Publications by authors named "Can Yurttas"

17 Publications

  • Page 1 of 1

[Impact of the SARS-CoV-2 Pandemic on Liver Surgery and Liver Transplantations in Germany].

Zentralbl Chir 2022 Aug 21;147(4):354-360. Epub 2022 Jul 21.

Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland.

Background: The SARS-CoV-2 pandemic has led to restrictions in surgical care worldwide and therefore also posed new challenges to liver surgery. The respective procedures often entail high perioperative risks and resource requirements. However, the indication for liver surgery is frequently without alternatives. To date, there is little knowledge about the impact of the pandemic on liver surgery in Germany.

Methods: A retrospective data analysis of liver surgery procedures in Germany as well as transplantations was conducted. Evaluations were based on procedure codes recorded between 2010 and 2020 according to diagnosis-related groups (DRG) by the Federal Statistical Office of Germany (Destatis) and data from the German Organ Procurement Organization (Deutsche Stiftung Organtransplantation; DSO).

Results: According to DRG procedure codes relating to liver surgery recorded between 2010 and 2020 in Germany, the annual fluctuation for the first year of the pandemic 2020 remained comparable to previous years. Furthermore, the development of post-mortem liver transplantations as well as living liver donations remained stable in Germany in 2020 and 2021.

Conclusions: The number of liver surgery procedures in Germany was subject to a dynamic development until 2020, without apparent changes in the first year of the SARS-CoV-2 pandemic. The most frequently performed liver procedures, as well as liver transplantations, remained stable with respect to their annually recorded numbers. Publication of data regarding procedures in liver surgery and transplantation in 2021 need to be awaited and analyzed to evaluate whether the observations presented in this article prove stable any further.
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http://dx.doi.org/10.1055/a-1845-1321DOI Listing
August 2022

Retrospective analysis of different therapeutic approaches for retroperitoneal duodenal perforations.

Sci Rep 2022 Jun 17;12(1):10243. Epub 2022 Jun 17.

Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Surgical therapy of duodenal perforation into the retroperitoneum entails high morbidity. Conservative treatment and endoscopic negative pressure therapy have been suggested as promising therapeutic alternatives. We aimed to retrospectively assess outcomes of patients treated for duodenal perforation to the retroperitoneum at our department. A retrospective analysis of all patients that were treated for duodenal perforation to the retroperitoneum at our institution between 2010 and 2021 was conducted. Different therapeutic approaches with associated complications within 30 days, length of in-hospital stay, number of readmissions and necessity of parenteral nutrition were assessed. We included thirteen patients in our final analysis. Six patients underwent surgery, five patients were treated conservatively and two patients received interventional treatment by endoscopic negative pressure therapy. Length of stay was shorter in patients treated conservatively. One patient following conservative and surgical treatment each was readmitted to hospital within 30 days after initial therapy whereas no readmissions after interventional treatment occurred. There was no failure of therapy in patients treated without surgery whereas four (66.7%) of six patients required revision surgery following primary surgical therapy. Conservative and interventional treatment were associated with fewer complications than surgical therapy which involves high morbidity. Conservative and interventional treatment using endoscopic negative pressure therapy in selected patients might constitute appropriate therapeutic alternatives for duodenal perforations to the retroperitoneum.
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http://dx.doi.org/10.1038/s41598-022-14278-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205956PMC
June 2022

Current Medical Care Situation of Patients in Germany Undergoing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Cancers (Basel) 2022 Mar 11;14(6). Epub 2022 Mar 11.

Department of General, Visceral and Thoracic Surgery, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6807 Feldkirch, Austria.

Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases.

Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed.

Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1-4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43-636 days).

Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.
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http://dx.doi.org/10.3390/cancers14061443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946267PMC
March 2022

Prolonged Exposure to Oxaliplatin during HIPEC Improves Effectiveness in a Preclinical Micrometastasis Model.

Cancers (Basel) 2022 Feb 24;14(5). Epub 2022 Feb 24.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients' samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.
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http://dx.doi.org/10.3390/cancers14051158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909393PMC
February 2022

Limitations of laparoscopy to assess the peritoneal cancer index and eligibility for cytoreductive surgery with HIPEC in peritoneal metastasis.

Langenbecks Arch Surg 2022 Jun 2;407(4):1667-1675. Epub 2022 Feb 2.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Purpose: We aimed to determine the value of laparoscopy to assess the intra-abdominal tumor extent and predict complete cytoreduction.

Methods: All patients at our department in the period from 2017 to 2021 that underwent laparoscopy to assess peritoneal metastasis and subsequent open exploration with the intention to perform cytoreductive surgery (CRS) with HIPEC were retrospectively identified in a continuously maintained database.

Results: Forty-three patients were analyzed. Peritoneal cancer index (PCI) determination by laparoscopy compared to open surgery was overestimated in five patients (11.6%), identical in eleven patients (25.6%), and underestimated in 27 patients (62.8%). PCI differences were independent of surgeons, tumor entities, and prior chemotherapy. Thirty-four patients (79.1%) were determined eligible for CRS with HIPEC during open exploration, whereas nine patients (20.9%) underwent a non-therapeutic laparotomy. Complete or almost complete cytoreduction was achieved in 33 patients (76.7%). In one patient, completeness of cytoreduction was not documented.

Conclusions: We demonstrate a moderate agreement according to weighted Cohen's kappa analysis of PCI values calculated during laparoscopy and subsequent open exploration for CRS with HIPEC. Uncertainty of PCI assessment should therefore be kept in mind when performing laparoscopy in patients with peritoneal metastasis.
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http://dx.doi.org/10.1007/s00423-022-02455-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809494PMC
June 2022

Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy.

J Immunother Cancer 2021 12;9(12)

Department of Dermatology, University Medical Center, Tübingen, Germany

Background: Anti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB).

Methods: Peripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS).

Results: The initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p>0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB.

Conclusions: Our findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.
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http://dx.doi.org/10.1136/jitc-2021-003439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693089PMC
December 2021

Endoscopic negative pressure therapy as stand-alone treatment for perforated duodenal diverticulum: presentation of two cases.

BMC Gastroenterol 2021 Nov 21;21(1):436. Epub 2021 Nov 21.

Department of General, Visceral and Transplantation Surgery, University Hospital of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Background: Endoscopic negative pressure therapy is a novel and successful treatment method for a variety of gastrointestinal leaks. This therapy mode has been frequently described for rectal and esophageal leakages. Duodenal diverticular perforations are rare but life-threatening events. The early diagnosis of duodenal diverticular perforation is often complicated by inconclusive symptoms. This is the first report about endoscopic negative pressure therapy in patients with perforated duodenal diverticula.

Case Presentation: We present two cases of duodenal diverticula perforations treated with endoscopic negative pressure therapy as stand-alone treatment. Start of symptoms varied from one to three days before hospital admission. Early sectional imaging led to the diagnosis of duodenal diverticular perforation. Both patients were treated with endoluminal endoscopic negative pressure therapy with simultaneous feeding option. Three respective changes of the suction device were performed. Both patients were treated with antibiotics and antimycotics during their hospital stay and be discharged from hospital after 20 days.

Conclusions: This is the first description of successful stand-alone treatment by endoscopic negative pressure therapy in two patients with perforated duodenal diverticulum. We thus strongly recommend to attempt interventional therapy with endoluminal endoscopic negative pressure therapy in patients with duodenal diverticular perforations upfront to surgery.
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http://dx.doi.org/10.1186/s12876-021-02018-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607673PMC
November 2021

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma.

Ann Surg Oncol 2021 Dec 15;28(13):9086-9095. Epub 2021 Jun 15.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery.

Methods: This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m body surface area heated to 42 °C for 1 hour.

Results: Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk.

Conclusion: Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified.

Registration Number: NCT02863471 ( http://www.clinicaltrials.gov ).
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http://dx.doi.org/10.1245/s10434-021-10187-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205203PMC
December 2021

ASO Author Reflections: First Do No Harm-Revisiting Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Trials to Reduce the Risk of Peritoneal Metastasis.

Ann Surg Oncol 2021 12 11;28(13):9096-9097. Epub 2021 Jun 11.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.

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http://dx.doi.org/10.1245/s10434-021-10263-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590993PMC
December 2021

Twelve-Year Single Center Experience Shows Safe Implementation of Developed Peritoneal Surface Malignancy Treatment Protocols for Gastrointestinal and Gynecological Primary Tumors.

Cancers (Basel) 2021 May 19;13(10). Epub 2021 May 19.

Comprehensive Cancer Center, Department of General, Visceral and Transplant Surgery, University of Tübingen, 72076 Tübingen, Germany.

(1) : Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy provide survival benefits to selected patients. We aimed to report our experience and the evolution of our peritoneal surface malignancy program. (2) : From June 2005 to June 2017, 399 patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at the Tübingen University Hospital were analyzed from a prospectively collected database. (3) : Peritoneal metastasis from colorectal cancer was the leading indication (group 1: 28%; group 2: 32%). The median PCI was 15.5 (range, 1-39) in group 1 and 11 (range, 1-39) in group 2 ( = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively ( = 0.010). Median overall survival rates for patients in group 1 and 2 for colon cancer, ovarian cancer, gastric cancer and appendix cancer were 34 and 25 months; 45 months and not reached; 30 and 16 months; 39 months and not reached, respectively. The occurrence of grade-III and -IV complications slightly differed between groups (14.5% vs. 15.6%). No 30-day mortality occurred. (4) : Specialized centers are able to provide low-morbidity cytoreductive surgery and hyperthermic intraperitoneal chemotherapy without mortality. Strict patient selection during the time period significantly improved CC scores.
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http://dx.doi.org/10.3390/cancers13102471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159136PMC
May 2021

Reply to: "Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Definitively Does Not Deserve Its Bad Reputation".

Ann Surg Oncol 2021 09 26;28(9):5450-5451. Epub 2021 Feb 26.

Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.

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http://dx.doi.org/10.1245/s10434-021-09743-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349317PMC
September 2021

In-Hospital Mortality and Complication Rates According to Health Insurance Data in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies in Germany.

Ann Surg Oncol 2021 Jul 9;28(7):3823-3830. Epub 2020 Nov 9.

Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.

Background: Morbidity and in-hospital mortality rates of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany are not known.

Methods: From 2009 to 2018 all patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRG). The "failure to rescue" (FTR) index, characterizing patients who died after severe but potentially manageable complications, was calculated.

Results: In total, 8463 patients were included and analyzed. Female sex predominated (1.5:1). Colonic origin of peritoneal metastasis was highest throughout all years, reaching its highest level in 2017 (55%; n = 563) and its lowest level in 2012 (40%; n = 349). Median length of hospital stay reached its maximum in 2017 at 23.9 days and its minimum in 2010 at 22.0 days. Analysis of the total FTR index showed a noticeable improvement over the years, reaching its lowest values in 2017 (9.8%) and 2018 (8.8%). The FTR index for sepsis, peritonitis, and pulmonary complications significantly improved over time. Of the 8463 included patients, 290 died during hospital stay, reflecting an in-hospital mortality rate of 3.4%.

Conclusion: In-hospital mortality after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is reasonably low compared with other surgical procedures. The improvement in the FTR index reflects efforts to centralize treatment at specialized high-volume centers.
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http://dx.doi.org/10.1245/s10434-020-09301-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184558PMC
July 2021

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases in Solid Organ Graft Recipients: First Experience.

Ann Transplant 2019 Jan 15;24:30-35. Epub 2019 Jan 15.

Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.

BACKGROUND Therapy of peritoneal metastases (PM) in solid organ transplant recipients is challenging. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might constitute a new therapeutic opportunity for these patients. MATERIAL AND METHODS This was a single-center, retrospective analysis of prospective registry data (NCT03210298) in a tertiary care center between 1.7.2016 and 31.12.2017. Intraperitoneal administration of oxaliplatin 92 mg/m² body surface or a combination of cisplatin 7.5 mg/m² and doxorubicin 1.5 mg/m², repeated every 6 weeks. Objective tumor response was documented via histology (Peritoneal Regression Grading Score, PRGS), adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. RESULTS Out of 71 consecutive patients treated with PIPAC, 2 patients (2.8%) were solid organ transplant recipients. The first patient had metachronous PM of colonic cancer origin after liver transplantation. The second patient had synchronous PM of pancreatic cancer origin after combined kidney-pancreas transplantation. After repeated combined systemic and PIPAC chemotherapy, objective histological response was documented in both patients. No adverse events >CTCAE 2 were recorded. There was no measurable liver or renal toxicity. PIPAC procedures could be repeated (2, resp. 3 cycles) without any interruption of immunosuppressive medication or impairment of respective plasmatic drug levels. The first patient passed away 7 months after the first PIPAC, the second patient was still alive after 8 months. CONCLUSIONS PIPAC can induce objective regression of PM in solid organ transplant recipients without inducing organ toxicity or interfering with immunosuppressive therapy.
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http://dx.doi.org/10.12659/AOT.911905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346813PMC
January 2019

Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer.

J Clin Med 2018 Dec 19;7(12). Epub 2018 Dec 19.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany.

Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords "HIPEC" and "colorectal cancer", according to established guidelines. Articles were systematically screened, selecting 87 publications complemented by 48 publications identified through extended search for subsequent synthesis and evaluation, extracting inter alia details on used drugs, dosage, temperature, exposure times, and carrier solutions.

Results: Compiled publications contained 171 reports on HIPEC conduct foremost with mitomycin C and oxaliplatin, but also other drugs and drug combinations, comprising at least 60 different procedures. We hence provide an overview of interconnections between HIPEC protocols, used drugs and carrier solutions as well as their volumes. In addition, HIPEC temperatures and dosing benchmarks, as well as an estimate of in vivo resulting drug concentrations are demonstrated.

Conclusions And Implications: Owing to recent developments, HIPEC conduct and practices need to be reassessed. Unfortunately, imprecise and lacking reporting is frequent, which is why minimal information requirements should be established for HIPEC and the introduction of final drug concentrations for comparability reasons seems sensible.
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http://dx.doi.org/10.3390/jcm7120567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306814PMC
December 2018

Cellularity in low-grade Pseudomyxoma peritonei impacts recurrence-free survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Langenbecks Arch Surg 2018 Dec 1;403(8):985-990. Epub 2018 Dec 1.

Department of General, Visceral and Transplant Surgery, University of Tübingen, Comprehensive Cancer Center, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.

Purpose: Documentation of cellularity in Pseudomyxoma peritonei (PMP) is not performed on a regular basis in everyday clinical practice, but is recommended by the PSOGI (Peritoneal Surface Oncology Group International). We investigated the impact of cellularity in PMP following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on recurrence-free survival.

Methods: Data from 25 patients with low-grade (American Joint Committee on Cancer grade G1) PMP were retrospectively evaluated. Cellularity was categorized as acellular mucin, scant (< 2% cellularity), moderate (2-19% cellularity), or high cellularity (> 20% cellularity). Impact of cellularity, PCI, CC-score, and HIPEC regimen on recurrence-free and overall survival was primarily assessed.

Results: Assessment of cellularity showed acellular mucin in ten patients (40%), scant cellularity in 11 (44%) patients, moderate cellularity in one (4%) patient, and high cellularity in three (12%) patients. Median PCI was 15 (range, 1-39). A CC-0 score was achieved in 13 (52%) patients and a CC-1 score was achieved in 12 (48%) patients. After a median follow-up of 25 (range, 2-74) months, all patients were still alive. Overall, four (16%) patients suffered from recurrent disease after a median of 38 (range, 36-60) months. PCI above 17 (p = 0.03) and moderate and high cellularity (p = 0.007) were statistically significantly associated with recurrent disease. CC-score and HIPEC compound used did not impact on recurrence-free survival.

Conclusions: Recurrent disease occurs more often in patients with PCI values above 17 and with moderate and high cellularity in low-grade PMP. Pathological assessment of cellularity is crucial for identification of patients at risk for recurrence.
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http://dx.doi.org/10.1007/s00423-018-1735-5DOI Listing
December 2018

Three-dimensional tumor cell cultures employed in virotherapy research.

Oncolytic Virother 2018 5;7:79-93. Epub 2018 Sep 5.

Department of Clinical Tumor Biology, University Hospital, University of Tübingen, Tübingen, Germany,

Oncolytic virotherapy constitutes an upcoming alternative treatment option for a broad spectrum of cancer entities. However, despite great research efforts, there is still only a single US Food and Drug Administration/European Medicines Agency-approved oncolytic virus available for clinical use. One reason for that is the gap between promising preclinical data and limited clinical success. Since oncolytic viruses are biological agents, they might require more realistic in vitro tumor models than common monolayer tumor cell cultures to provide meaningful predictive preclinical evaluation results. For more realistic invitro tumor models, three-dimensional tumor cell-culture systems can be employed in preclinical virotherapy research. This review provides an overview of spheroid and hydrogel tumor cell cultures, organotypic tumor-tissue slices, organotypic raft cultures, and tumor organoids utilized in the context of oncolytic virotherapy. Furthermore, we also discuss advantages, disadvantages, techniques, and difficulties of these three-dimensional tumor cell-culture systems when applied specifically in virotherapy research.
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http://dx.doi.org/10.2147/OV.S165479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130269PMC
September 2018

Three-dimensional tumor cell cultures employed in virotherapy research.

Oncolytic Virother 2018 5;7:79-93. Epub 2018 Sep 5.

Department of Clinical Tumor Biology, University Hospital, University of Tübingen, Tübingen, Germany,

Oncolytic virotherapy constitutes an upcoming alternative treatment option for a broad spectrum of cancer entities. However, despite great research efforts, there is still only a single US Food and Drug Administration/European Medicines Agency-approved oncolytic virus available for clinical use. One reason for that is the gap between promising preclinical data and limited clinical success. Since oncolytic viruses are biological agents, they might require more realistic in vitro tumor models than common monolayer tumor cell cultures to provide meaningful predictive preclinical evaluation results. For more realistic invitro tumor models, three-dimensional tumor cell-culture systems can be employed in preclinical virotherapy research. This review provides an overview of spheroid and hydrogel tumor cell cultures, organotypic tumor-tissue slices, organotypic raft cultures, and tumor organoids utilized in the context of oncolytic virotherapy. Furthermore, we also discuss advantages, disadvantages, techniques, and difficulties of these three-dimensional tumor cell-culture systems when applied specifically in virotherapy research.
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http://dx.doi.org/10.2147/OV.S165479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130269PMC
September 2018
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