Will the dream of "leave nothing behind" remain a utopia if we forget to optimise the systemic medical therapy?

Although systemic therapies are recommended for hepatocellular carcinoma (HCC) patients with main portal vein (MPV) invasion and preserved liver function, the outcome is limited. In the real-world, chemoembolization is a commonly used local treatment for advanced HCC. To evaluate whether the additional chemoembolization treatment yields survival benefits compared to systemic therapy for HCC patients with MPV invasion and preserved liver function (Child-Pugh score ≤ B7) in a real-world study from multiple centers. Between January 2020 and December 2022, 91 consecutive HCC patients with MPV invasion who received either systemic medical therapy (i.e., tyrosine kinase inhibitors (TKIs) plus anti-PD-1 immunotherapy, S group, n = 43) or in combination with chemoembolization treatment (S-T group, n = 48) from five centers were enrolled in the study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and treatment response. Adverse events (AEs) related to treatment were also recorded. Survival curves were constructed with the Kaplan-Meier method and compared using the log-rank test. The baseline characteristics were comparable between the two groups. The mean number of chemoembolization sessions per patient was 2.1 (range 1-3). The median OS was 10.0months and 8.0months in the S-T group and S group, respectively (P = 0.254). The median PFS between the two groups was similar (4.0months vs. 4.0months, P = 0.404). The disease control rate between the S-T and S groups were comparable (60.4% vs. 62.8%, P = 0.816). Although no chemoembolization-related deaths occurred, 13 grade 3-4 AEs occurred in the S-T group. The results of the real-world study demonstrated that additional chemoembolization treatment did not yield survival benefits compared to TKIs plus anti-PD-1 immunotherapy for the overall patients with advanced HCC and MPV invasion.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide. Despite the decreasing prevalence of hepatitis C, the burden of HCC is expected to rise owing to the increasing prevalence of metabolic syndrome and increased global alcohol consumption. Guideline-concordant screening with ultrasound every 6 months has been associated with increased rates of early-stage detection and receipt of curative treatment. However, most patients with cirrhosis do not undergo screening, with HCC often diagnosed only at an advanced stage when curative resection or ablation is not feasible. Systemic medical therapy is indicated in patients diagnosed with infiltrative or advanced HCC, or when early-stage disease progresses or recurs after resection, transplant, or other locoregional therapy. Sorafenib was approved as first-line therapy for HCC in 2007. Since 2017, there has been an exponential rate of approval of novel agents targeting HCC, including lenvatinib, regorafenib, and cabozantinib. Checkpoint inhibitors, including pembrolizumab, nivolumab, ipilimumab, and combination therapy with atezolizumab plus bevacizumab and durvalumab plus tremelimumab, have expanded treatment options. This article describes treatment for all HCC stages, with a brief discussion of locoregional therapy for context, as some emerging treatment regimens combine locoregional and systemic therapies. The article highlights approved systemic therapies that are guideline-endorsed and emerging therapies for advanced HCC.

The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear. We performed a retrospective multicenter analysis of serial cranial MRI in patients with recurrent WHO II and III meningiomas treated with antineoplastic systemic therapies. Growth rates for tumor volume and diameter, as well as change rates for edema size, were calculated for all lesions. We identified a total of 34 patients (23 atypical, 11 anaplastic meningiomas) with a total of 57 meningioma lesions who had been treated at 6 European institutions. Systemic therapies included bevacizumab, cytotoxic chemotherapy, somatostatin analogues, and tyrosine kinase inhibitors. Overall, tumor growth rates decreased during systemic therapy by 51% for tumor diameter and 14% for tumor volume growth rates compared with the period before initiation of systemic therapy. The most pronounced decrease in meningioma growth rates during systemic therapy was evident in patients treated with bevacizumab, with a reduction of 80% in diameter and 59% in volume growth. Furthermore, a decrease in size of peritumoral edema after initiation of systemic therapy was exclusively observed in patients treated with bevacizumab (-107%). Our data indicate that systemic therapy may inhibit growth of recurrent WHO grades II and III meningiomas to some extent. In our small cohort, bevacizumab had the most pronounced inhibitory effect on tumor growth, as well as some anti-edematous activity. Prospective studies are needed to better define the role of medical therapies in this tumor type.

Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23months (range 5.5-105.8), and 21.8months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8months (range 5-47). There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Reassessing the Role for Sympathetic Neurolysis in Patients with Pancreatic Cancer.

Superficial Fungal Infections

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and fourth leading cause of cancer-related death worldwide. Recent advances in systemic and locoregional therapies have led to changes in many guidelines regarding systemic therapy, as well as the possibility to downstage patients to undergo resection. This review examines the advances in surgical and medical therapies relative to multidisciplinary treatment strategies for HCC. HCC is a major health problem worldwide. The obesity epidemic has made nonalcoholic fatty liver disease a major risk factor for the development of HCC. Multiple societies, such as the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, the Asian Pacific Association for the Study of the Liver, and the National Comprehensive Cancer Network, provide guidelines for screening at-risk patients, as well as define staging systems to guide optimal treatment strategies. The Barcelona Clinic Liver Cancer staging system is widely accepted and has recently undergone updates with the introduction of new systemic therapies and stage migration. The treatment of patients with HCC should involve a multidisciplinary approach with collaboration among surgeons, medical oncologists, radiation oncologists, and interventional radiologists to provide optimal care. Treatment paradigms must consider both tumor and patient-related factors such as extent of liver disease, which is a main driver of morbidity and mortality. The advent of more effective systemic and locoregional therapies has prolonged survival among patients with advanced disease and allowed some patients to undergo surgical intervention who would otherwise have disease considered unresectable.

Purpose The purpose of this meta-analysis was to assess the percent reduction in the intraocular pressure (IOP) after argon laser peripheral iridoplasty (ALPI) and systemic medical therapy in patients with acute primary angle closure (APAC). Methods We searched a number of electronic databases, including MEDLINE, EMBASE, PubMed, and Cochrane Library. We searched the electronic databases from the inception of the databases to August 2018. The primary outcomes included the IOP reduction (IOPR), percent reduction in IOP (IOPR%) from baseline to the endpoint and peripheral anterior synechiae (PAS). The secondary outcomes included the cup-to-disc ratio (CDR), mean endothelial count, and percent of patients requiring topical glaucoma medication. Summary weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs) were calculated. Results Four eligible studies including 183 eyes (92 in the ALPI group and 91 in the medical therapy group) were identified. When comparing ALPI to medical therapy, the WMDs of the IOPR% were 30.03 (95% CI: 21.33 to 38.72, p < 0.00001) at 15 minutes, 27.39 (95% CI: 18.89 to 35.89, p < 0.00001) at 30 minutes, 18.15 (95% CI: 10.63 to 25.68, p < 0.00001) at 1 hour, and 12.91 (95% CI: 4.50 to 21.32, p=0.003) at 2 hours. There was no statistically significant difference between the two groups at 24 hours and at more than 6 months after therapy. Meanwhile, no significant difference was observed in the degree of PAS, CDR, mean endothelial count, and percent of patients requiring topical glaucoma medication after treatment between the two groups. Conclusions Both ALPI and systemic medications were effective with regard to decreasing the IOP. ALPI was more effective in lowering the IOP within the first two hours. Therefore, ALPI may be a better choice for rapidly lowering the IOP in patients with APAC within a short period.

CORR Insights®: Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Metastatic Bone Disease from Lung Cancer? A Systematic Review and Network Meta-Analysis.

For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial. Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis. Of 291 patients with complete data for stage IV recurrence, 161 (55 %) underwent surgery with or without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was 20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT alone (p < 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4-year survival 69.3 % vs. 0; p = 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year survival 24.1 vs. 14.3 %; p = 0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year survival 10.5 vs. 4.6 %; p = 0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42 %) who had multiple surgeries for distant melanoma. Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site and number of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.

Cesarean scar pregnancy (CSP) is becoming more common with the increasing Cesarean section rate1. Among the various treatment modalities reported, local injection of therapeutic agents, either transabdominally or transvaginally, is a minimally invasive option that targets the lesion while minimizing systemic side effects2. Nevertheless, transvaginal access is not always possible, and a CSP hidden underneath the maternal pubic symphysis or maternal bowel loops makes transabdominal access challenging. In such cases, an unconventional transvesical approach may be helpful. We report two cases in which transvesical injection was used to treat CSP. In the first case, a 35-year-old woman with two previous Cesarean deliveries presented with vaginal bleeding and abdominal pain at 7 weeks of amenorrhea. Ultrasound examination revealed a single viable pregnancy outside of the uterine cavity at the site of the Cesarean scar, with a serosal bulge. The crown–rump length (CRL) measured 3.7 mm. Maternal bowel loops were overlying the CSP. Maternal serum human chorionic gonadotropin (hCG) was 37 728 IU/L. Treatment options, including medical therapy (systemic and/or local), embolization and surgery were discussed. The woman opted for combined local and systemic medical therapy. A vaginal needle guide was not available, so transvaginal injection could not be performed. After the maternal bladder was filled, bowel loops overlying the CSP were displaced (Figure 1). Potassium chloride 14.9% solution was injected transabdominally into the gestational sac by passing a 22-G needle through the distended maternal bladder under local anesthesia. Immediate fetal heart beat cessation was observed. One dose of systemic methotrexate (50 mg/m2 of body surface area) was also administered. Maternal serum hCG dropped to 21 923 IU/L on day 4, to 14 555 IU/L on day 7, and returned to normal by 2 months. Normal menstruation returned in 4 months, followed by sonographic resolution of CSP at 7 months. In the second case, a 42-year-old woman presented with vaginal bleeding at 7 weeks of amenorrhea. She had a previous Cesarean delivery and two terminations of pregnancy. Ultrasound examination showed a viable CSP with CRL of 9.8 mm. Maternal serum hCG level was 89 227 IU/L. After a detailed discussion of the management options, the woman opted for combined local and systemic medical therapy. Maternal bowel loops were obscuring the CSP, and a vaginal needle guide was not available. After the maternal bladder was filled, bowel loops overlying the CSP were displaced and a window for access became apparent. Dextrose 10% solution (total, 8 mL) was injected transabdominally into the gestational sac via a 22-G needle through the distended maternal bladder under local anesthesia (Figure 2). Fetal asystole was observed. A dose of systemic methotrexate was also administered. Maternal serum hCG was 102 978 IU/L and 84 288 IU/L on days 4 and 7 respectively, and returned to normal by 2 months. Transvesical access is an established surgical approach in urology3, 4. It is also used in exceptionally difficult cases of chorionic villus sampling5. Despite a lack of reports in the literature, a transvesical approach renders transabdominal injection feasible in CSPs that would otherwise be inaccessible by this route. The method is well tolerated by women. Neither of our two patients experienced significant hematuria or urinary symptoms after the procedure, nor did they experience any complications. Using a transvesical approach enables more CSPs to become accessible for local treatment.

Scedosporium apiospermum (SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies. An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining con- junctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the con- dition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up. Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses.

296 Background: Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant is challenging. All the clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. Here we review outcome, and the safety and efficacy of the application of systemic medical therapies in this clinical setting. Methods: This is a retrospective cross-sectional study of consecutive adult patients with recurrence of HCC following liver transplant for the indication of treatment of HCC in Queen Mary Hospital from January 2005 to January 2018. Results: Forty-three consecutive patients with a recurrence of HCC following liver transplant were identified from 2005 to 2018. Median survival from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p&lt; 0.001) after adjustment with peritumoural vascular invasion, first line therapy with sorafenib, any second line therapy and use of mTOR inhibitors as immunosuppressants, with a hazard ratio of 0.104 (log-rank test, p&lt;0.001). 41 patients who received medical systemic therapies, 34 (79.1% ) received sorafenib as the first line systemic therapy. 47.1% (N= 16) received subsequent lines of systemic therapies (ranging from 1 to 4 lines). Hand-foot syndrome was most common among the adverse events and it was observed in 34.7% patients treated with sorafenib. It led to dose interruptions in 8.8 % of patients who were given sorafenib. 26.7% had grade 1 diarrhoea. 14.3% had grade 1 transaminase rise. Conclusions: Early recurrence within one year from transplant was the most significant risk factor. Treatment efficacy and adverse events and tolerability of sorafenib were comparable with those in the setting of advanced HCC without transplant.

Background and purposeThis nationwide population-based study analyzed the outcomes of local treatment (i.e. stereotactic body radiotherapy [SBRT] or metastasectomy) or systemic therapy for oligometastatic disease (OMD) in patients with esophagogastric cancer in The Netherlands. Materials and methodsBetween 2015 and 2016, all patients in The Netherlands with esophagogastric cancer and synchronous or metachronous OMD were eligible for inclusion. Patients who underwent local treatment of OMD (SBRT or metastasectomy) and/or systemic therapy were included. OMD was defined as distant metastases in 1 organ or 1 extra-regional lymph node region. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. OS was calculated from diagnosis of OMD. Prognostic factors for OS were analyzed using a multivariable Cox proportional hazard model. ResultsA total of 594 patients were included, of whom 83 underwent local treatment for OMD alone, 22 local treatment plus systemic therapy, and 489 systemic therapy alone. Median OS after local treatment for OMD alone was 16.0 months, local treatment plus systemic therapy 22.7 months, and after systemic therapy alone 8.5 months. Improved OS was independently associated with local treatment for OMD alone or combined with systemic therapy as compared with systemic therapy alone (hazard ratio [HR] 0.52, 95% CI: 0.31–0.90 and HR 0.42, 95% CI: 0.22-0.82, respectively) and a controlled primary tumor(HR 0.48, 95% CI: 0.27–0.86). Worse OS was independently associated with worse performance scores (HR 1.41, 95%: 1.32-1.75), poorly or undiffertumor as compared with good or moderadifferentiated tumor (HR 1.37, 95% CI: 1.06-1.76), and peritoneal as compared with lymph mode metastases (HR 1.39, 95% CI: 1.00-1.93). ConclusionLocal treatment of OMD alone or combined with systemic therapy was independently associated with improved OS as compared with systemic therapy alone in this population-based cohort study in The Netherlands. Randomized controlled trials are warranted to confirm these results.

Minimal Toxicity From Systemic Therapy Given Concurrently With Stereotactic Radiosurgery for Brain Metastases