Morbidity and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Data from the DGAV StuDoQ Registry with 2149 Consecutive Patients.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are performed for well-selected patients with peritoneal surface malignancies. This combined treatment is potentially associated with an increased rate of complications. OBJECTIVE: The aim of this paper was to analyze the morbidity and mortality of CRS and HIPEC in the German national registry. METHODS: We present a retrospective analysis of 2149 consecutive patients from 52 hospitals. The data were prospectively documented in the DGAV StuDoQ Registry between February 2011 and December 2016. RESULTS: Almost two-thirds of all patients had a colorectal malignancy; therefore, the most frequently performed resections were colectomies (54%) and rectal resections (30%). Only 36.2% of all patients had no anastomosis, and fewer than 20% of all patients were older than 70 years of age (16.4%). Enteric fistula and anastomotic leaks occurred in 10.5% of all cases. The reoperation rate was 14.6% (95% confidence interval [CI] 11.51-18.1). Major grade 3 and 4 complications (Clavien-Dindo classification) occurred in 19.3% of all patients, half of which were due to surgical complications. The overall 30-day postoperative hospital mortality was 2.3% (95% CI 1.02-3.85). Multivariate analysis showed an increased risk for morbidity associated with pancreatic resections (odds ratio [OR] 2.4), rectal resection (OR 1.5), or at least one anastomosis (OR 1.35), and mortality with reoperation (OR 8.7) or age > 70 years (OR 3.35). CONCLUSIONS: CRS and HIPEC are associated with acceptable morbidity and low mortality. These results show that CRS and HIPEC can be safely performed nationwide when close mentoring by experienced centers is provided.

Less pain after transvaginal/transumbilical cholecystectomy than after the classical laparoscopic technique: short-term results of a matched-cohort study.

BACKGROUND: Natural orifice surgery (NOS) is gaining acceptance as an alternative to the traditional laparoscopic technique, especially for cholecystectomy through the transvaginal route. However, NOS remains controversial concerning expected advantages in terms of short- and long-term outcomes and potential side effects. This study was designed to compare short-term outcomes between transvaginal/transumbilical and classical laparoscopic cholecystectomy (LC). METHODS: A prospective matched-cohort study compared the authors' first 50 transvaginal/transumbilical cholecystectomies (TVC) with a group of 50 classical LCs from the corresponding period matched in terms of age, body mass index, and American Society of Anesthesiology classification. In both groups, elective surgery was performed for symptomatic cholecystolithiasis. In the NOS group, a hybrid procedure was performed with one transumbilical rigid instrument and two transvaginal rigid instruments. A numeric rating scale was used for daily pain assessment, initiated postoperatively in the recovery room. Both groups were compared with regard to length of surgery, intra- and postoperative complications, length of hospital stay, postoperative pain, and consumption of analgesics. RESULTS: The length of surgery and the rate of complications were similar in the two groups. But significant advantages were found for the transvaginal access in terms of pain using Numeric Rating Scale (NRS) on the day of surgery (NRS, 1.5/10 vs 3.1/10; p = 0.003) as well as in the morning (NRS, 1.9/10 vs 2.8/10; p = 0.047) and in the evening (NRS, 1.1/10 vs 1.8/10; p = 0.025) of postoperative day 1, and with regard to the length of the postoperative hospital stay (2.7 vs 3.4 days; p = 0.035). CONCLUSIONS: The findings show that TVC is a safe procedure for female patients. It has a risk comparable with that of classic LC, causes significantly less pain in the early postoperative period, and leads to a significantly shorter hospital stay. Prospective randomized trials are necessary to confirm these results.

[Treatment options for peritoneal metastases from hepato-pancreato-biliary tumors and neuroendocrine tumors]. / Therapeutische Optionen bei peritonealer Metastasierung hepatopankreatikobiliärer Tumoren und neuroendokriner Tumoren.

Peritoneal metastasis (PM) in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and hepato-pancreato-biliary (HPB) tumors has a low incidence and has rarely been studied as a stand-alone condition. The clinical relevance of PM in HPB tumors and GEP-NET arises from the fact that PM significantly worsens the prognosis of the underlying tumors. In GEP-NET, the particular situation is that PM has a negative prognostic impact compared to patients without metastases, which is not evident compared to patients with metastases in other locations. Complete surgical cytoreduction (CRS) is a curative treatment option for patients with PM in GEP-NET. Complete surgical resection should always be strived for, although patients may benefit from incomplete resection (70-90%) or resection of the primary tumor alone. Additional hyperthermic chemoperfusion (HIPEC) is currently not recommended. For nonresectable GEP-NET, systemic treatment is available that is oriented to the studies for generally metastasized GEP-NET. For PM in carcinomas of the bile duct and pancreatic carcinomas, there are no valid data or indications for CRS and HIPEC. In contrast, case series for PM in hepatocellular carcinoma (HCC) after CRS or CRS/HIPEC show good survival outcomes that justify a surgical approach under the condition of a complete resection. Patients with PM in GEP-NET and HCC should therefore be referred to a center for peritoneal tumor surgery to evaluate the option of complete CRS and use it as a curative option.

Immunotherapy of peritoneal carcinomatosis with the antibody catumaxomab in colon, gastric, or pancreatic cancer: an open-label, multicenter, phase I/II trial.

BACKGROUND: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. METHODS: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 µg; day 3: 10 or 20 µg; day 7: 30, 50, or 100 µg; and day 10: 50, 100, or 200 µg. Dose escalation was guided by dose-limiting toxicities. RESULTS: The MTD was 10, 20, 50, and 200 µg on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. CONCLUSIONS: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer.

The trifunctional antibody catumaxomab in treatment of malignant ascites and peritoneal carcinomatosis.

Peritoneal carcinomatosis remains an unsolved medical problem in modern oncologic treatment. Excruciating symptoms such as malignant ascites, ileus, nausea, vomiting, dyspnoea and pain deteriorate the quality of life for affected patients. There is still no effective standard treatment for peritoneal carcinomatosis. The trifunctional antibody catumaxomab (antiepithelial cell adhesion molecule x anti-CD3) is able to direct T lymphocytes and Fcg-receptor-positive accessory cells to epithelial cell adhesion molecule-positive tumor cells. Intraperitoneal catumaxomab therapy was shown to be the first effective therapy against accumulation of malignant ascites in patients with peritoneal carcinomatosis of epithelial cancer, reducing the need of paracentesis and prolonging puncture-free survival. This paper reviews the mode of action of catumaxomab and analyzes different fields of local immunotherapy in patients with peritoneal carcinomatosis. A summary of completed and ongoing studies is included. Catumaxomab is discussed to be an outstanding option for local control and therapy of peritoneal carcinomatosis, which could be an optimal modular therapy in addition to systemic chemotherapy and surgical tumor resection.

Transvaginal hybrid-NOTES vs. traditional laparoscopic sigmoid resection for diverticulitis: a short-term comparative study.

The aim was to compare short-term results of transvaginal hybrid-NOTES (NSR) with traditional laparoscopic technique in sigmoid resection (LSR) in cases of diverticulitis. Natural Orifice Transluminal Endoscopic Surgery has been evolved as a minimally invasive procedure to reduce the operative trauma due to the absence of specimen extraction through the abdominal wall causing less postoperative pain, and shorter hospital stay. Despite the increasing use and published case series of NSR for diverticulitis as a laparoscopic procedure with transvaginal stapling and specimen extraction, there are no studies comparing this procedure with LSR. Twenty NSR patients operated at the Cologne-Merheim Medical Center have been documented and compared with 20 female LSR patients matched for body mass index, American Society of Anesthesiologists-classification (ASA), Hansen/Stock classification, and age. To ensure comparability regarding peri- and postoperative care, only procedures performed by the same surgeon were included. Procedural time, intra- and postoperative complications, conversion rate, postoperative pain, the duration of an epidural catheter, analgesic consumption, and postoperative length of hospital stay were analyzed. There were no significant differences in the sum of pain levels (p = 0.930), length of procedure (p = 0.079), intra- and postoperative complications, as well as duration of an epidural catheter. On the contrary, there were significant positive effects for NSR on morphine requirement at day seven and eight (p = 0.019 and p = 0.035 respectively) as well as the postoperative length of hospital stay (p = 0.031). This retrospective study reveals significant positive effects for NSR compared to LSR regarding length of hospital stay as well as morphine consumption after removal of the epidural catheter, whereas there were no significant differences in complication rate and procedural time. In summary, NSR is an adequate alternative to traditional laparoscopic sigmoid resection considering the surgeons experience and the patient's personal preferences.

Intraperitoneal immunotherapy to prevent peritoneal carcinomatosis in patients with advanced gastrointestinal malignancies.

Prognosis of peritoneal carcinomatosis (PC) from GI tract cancers remains poor. As 30% of patients develop PC after curative surgery, prevention of PC during cancer resection would be desirable. Regarding physiopathology of PC and intraperitoneal immunology, intraoperative application of trifunctional antibodies offers advanced opportunities for destruction of intraperitoneal tumor cells and prevention of PC. First results indicated, the intraoperative treatment with trifunctional antibodies was safe and clinically feasible. Long-term results will be available in 2010.

Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study.

PURPOSE: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) enhances the antitumor activity by redirecting T cells and Fcgamma receptor I/III--positive accessory cells to the tumor. This multicenter phase I/II dose-escalating study investigated tolerability and efficacy of i.p. catumaxomab application in ovarian cancer patients with malignant ascites containing epithelial cell adhesion molecule (EpCAM)--positive tumor cells. EXPERIMENTAL DESIGN: Twenty-three women with recurrent ascites due to pretreated refractory ovarian cancer were treated with four to five i.p. infusions of catumaxomab in doses of 5 to 200 microg within 9 to 13 days. RESULTS: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 microg for the first through fifth doses. Side effects included transient fever (83%), nausea (61%), and vomiting (57%), mostly CTCAE (Common Terminology Criteria for Adverse Events) grade 1 or 2. A total of 39 grade 3 and 2 grade 4 treatment-related adverse events (AE), 9 of them after the highest dose level (200 microg), were observed in 16 patients. Most AEs were reversible without sequelae. Treatment with catumaxomab resulted in significant and sustained reduction of ascites flow rate. A total of 22/23 patients did not require paracentesis between the last infusion and the end of study at day 37. Tumor cell monitoring revealed a reduction of EpCAM-positive malignant cells in ascites by up to 5 log. CONCLUSION: I.p. immunotherapy with catumaxomab prevented the accumulation of ascites and efficiently eliminated tumor cells with an acceptable safety profile. This suggests that catumaxomab is a promising treatment option in ovarian cancer patients with malignant ascites.

Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. PATIENTS AND METHODS: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. RESULTS: Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. CONCLUSION: The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.

Extended Pancreas Donor Program-The EXPAND Study: A Prospective Multicenter Trial Testing the Use of Pancreas Donors Older Than 50 Years.

BACKGROUND: Pancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists, leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age, 50-60 years; body mass index, 30-34 kg/m). METHODS: Utilization of EDC organs required the implementation of a new allocation system within Eurotransplant. The study was a prospective, multicenter, 2-armed trial. The primary endpoint was pancreas function after 3 months. Rejection episodes, kidney function, and waitlist time were secondary endpoints. Patients receiving an EDC organ were study group patients; recipients of standard organs were control group patients. Follow-up was 1 year. RESULTS: Seventy-nine patients were included in 12 German centers, 18 received EDC organs and 61 received standard organs. Recipient demographics were similar. Mean EDC donor age was 51.4 ± 5 years versus 31.7 ± 12 in the control group. Insulin-free graft survival was 83.3% for EDC and 67.2% for standard organs (P = 0.245) after 3 months. One-year pancreas survival was 83.3% and 83.5% in the EDC versus standard group. One-year kidney allograft survival was approximately 94% in both groups. Rejection episodes and morbidity were similar. CONCLUSIONS: The Extended Pancreas Donor Program (EXPAND) shows in a prospective trial that selected EDC organs of donors older than 50 years can be used with outcomes similar to standard-criteria organs, therefore showing potential to reduce organ shortage and waiting times. This study substantiates the full implementation of EDC organs in a pancreas allocation system.

The role of relative lymphocyte count as a biomarker for the effect of catumaxomab on survival in malignant ascites patients: results from a phase II/III study.

PURPOSE: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites. EXPERIMENTAL DESIGN: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥ 1 dose of catumaxomab (n = 157) and paracentesis alone (n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria. RESULTS: OS was significantly longer with catumaxomab versus paracentesis alone (P = 0.0219). The 6-month OS rate with catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor (P < 0.0001). In patients with RLC > 13% (n = 159: catumaxomab, 100 and control, 59), catumaxomab was associated with a favorable effect on OS versus paracentesis alone (P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening (n = 74: catumaxomab, 50 and control, 24), the median (mean) OS difference between the catumaxomab and the control group was 3 (16) days, respectively (P = 0.2561). CONCLUSIONS: OS was significantly improved after catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker.

Extended pancreas donor program - the EXPAND study rationale and study protocol.

BACKGROUND: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. METHODS/DESIGN: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. DISCUSSION: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future. TRIAL REGISTRATION: Trial registered at: NCT01384006.

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer.

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.

Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb) are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC.9 patients with progressive PC from gastric (n = 6) and ovarian cancer (n = 2), and cancer of unknown primary (n = 1) received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM x CD3 (10, 20, 40 microg) or HER2/neu x CD3 (10, 40, 80 microg) were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-gamma secretion assay.In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression) has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months) after trAb therapy.TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

Comparison of laparoscopic vs. open access surgery in patients with rectal cancer: a prospective analysis.

PURPOSE: Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection. However, the situation in rectal cancer remains unclear, because anatomy and complex surgical procedures might specifically influence the long-term outcome. This study was designed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery. METHODS: A total of 389 patients (1998-2005) were prospectively analyzed; 114 patients had laparoscopic beginning, and 25 patients had conversion and were separately analyzed. Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery. RESULTS: Both groups were comparable regarding age, gender, tumor localization, stage, and complications. Differences were found in harvested lymph nodes (laparoscopic 13.5/open access 16.9; P = 0.001) and hospitalization (15.1/18.7 days; P = 0.037). Local recurrence rate and metachronous metastasis were comparable. In patients with deep anterior resection with total mesenteric excision, favorable long-term survival in the laparoscopic group was found (P = 0.035, log-rank). CONCLUSIONS: Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery. Especially in patients with low rectal cancer, minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery.

Immunotherapy of malignant ascites with trifunctional antibodies.

A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fcgamma receptor type I/III+ cells (macrophages, NK-cells and DC). These trifunctional antibodies (trAb) lead to efficient specific killing of targeted tumor cells without any pre- or co-stimulation. This concept was investigated in vivo in patients with malignant ascites in a clinical situation that allowed monitoring of tumor cell elimination and correlation with clinical effects. In a prospective study, 8 patients with malignant ascites due to peritoneal carcinomatosis were treated with intraperitoneal application of trAb, which bound either the EpCAM- or Her2/neu-antigen on tumor cells. Treatment consisted of 4-6 applications within 9-23 days with a total amount of 145-940 microg. Seven of eight patients required no further paracentesis during follow-up or until death with a mean paracentesis-free interval of 38 weeks (median = 21.5, range = 4-136). Tumor cell monitoring showed a complete elimination of tumor cells in ascites already at total doses as low as 40-140 microg. Clinical response with disappearance of ascites accumulation was seen in all patients, which was correlated with elimination of tumor cells (p = 0.0014). Severe adverse events were not observed. Clinically relevant side effects were fever, moderate abdominal pain and skin reactions. Intraperitoneal immunotherapy with trAb showed convincing efficacy in patients with malignant ascites. This treatment offers new therapeutic options for patients with peritoneal carcinomatosis.