Questions to consider when caring for patients with ulcerative colitis.

Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.

Endoscopic R1/Rx Resection of T1 Colorectal Cancer-What Next?

ABSTRACT: T1 carcinoma is often not recognized as such, and inappropriate endoscopic resection techniques are selected, resulting in positive (R1) or nonassessable (Rx) resection margins. Full-thickness resection has been proposed as an alternative to completion surgery. Gijsbers et al. compared oncological outcomes of both strategies. The main finding was that colorectal cancer recurrence was significantly higher in the full-thickness excision of the scar compared with the completion surgery group (9.0% vs 2.2%). However, metastasis-free survival and overall survival were not significantly different in both groups. The results of this study favor full-thickness excision of the scar as the first-line approach for Rx/R1-resected margins but otherwise low-risk tumors.

Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset.

Conditioning-induced damage of the intestinal tract plays a critical role during the onset of acute graft-versus-host disease (GVHD). Therapeutic interference with these early events of GVHD is difficult, and currently used immunosuppressive drugs mainly target donor T cells. However, not donor T cells but neutrophils reach the sites of tissue injury first, and therefore could be a potential target for GVHD prevention. A detailed analysis of neutrophil fate during acute GVHD and the effect on T cells is difficult because of the short lifespan of this cell type. By using a novel photoconverter reporter system, we show that neutrophils that had been photoconverted in the ileum postconditioning later migrated to mesenteric lymph nodes (mLN). This neutrophil migration was dependent on the intestinal microflora. In the mLN, neutrophils colocalized with T cells and presented antigen on major histocompatibility complex (MHC)-II, thereby affecting T cell expansion. Pharmacological JAK1/JAK2 inhibition reduced neutrophil influx into the mLN and MHC-II expression, thereby interfering with an early event in acute GVHD pathogenesis. In agreement with this finding, neutrophil depletion reduced acute GVHD. We conclude that neutrophils are attracted to the ileum, where the intestinal barrier is disrupted, and then migrate to the mLN, where they participate in alloantigen presentation. JAK1/JAK2-inhibition can interfere with this process, which provides a potential therapeutic strategy to prevent early events of tissue damage-related innate immune cell activation and, ultimately, GVHD.

Simultaneous ipsilateral nephrectomy during kidney transplantation in autosomal dominant polycystic kidney disease: a matched pair analysis of 193 consecutive cases.

BACKGROUND: In end-stage renal transplant recipients with autosomal-dominant polycystic kidney disease (ADPKD), the imperative, optimal timing, and technique of native nephrectomy remains under discussion. The Freiburg Transplant Center routinely performs a simultaneous ipsilateral nephrectomy. METHODS: From April 1998 to May 2017, we retrospectively analyzed 193 consecutive ADPKD recipients, receiving per protocol simultaneous ipsilateral nephrectomy and compared morbidity, mortality, and outcome with 193 non-ADPKD recipients of a matched pair control. RESULTS: The incidence of surgical complications was similar with respect to severe medical, surgical, urological, vascular, and wound-related complications as well as reoperation rates and 30-day mortality. Intraoperative blood transfusions were required more often in the ADPKD (22.8%) compared with the control group (6.7%; p < 0.0001). Early postoperative urinary tract infections occurred more frequent (ADPKD 40.4%/control 29.0%; p = 0.0246). Time of surgery was prolonged by 30 min (ADPKD 169 min; 95%CI 159.8-175.6 min/control 139 min; 95%CI 131.4-145.0 min; p < 0.0001). One-year patient (ADPKD 96.4%/control 95.8%; p = 0.6537) and death-censored graft survival (ADPKD 94.8%/control 93.7%; p = 0.5479) were comparable between both groups. CONCLUSIONS: With respect to morbidity and mortality, per protocol, simultaneous native nephrectomy is a safe procedure. Especially in asymptomatic ADPKD KTx recipients, the number of total operations can be reduced and residual diuresis preserved up until transplantation. In living donation, even preemptive transplantation is possible.

Repeated SBRT for in- and out-of-field recurrences in the liver.

PURPOSE: To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors. METHODS: Consecutive patients with primary (hepatocellular carcinoma [HCC] or cholangiocarcinoma [CCC]) or secondary liver cancer (LM), with intrahepatic recurrence or progression after SBRT, underwent re-SBRT in 3 to 12 fractions with a median time of 15 (range 2-66) months between treatments. RESULTS: In all, 24 patients which were previously treated with SBRT (30 lesions) were retreated with SBRT for "in- and out-of-field" recurrences (2nd SBRT: n = 28, 3rd SBRT: n = 2). The median follow-up after re-irradiation was 14 months. The median prescribed dose for the first SBRT was 46.5 (range 33-66 Gy, EQD210 = 70.5) Gy and 48 (range 27-66 Gy, EQD210 = 71) Gy for the re-SBRT. The median mean liver dose (Dmean, liver) was 6 Gy (range 1-25, EQD22 = 7 Gy) for the first SBRT and 10 Gy (range 1-63 Gy, EQD22 = 9 Gy) for the re-SBRT. Of the 30 re-irradiated lesions 6 were re-irradiated in-field resulting in a median EQD22, maximum of 359 (range 120-500) Gy for both treatments, with an α/ß = 2 to account for liver parenchyma. Treatment was well tolerated. Two patients with stent placement before SBRT developed cholangitis 4 and 14 months after re-SBRT. There were no elevations of the serum liver parameters after re-SBRT. One patient developed a grade 3 gastrointestinal bleeding. There was no radiation induced liver disease (RILD) observed. CONCLUSIONS: Repeated liver SBRT is feasible, without excessive liver toxicity, when there is no considerable overlapping with pre-irradiated portions of the stomach or bowel and enough time for the liver to regenerate.

The role of albumin-bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy.

PURPOSE: We evaluated the prognostic accuracy of the albumin-bilirubin (ALBI) grade and the inflammation-based index (IBI) in estimating overall survival (OS) and toxicity in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty patients with 47 HCC lesions with a Barcelona Clinic Liver Cancer (BCLC) classification stage B or C were treated with SBRT in 3-12 fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during, at the end of treatment and at follow-up) and compared with the Child-Pugh (CP) score as well as other patient- and treatment-related parameters, concerning OS and toxicity. RESULTS: The median follow-up was 14.3 months for patients alive. The median OS from SBRT was 10 (95% confidence interval 8.3-11.6) months. The local control at 1 year was 79%. A lower IBI during treatment was associated with better OS (p = 0.034) but not CP and ALBI. Higher C­reactive protein levels as well as higher alpha-fetoprotein concentrations correlated with worse survival (p = 0.001). Both higher ALBI (p = 0.02) and CTP (p = 0.001) at baseline correlated with a higher incidence of acute and late toxicities (CTC ≥2). Neither the mean radiation dose to the liver nor the dose to 700 cc of the liver correlated with the occurrence of toxicities. CONCLUSIONS: In this analysis, a higher ALBI grade as well as a higher CP were predictors of higher incidence of toxicity, whereas a lower IBI during treatment correlated with a better OS. These results should be further evaluated in prospective studies.

Prognostic influence of hepatic margin after resection of colorectal liver metastasis: role of modern preoperative chemotherapy.

PURPOSE: Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status. METHODS: Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database. RESULTS: Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001). CONCLUSION: In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.

Outcome after hepatic resection for isolated non-colorectal, non-neuroendocrine liver metastases in 100 patients - the role of the embryologic origin of the primary tumor.

BACKGROUND: The indication for hepatic resection (HR) in patients suffering from liver metastases (LM) other than colorectal and neuroendocrine tumors is one focus of current multidisciplinary, oncologic considerations. This study retrospectively analyzes outcome after HR for non-colorectal, non-neuroendocrine (NCNNE) LM in the absence of distant or extrahepatic metastases. METHODS: We included 100 consecutive patients undergoing HR for isolated NCNNE LM from a prospective database in our institution, including postoperative follow-up. Primary tumors were of mesodermal origin in 44%, of ectodermal origin in 29% and of entodermal origin in 27%. Survival analysis was performed by univariate and multivariable methods. Mean follow-up after hepatic surgery was 3.6 years (0.25-16). RESULTS: Median age at the time of HR was 59.5 years. Kaplan-Meier-estimated survival after liver resection was 56.8%, 34.3% and 24.5% after 5, 10 and 15 years, respectively. Univariate analysis after HR revealed residual disease (hepatic or primary; p = 0.02), female gender (p = 0.013), entodermal origin (p = 0.009) and early onset of metastatic disease (≤24 months, p = 0.002), as negative prognostic factors. Multivariable survival analysis confirmed residual disease, female gender, entodermal embryologic origin and early onset of metastatic disease (≤24 months) as independent negative prognostic factors. CONCLUSION: Overall outcome after HR of NCNNE LM results in acceptable long-term outcome. Although individual decision-making today mostly relies on clinical experience for this type of disease, risk factors derived from the embryologic origin of the tumor might help in patient selection.

Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND: To evaluate the role of ablative radiotherapy doses in the treatment of hilar or intrahepatic cholangiocarcinoma (CCC) using stereotactic body radiotherapy (SBRT). METHODS: Consecutive patients treated from 2007 to 2016 with CCC were evaluated. Local control and toxicities were assessed every 3 months according to the Response Evaluation Criteria In Solid Tumors (RECIST) and the Common Terminology Criteria for Adverse Events v4.0, respectively. Overall survival (OS), local control (LC) and progression free survival were calculated from SBRT. RESULTS: Thirty seven patients with 43 lesions were retrospectively evaluated. The median dose delivered was 45 Gy (range 25-66 Gy) in 3-12 fractions, corresponding to a median equivalent dose in 2 Gy fractions (EQD210) of 56 (range 25-85) Gy. The median follow up was 24 months. The OS at 1 year was 56% with a median OS of 14 (95% CI: 7.8-20.2) months from start of SBRT and 22 (95% CI: 17.5-26.5) months from diagnosis. Eight lesions progressed locally. The local control rate (LC) at 1 year was 78%. The median progression free survival was 9 months (95% CI 2.8-15.2) 21 patients progressed in the liver but out of field and 15 progressed distantly. SBRT was well tolerated. Three patients (9%) developed a Grade III bleeding. Seven patients developed a cholangitis, one due to progression and the other because of a stent dysfunction 2-21(median 8) months from SBRT. CONCLUSION: In patients with locally advanced cholangiocarcinoma, SBRT is a local treatment option with an acceptable toxicity profile which warrants further investigation in prospective trials.

Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver.

Background: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression. Methods: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry. Results: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding. Conclusions: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.

One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease.

PURPOSE: Surgical management of autosomal dominant polycystic kidney disease (ADPKD) in patients awaiting renal transplantation is a challenging task. METHODS: From 1998 to 2009, a total of 100 consecutive renal transplantations with simultaneous unilateral nephrectomy were performed in 59 men and 41 women with ADPKD and end-stage renal failure. About 38% received kidney allografts from living donors. The ipsilateral polycystic kidney was removed at the time of renal transplantation. Immunosuppressive therapy was not modified. Cold ischaemia time was 155 (38-204 min) versus 910 min (95-2760 min) for living versus deceased donor transplantation. Mean weight of removed kidneys was 2002 g (414-8850 g). Mean follow-up was 3.0 years (0.8-10.0 years). RESULTS: Overall patient and graft survival were 97 and 96% at 1 year and 93 and 80% at 5 years, respectively. Serum creatinine at current follow-up was 1.49 (0.8-2.8) mg/dL. Surgical complications, which might be associated with simultaneous nephrectomy requiring re-operation, occurred in 12% (lymphocele 4%, hernia 4%, post-operative haematoma or bleeding 4%). None of the patients died peri-operatively. CONCLUSION: Renal transplantation with simultaneous unilateral nephrectomy in ADPKD is a reasonable procedure for patients suffering from massively enlarged native kidneys.

Epidemiology of autosomal-dominant polycystic kidney disease: an in-depth clinical study for south-western Germany.

BACKGROUND: As we emerge into the genomic medicine era, the epidemiology of diseases is taken for granted. Accurate prevalence figures, especially of rare diseases (RDs, ≤50/100,000), will become even more important for purposes of health care and societal planning. We noticed that the numbers of affected individuals in regionally established registries for mainly hereditary RDs do not align with published estimated and expected prevalence figures. We therefore hypothesized that such non-population-based means overestimate RDs and sought to address this by recalculating prevalence for an important 'common' hereditary disease, autosomal-dominant polycystic kidney disease (ADPKD) whereby presumed-prevalence is 100-250/100,000 METHODS: The Else-Kroener-Fresenius-ADPKD-Study in south-west Germany with a population of 2,727,351 inhabitants was established with the cooperation of all nephrology centres. Furthermore, general practitioners, internists, urologists, human geneticists and neurosurgery centres were contacted with questionnaires for demographic, family and kidney function data. Germline-mutation screening of susceptibility genes PKD1 and PKD2 was offered. Official population data for 2010 were used for overall and kidney function-adjusted prevalence estimations. RESULTS: A total of 891 subjects, 658 index-cases and 233 relatives, aged 10-89 (mean 52), were registered, with >90% response rate, 398 by nephrologists and 493 by non-nephrologists. Molecular-genetic analyses contributed to confirmation of the diagnosis in 57%. The overall prevalence of ADPKD was 32.7/100,000 reaching a maximum of 57.3/100,000 in the 6th decade of life. CONCLUSIONS: Prevalence of ADPKD is overestimated by 2- to 5-fold and close to the limit of RDs which may be of broad clinical, logistic and policy implications.

Outcome after repeat resection of liver metastases from colorectal cancer.

INTRODUCTION: Although advances in multimodal treatment have led to prolongation of survival in patients after resection of colorectal liver metastasis (CRC-LM), most patients develop recurrence, which is often confined to the liver. Repeat hepatic resection (RHR) may prolong survival or even provide cure in selected patients. We evaluated the perioperative and long-term outcomes after RHR for CRC-LM in a single institution series. PATIENTS AND METHODS: Since 1999, 92 repeat hepatic resections (63% wedge/segmental, 37% hemihepatectomy or greater) for recurrent CRC-LM were performed in 80 patients. Median interval from initial liver resection to first RHR was 1.25 years. Any kind of chemotherapy (CTx) had been given in 88% before RHR. Neoadjuvant CTx was given in 38%. RESULTS: Hepatic margin-negative resection was achieved in 79%. Mortality was 3.8%. Overall complication rates were 53%, including infection (17%), operative re-intervention (12%), and hepatic failure (5.4%). Overall 5-year survival after first RHR was 50.3%. Univariately, primary tumor stage, the extent of liver resection, postoperative complications, and the overall resection margin correlated with survival. By multivariate analysis, primary T stage, size of metastasis, and overall R0 resection influenced survival. Survival was not independently influenced by hepatic resection margins or (neoadjuvant) CTx. CONCLUSIONS: Repeat hepatic resection for recurrent CRC-LM can be performed with low mortality and acceptable morbidity. Survival after repeat hepatic resection in this selected group of patients is encouraging and comparable to results after first liver resections.

Autosomal dominant polycystic kidney disease: prevalence of renal neoplasias in surgical kidney specimens.

BACKGROUND: The role of autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for renal cell carcinoma (RCC) is still under discussion. Data on prevalence of RCC in ADPKD are limited, especially on a large population scale. The aim of this study was to analyze the prevalence of RCC in ADPKD kidneys and characterize the clinical features of this coincidence. METHODS: Based on our histopathological registry for ADPKD and the Else Kröner-Fresenius Registry, we retrospectively reviewed malignant and benign renal lesions in patients with ADPKD who had undergone renal surgery from 1988 to 2011. RESULTS: 240 ADPKD patients underwent 301 renal surgeries. Mean age at surgery was 54 years. Overall, 16 malignant and 11 benign lesions were analyzed in 301 kidneys (5.3%; 3.7%), meaning that 12/240 (5%; 1:20) patients presented with malignant renal lesions. 66.7% (8/12) of these patients had undergone dialysis prior to surgery. We found 10/16 (63%) papillary RCC, 5/16 (31%) clear cell RCC, and 1/16 (6%) papillary noninvasive urothelial cancer. Regarding all renal lesions, 6/17 (35.3%) patients had more than one histological finding in their kidneys. In 2 cases, metachronous metastases were removed. Mean follow-up was 66.7 months. CONCLUSION: Kidney-related prevalence of RCC in ADPKD kidneys was surprisingly high. Whether or not this is due to chronic dialysis or due to the underlying disease is still speculative. Like other cystic renal diseases with an increased risk for RCC, the attending physician should be aware of the malignant potential of ADPKD, especially with concomitant dialysis.

Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer.

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.

Impact of preoperative targeted therapy on postoperative complications after resection of colorectal liver metastases.

PURPOSE: The impact of chemotherapy (CTx) on morbidity after liver resection for colorectal metastases (CRC-LM) has been increasingly investigated during recent years. Biologic agents like bevacizumab (BEV) or cetuximab (CET) are now added as "targeted therapy" (TT), also in neoadjuvant settings. Initial series could demonstrate the safety of those regimens in liver resection but data are still scarce. We evaluated the impact of CTx with BEV or CET (CTx + TT) on perioperative morbidity and mortality. METHODS: Two hundred thirty-seven patients who underwent liver resections for CRC-LM after chemotherapy before surgery since 1999 were included. One hundred eighty-five patients (78%) had preoperative CTx regimen without biologic agents (fluoropyrimidine-, oxaliplatin-, or irinotecan-based) and 52 (22%) had CTx + TT (39 BEV, 11 CET, 2 CET/BEV). After preoperative CTx + TT, a time interval of at least 4-6 weeks and a residual liver volume of >35% before surgery were required. RESULTS: Hemihepatectomy or more was performed in about half of the patients. The median amount of intraoperatively transfused blood was 0 ml in both groups (p = 0.34). Overall mortality was 1.7% and slightly elevated in patients with CTx + TT (3.8% vs. 1.1%, p = 0.17). Any complication occurred in (CTx + TT vs. CTx) 52% and 46%, respectively (p = 0.47). The rates of liver failure (9.6% vs. 9.7%, p = 0.98), infectious complications such as wound infection (19% vs. 16%, p = 0.62) and abdominal abscess (8% vs. 6.5%, p = 0.71), as well as the rate of relaparotomies (11.5% vs. 7.0%, p = 0.29) showed no significant differences between the groups with TT or without. In multivariate analyses, neither type nor duration of CTx nor the time interval between CTx and surgery showed any influence on complication rates. CONCLUSIONS: Our data confirm the safety of targeted therapy before liver resection for CRC-LM. This effect may in part be due to our treatment policy (time interval to resection and residual liver volume) after intensive preoperative CTx.

Efficacy of Stereotactic Body Radiotherapy in Patients With Hepatocellular Carcinoma Not Suitable for Transarterial Chemoembolization (HERACLES: HEpatocellular Carcinoma Stereotactic RAdiotherapy CLinical Efficacy Study).

The aim of this prospective observational trial was to evaluate the efficacy, toxicity and quality of life after stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to assess the results of this treatment in comparison to trans-arterial chemoembolization (TACE). Patients with HCC, treated with TACE or SBRT, over a period of 12 months, enrolled in the study. The primary endpoint was feasibility; secondary endpoints were toxicity, quality of life (QOL), local progression (LP) and overall survival (OS). Between 06/2016 and 06/2017, 19 patients received TACE and 20 SBRT, 2 of whom were excluded due to progression. The median follow-up was 31 months. The QOL remained stable before and after treatment and was comparable in both treatment groups. Five patients developed grade ≥ 3 toxicities in the TACE group and 3 in the SBRT group. The cumulative incidence of LP after 1-, 2- and 3-years was 6, 6, 6% in the SBRT group and 28, 39, and 65% in the TACE group (p = 0.02). The 1- and 2- years OS rates were 84% and 47% in the TACE group and 44% and 39% in the SBRT group (p = 0.20). In conclusion, SBRT is a well-tolerated local treatment with a high local control rates and can be safely delivered, while preserving the QOL of HCC patients.

Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer.

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited. AIM: To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors. METHODS: One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient's demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival. RESULTS: The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis. CONCLUSION: In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.