IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer.

Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.

Advantages of one-stage repair in case of gallstone ileus.

BACKGROUND/AIMS: The commonly used procedure to treat gallstone ileus is enterolithotomy in combination with late cholecystectomy for persistent symptoms. It is related to a high mortality rate up to 20%. To date it has been impossible to reduce the mortality associated with this accepted surgical technique. PATIENTS AND METHODS: A seven-year retrospective study with a follow up over a period of four years and five months. Sixteen patients with gallstone ileus were entered into the study. Twelve patients were female and fourteen were more than 70 years of age. Fourteen patients were treated by enterolithotomy as well as additional cholecystectomy and resection of the fistula in a one-stage repair. RESULTS: Mortality during hospitalization amounted to one (6%) and postoperative complications to five patients (31%). Follow-up over a period of four years and five months showed one patient had died 3 years postoperatively of an advanced renal tumor. All other patients were alive and without symptoms. CONCLUSION: Our results prove that the concomitant one-stage repair for gallstone ileus significantly reduces the overall mortality rate compared to the single enterolithotomy alone and later cholecystectomy based on patient symptoms.

Value of liver biopsy combined with cholecystectomy.

BACKGROUND/AIMS: Many authors value routinely performed liver biopsy concomitant with cholecystectomy as a procedure of great diagnostic importance in regard to diagnosis and treatment of liver disease. Without reason, fewer perioperative liver punctures have been performed since the beginning of minimal invasive surgery, even so, laparoscopic cholecystectomy provides an equal opportunity for taking liver biopsies for diagnostic purposes. This study aims to determine the prevalence and extent of liver disease in patients undergoing cholecystectomy for gall stone disease. METHODOLOGY: Within the pre-laparoscopic era, 565 cholecystectomies with concomitant liver biopsies were performed. The results were evaluated retrospectively. Serious pathohistologic findings were defined by the stage of pathologic changes demanding prognostic and/or therapeutic consequences. RESULTS: One hundred and ten patients (19.5%) had normal liver biopsies. Severe pathologic liver changes were diagnosed in 58 (10.3%). Taking all liver biopsies showing liver changes, prognostic and therapeutic relevance were represented in 52% of our patients. CONCLUSIONS: Having proof of the high rate of pathologic liver changes resulting in liver disease we advocate liver biopsy in connection with cholecystectomy as an important procedure, if open or laparoscopic surgery of the extrahepatic biliary tract is performed.

Technique and results of vascular endoscopy in arterial and venous reconstructions.

In an effort to maximize results, vascular endoscopy was used in our institution to monitor arterial and venous reconstructions. Since 1982, angioscopy was applied as a control method in 182 venous thrombectomies to treat iliofemoral thrombosis and 114 aortoiliac thromboendarterectomies. Of the cases with venous thrombectomy reviewed, 50% were incomplete by endoscopic evidence; of these, in 80% the remaining clots could be partly or completely removed. Additionally, in six patients a venous spur was found. Of 114 attempted aortoiliac thromboendarterectomies, only 91 could be completed. In the remainder, endoscopic evidence of persistent intimal flaps forced us to bypass the affected segments. With further miniaturization of the angioscopes, the method was also applied to check vessel repair on small-caliber arteries. In an initial study with 220 femorodistal bypasses we were unable to find a statistically significant difference of primary patency in grafts that were endoscopically controlled or not. In the learning phase with the in situ technique, we identified competent valve remnants in 40%, but this rate could be reduced to 12.7% with growing experience in valvulotomy. We conclude from our data that angioscopy is very helpful in assessing the morphological integrity of aortoiliac thromboendarterectomies and venous thrombectomies. The actual value in infrainguinal arterial reconstructions still remains to be proven.

Stabilization of high tibial osteotomy with staples.

Patients presenting with painful arthritis of the medial knee compartment with an intact lateral compartment are treated by high tibial valgus osteotomy at our institution. Between 1989 and 1993, 75 high tibial valgus osteotomies were done. Of these, 52 were idiopathic, 22 post-traumatic, and 1 subsequent to an intra-articular infection of the knee. The condition of the lateral compartment was routinely checked arthroscopically. All osteotomies were stabilized with osteotomy staples. This provided immediate stability, allowing partial weight-bearing (15 kg). Because of the simplicity and the low complication rate, we recommend this technique as a suitable treatment for arthritis of the medial condyle of the knee.

In situ saphenous vein grafts for femorodistal bypass: evaluation of endoscopically monitored valvulotomy on graft patency.

An overview of a total of 135 in situ femorocrural bypass operations is given. In the operations all grafts were anastomosed distally to the infrapopliteal arteries: to the proximal half of the crural vessels 52 times and to the distal half 83 times. The indication for surgery was critical limb ischaemia. In addition to routine intraoperative angiography, orthograde angioscopy of the graft was carried out to assess the completeness of valvulotomy in 96 patients (group A). In 39 patients (group B) for whom an endoscope was not available, completion angiography was conducted to ensure graft integrity. The two groups were comparable with respect to their composition. On the basis of the endoscopic findings, revisions were performed in 17 patients with incomplete valve ablation in group A, whereas in group B there were no interventions (P < 0.01, chi 2 test). Using life-table analysis, cumulative primary patency rates for groups A and B were 76% and 76% at 30 days, 62% and 44% at 1 year and 43% and 27% at 4 years, respectively. By comparison with the log rank test, a significant difference in patency among both groups could not be established (P = 0.18).