Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.

Long-term recurrence-free survival following pancreatic surgery with HIPEC treatment for locally advanced pancreatic adenocarcinoma.

More than 5 years previous to this report, a female patient in her 60s underwent oncological left-sided pancreatic resection and adrenalectomy including splenectomy for locally advanced pancreatic adenocarcinoma (PDAC), recommended by a multidisciplinary tumour board (MDT). Additionally, she was treated with gemcitabine-containing hyperthermic intraperitoneal chemotherapy (HIPEC) for 60 minutes in the framework of a clinical trial (PanHIPEC), aiming to determine the safety and feasibility (not efficacy) of this approach. Following the postoperative MDT recommendation, she subsequently received adjuvant chemotherapy consisting of six cycles of gemcitabine and cisplatin for a histopathologically confirmed PDAC of the pancreatic tail with infiltration of the left-sided adrenal gland (pT3, pN1 (3/16), cM0, L0, V0, Pn1, R0, G2). Five years and five months after pancreatic surgery and HIPEC, the patient has no signs of tumour recurrence as determined by follow-up examination including CT scan and CA19-9 tumour marker serology.

Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma.

Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.

High-dimensional in situ proteomics imaging to assess γδ T cells in spatial biology.

This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify γδ T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight γδ T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to γδ T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess γδ T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics.

Possible Advantages of Minimal-Invasive Approaches in Rectal Cancer Surgery: A Nationwide Analysis.

(1) Background: Laparoscopic resection for colon and rectal cancer was introduced in the early 1990s; the aim of this analysis was to show possible advantages of minimal-invasive approaches in rectal cancer surgery. (2) Methods: From 2016 to 2020, all patients undergoing open, laparoscopic or robotic-assisted rectal cancer surgery in Germany were retrospectively analyzed regarding sex distribution, conversion rates and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRGs). (3) Results: In total, 68,112 patients were analyzed, and most commonly, low anterior rectal resections with primary anastomosis (n = 25,824) were performed with an increase of minimal-invasive procedures over the years (open: 51% to 27%; laparoscopic: 47% to 63% and robotic: 2% to 10%). In-hospital mortality rate was 2.95% (n = 2012). In total, 4.61%, 1.77%, 1.14% and 3.95% of patients with open, laparoscopic, robotic and converted-to-open surgery died during hospital stay, respectively (open vs. laparoscopic p < 0.0001; open vs. robotic p < 0.00001; laparoscopic vs. robotic p = 0.001). Conversion rates were significantly more favorable in the robotic compared to the laparoscopic group. (11.94% vs. 2.53%; p < 0.0001). (4) Conclusion: Minimal-invasive rectal cancer surgery might have some advantages in terms of a reduced in-hospital mortality, and an improved conversion rate for the robotic approach.

Primary admission to a surgical service facilitates early cholecystectomy in acute cholecystitis but does not influence patient outcome.

PURPOSE: Early cholecystectomy is recommended for acute calculous cholecystitis to reduce complications and lower health care costs. However, not all patients admitted to emergency services due to acute calculous cholecystitis are considered for surgery immediately. Our intention was therefore to evaluate patient management and outcome parameters following cholecystectomy depending on the type of emergency service patients are primarily admitted to. METHODS: We performed a retrospective analysis of all patients that were treated for acute cholecystitis at our hospital between 2014 and 2021. Only patients that underwent surgical treatment for acute calculous cholecystitis were included. Patients with cholecystectomies that were performed due to other medical conditions were not incorporated. Primary outcomes were the perioperative length of stay and postoperative complications. Perioperative antimicrobial management and disease deterioration according to Tokyo Guidelines from 2018 due to inhouse organization were assessed as secondary outcome parameters. RESULTS: Of 512 patients included in our final analysis, 334 patients were primarily admitted to a surgical emergency service (SAG) whereas 178 were initially treated in a medical service (MAG). The latency between admission and cholecystectomy was significantly prolonged in the MAG with a median time to surgery of 2 days (Q25 1, Q75 3.25, IQR 2.25) compared to the SAG with a median time to surgery of 1 day (Q25 1, Q75 2, IQR 1) (p < 0.001). The duration of surgery was comparable between both groups. Necrotizing cholecystitis (27.2% vs. 38.8%, p = 0.007) and pericholecystic abscess or gallbladder perforation (7.5% vs. 14.6% p = 0.010) were less frequently described in the SAG. In the SAG, 85.7% of CCEs were performed laparoscopically, 6.0% were converted to open, and 10.4% were performed as open surgery upfront. In the MAG, 80.9% were completed laparoscopically, while 7.2% were converted and 11.2% were performed via primary laparotomy (p = 0.743). Histologically gangrenous cholecystitis was confirmed in 38.0% of the specimen in the SAG compared to 47.8% in the MAG (p = 0.033). While the prolonged preoperative stay led to prolonged overall length of stay, the postoperative length of stay was similar at a median of 3 days in both groups. CONCLUSIONS: To our knowledge, we present the largest single center cohort of acute calculous cholecystitis evaluating the perioperative management and outcome of patients admitted to either medical or surgical service prior to undergoing cholecystectomy. In patients that were primarily admitted to medical emergency services, we found disproportionately more gallbladder necrosis, perforation, and gangrene. Despite prolonged time intervals between admission and cholecystectomy in the MAG and advanced cases of cholecystitis, we did not record a prolonged procedure duration, conversion to open surgery, or complication rate. However, patients with acute calculous cholecystitis should either be primarily admitted to a surgical emergency service or at least a surgeon should be consulted at the time of diagnosis in order to avoid disease progression and unnecessary health care costs.

Role of HIPEC after Complete Cytoreductive Surgery (CRS) in Peritoneal Recurrence of Platinum-Sensitive Recurrent Ovarian Cancer (OC): The Aim for Standardization at Two Reference Centers for CRS.

BACKGROUND: This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. METHODS: The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. RESULTS: The median follow-up was 4.7 years (95%-CI 4.6-5.5). The median age was 55.8 years (IQR: 50.3-66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0-20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1-52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. CONCLUSION: In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.

Management of Symptomatic Gallstone Disease during COVID-19 Lockdown in a High-Resource Setting: Is There a Need for Treatment Alterations?

Introduction: Cholecystectomy (CCE) is the treatment of choice of symptomatic gallstones. Due to the SARS-CoV-2 pandemic, operating room (OR) capacities have been reduced. The goal of this study was to evaluate the duration of symptoms of patients presenting with gallstone disease during a lockdown, the surgical management, and the severity grade of their disease. Materials and Methods: A cohort study of 353 CCEs performed at a university hospital over two 10-week periods during 2 pandemic lockdowns in Germany compared to corresponding periods in 2018 and 2019. Results: During the lockdowns, 101 CCEs were performed compared to 252 in the prior years. The number of elective CCEs was reduced to save OR capacities (p < 0.001), and the most common indication for CCE was acute cholecystitis. The median time to CCE after symptom onset was 3 days in both groups for acute cholecystitis. The severity of cholecystitis was comparable (p = 0.760). The time to CCE after choledocholithiasis was shorter during the lockdowns (median of 4 days vs. 9 days; p = 0.006). Conclusions: The incidence and severity of acute cholecystitis during the lockdowns were comparable to the prior years. Acute care surgery was provided at the expense of elective procedures, and there was no need for treatment alterations.

[Current status of surgical treatment of peritoneal metastases from colorectal cancer]. / Aktueller Stand der chirurgischen Therapie peritonealer Metastasen bei kolorektalen Karzinomen.

Cytoreductive surgery, often in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), has been instrumental in improving the survival of patients with peritoneal metastases from colorectal cancer. Recent studies have highlighted the benefits of complete cytoreduction, while the role of the HIPEC treatment remains unclear. An oxaliplatin-based HIPEC over 30 min could not achieve any clear benefits in studies on colorectal cancer, neither in the therapeutic nor in the prophylactic setting, but caused relevant side effects and increased the morbidity. The negative results of these studies with respect to oxaliplatin-based HIPEC require critical appraisal; however, they should by no means be regarded as a general setback for surgical treatment of peritoneal metastases and be misunderstood as a general failure of this treatment. While HIPEC after complete surgical cytoreduction of peritoneal metastases from colorectal cancer requires further research, cytoreductive surgery should still be regarded as a highly effective treatment for suitable patients with limited abdominal tumor dissemination.

Beware of gastric tube in esophagectomy after gastric radiotherapy: A case report.

BACKGROUND: Gastric tube formation and pull-up is the most common technique of reconstruction following esophagectomy for esophageal cancer. If previous treatment with radiotherapy for gastric mucosa-associated lymphoid tissue (MALT)-lymphoma restricts suitability of the stomach for anastomosis to the esophagus is unknown. CASE SUMMARY: A 57-year-old man underwent sequential chemotherapy and radiotherapy for gastric MALT-lymphoma seven years prior to diagnosis of esophageal adenocarcinoma. Esophagectomy without neoadjuvant treatment was recommended by the multidisciplinary tumor board due to early tumor stage [uT1 (sm2) uN+ cM0 according to TNM-classification of malignant tumors, 8th edition] without lymph node involvement. Minimal invasive esophageal resection with esophagogastrostomy was performed. Due to gastric tube necrosis with anastomotic leakage on the twelfth postoperative day, diverting resection with construction of a cervical salivary fistula was necessary. Rapid recovery facilitated colonic interposition without any complications six months afterwards. CONCLUSION: This case report may represent the start for further investigation to know if it is reasonable to refrain from esophagogastrostomy in patients with a long interval between gastric radiotherapy and surgery.

[Impact of the SARS-CoV-2 Pandemic on Liver Surgery and Liver Transplantations in Germany]. / Einfluss der Coronapandemie auf die Leberchirurgie und Lebertransplantationen in 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.

Retrospective analysis of different therapeutic approaches for retroperitoneal duodenal perforations.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

(1) Background: 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) Methods: 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) Results: 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 (p = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively (p = 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) Conclusions: 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.

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

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/m2 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 ).