Enhanced recovery and reduced conversion rates in robotic rectal cancer surgery: a single-center retrospective cohort study.

PURPOSE: This study aimed to compare the outcomes of robotic-assisted rectal resection with conventional laparoscopic and open approaches, focusing on complication rates, conversion rates, length of hospital stay, and oncologic outcomes. METHODS: A retrospective single-center cohort study included 106 patients with non-metastatic rectal cancer (UICC stages I-III) who underwent rectal resection from January 2013 to December 2023. Patients were assigned to open surgery (n = 23), conventional laparoscopic surgery (n = 55), or robotic-assisted surgery (n = 28). RESULTS: Robotic surgery demonstrated significantly lower conversion rates compared to minimal-invasive surgeries (p = 0.047) and shorter hospital stays (11.5 ± 8 days) compared to open (17.91 ± 12 days) and laparoscopic (17.2 ± 14 days) surgeries (p = 0.001). The quality of the specimen was significantly better (Score 1) in robotic (85.71%) and open (89.09%) cases compared to laparoscopic approaches (47.83%) (p < 0.001). Laparoscopic surgery was identified as a risk factor for worse specimen quality (p < 0.001). Older patients (> 63 years) had a higher risk for conversion in univariate analysis (p = 0.049). Morbidity was comparable between the groups (p = 0.131), and the anastomotic leakage rate did not differ significantly (laparoscopic: 18.18%, open: 13.04%, robotic: 17.86%). Kaplan-Meier survival curves showed no significant differences in overall survival probabilities among the groups. CONCLUSION: Robotic-assisted rectal resection provides significant advantages in terms of lower conversion rates, better specimen quality, and shorter hospital stays while maintaining comparable complication rates and oncologic outcomes to conventional laparoscopic and open approaches. These findings support robotic surgery as a standard treatment option for rectal cancer.

"Before skin incision" high-resolution ultrasound in primary hyperparathyroidism: a new imaging tool for surgeons?

PURPOSE: Various diagnostic methods have been utilized for localizing pathologic parathyroid glands to consequently provide the possibility of avoiding bilateral neck dissection in cases of primary hyperparathyroidism. Scintigraphy, combined with ultrasound, became established as the standard method of localization in the 2000s. The aim of this study was to evaluate the role of the "before skin incision" surgeon-performed ultrasound in determining the improvement in the diagnostic accuracy in a large case series. METHOD: The method used in this research is a retrospective observational study (study period: between 1-2014 and 12-2020) comparing two patient groups before (control group: 31 patients) and after (study group: 70 patients) the introduction of the ultrasonography surgical protocol: combined preoperative and "before skin incision" surgeon-performed ultrasound. RESULTS: The sensitivity of the combined preoperative "before skin incision" surgeon-performed ultrasound was 97%, and the positive predictive value was 93% in regard to detecting the number of diseased glands and the appropriate anatomic location (right versus left, upper versus lower). The sensitivity of the parathyroid scan (Tc-MIBI-scintigraphy) was 74%, and the positive predictive value was 92%. The duration of surgery was significantly shorter in the test group (84.7 vs. 66.4 min; Mann‒Whitney U: 0.006). No differences were detected between the two groups in regard to avoiding intraoperative or postoperative complications. CONCLUSION: The combination of the preoperative "before skin incision" surgeon-performed ultrasound could improve the efficiency of the preoperative location and anatomic classification using the standard literature-suggested diagnostic methods.

Incidence and risk factors for umbilical incisional hernia after reduced port colorectal surgery (SIL + 1 additional port)-is an umbilical midline approach really a problem?

PURPOSE: Umbilical midline incisions for single incision- or reduced port laparoscopic surgery are still discussed controversially because of a higher rate of incisional hernia compared to conventional laparoscopic techniques. The aim of this study was to evaluate incidence and risk factors for incisional hernia after reduced port colorectal surgery. METHODS: A total 241 patients underwent elective reduced port colorectal surgery between 2014 and 2020. Follow-up was achieved through telephone interview or clinical examination. The study collective was examined using univariate and multivariate analysis. RESULTS: A total of 150 patients with complete follow-up were included into this study. Mean follow-up time was 36 (IQR 24-50) months. The study collective consists of 77 (51.3%) female and 73 (48.7%) male patients with an average BMI of 26 kg/m2 (IQR 23-28) and an average age of 61 (± 14). Indication for surgery was diverticulitis in 55 (36.6%) cases, colorectal cancer in 65 (43.3%) patients, and other benign reasons in 30 (20.0%) cases. An incisional hernia was observed 9 times (6.0%). Obesity (OR 5.8, 95% CI 1.5-23.1, p = 0.02) and pre-existent umbilical hernia (OR 161.0, 95% CI 23.1-1124.5, p < 0.01) were significant risk factors for incisional hernia in the univariate analysis. Furthermore, pre-existent hernia is shown to be a risk factor also in multivariate analysis. CONCLUSION: We could demonstrate that reduced port colorectal surgery using an umbilical single port access is feasible and safe with a low rate of incisional hernia. Obesity and pre-existing umbilical hernia are significant risk factors for incisional hernia.

Are risk factors for anastomotic leakage influencing long-term oncological outcomes after low anterior resection of locally advanced rectal cancer with neoadjuvant therapy? A single-centre cohort study.

PURPOSE: Anastomotic leakage (AL) poses the most serious problem following low anterior resection in patients with rectal cancer independent of surgical approach or technique. The aim of this study was to evaluate risk factors for the occurrence of AL and how they affect the oncological long-term outcome of patients who received neoadjuvant therapy. METHODS: A single centre cohort study of 163 consecutive locally advanced rectal cancer patients (cT3, cT4, N +) that received neoadjuvant therapy followed by resection with primary anastomosis between January 1998 and December 2020 were included in this study. Short- and long-term findings were compared between patients with AL (Leakage +) and without AL (Leakage -). RESULTS: A complete follow-up was obtained from 163 patients; thereby, 33 patients (20%) developed an AL. We observed more patients with comorbidities (38% vs. 61%, p = 0.049) which developed a leakage in the course. Permanent stoma rate (36% vs. 18%, p = 0.03) was higher, and time between primary operation and stoma reversal was longer (219 days [172-309] vs. 93 days [50-182], p < 0.001) in this leakage group as well. Tumour distance lower than 6 cm from the anal verge (OR: 2.81 [95%CI: 1.08-7.29], p = 0.04) and comorbidities (OR: 2.22 [95%CI: 1.01-4.90], p = 0.049) was evaluated to be independent risk factors for developing an AL after rectal cancer surgery. Oncological outcome was not influenced by AL nor by other associated risk factors. CONCLUSION: We could clearly detect the distance of tumour from the anal verge and comorbidities independent risk factors for the occurrence of AL. Oncological findings and long-term outcome were not influenced by these particular risk factors.

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

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 ).

Reduced port versus open right hemicolectomy for colorectal cancer: a retrospective comparison study of two centers.

PURPOSE: The concept of complete mesocolic excision (CME) in right-sided colorectal cancer is well known for open and laparoscopic surgery. The aim of this study was to evaluate and compare perioperative and oncological outcomes of reduced port and open surgery for right-sided colorectal cancer. METHODS: One hundred forty-one patients received elective surgery for right-sided colonic cancer between January 2015 and December 2019 and were included in a retrospective database. RESULTS: We observed longer operation time in the RP-CME group (145 min vs. 119.43 min, p<0.01). Hospital stay (8 days vs. 14 days, p<0.01) and time to first intestinal passage (42 h. vs. 59 h, p<0.01) were significantly shorter in the reduced port group. Postoperative complications were more likely to be observed in the O-CME group (7.2% vs. 14.1%, p=0.28); anastomotic leakage rate was low in both groups (1.8% vs. 2.4%, p=1.00). Specimen scores (score 1= good: 93.8% vs. 91.7%, p=1.00) and average number of retrieved lymph nodes were comparable (24 vs. 23 p=0.69). In O-CME patients, we observed more advanced tumor stages (UICC III: 21.4% vs. 45.9%, p<0.01). CONCLUSION: To our knowledge, this is the first study comparing reduced port to open surgery for right-sided colorectal cancer. We could demonstrate that this technique is feasible for oncological right hemicolectomy with observation of shorter hospital stay and lower morbidity rates compared to open surgery. The oncological outcome did not differ in the present study.

Peritoneal metastasis in gastric cancer: results from the German database.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). METHODS: The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. RESULTS: A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1-30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien-Dindo grades 3-4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0-6 (n = 74); 7-15 (n = 70) and 16-39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CONCLUSIONS: CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

Paradigm Shift in the Management of Irresectable Colorectal Liver Metastases: Living Donor Auxiliary Partial Orthotopic Liver Transplantation in Combination With Two-stage Hepatectomy (LD-RAPID).

OBJECTIVE: to report the first case of resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (RAPID) from living donor in a patient affected of irresectable colorectal liver metastases (i-CRLM) BACKGROUND:: A renaissance of liver transplantation (LT) for i-CRLM has been recently observed. The Norwegian SECA trial demonstrated a 5-year overall survival rate of approximately 60%, notwithstanding early tumor recurrence. The RAPID technique was recently introduced as alternative to whole deceased donor LT, but it is limited by poor availability of splittable organs and many organisational aspects. In this context left lateral living donor LT may be the ideal solution. METHODS: Report about the technique and results of living donor RAPID procedure. TECHNIQUE: A 49 years old woman affected with i-CRLM from adenocarcinoma of right colon, underwent a left hepatectomy with ligation of right portal vein maintaining the right hepatic artery patent. Subsequently, the left lateral lobe from her son was implanted as auxiliary partial orthotopic LT. Two weeks later completion of hepatectomy was performed. RESULTS: The donor postoperative course was uneventful. The recipient developed postoperatively a slight small for size syndrome which spontaneously resolved. No graft dysfunction and no rejection were observed. At POM 5 micrometastases occurred in bones and lungs, which were treated with radiotherapy and chemotherapy, respectively. Almost 2 years later the patient is alive, in good general condition, although slight progression of bone and lung metastases. CONCLUSIONS: LT poses a valid treatment option for i-CRLM. In times of organ paucity, "living donor-RAPID" procedure may represent a paradigm shift in the management of i-CRLM.

The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans.

The liver is a central regulator of whole body glucose, and lipid homeostasis and hepatokines, like fetuin-A, have been identified as markers and mediators of fatty liver-induced cardiometabolic risk. The closely related protein fetuin-B was shown to be upregulated in the fatty liver and to impact on glucose homeostasis in mice. In the present study we aimed to test the relevance of these findings in humans. In 55 subjects, hepatic mRNA expression of both hepatokines, fetuin-A and fetuin-B, associated positively with liver triglyceride content, whereas only fetuin-A expression associated with the homeostatic model assessment of insulin resistance. In 220 subjects who underwent precise metabolic phenotyping, circulating fetuin-A, but not fetuin-B, associated positively with liver fat content, and negatively with insulin sensitivity, measured during the oral glucose tolerance test (OGTT) and during the euglycemic, hyperinsulinemic clamp. Both circulating fetuin-A and fetuin-B correlated positively with the glucose area under the curve during the OGTT, but after additional adjustment for insulin sensitivity this relationship remained significant only for fetuin-B. In conclusion, despite the fact that the two hepatokines, fetuin-A and fetuin-B, are upregulated in the state of hepatic steatosis in humans, it appears that they differently impact on glucose homeostasis. Our data are in agreement with observations that fetuin-A can alter insulin signaling and that fetuin-B may regulate glucose homeostasis via so far unknown effects, possibly on glucose effectiveness.

First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications.

BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported. CASE PRESENTATION: We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing. DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies with application of cytostatic drugs such as oxaliplatin (OX) after cytoreductive surgery. Despite its increased use, evidence for optimal drug dosage, and notably duration of HIPEC, is scarce. METHODS: In this study, OX distribution was comprehensively assessed in nine patients during HIPEC (300 mg OX/m2 body surface area in Physioneal solution for 30 min). Oxaliplatin and its derivatives were measured in peritoneal perfusates over time by liquid chromatography coupled with mass spectrometry (LC-MS), and the resulting total platinum concentration in tissue was analyzed by atomic absorption spectrometry. Additionally, a novel impedance-based real-time cytotoxicity assay was used to evaluate the bioactivity of perfusates ex vivo. RESULTS: Compared with amounts of OX expected in peritoneal perfusates by calculation, only 10-15% of the parent drug could be detected by LC-MS during HIPEC. Notably, the study additionally detected platinum compounds consistent with OX transformation, accounting for a further fraction of the applied drug. The cytotoxic properties of perfusates remained unchanged during HIPEC, with only a slight but significant attenuation evidenced after 30 min. CONCLUSIONS: The bioactivity of peritoneal perfusates ex vivo is a useful parameter for evaluating the actual cytotoxic potential of OX and its derivatives used in HIPEC over time, overcoming important limitations and disadvantages associated with respective drug monitoring only. Ex vivo cytotoxicity assays may be a promising tool to aid guiding future standardization and harmonization of HIPEC protocols based on drug-mediated effects.

Overall morbidity but not mortality is increased in elderly patients following cytoreductive surgery and HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) prolongs survival in selected patients with peritoneal metastases. Since this procedure is likely to be associated with increased morbidity and mortality, it remains controversial whether it is also suitable for patients older than 70 years. METHODS: Consecutive patients with radiographic evidence of peritoneal metastases (PM) were scheduled for CRS and HIPEC at the Comprehensive Cancer Center, University Hospital Tübingen, Germany. Clinical data were retrospectively analyzed categorizing patients with respect to age into elderly (age ≥ 70) and non-elderly patients (age < 70). RESULTS: Between June 2005 and March 2014, 381 patients with a median age of 55 [14-77] years could be enrolled with 29 patients (8 %) being at least 70 years old. Both groups were comparable for tumor-related parameters including PCI, CC-status, time in operating room, and visceral resections. However, there was a difference in patient-related factors such as cardio-pulmonary comorbidities and ASA score. We found no difference in overall and recurrence-free survival between the two groups. Surgery-related mortality was 0.9 % in patients younger than 70 years whereas no patient died in the elderly group. Overall morbidity was 47 % in the younger and 76 % in the elderly group (p = 0.048). There was no difference in Clavien-Dindo grade III-IV morbidity. Logistic regression analysis proved age as an independent risk factor for increased overall morbidity in elderly patients. CONCLUSION: In elderly patients, CRS and HIPEC are associated with increased overall morbidity but neither Dindo III-IV morbidity nor surgery-related mortality.

Measurement of apparent diffusion coefficient with simultaneous MR/positron emission tomography in patients with peritoneal carcinomatosis: comparison with 18F-FDG-PET.

PURPOSE: To characterize peritoneal carcinomatosis (PC) of different histologically proven primary tumors based on diffusion-weighted imaging (DWI) and (18) F-FDG positron emission tomography (PET). MATERIALS AND METHODS: Forty-one patients underwent simultaneous MR/PET after clinically indicated (18) F-FDG-PET/CT. For all patients, histology of the primary tumor was obtained. MR protocol comprised anatomical imaging and axial DWI. Apparent diffusion coefficient (ADC) maps and FDG-PET were co-registered for evaluation of ADC and standard uptake value (SUV) of peritoneal lesions. Both lesion- and patient-based analysis was performed. Up to four peritoneal lesions were evaluated per patient. Mean and maximum standard uptake value (SUVmean , SUVmax ), mean and minimum ADC (ADCmean , ADCmin ) of each lesion were assessed. Spearman rank correlation (rs ) of ADC and SUV were calculated. SUV and ADC of ovarian and colorectal cancer lesions were compared using Wilcoxon test. RESULTS: Measurable lesions (n = 52) were found in 20 of 41 PC patients. Moderate, but significant correlation existed between ADC and SUV in the lesion-based as well as the patient-based analysis (lesion-based: SUVmean versus ADCmean rs = -0.58; SUVmax versus ADCmin rs = -0.56, all P < 0.0001; patient-based: SUVmean versus ADCmean rs = -0.64, P = 0.002; SUVmax versus ADCmin rs = -0.60, P = 0.005). ADC and SUV differed significantly between ovarian and colorectal cancer lesions (ADCmin : P < 0.0001; ADCmean : P < 0.0001; SUVmax : P = 0.002; SUVmean : P = 0.005). Overall, mucinous tumor entities showed a tendency to higher ADC and lower SUV. CONCLUSION: PC lesions showed significant differences in glucose uptake and diffusion characteristics depending on primary tumor histology. These differences should be considered when interpreting FDG-PET and DWI in PC patients.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in recurrent epithelial ovarian cancer with peritoneal metastases: a single centre experience.

BACKGROUND: This investigation aims to assess morbidity, mortality and postoperative outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (REOC) with peritoneal metastases (PM). METHODS: Consecutive patients with radiographic evidence of REOC with PM were scheduled for CRS and HIPEC at the Comprehensive Cancer Center, University Hospital Tübingen, Germany. Clinical data were retrospectively analyzed. RESULTS: In total, 90 patients were analyzed. Complete cytoreduction and HIPEC could be performed in 69 % of patients. When categorizing patients with respect to the completeness of cytoreduction (CC-0/1 vs CC-2/3), there was no difference considering baseline demographic characteristics. Cumulative morbidity was 42 %. Morbidity rates did not statistically differ between CC-0/1 patients with HIPEC and CC-2/3 patients without HIPEC. No surgery-related and 90-day postoperative mortality was observed. In CC-0/1 patients, median overall survival was 35 months as opposed to 14 months in CC-2/3 patients. There was no difference in survival with respect to the peritoneal carcinomatosis index (PCI) as long as complete cytoreduction could be achieved. CONCLUSIONS: CRS and HIPEC can be performed with acceptable morbidity and low mortality in specialized centres. Our data do not suggest that HIPEC necessarily increases the risk of postoperative adverse events.

Do patient- and tumor-related factors predict the peritoneal spread of pancreatic adenocarcinoma?

PURPOSE: In pancreatic cancer, the presence of peritoneal carcinomatosis (PC) precludes the possibility of a surgical cure, irrespective of the resectability of the primary tumor. However, peritoneal spread cannot be reliably detected radiographically during preoperative tumor staging. METHODS: The pancreatic adenocarcinoma database of the Tübingen Comprehensive Cancer Center included 29 patients in whom PC was incidentally detected during the surgery. These patients were retrospectively compared for patient- and tumor-related factors with 29 randomly selected patients without PC who underwent curative resection. RESULTS: Clinical jaundice and diarrhea were more frequently present in patients without PC. The CA 19-9 levels were significantly higher in patients with PC compared to those in patients without PC. No other differences were observed in the patient- or tumor-related factors between the two groups. CONCLUSION: In pancreatic cancer patients, markedly elevated CA 19-9 levels may serve as surrogate marker for peritoneal dissemination, irrespective of the local resectability of the tumor. In such patients, laparoscopy should be considered as an additional staging tool to rule out peritoneal carcinomatosis.

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.

Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies.

PURPOSE: Recurrent disease following complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a relevant clinical scenario. We aimed to determine risk factors for recurrence. METHODS: Prospectively collected data of patients enrolled in the Peritoneal Surface Malignancy Program at the University of Tübingen between 2005 and 2011 were retrospectively analyzed. All patients were treated by standardized CRS and HIPEC. Recurrence was defined either radiographically by CT, PET-CT scan, or reoperation. RESULTS: Fifty-two patients received complete CRS (CC-0/CC-1) and HIPEC. Median time to recurrence was 229 days (103-1,028). Overall recurrence rate within follow-up was 48 %. Of patients with recurrent disease, 44 % experienced extraperitoneal systemic tumor spread. In multivariate analysis, grading of ≥ 3 was shown as an independent risk factor for recurrent disease, while a trend was observed for maximal tumor load in the upper abdominal region. Clinical parameters did not show an impact on recurrence. CONCLUSIONS: Primary tumor grading seems to be an independent risk factor for recurrence following complete CRS and HIPEC in colorectal cancer-derived peritoneal surface malignancies.

Induction of tumor stem cell differentiation--novel strategy to overcome therapy resistance in gastric cancer.

PURPOSE: Metastases are a frequent finding in gastric cancer and are associated with poor prognosis. A recently discovered link between metabolic changes, differentiation, and therapy resistance due to tumor stem cells could depict a novel approach in cancer research and therapy. Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme and is known to be involved in enabling gastric cancer cells to be invasive and to disseminate. In this study, we investigated if PGK1 is a promising candidate in inducing stem cell differentiation in gastric cancer. MATERIALS AND METHODS: MKN45 gastric cancer cells were used due to their known cancer stem cell population, which is defined by the surface marker CD44. MKN45 cells were separated between CD44+ and CD44- cells and, in equal parts, incubated with shRNA anti-PGK1 using fluorescence-activated cell sorting (FACS) analysis; they were then injected into nude mice to evaluate their tumor growth behavior in vivo. Further, the invasive potential of gastric cancer cells was evaluated in vitro using the xCelligence analyzing system. RESULTS: CD44+ gastric cancer cells treated with and without shRNA anti-PGK1 were capable to cause tumor growth in vivo, whereas tumor growth in CD44+ cells treated with shRNA anti-PGK1 was considerably smaller in comparison with that in CD44+ cells without treatment. CD44- cells did not show any noticeable tumor growth in vivo. By targeting PGK1, the invasive potential of gastric cancer cells was impressively reduced in vitro. In all our cells, which were targeted with shRNA anti-PGK1, we did not find any change that is in accordance with the phenotype of the cells using FACS analysis. CONCLUSIONS: Our findings suggest that targeting the key metabolic enzyme PGK1 in gastric cancer cells may open a new chapter in cancer treatment, which is well worth for further exploration in combination with recent chemotherapy, and might be a promising possibility to overcome therapy resistance in gastric cancer.