Successful Radical Research Articles

Anesthetic Management of Renal Tumor with Level 3 Inferior Vena Cava Extension at a University Hospital in Vietnam: A Case Report

Background: Renal tumors with inferior vena cava (IVC) invasion pose significant challenges for surgical and anesthetic management. This report presents the anesthetic management of a patient with a level 3 IVC-invading renal tumor, emphasizing the complexity and multidisciplinary approach required. Case Presentation: A 55-year-old woman with a large left renal tumor causing complete obstruction of the left renal vein and near-total obstruction of the IVC was admitted for surgery. Multidisciplinary planning included a nephrectomy with removal of tumor from the IVC. The patient underwent general anesthesia with extensive hemodynamic monitoring and fluid management to mitigate potential blood loss and cardiovascular instability. The surgery, lasting 5 h, involved successful radical nephrectomy, tumor removal from the IVC, and resection of liver metastases. Postoperative recovery was without complications, and the patient was discharged 7 days. Conclusion: Managing anesthesia for renal tumors with IVC invasion requires careful preoperative planning, invasive monitoring, and multidisciplinary approach.

8120 Effective Management of Neonatal Hypercalcemia in Congenital Mesoblastic Nephroma: A Case Report on the Use of Calcitonin

Abstract Disclosure: C.S. Galvez: None. K. Rifai: None. C. Moorthy: None. S. Chheda: None. M. Zerah: None. Introduction: Pediatric patients with hypercalcemia of malignancy are typically treated with hyperhydration, loop diuretics and bisphosphonates. Calcitonin, a peptide functionally antagonizes the effects of PTH. Calcitonin has limited pharmacokinetic data in neonates, especially those with Congenital Mesoblastic Nephroma (CMN), making treatment challenging with unclear safety and efficacy parameters. We present the fourth published case describing the use of calcitonin for likely PTH-rP-mediated severe hypercalcemia in a neonate with CMN. Clinical Case: A 15-day-old late preterm male, presented with lethargy, poor feeds, severe failure to thrive and a large abdominal mass. The mother is a G4P4, with good prenatal care. On admission, the patient was hypertensive (138/84 mmHg) and appeared dehydrated. Physical examination revealed a firm mass in the right abdomen crossing the midline. Serum calcium levels were 13.5 mg/dL (normal 9.0-10.9 mg/dL), with an ionized calcium 1.71 mmol/L (normal 1.15 and 1.30 mmol/L). Abdominal ultrasound showed a large, 9.1 x 8 cm dominant solid right renal mass, most likely CMN, with left-sided medullary nephrocalcinosis. Cardiac Echo and EKG were within normal limits. The patient received hydration, nicardipine (titrated to decrease blood pressure by 10-15 mmHg per day) and furosemide at 1 mg/kg/day IV q6h. Due to the persistence of hypercalcemia after 24 hours of treatment (14.7 mg/dL serum calcium with ionize of 1.81 mmol/L), the patient received one dose of calcitonin (4 units/kg subcutaneously), resulting in a decrease in serum calcium to 11.5 mg/dL in 4 hours. The patient underwent a successful radical right uretero-nephrectomy, with post-surgery improvement of neurological, cardiovascular and electrolyte status. Unfortunately, PTH-rP sample was insufficient. Pathology reported CMN of the cellular type. CMN is a rare tumor with low malignant potential, representing approximately 3% of all pediatric renal tumors. It is the most common renal neoplasm diagnosed in the first 6 months of life. The most common symptom is an abdominal mass (76%), with hypertension (19%). Hypercalcemia was reported in only 4% which can be secondary to paraneoplastic secretion of PTH or PTH-rP. Conclusion: This case represents the fourth instance of calcitonin use in a neonate with CMN to manage persistent hypercalcemia. Subcutaneous administration of calcitonin at 4 units/kg proved effective with a short onset of action (within 2 hours) and duration of 6 to 8 hours, making it a viable alternative to bisphosphonates (action around 48 hours and duration of 7 to 14 days). Calcitonin's advantages include less significant side effects and a faster resolution of complications like "Hungry bone Syndrome." The flexibility of repeated dosing every 6 hours, with the option to increase the dose, if necessary, adds to its clinical utility. Presentation: 6/3/2024

Perioperative chemotherapy with nivolumab for HER2-negative locally advanced gastric cancer: a case series

BackgroundNivolumab with chemotherapy has been transformative for metastatic gastric cancer (GC). The potential of this regimen for local tumor control could be utilized for perioperative chemotherapy in locally advanced GC with bulky tumors or lymph node metastasis involving other organs.Case presentationFive patients with HER2-negative advanced GC were treated with nivolumab and oxaliplatin-based chemotherapy. All patients presented with clinical stage III or IVA GC with tumors in contact with either the pancreas or liver. Following chemotherapy, all tumors demonstrated shrinkage, allowing successful radical gastrectomies including four minimally invasive approach without postoperative complications. Four patients avoided combined resection of other organs.ConclusionsPerioperative chemotherapy with nivolumab was effective for local disease control in this case series. This regimen could be a promising treatment approach for locally advanced GC; however, its survival benefits should be evaluated in clinical trials.

Successful radical surgery for lymph node metastasis in a patient with hepatocellular carcinoma following atezolizumab plus bevacizumab combination therapy: a case report and literature review.

A woman in her early 80 s was followed up in our hospital for chronic hepatitis C after viral eradication. We detected rapid-growing lymph node metastasis of hepatocellular carcinoma (HCC) after treatment with transcatheter arterial chemoembolization and/or radiofrequency ablation. We found that the metastasis was operable, but the size and location of the metastasis obliged the patient to receive pancreatoduodenectomy, which was too invasive. Then we initiated systemic chemotherapy to perform radical minimally invasive surgery. We treated the patient with 3 weekly cycles of atezolizumab 1200mg plus bevacizumab 15mg/kg. The patient tolerated the treatment well, and treatment-emergent adverse events included deterioration of hypertension and increased uric protein. After a total of 4 cycles of therapy, abdominal computed tomography findings showed that the metastasis evidently decreased, and a complete response was achieved based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Seventeen days later, the metastasis was dissected. Subsequently, we confirmed that there was no pathological metastatic lesion in the resected lymph node. Our case is the first report of successful application of the radical therapy to lymph node metastasis of HCC via combination therapy with atezolizumab/bevacizumab.

Successful intrahepatic cholangiocarcinoma conversion surgery after administration of fibroblast growth factor receptor inhibitor

We describe a case of a 47-year-old male patient with initially unresectable intrahepatic cholangiocarcinoma of the right liver lobe with tumor thrombi extending from the right bile duct to the common and left bile ducts. Conventional chemotherapy with gemcitabine and cisplatin for 19 months resulted in progressive disease. Subsequently, a comprehensive genome profile revealed fibroblast growth factor receptor 2 rearrangement, and hence, pemigatinib administration was initiated. After 6 months of pemigatinib therapy, significant shrinking of the tumor and disappearance of the tumor thrombi in the common and left bile duct were observed. Subsequently, the patient underwent conversion surgery, resulting in successful radical resection of the tumor. The patient has been disease-free for 7 months.

Primary outcome analysis of the ORCHESTRA trial: A randomized phase III trial of additional tumor debulking to first-line palliative systemic therapy for patients with multiorgan metastatic colorectal cancer.

LBA3502 Background: The phase-3, investigator-initiated, ORCHESTRA trial (NCT01792934) was conducted to prospectively evaluate overall survival (OS) benefit from tumor debulking in addition to standard palliative systemic therapy in patients with multiorgan metastatic colorectal cancer (mCRC). Local therapy of metastases is increasingly discussed as part of the treatment plan for patients with multiorgan mCRC in analogy to selected patients with oligometastatic disease for whom this is standard of care. Treatment decisions are made on a daily base in multidisciplinary teams (MDT) worldwide, but evidence of superiority for additional local therapy over systemic therapy alone based on a head-to-head comparison is lacking. Methods: Between May 2013 and May 2023, 454 patients were enrolled in 28 hospitals. Patients with multiorgan mCRC as described in Table, were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy at the start of first-line palliative systemic therapy according to the MDT. Upon clinical benefit after 3 or 4 cycles of respectively capecitabine or 5-fluorouracil/leucovorin and oxaliplatin ± bevacizumab, 382 patients were randomized 1:1 to continuation with systemic therapy alone in the standard arm or to tumor debulking followed by restart of the systemic therapy in the experimental arm. The primary endpoint was OS, from the date of inclusion to the date of death. Secondary endpoints included progression free survival (PFS) and treatment related adverse events. OS and PFS were analyzed by means of multivariable Cox proportional hazards regression analysis where the variables used in the randomization process were included as covariates. Results: 382 patients were randomized to either receive standard palliative systemic therapy in the standard arm (N=192) or to receive additional tumor debulking to palliative systemic therapy in the experimental arm (N=190). Baseline characteristics of patients were in standard arm versus (vs) experimental arm: median age 64 vs 64 years, male 69% vs 67%, >2 organs involved 38% vs 40%, baseline LDH >250 U/L 17% vs 16%, baseline CEA >200 ng/ml 5% vs 8%. At data cut-off on April 4th, 2024, a total of 153 OS events were observed in the standard arm and 155 OS events in the experimental arm. Median follow up was 32.3 months. Median OS in the standard arm was 27.5 months versus 30.0 months in the experimental arm (adjusted HR 0.88 [95% CI 0.70-1.10] p=0.225). Median PFS in the standard arm was 10.4 months versus 10.5 months in the experimental arm (adjusted HR 0.83 [95% CI 0.67-1.02], p=0.076). Details on local treatment modalities being applied, including rate of successful radical debulking and related adverse events, will be presented at the meeting. Conclusions: Additional tumor debulking to standard first-line palliative systemic therapy failed to improve overall survival for patients with multiorgan metastatic colorectal cancer. The increasing use of local therapies for patients with mCRC needs further consideration. Clinical trial information: NCT01792934 . [Table: see text]

Outstanding safety and efficacy data of IMC002, an autologous CLDN18.2-targeting CAR-T, in CLDN18.2+ advanced solid tumors.

e16012 Background: Claudin 18.2 (CLDN18.2) is a promising therapeutic target for advanced solid tumors with CLDN18.2 expression. IMC002 is an autologous CLDN18.2-targeting CAR-T cell directed by a CLDN18.2-specific VHH, the specificity of which was confirmed by a membrane proteome array assay. Preclinical studies showed that IMC002 exhibited high tumor specificity, anti-tumor efficacy, and excellent safety profile in both cell and animal models. Methods: This is an open label first in human Phase 1 dose escalation study to evaluate the safety and efficacy of IMC002 in advanced solid tumors with CLDN18.2 expression which is defined as CLDN18.2 expression of ≥1+ membrane staining intensity in ≥10% tumor cells. Accelerated titration followed by Bayesian optimal interval design was adopted with a total of 4 dose levels planned at 1, 3, 5 and 7 million (mil) CAR-T cells/kg respectively. All patients (pts) were given a single dose of IMC002 infusion after lymphodepletion chemotherapy. Dose limiting toxicity (DLT) was evaluated during the 28-day period after IMC002 infusion. Safety, anti-tumor activity, pharmacokinetics and pharmacodynamics were explored in this study. Here, we present preliminary safety and efficacy data for the pts dosed with up to 3 mil CAR-T cells/kg. Results: As of January 17, 2024, 3 advanced unresectable gastric cancer pts received IMC002 infusion, 1 patient at 1 mil CAR-T cells/kg and 2 pts at 3 mil CAR-T cells/kg. No DLT or SAE was reported. Manageable CRS (grade 1) was reported in all 3 pts. Other adverse events related to cell therapy included grade 1-2 lipase increase (3/3), diarrhea (1/3), pruritis (1/3) and γ-GGT increase (1/3). All adverse events recovered quickly. Preliminary efficacy data showed that best overall response of the 3 pts was all stable disease as evaluated by RECIST 1.1. The two pts at the dose level of 3 mil CAR-T cells/kg underwent successful radical surgery at week (W) 11 and 44 after IMC002 infusion respectively. Pathological complete response (pCR) was achieved in the patient with surgery at W44. Distinct CAR-T cell expansion in peripheral blood was observed in all 3 pts, with the peak number of CAR+ cells reaching on day 7-11 in the peripheral blood after the infusion. Moreover, CAR-T cell infiltration was detected in the W11 and W44 surgical samples. Significant elevations of serum levels of IFN-γ, IL-10, IP-10, IL-2 and IL-6 were observed in the 3 pts. The trial is ongoing. Conclusions: IMC002 showed a favorable safety profile, encouraging anti-tumor activities with observed pCR and persistent expansion in the tumor tissue at the low dosage levels in pts with advanced CLDN18.2+ gastric cancer. In addition, our trial has successfully provided a surgical treatment opportunity after CAR-T therapy downstaging of unresectable gastric cancers. Clinical trial information: NCT05472857 .

Efficacy of EpCAM CAR-T IMC001 in advanced gastric cancers.

4043 Background: EpCAM is highly expressed in various cancer types of the GI system and serves as a promising prognostic/predictive marker and therapeutic target. IMC001 is an autologous EpCAM-targeting CAR-T cell exhibited promising anti-tumor activity in preclinical studies. The specificity of the extracellular humanized scFv of IMC001 was confirmed by membrane proteome array. Patient derived organoids study and murine GLP study indicated a favorable safety profile of IMC001. Previous IIT data showed promising safety and efficacy. Here we present updated clinical data with longer follow up and more pts treated in the expansion recommended dose of 1 million (M) CAR-T cells/kg. Methods: This first-in-human, open-label trial followed a 3+3 design with IMC001 monotherapy dose escalation of 0.3 (n=3), 1 (n=3) or 3 (n=3) M/kg after lymphodepletion chemotherapy, 2 additional pts had been enrolled at dose-expansion (1M/kg). Eligible patients were those with EpCAM-positive (expression ≥1+ staining intensity in ≥10% tumor cells) advanced gastric cancers who had failed or not tolerated at least 2 lines of chemotherapy and were ECOG 0 or 1. The objective was to assess the safety, PK/PD profile and preliminary efficacy of IMC001. Results: As of Dec 30, 2023, 11 pts were infused with IMC001, 10 with evaluable efficacy are included in the efficacy analysis. The median time from diagnosis to enroll was 17.0 months (range 6.9-31.2). All pts were in stage IV, with more than 2 lines previous chemotherapy (1 pt failed 1st line and refused a 2nd line treatment), all had metastasis and 72.7% (8/11) had 2 or more metastasis organs. CAR T-cell expansion was observed in most pts; the median Cmax was 547, 500 and 9540 copies/μg gDNA in the 0.3, 1, and 3M/kg dose groups respectively, median Tmax was 7 days (7-28), with a persistence of IMC001 range from 4 to 12 weeks. Significant elevations of serum levels of cytokines were observed in most patients. Three out of 10 evaluable pts achieved PR response and 6 remained SD, with a DCR of 90%. For the recommended dose of 1M/kg, 2 out of 5 pts had PR (ORR 40%), including 1 pt underwent successful radical gastrectomy around W27 after IMC001 infusion and remained survival for more than 81 wks. The other PR pt had a tumor reduction of 48% at W16. The other 2 SD pts had an OS of 55 wks and 43 wks. Patients were well tolerated with no unexpected safety signals were observed at the recommended dose. Conclusions: This phase I study in advanced gastric cancer resulted in durable response with a favorable safety and efficacy profile especially for the recommended dose of 1M/kg, demonstrate a promising of EpCAM CAR-T therapy in advanced GC pts. Further expanding of this dose with larger patient population and longer follow-up shall bring the hope to this unmet medical need. Clinical trial information: ChiCTR2100047129.

Interventional Bridging Therapy for Radical Cardiac Surgery in a Patient Seemed to be Inoperable Due to Very Poor Left Ventricular Function: A Case Report

Cases that are inoperable owing to poor preoperative conditions are sometimes encountered. However, there are some cases that are led to radical treatment by performing bridge therapy. Here, we presented a case of a patient with complex cardiac disease in an inoperable state who underwent bridging therapy that led to successful surgical treatment. A 73-year-old male who received hemodialysis treatment and had severe aortic valve stenosis and coronary artery disease planned surgical treatment. However, he was deemed inoperable owing to his low cardiac function and hemodynamic instability. Therefore, to escape from a fatal condition, we first performed balloon aortic valvuloplasty and percutaneous coronary intervention as palliative procedures. Subsequently, his cardiac function and hemodynamic stability remarkably improved; therefore, after 1 month, we performed a successful radical surgical treatment. Even in inoperable patients, bridging therapy leading to radical treatment is possible.

Small Aromatics Bearing Two Diarylamino Termini: Highly Reducing Organic Photocatalysts

AbstractSmall aromatics such as anthracene, naphthalene, or benzene bearing two diarylamino termini function as highly reducing organic photocatalysts (OPCs). In particular, the small aromatic core remarkably enhances the reducing power of the catalyst in the excited state. An appropriate combination of an OPC and an electron-accepting fluoroalkylating reagent is the key to successful radical fluoroalkylation. The basic design of the photocatalyst and the photocatalytic fluoroalkylation of olefins are discussed.1 Introduction2 Basic Catalyst Design and Photo- and Electrochemical Properties3 Photocatalytic Reactions of 9,10-Bis(diphenylamino)anthracene Derivatives4 Photocatalytic Reactions of 1,4-Bis(diphenylamino)naphthalene Derivatives5 Photocatalytic Reactions of 1,4-Bis(diphenylamino)benzene6 Summary and Outlook

Successful radical surgical resection of a giant neurofibroma.

Large neurofibromas often cause significant patient morbidity and present a unique challenge to dermatologists and surgeons. Radical resection offers the lowest rate of recurrence but is not often pursued due to the high risk of intraoperative hemorrhage and difficulty in repairing large defects. Subtotal resection and debulking are more frequently performed, leading to higher rates of recurrence. This case highlights a particularly large neurofibroma and demonstrates how surgical techniques like preoperative embolization and advancement flaps can improve outcomes in the radical resection of large neurofibromas.

Risk factors for prostate-specific antigen persistence in pT3aN0 prostate cancer after robot-assisted laparoscopic radical prostatectomy: a retrospective study.

The aim of this study was to evaluate the risk factors for prostate-specific antigen (PSA) persistence in pathological stage T3aN0 prostate cancer (PCa) after robot-assisted laparoscopic radical prostatectomy (RALP). A retrospective study was performed on 326 patients with pT3aN0 PCa who underwent RALP between March 2020 and February 2022. PSA persistence was defined as nadir PSA of >0.1 ng/mL after RALP, and the risk factors for PSA persistence were evaluated using logistic regression analysis. Among 326 patients, 61 (18.71%) had PSA persistence and 265 (81.29%) had PSA of <0.1 ng/mL after RALP (successful radical prostatectomy [RP] group). In the PSA persistence group, 51 patients (83.61%) received adjuvant treatment. Biochemical recurrence occurred in 27 patients (10.19%) in the successful RP group during the mean follow-up period of 15.22 months. Multivariate analysis showed that the risk factors for PSA persistence were large prostate volume (hazard ratio [HR], 1.017; 95% confidence interval [CI], 1.002-1.036; p=0.046), lymphovascular invasion (LVI) (HR, 2.605; 95% CI, 1.022-6.643; p=0.045), and surgical margin involvement (HR, 2.220; 95% CI, 1.110-4.438; p=0.024). Adjuvant treatment may be needed for improved prognosis in patients with pT3aN0 PCa after RALP with a large prostate size, LVI, or surgical margin involvement.

Reimagining Democracy: The Socialist Origins of the Initiative and Referendum in the United States

AbstractThe initiative and referendum are commonly characterized as quintessentially Populist or Progressive reforms, but transatlantic socialism deserves pride of place in the intellectual history of direct legislation in the United States. A decade and a half before the People’s Party famously commended the idea of direct legislation at its 1892 nominating convention in Omaha, Nebraska, the Socialist Labor Party (SLP) made the demand for direct legislation a plank in its first party platform. That demand was shaped by the 1875 Gotha Program formulated by the Socialist Workers Party of Germany and informed by socialist debates during the First International and the pioneering work of Moritz Rittinghausen. The diffusion of these ideas among Gilded Age labor radicals is a crucial and underappreciated part of the story of the origins of the initiative and referendum in the United States. That socialists’ pioneering role in the origins of the initiative and referendum in the United States has largely been slighted is particularly ironic since the individual arguably most responsible for securing the direct legislation resolution at Omaha was among the nation’s most successful radical labor organizers and a committed socialist, Joseph R. Buchanan.

Reconstructive endovascular treatment of distal cerebral aneurysm associated with cardiac myxoma

Introduction. The etiology and pathogenesis of cerebral aneurysms are diverse. The rare cause of cerebral aneurysms occurrence is cardioembolism in cases of heart tumors, in particular in myxoma. Cardiac myxoma (from Latin muxa, mucus) is the most common (about 50 %) benign tumor of heart. With untimely diagnosis and absence of the disease treatment, embolisms in cerebral vessels may occur with typical symptoms of ischemic stroke as well as in some cases the myxomal aneurysms may develop. There are several theories of their origin. The myxomal aneurysms of cerebral vessels are more common in women and in the vast majority of cases they develop in carotid basins. In a quarter of cases, the disease onsets as intracranial hemorrhage caused by rupture of an oncotic (myxomal) aneurysm, that significantly exceeds the frequency of ruptures (1–3 % per year) in cases of “normal” bifurcation‑hemodynamic intracranial aneurysms. The mortality rate is 3.4 %. The majority (80 %) of ruptures were observed within 2 years after the diagnosis of cardiac myxoma, and in half (48.6 %) of cases clinically significant episodes of embolism were noted. Timely treatment can prevent the hemor rhagic type of course of these aneurysms. Various methods of treatment are described in the literature: different options for surgical eradication as well as the possibilities of chemotherapy and radiation exposure.Aim. To present a case of successful radical reconstructive endovascular treatment of patient with distal cerebral aneurysm associated with cardiac myxoma, combined with presence of multiple cavernous malformations and also to highlight issues of diagnosis, differential diagnosis and existing treatment options for these diseases.Clinical observation. The article presents a clinical observation of multiple aneurysms associated with myxoma of the heart in combination with multiple cavernous angiomas of the brain. The possibility of reconstructive eradication of distal aneurysm after its transformation from fusiform to saccular is demonstrated. The etiology and pathogenesis of occurrence, the nuances of differential diagnosis, possible methods and the algorithm for choosing a method for treating brain aneurysms associated with myxomas are reflected. The patient underwent reconstructive aneurysm shutdown by embolization with microspirals, which became possible due to the anatomical shape that favored this type of treatment. Conversion to destructive intervention was not required. Due to the natural course of the disease, the patient remains at risk of progression of a distal aneurysm in the basin of the same artery, and therefore it will be observed in dynamics.Conclusion. All patients with cardiac myxomas, both before and in dynamics after their removal, are recommended to perform noninvasive visualization of brain vessels for verification of such complication as metastatic (myxomal) aneurysms. The prognosis in most patients with multiple intracranial aneurysms associated with myxoma is favorable and most aneurysms associated with myxoma are stable. However, in cases with progressive or ruptured aneurysms, surgical treatment options should be considered including microsurgical or endovascular eradication. Radiation and chemotherapy methods may have a certain therapeutic value.

Fluoroalkyl Sulfoximines for Versatile Photocatalytic Radical Fluoroalkylations.

Fluoroalkyl sulfoximines, which serve as electron-accepting fluoroalkyl radical sources, are easy-to-handle, solid, and bench-stable chemicals. Fluoroalkyl radicals can be generated from sulfoximine reagents using strong one-electron injectors, such as a highly reducing photoredox catalyst in the excited state. Our group has developed photocatalytic radical di- and mono-fluoromethylation and α-monofluoroalkylation of olefins with the corresponding fluoroalkyl sulfoximines. In this personal account, appropriate combinations of fluoroalkyl sulfoximines and photoredox catalysts, leading to successful radical fluoroalkylation, have been discussed.

The strategic ambiguity of the radical right: A study of the Danish People’s Party

Though radical right parties are easily identified by their strong nationalism and anti-immigrant sentiment, significant confusion surrounds their positions on core economic issues, such as taxation and redistribution. This uncertainty may reflect an electoral strategy in which these parties intentionally blur their positions to avoid taking stances on economic issues that divide their target constituencies. Existing research on position blurring and the radical right focuses exclusively on expert surveys and party manifesto statements, providing little information about voter-level perceptions of these parties. This study directly investigates public perception of the positions of the Danish People’s Party, one of the most successful radical right parties in Europe. The study finds strong evidence that the DPP draws on a voter base with below average political awareness, allowing it to more easily recruit voters on opposing sides of economic issues by obscuring its own positions.

Adjuvant radiotherapy post microvascular reconstructive surgery (MRS) for patients with locally advanced head and neck cancer – when and how?

For many decades palliation (radiotherapy, chemotherapy or symptomatic treatment) was the only therapeutic solu­tion for locally very advanced head and neck cancer. In the mid 70s, H. Buncke carried out pioneering microvascular reconstructive surgery (MRS) as a radical treatment. Since that time, the MRS has been accepted around the world as a successful radical therapy, not only for head and neck (H&amp;N) cancers. A part of the H&amp;N cancers need however post­-MRS radiotherapy (RT). Based on the 20 year experience of the Institute of Oncology in Gliwice with MRS (about 2500 patients), D. Bula has defined local recurrence risk factors. Dutch studies convincingly documented the prognostic value of the estimated molecular profiles of the resected margins as additional risk factors. The use of conventional 2.0 Gy/ fraction post-MRS-RT result in a high risk of the inserted reconstructive flap necrosis or rejection. Therefore, a novel IMRT­-VMAT technique with 50 Gy given in 1.5–1.6 Gy/fraction has been designed which allows to almost eliminate the flap from the irradiated volume and therefore minimizes recurrence and/or flap rejection to almost zero. The present paper shows objectively selected a cluster of patients being the candidate to post-MRS safe and effective VMAT radiotherapy.

A case of successful multi-stage surgical treatment of liver echinococcosis

A clinical case of successful radical multi-stage surgical treatment of a patient with bilobar parasitic lesion of the liver with echinococcosis complicated by infection of one of the cysts is presented. The patient was admitted to the clinic with volumetric lesions in both lobes of the liver. At the stage of differential diagnosis, on the basis of process verification by puncture biopsy under ultrasound control, the ethiology of mass lesions was reliably established. At the primary stationary stage, infection of one of the echinococcal cysts was diagnosed, for which the cyst was drained under ultrasound control. After that, the patient was discharged to the outpatient care for compensation, correction of the general level of health and nutritional status. At the next stage of the inpatient examination, the patient was determined to have an insufficient level of functional reserves of the liver to perform a radical operation. For this reason, laparoscopic ligation of the right branch of the portal vein was performed in order to develop vicarious hypertrophy of the contralateral lobe. After 30 days, the increased level of functional reserves of the liver made it possible to plan radical surgical treatment with an acceptable risk for the patient. The operation was performed in the amount of right-sided extended hemihepatectomy with marginal resection of the 3rd segment of the liver. The symptoms of liver failure in the postoperative period according to the ISGLS scale were regarded as Grade A. The patient was discharged from the hospital in a satisfactory condition on day 10 after the operation. In the postoperative period, courses of therapy with albendazole were prescribed according to the standard scheme. The patient is under observation for more than a year after treatment. The condition is satisfactory. No recurrence of the disease was noted.

Analysis of safety and efficacy of laparoscopic radical gastrectomy combined with or without indocyanine green tracer fluorescence technique in treatment of gastric cancer: a retrospective cohort study.

BackgroundAn adequate resection margin and lymph node dissection are important factors for successful radical gastrectomy. The presence of near-infrared camera imaging with indocyanine green (ICG) gives new insight into radical gastrectomy. Laparoscopic radical gastrectomy with ICG is still in its initial stages and requires more evidence-based medical research. The aim of the present study was to evaluate the safety and availability of lymph node dissection and precise gastrectomy for gastric cancer patients undergoing radical resection under laparoscope with ICG, in the hope of providing evidence of application of ICG tracer fluorescence technique in radical gastrectomy.MethodsA retrospective cohort study was performed with 56 patients who underwent laparoscopic radical gastrectomy. The patients were categorized into the ICG (n=18) or the non-ICG (n=38) group based on whether preoperative endoscopic mucosal ICG injection was performed. Their clinical characteristics (age, tumor size, location, TNM stage and so on) were compared as baseline data. Perioperative outcomes (blood loss, time of first intestinal exhaust, early or long-term complications and so on) were used to assess safety. The status of lymph node dissection and tumor localization were analyzed to testify efficacy. SPSS version 26.0 was used for the statistical analysis.ResultsThere was no difference in clinical data at baseline. From the safety point of view, there was no difference in perioperative outcomes (operative time, blood loss, time of first intestinal exhaust and so on) between the two groups (all P>0.05). From the efficacy point of view, the number of lymph nodes <5 mm (21.84±1.86 vs. 16.24±2.10, P<0.001), the total number of lymph nodes (34.61±5.87 vs. 29.92±5.27, P=0.004), the number of lymph nodes dissected in perigastric regions (groups 1–7, 22.89±3.64 vs. 20.29±3.00, P=0.007), and the number of lymph nodes in extraperigastric regions (groups 8–12, 11.72±3.06 vs. 9.61±3.18, P=0.022) were greater in ICG group compared with non-ICG group. In ICG group, the average vertical distances between the top and bottom of the fluorescent edge and neoplastic edge were 2.65±0.58 and 2.67±0.65 cm, respectively. Fluorescent edge pathology was negative.ConclusionsICG fluorescence could be conducive to lymph node dissection and precise gastrectomy in laparoscopic radical gastrectomy.

(Invited) Titanium-Catalyzed Intermolecular Radical Addition to Ketones Via Sp 3 C-H Bond Activation

Tertiary alcohols are widely present in natural products, pharmaceuticals, and agrochemicals. Radical addition reaction to ketones is a simple and waste-free synthetic method for preparation of tertiary alcohols with high functional group tolerance. Therefore, direct radical addition reactions to ketones can be applied to a wider range of substrates. However, radical addition to carbonyl groups is a thermodynamically unfavored process, especially in the case of intermolecular radical addition to ketones, where the resulting alkoxy radical can easily undergo β-fragmentation to yield the starting material. For successful radical addition, therefore, the alkoxy radical must be trapped by a proper trapping reagent. In this study, we have found that a ternary hybrid catalytic system consisting of acridinium photoredox catalyst, thiophosphoric imide (TPI) catalyst, and titanium complex catalyst can promote intermolecular addition reactions of various ketones with organic molecules by activation of sp3 C-H bonds. The thiyl radicals generated by the excited photoredox-catalyzed one-electron oxidation of TPI extracted hydrogen atoms from organic molecules such as toluene, benzyl alcohol, alkenes, aldehydes, and THF. The carbon-centered radical species thus generated are added to various ketones and aldehydes. This method can be applied to the first direct reaction to aliphatic ketones using a variety of hydrocarbon feedstocks. The unfavorable bond-forming step was facilitated by the simultaneous one-electron reduction of the intermediate alkoxy radical by catalytically generated titanium(III) species. This reaction provided an efficient and simple approach to tertiary alcohols and was successfully applied in the late-stage functionalization of drugs and their derivatives. The proposed mechanism was supported by both experimental and theoretical studies. Figure 1