Late Local Recurrence after Neoadjuvant Therapy and Radical Resection for Locally Advanced Rectal Cancer.

Neoadjuvant radiochemotherapy (RCT) and lately total neoadjuvant therapy (TNT) improved local recurrence rates of rectal cancer significantly compared to total mesorectal excision (TME) alone. Yet the occurrence and impact of late local recurrences after many years appears to be a distinct biological problem. We included n = 188 patients with rectal cancer after RCT and radical resection in this study; n = 38 of which had recurrent disease (sites: local (8.0%), liver (6.4%), lung (3.7%)). We found that 68% of all recurrences developed within the first two years. Four patients, however, experience recurrence >8 years after surgery. Here, we report and characterize four cases of late local recurrence (10% of patients with recurrent disease), suggesting that neoadjuvant therapy in principle delays local recurrence.

Mesenchymal Stromal Cell-Based Therapy.

The use of mesenchymal stromal cells (MSCs) for clinical application is intensively investigated for a variety of areas, such as bone repair, haematological and autoimmune diseases, and solid organ transplantation [...].

Surgical Site Infections and their economic significance in hepatopancreatobiliary surgery: A retrospective incidence, cost, and reimbursement analysis in a German centre of the highest level of care.

Surgical site infections (SSI) in open Hepatopancreatobiliary (HPB) surgery are common complications. They worsen patients' outcomes and prolong hospital stays. Their economic significance in the German diagnosis related groups (DRG) system is mostly unknown. To investigate their economic importance, we evaluated all cases for SSIs as well as clinical and financial parameters undergoing surgery in our centre from 2015 and 2016. Subsequently, we carried out a cost-revenue calculation by assessing our billing data and the cost matrix of the InEK (German Institute for the Payment System in Hospitals). A total of 13.5% of the patients developed a superficial, 9% a deep incisional, and 2.4% of the patients an organ space SSI. Compared with Patients without SSI, Patients with SSI had more comorbidities, were older, and their average length of stay was extended by 19 days (P < .001). The financial loss per SSI-case was €-7035.65 despite increased reimbursement, which resulted in a calculated total loss for the hospital of €-802 064.62 in 2015 and 2016. Surgical site infections are common complications of open HPB surgery, which lead to a significant increase in the cost per case. Further prevention strategies need to be developed. Besides, an adjustment of revenues must be demanded.

Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs.

Expectations on mesenchymal stem cell (MSC) treatment are high, especially in the fields of sepsis, transplant medicine, and autoimmune diseases. Various pre-clinical studies have been conducted with encouraging results, although the mechanisms of action behind the observed immunomodulatory capacity of mesenchymal stem cells have not been fully understood. Previous studies have demonstrated that the immunomodulatory effect of MSCs is communicated via MSC-secreted cytokines and has been proven to rely on the local microenvironment as some of the observed effects depend on a pre-treatment of MSCs with inflammatory cytokines. Nonetheless, recent findings indicate that the cytokine-mediated effects are only one part of the equation as apoptotic, metabolically inactivated, or even fragmented MSCs have been shown to possess an immunomodulatory potential as well. Both cytokine-dependent and cytokine-independent mechanisms suggest a key role for regulatory T cells and monocytes in the overall pattern, but the principle as to why viable and non-viable MSCs have similar immunomodulatory capacities remains elusive. Here we review the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation and focus on the viability of MSCs, as there is still uncertainty concerning the tumorigenic potential of living MSCs.

Unconventional RORγt+ T cells drive hepatic ischemia reperfusion injury.

An emerging body of evidence suggests a pivotal role of CD3(+) T cells in mediating early ischemia reperfusion injury (IRI). However, the precise phenotype of T cells involved and the mechanisms underlying such T cell-mediated immune responses in IRI, as well as their clinical relevance, are poorly understood. In this study, we investigated early immunological events in a model of partial warm hepatic IRI in genetically targeted mice to study the precise pathomechanistic role of RORγt(+) T cells. We found that unconventional CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells are the major RORγt-expressing effector cells in hepatic IRI that play a mechanistic role by being the main source of IRI-mediating IL-17A. We further show that unconventional IRI-mediating T cells are contingent on RORγt, as highlighted by the fact that a genetic deficiency for RORγt, or its therapeutic antagonization via digoxin, is protective against hepatic IRI. Therefore, identification of CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells as the major source of IL-17A via RORγt in hepatic IRI opens new therapeutic options to improve liver transplantation outcomes.

Quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity. The Quality of Life (QoL) assessment in this patient group with a limited life expectancy and high recurrence rate is important. Published data show an impairment of postoperative Quality of Life at 3 months postoperatively with an improvement over 6-12 months at levels higher than the baseline. Standardized instruments QoL have to be included in clinical trials assessing the efficacy of CRS and HIPEC.

Safety of gastric resections during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) including gastric resection combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of selected patients with peritoneal surface malignancies. Perioperative morbidity of this aggressive treatment strategy is high; however, overall mortality can be low in specialized centers. The aim of this study was to assess the safety of gastric resections with anastomosis during CRS and HIPEC. METHODS: Between 2005 and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre. Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric resections. The clinical data of all patients were introduced into a database and analyzed with respect to the morbidity associated with the gastric resections. RESULTS: Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12 distal gastrectomies, and 7 gastric wedge resections were performed during CRS. The overall postoperative morbidity was 45%; main surgical complications were pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and digestive fistula (leakage of ileorectostomy and small bowel perforation) (n = 2). However, no complications occurred at the site of the esophageal anastomosis (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died postoperatively during the hospitalization period. CONCLUSIONS: CRS in combination with HIPEC is associated with high postoperative morbidity; however, anastomosis following total or subtotal gastrectomy is safe in experienced centers. No leakages related to gastric resections occurred in this high-risk patient group.

Total mesorectal excision for middle and lower rectal cancer: a single institution experience with 337 consecutive patients.

BACKGROUND AND OBJECTIVES: There have been reports on improved prognosis after TME for middle and lower rectal cancer. No prospective randomized studies have yet been performed. This is a large single institution series evaluating its own results of TME. METHODS: This retrospective study analyses data of 337 patients with middle and lower rectal cancer, treated with either curative or palliative intention between 1990 and 1998. RESULTS: Of all patients, 212 had lower rectal and 125 middle rectal carcinomas. The rate of rectal resections with TME was 96%. A total of 223 patients were treated by anterior rectal resection; 92 patients had to undergo abdomino-perineal resection. Ten patients were operated by a Hartmann resection. Postoperative morbidity was 35% with a leakage rate of 9%. Postoperative mortality was 4%. The rate of local recurrence was 8.6%. The 5-year survival rate after curative resection was 69.3%. The multivariate analysis outlined the tumor stage as independent prognostic factor. CONCLUSIONS: In our experience, TME is feasible with acceptable postoperative morbidity and low mortality. The local recurrence rate can be decreased to lower than 10%. The almost 70% 5-year survival rate indicates a clear benefit for the patients. These findings recommend TME as standard procedure for middle and lower rectal cancer.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer.

BACKGROUND: In selected patients with peritoneal carcinomatosis from ovarian cancer prognosis can be improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Between September 1995 and February 1999, 19 patients (mean age 52 years, range 30-72 years) with peritoneal carcinomatosis from primary or recurrent epithelial ovarian carcinoma were operated with the aim of complete macroscopical cytoreduction. Surgery was followed by intraoperative HIPEC. The data was analyzed retrospectively. RESULTS: Eleven patients had recurrent and 8 primary ovarian cancer. The median progression free interval was 18 months (range 6-36 months). Macroscopically complete cytoreduction was achieved in 9 patients. Cisplatin (n = 16) or mitoxantrone (n = 3) were used for the intraoperative chemotherapy. The median intraabdominal inflow temperature was 41.5 degrees C. Complications occurred in seven patients. Most frequent complications were anastomotic leakage (2/19) and intraabdominal abscess formation (2/19). One patient died postoperatively. The mean (+/- SD) overall survival time was 33(+/- 6) months with a 5-year survival rate of 15%. The survival was found to be influenced by the completeness of cytoreduction (44 +/- 11 vs. 25 +/- 6 months, p = 0.40), tumor volume (54 +/- 10 versus 16 +/- 4, p = 0.002) and presence of lymph node (38 +/- 8 vs. 20 +/- 8 months, p= 0.2) or liver metastases (51 +/- 9 vs. 21 +/- 6 months, p = 0.06). CONCLUSIONS: Cytoreductive surgery combined with HIPEC is feasible and is associated with a reasonable morbidity and mortality. Complete cytoreduction may improve survival in select group of patients with low tumor volume and no organ metastases.