book" model was developed, consisting of symbolic pages representing the corresponding dissection planes (retroperitoneal, ileocolic, transverse mesocolic, and mesogastric), vascular relations, and radicality criteria. The description of the procedure is based on eight preparative milestones, which all serve as critical views of safety. The chosen sequence of the milestones was designed to maximize control during central vascular dissection. Failure to reach any of the critical views should alert the surgeon to a possible incorrect dissection and to consider converting to an open procedure. CONCLUSION: Combining the open-book anatomical model with a clearly structured dissection sequence, using critical views as safety checkpoints, may provide a safe and efficient platform for teaching laparoscopic right hemicolectomy with CME.

[Cylindric Abdominoperineal Rectum Exstirpation with Partial Vulvar and Vaginal Resection as well as Perineal and Vaginal Defect Reconstruction by a Vertical Rectus Abdominis Myocutaneous (VRAM) Flap]. / Zylindrische abdominoperineale Rektumexstirpation mit partieller Vulva- und Vaginaresektion sowie perinealer und vaginaler Defektrekonstruktion durch einen vertikalen Rectus-abdominis-Muskel-Haut-Lappen (VRAM-Lappen).

Introduction Patients with low rectal cancer or anal cancer undergoing abdominoperineal excision (APE) benefit from extended surgery and the subsequent avoidance of surgical "waisting" at the level of the puborectalis muscle. The method of cylindrical APE was introduced by T. Holm and led to a reduction of intraoperative perforations and involvement of circumferential resection margins, and subsequently reduced the risk of local recurrence. The use of myocutaneous flaps reduces perineal wound complications, which occur in up to 60% of patients with primary closure of perineal defects, especially following neoadjuvant radiochemotherapy. Flaps obliterate pelvic dead space, recruit well-vascularised tissue into irradiated regions, facilitate wound closure and allow for vaginal and perineal reconstructions. This video shows the technique of extended cylindrical APE with partial vulvar and vaginal resection and subsequent reconstruction of the posterior vaginal wall and the pelvic floor defect by a vertical rectus abdominis myocutaneous (VRAM) flap. Indication Locally advanced anal cancer with infiltration and fistula to the posterior vaginal wall without metastatic spread following neoadjuvant radiochemotherapy. Procedure Extended cylindric APE with partial vulvar and vaginal resection, construction of a descending colostomy with parastomal intraperitoneal onlay mesh augmentation, pelvic reconstruction with a VRAM flap and inlay mesh augmentation of the anterior rectus sheath. Conclusion From the oncological point of view, extralevator APE is superior to standard surgery. The use of myocutaneous flaps improves postoperative wound healing and quality of life.

Evidence-Based Surgical Treatments for Chronic Pancreatitis.

BACKGROUND: If conservative treatment of chronic pancreatitis is unsuccessful, surgery is an option. The choice of the most suitable surgical method can be difficult, as the indications, advantages, and disadvantages of the available methods have not yet been fully documented with scientific evidence. METHODS: In April 2015, we carried out a temporally unlimited systematic search for publications on surgery for chronic pancreatitis. The target parameters were morbidity, mortality, pain, endocrine and exocrine insuffi - ciency, weight gain, quality of life, length of hospital stay, and duration of urgery. Differences between surgical methods were studied with network meta-analysis, and duodenum-preserving operations were compared with partial duodenopancreatectomy with standard meta-analysis. RESULTS: Among the 326 articles initially identified, 8 randomized controlled trials on a total of 423 patients were included in the meta-analysis. The trials were markedly heterogeneous in some respects. There was no significant difference among surgical methods with respect to perioperative morbidity, pain, endocrine and exocrine insufficiency, or quality of life. Duodenumpreserving procedures, compared to duodenopancreatectomy, were associated with a long-term weight gain that was 3 kg higher (p <0.001; three trials), a mean length of hospital stay that was 3 days shorter (p = 0.009; six trials), and a duration of surgery that was 2 hours shorter (p <0.001; five trials). CONCLUSION: Duodenum-preserving surgery for chronic pancreatitis is superior to partial duodenopancreatectomy in multiple respects. Only limited recommendations can be given, however, on the basis of present data. The question of the best surgical method for the individual patient, in view of the clinical manifestations, anatomy, and diagnostic criteria, remains open.

Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit.

The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. ©2016 AACR.

Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion.

BACKGROUND: In neural invasion (NI), cancer cells are classically assumed to actively invade nerves and to cause local recurrence and pain. However, the opposite possibility, that nerves may reach cancer cells even in their preinvasive stage and thereby promote cancer spread, has not yet been genuinely considered. The present study analyzes the reaction of Schwann cells of peripheral nerves to carcinogenesis in pancreatic cancer and colon cancer. METHODS: Two novel 3D migration and Schwann cell outgrowth assays were developed to monitor the timing and the specificity of Schwann cell migration and cancer invasion toward peripheral neurons through digital-time-lapse microscopy and after blockade of nerve growth factor (NGF) signalling via siRNA or a small-molecule inhibitor of the p75(NTR) receptor. The frequency and emergence of the Schwann cell markers Sox10, S100, ALDH1L1, and glial-fibrillary-acidic-protein (GFAP) around cancer precursor lesions were studied in human and conditional murine pancreatic and colon cancer specimens using multiple immunolabeling. RESULTS: Schwann cells migrated toward pancreatic and colon cancer cells, but not toward benign cells, before the onset of cancer migration toward peripheral neurons. This chemoattraction was inhibited after blockade of p75(NTR)-signaling on Schwann and pancreatic cancer cells. Schwann cells were specifically detected around murine and human pancreatic intraepithelial neoplasias (PanINs) (mean percent of murine PanINs surrounded by Schwann cells = 78.9%, 95% CI = 70.9 to 86.8%, and mean percent of human PanINs surrounded by Schwann cells = 52.5%, 95% CI = 14.7 to 90.4%; human: n = 44, murine: n = 14) and intestinal adenomas (mean percent of murine adenomas surrounded by Schwann cells = 64.2%, 95% CI = 28.6 to 99.8%, and mean percent of human adenomas surrounded by Schwann cells = 17.2%, 95% CI = -126.9 to 161.4; human: n = 36, murine: n = 12). The Schwann cell presence in this premalignant stage was associated with the frequency of NI in the malignant phase. CONCLUSIONS: Schwann cells have particular and specific affinity to cancer cells. Emergence of Schwann cells in the premalignant phase of pancreatic and colon cancer implies that, in contrast with the traditional assumption, nerves-and not cancer cells-migrate first during NI.

Colorectal cancer surgery remains effective with rising patient age.

BACKGROUND: The incidence of colorectal cancer rises disproportionally in aging persons. With a shift towards higher population age in general, an increasing number of older patients require adequate treatment. This study aims to investigate differences between young and elderly patients who undergo resection for colorectal cancer, regarding clinical characteristics, morbidity, and prognosis. METHODS: By retrospective analysis of 6 years (2007 to 2012) of a prospectively documented database, a total of 636 patients were identified who underwent oncological resection for colorectal cancer at our institution. Of this total, all 569 patients with primary colorectal adenocarcinoma were included. Four hundred ten patients were 74 years or younger and 159 were 75 years or older. The median follow-up was 22 months. RESULTS: Older patients had significantly more comorbidities (85 % vs. 56 %, p < 0.001) and a higher ASA score (p < 0.001). The mean length of stay in the hospital was longer (24 vs. 20 days, p = 0.002), as was the length of postoperative intensive care stay (4 vs. 2 days, p = 0.003). However, elderly patients did not have significantly higher rates of intraoperative complications or surgical morbidity. Tumor-specific 2-year survival was 83 ± 4 % for the elderly and 87 ± 2 % for the younger patients, which was not significantly different (p = 0.90). CONCLUSIONS: Long-term outcome after oncologic resection for colorectal cancer does not differ between elderly and younger patients. Age in general should not be considered as a limiting factor for colorectal cancer surgery or tumor-specific prognosis.

Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis.

OBJECTIVES: To define the prognostic value of different histological subtypes of colorectal cancer. BACKGROUND: Most colorectal cancers are classical adenocarcinomas (AC). Less frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). In contrast to established prognostic factors such as TNM and grading, the histological subtype has no therapeutical consequences so far, although it may reflect different biological behavior. METHODS: Between 1982 and 2012, a total of 3479 consecutive patients underwent surgery for primary colorectal cancer (AC, MAC, or SC). Clinical, histopathological, and survival data were analyzed. RESULTS: Of all 3479 patients, histological subtype was AC in 3074 cases (88%), MAC in 375 cases (11%), and SC in 30 cases (0.9%). MAC (51%, P < 0.001) and SC (50%, P = 0.029) occurred more frequently in right-sided tumors than AC (28%). Compared with AC, tumor stages and histological grading were higher in MAC and SC (P < 0.001 for each). Rates of angioinvasion were lower in MAC than in AC (5% vs 9%, P = 0.011). Rates of lymphatic invasion were higher in SC than in AC (67% vs 25%, P < 0.001). Five-year cause-specific survival was 67 ± 1% for AC, 61 ± 3% for MAC, and 21 ± 8% for SC (P < 0.001 for difference between the groups). In multivariable analysis, survival did not differ significantly between AC and MAC after correction for tumor stage. However, SC remained an independent prognostic factor associated with worse survival (hazard ratio = 2.5, 95% confidence interval = 1.6-3.8, P < 0.001). CONCLUSIONS: MAC and SC are histological subtypes of colorectal cancer with different characteristics than classical AC. Both are diagnosed in more advanced tumor stages, but the dismal prognosis of SC seems to be caused by its intrinsic tumor biology.

Independent validation of a prognostic genomic signature (ColoPrint) for patients with stage II colon cancer.

OBJECTIVES: The aim of this study was to independently validate a genomic signature developed both to assess recurrence risk in stage II patients and to assist in treatment decisions. BACKGROUND: Adjuvant therapy is recommended for high-risk patients with stage II colon cancer, but better tools to assess the patients' prognosis accurately are still required. METHODS: Previously, an 18-gene signature had been developed and validated on an independent cohort, using full genome microarrays. In this study, the gene signature was translated and validated as a robust diagnostic test (ColoPrint), using customized 8-pack arrays. In addition, clinical validation of the diagnostic ColoPrint assay was performed on 135 patients who underwent curative resection (R0) for colon cancer stage II in Munich. Fresh-frozen tissue, microsatellite instability status, clinical parameters, and follow-up data for all patients were available. The diagnostic ColoPrint readout was determined blindly from the clinical data. RESULTS: ColoPrint identified most stage II patients (73.3%) as at low risk. The 5-year distant-metastasis free survival was 94.9% for low-risk patients and 80.6% for high-risk patients. In multivariable analysis, ColoPrint was the only significant parameter to predict the development of distant metastasis with a hazard ratio of 4.28 (95% confidence interval, 1.36-13.50; P = 0.013). Clinical risk parameters from the American Society of Clinical Oncology (ASCO) recommendation did not add power to the ColoPrint classification. Technical validation of ColoPrint confirmed stability and reproducibility of the diagnostic platform. CONCLUSIONS: ColoPrint is able to predict the development of distant metastasis of patients with stage II colon cancer and facilitates the identification of patients who may be safely managed without chemotherapy.

The severity of neural invasion is associated with shortened survival in colon cancer.

PURPOSE: Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer. EXPERIMENTAL DESIGN: NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined. RESULTS: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer. CONCLUSION: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer.