Surgery for Colorectal Cancer - Trends, Developments, and Future Perspectives

Background: Although colorectal surgery is long established as the mainstay treatment for colon cancer, certain topics regarding technical fine-tuning to increase postsurgical recurrence-free survival have remained a matter of debate throughout the past years. These include complete mesocolic excision (CME), treatment strategies for metastatic disease, significance of hyperthermic intraperitoneal chemotherapy (HIPEC), and surgical techniques for the treatment of colorectal cancer recurrence. In addition, new surgical techniques have been introduced in oncologic colorectal surgery, and their potential to provide sufficiently radical resection has yet to be proven. Methods: A structured review of the literature was performed to identify the current state of the art with regard to the mentioned key issues in colorectal surgery. Results: This article provides a comprehensive review of the current literature addressing the above-mentioned current challenges in colorectal surgery. The focus lies on the impact of CME and, in relation to this, on lymph node dissection, as well as on treatment of metastatic disease including peritoneal spread, and finally on the treatment of recurrent disease. Conclusion: Uniformly, the current literature reveals that surgery aiming at complete malignancy elimination within multimodal treatment approaches represents the fundamental quantum leap for the achievement of long-term tumor-free survival. (C) 2016 S. Karger GmbH, Freibur

Management of acute upside-down stomach

Background: Upside-down stomach (UDS) is characterized by herniation of the entire stomach or most gastric portions into the posterior mediastinum. Symptoms may vary heavily as they are related to reflux and mechanically impaired gastric emptying. UDS is associated with a risk of incarceration and volvulus development which both might be complicated by acute gastric outlet obstruction, advanced ischemia, gastric bleeding and perforation. Case presentation: A 32-year-old male presented with acute intolerant epigastralgia and anterior chest pain associated with acute onset of nausea and vomiting. He reported on a previous surgical intervention due to a hiatal hernia. Chest radiography and computer tomography showed an incarcerated UDS. After immediate esophago-gastroscopy, urgent laparoscopic reduction, repair with a 360 degrees floppy Nissen fundoplication and insertion of a gradually absorbable GORE (R) BIO-A (R)-mesh was performed. Conclusion: Given the high risk of life-threatening complications of an incarcerated UDS as ischemia, gastric perforation or severe bleeding, emergent surgery is indicated. In stable patients with acute presentation of large paraesophageal hernia or UDS exhibiting acute mechanical gastric outlet obstruction, after esophago-gastroscopy laparoscopic reduction and hernia repair followed by an anti-reflux procedure is suggested. However, in cases of unstable patients open repair is the surgical method of choice. Here, we present an exceptionally challenging case of a young patient with a giant recurrent hiatal hernia becoming clinically manifest in an incarcerated UDS

Nonparametric change point estimation for survival distributions with a partially constant hazard rate

We present a new method for estimating a change point in the hazard function of a survival distribution assuming a constant hazard rate after the change point and a decreasing hazard rate before the change point. Our method is based on fitting a stump regression to p-values for testing hazard rates in small time intervals. We present three real data examples describing survival patterns of severely ill patients, whose excess mortality rates are known to persist far beyond hospital discharge. For designing survival studies in these patients and for the definition of hospital performance metrics (e.g. mortality), it is essential to define adequate and objective end points. The reliable estimation of a change point will help researchers to identify such end points. By precisely knowing this change point, clinicians can distinguish between the acute phase with high hazard (time elapsed after admission and before the change point was reached), and the chronic phase (time elapsed after the change point) in which hazard is fairly constant. We show in an extensive simulation study that maximum likelihood estimation is not robust in this setting, and we evaluate our new estimation strategy including bootstrap confidence intervals and finite sample bias correction

Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer

Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of β-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high β-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns

Concurrent isolation of hepatic stem cells and hepatocytes from the human liver

Hepatocytes differentiated from induced pluripotent stem cells or stem cells have the potential to be representative in vitro models of the human liver for research as well as early safety assessment programs. However, up until now, there has been no definitive proof that differentiated hepatocytes recapitulate the phenotype and functional characteristics of primary hepatocytes from the same individual. Thus, a method for the concurrent isolation of hepatocytes and hepatic stem cells is presented here to provide the cells necessary for the evaluation of the required benchmarking. The method presented here generated high-quality hepatocytes with a purity of 94 ± 1% and a high percentage viability of 79 ± 2%. Furthermore, the hepatic stem cells isolated were found to be actively proliferating and have a purity of 98 ± 1%. Thus, these isolated cells can be used as a powerful tool for the validation of differentiated hepatocyte in vitro models

Endoscopic vacuum therapy for in- and outpatient treatment of colorectal defects

Background. Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment. Methods. Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (n=281). Results. The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (P = 0.037) and recent surgical revision after primary surgery (P = 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (P = 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (P = 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%. Conclusions. In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment

Kupffer cell activation by different microbial lysates: Toll‐like receptor‐2 plays pivotal role on thromboxane A2 production in mice and humans

Thromboxane (TX) A2 has been identified as an important intrahepatic vasoconstrictor upon Kupffer cell (KC) activation during infections such as spontaneous bacterial peritonitis (SBP). The study aimed to investigate the role of TLRs in the TXA2 increase in liver nonparenchymal cells and their related mechanisms. Here, we identified TLR‐2 as a common pathway for different microbials: microbial lysates including Gram‐positive bacteria, Gram‐negative bacteria, and fungi all increased TXA2 secretion via activation of TLR‐2 in human KCs, accompanied by increased expression and phosphorylation of Myd88‐related pathway. Of all TLR agonists, only TLR‐1, ‐2, and ‐4 agonists increased TXA2 in human KCs. These results were further confirmed by mouse liver nonparenchymal cells. Comparing the effects of TLR‐1, ‐2, and ‐4 antagonists, only TLR‐2 antagonist showed inhibitory effects with all tested microbial lysates. Pretreatment with TLR‐2 antagonist in human KCs blocked the secretion of IL‐10, CXCL‐10, TNF‐α, and IL‐6 induced by Gram‐positive and Gram‐negative bacterial stimulation. IL‐23 and IL‐1β were only induced by Gram‐negative bacteria. Thus, TLR‐2 might be a potential marker and an attractive target for future treatment of patients with SBP. In addition, IL‐23 and IL‐1β might distinguish early between Gram‐positive and Gram‐negative SBP

Infections after kidney transplantation: A comparison of mTOR‐Is and CNIs as basic immunosuppressants. A systematic review and meta‐analysis

Background Side effects of the immunosuppressive therapy after solid organ transplantation are well known. Recently, significant benefits were shown for mTOR‐Is with respect to certain viral infections in comparison with CNIs. However, reported total incidences of infections under mTOR‐Is vs CNIs are usually not different. This raises the question to additional differences between these immunosuppressants regarding development and incidence of infections. Methods The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 954 trials screened of which 19 could be included (9861 pts.). The 1‐year incidence of infections, patient and graft survival were assessed in meta‐analyses. Results Meta‐analysis on 1‐year incidence of infections showed a significant benefit of an mTOR‐I based therapy when combined with a CNI vs CNI‐based therapy alone (OR 0.76). There was no difference between mTOR‐I w/o CNI and CNI therapy (OR 0.97). For pneumonia, a significant disadvantage was seen only for mTOR‐I monotherapy compared to CNI's (OR 2.09). The incidence of CMV infections was significantly reduced under mTOR‐I therapy (combination with CNI: OR 0.30; mTOR w/o CNI: OR: 0.46). There was no significant difference between mTOR‐I and CNI therapy with respect to patient survival (mTOR‐I w/o CNI vs CNI: OR 1.22; mTOR‐I with CNI vs CNI: OR 0.86). Graft survival was negatively affected by mTOR‐I monotherapy (OR 1.52) but not when combined with a CNI (OR 0.97). Conclusion Following renal transplantation the incidence of infections is lower when mTOR‐Is are combined with a CNI compared to a standard CNI therapy. Pneumonia occurs more often under mTOR‐I w/o CNI

Over-the-scope clip (OTSC (R)) closure of a recto-acetabular fistula

A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a rectoacetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC (R)). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic rectoacetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy

Pulmonary sclerosing hemangioma in a 21-year-old male with metastatic hereditary non-polyposis colorectal cancer: Report of a case

<p>Abstract</p> <p>Background</p> <p>Pulmonary sclerosing hemangioma (SH) is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described.</p> <p>Case Presentation</p> <p>We report the case of a 21-year-old Caucasian male with a history of locally advanced and metastatic rectal carcinoma (UICC IV; pT4, pN1, M1(hep)) that was eventually identified as having hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome). After neoadjuvant chemotherapy followed by low anterior resection, adjuvant chemotherapy and metachronous partial hepatectomy, he was admitted for treatment of newly diagnosed bilateral pulmonary metastases. Thoracic computed tomography showed a homogenous, sharply marked nodule in the left lower lobe. We decided in favor of atypical resection followed by systematic lymphadenectomy. Histopathological analysis revealed the diagnosis of SH.</p> <p>Conclusions</p> <p>Cases have been published with familial adenomatous polyposis (FAP) and simultaneous SH. FAP, Gardner syndrome and Li-Fraumeni syndrome, however, had been ruled out in the present case. To the best of our knowledge, this is the first report describing SH associated with Lynch syndrome.</p