An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer

Background The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells’ ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. Methods We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. Results We included 188 patients undergoing colon cancer resections in 2011–2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64–6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06–0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68–157.32] and HR = 7.56, 95%CI [1.06–54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. Conclusions In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

Intravitreal chemotherapy in the management of retinoblastoma in a resource-limited setting

Intravitreal chemotherapy (IVitC) in the management of retinoblastoma has increased the rate of globe salvage, specifically in patients with recurrent disease and associated vitreous seeds. A significant number of children with retinoblastoma in developing countries present late, resulting in higher intraocular tumour-stage at presentation. Treatment requirements for such tumours usually include intravenous chemotherapy (IVC) and/or intra-arterial chemotherapy (IAC). While IVC has a long usage track record and a good efficacy, it has been reported to be associated with higher recurrence rates in a significant number of patients. Intra-arterial chemotherapy has the advantage of lower recurrence rates but requires personnel with advanced interventional radiology skills and has limited efficacy in treating intravitreal seeds. Intravitreal chemotherapy has gained popularity recently, largely because of its superior efficacy in the management of vitreous seeds, subretinal seeds and recurrent retinal tumour. An 8-month-old male infant initially presented with bilateral retinoblastoma, International Classification System for Intraocular Retinoblastoma (ICRB) Group E in the right eye and Group B on the left eye. The right eye was enucleated and currently has a prosthesis. The left eye had tumours that initially responded to brachytherapy and transpupillary thermotherapy (TTT). Approximately two years later his tumours recurred with vitreous seeds and were successfully managed with the use of cryotherapy and intravitreal chemotherapy. The simplicity of the technique of IVitC and its efficacy in controlling vitreous seeds and recurrent retinal tumours makes this route of regional chemotherapy a viable one in areas with limited expertise and resources such as South Africa.

MANAGEMENT OF ADRENO CORTICAL CARCINOMA: CASE REPORT

Objective: Adreno cortical carcinoma (ACC) is a rare malignancy. Currently, surgical resection offers the best chance of cure with localized tumor. Multimodal therapy including systemic chemotherapy and radiation therapy are often required for locally advanced and metastatic disease aims to decrease these high recurrence rates. Case(s) presentation: A 42-year-old male patient was referred from internist due to mass in left adrenal. Solid mass with calcification on left adrenal gland within size 9 x 11.8 x 11.5 cm was found in MSCT. We performed complete surgical resection (adrenalectomy), and results from pathology anatomy was ACC functional T2N1M0 (stage 3). The patient was planned eight times chemotherapy with etoposide and carboplatin, but he decided to stop the treatment after six times due to no constitutional complaint. We found no residual mass on follow up six months after operation and patient demonstrated a good clinical outcome after one year. Discussion: We perform open adrenalectomy and after surgery mitotane plus etoposide, cisplatin, doxorubicin (EDP) administered as first-line therapy but we only did chemotherapy with etoposide and carboplatin because mitotane was not covered by patient insurance. We chose to not perform radiation therapy due to lesser benefit of adjuvant radiotherapy as evidenced by many studies in term of recurrence-free survival and overall survival. Conclusion: In our case, adreno cortical carcinoma treated with open adrenalectomy combined with 6 times chemotherapy used etoposide and carboplatin demonstrated a good clinical outcome after 1 year.

A Novel Plant-Derived Choline Transporter-like Protein 1 Inhibitor, Amb544925, Induces Apoptotic Cell Death via the Ceramide/Survivin Pathway in Tongue Squamous Cell Carcinoma

Background: Despite recent advances in the early detection and treatment of TSCC patients, recurrence rates and survival rates have not improved. The high frequency of lymph node metastasis is one of the causes, and the drug development of new therapeutic mechanisms such as metastasis control is desired. Choline transporter-like protein 1 (CTL1) has attracted attention as a target molecule in cancer therapy. In this study, we examined the antitumor effects of Amb544925, a plant-derived CTL1 inhibitor. Methods: The TSCC cell line HSC-3 was used to measure [3H]choline uptake, cell survival, caspase activity, and cell migration. Xenograft model mice were prepared to verify the antitumor effect of Amb544925. Results: Amb544925 inhibited cell viability and increased caspase-3/7 activity at concentrations that inhibited choline uptake. Amb544925 and ceramide increased SMPD4 expression and suppressed surivivin expression. Furthermore, Amb544925 and ceramide inhibited the migration of HSC-3 cells. In the xenograft model mice, Amb544925 suppressed tumor growth and CTL1 mRNA expression. Conclusions: The plant-derived CTL1 inhibitor Amb544925 is a lead compound of a new anticancer agent exhibiting antitumor effects and inhibition of cell migration through the ceramide/survivin pathway.

Outcomes of soft-tissue sarcoma in nonagenarians

Aims Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients. Methods Retrospective access to our prospectively maintained oncology database yielded a cohort of 48 patients across 23 years with a median follow-up of 12 months (0 to 78) and mean age at diagnosis of 92 years (90 to 99). Overall, 42 of 48 of 48 patients (87.5%) were managed surgically with either limb salvage or amputation. Results A lower overall local recurrence rate (LRR) was seen with primary amputations compared with limb salvage (p > 0.050). The LRR was comparable between free (R0), microscopically (R1), and macroscopically positive (R2) resection margins in the limb salvage group. Amputation was also associated with longer survival times (p < 0.050). Overall median survival time was limited to 20 months (0 to 80). Conclusion Early and aggressive treatment with appropriate oncological surgery confers the lowest LRR and a survival advantage versus conservative treatment in this cohort of patients. With limited survival, follow-up can be rationalized on a patient-by-patient basis using alternative means, such as GP, local oncology, and/or patient-led follow-up. Cite this article: Bone Joint J 2022;104-B(1):177–182.

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study

Objective 17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. Study Design A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. Results Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9–1.4). Conclusion We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. Key Points

Observational Study for Adverse Effects and Discontinuation with Long-Term Post-Operative Hormonal Treatment for Endometriosis in Real-World Practice

Objectives: To evaluate the side effects and causes of discontinuation of either combined oral contraceptives or dienogest (DNG) used to prevent recurrence in patients with surgically confirmed endometriosis.Methods: We retrospectively analyzed the medical records of 213 women with endometriosis who had been treated with combined oral contraceptives (ethinyl estradiol 0.02 mg/drospirenone 3 mg [EE/DRSP]) or DNG 2 mg for 12 months or more. The side effects reported by the patients, laboratory parameters, causes of discontinuation of medication, and recurrence rates were evaluated one, two, three, four, and five years after starting medication (Y1, Y2, Y3, Y4, and Y5).Results: EE/DRSP were administered to 59 patients, while DNG was administered to 154 patients. The mean durations of postoperative use of EE/DRSP and DNG were 44.5 ± 22.6 months and 23.6 ± 13.5 months, respectively. The prevalence of side effects was 27.1%, 19.0%, 10.0%, 10.5%, and 7.4% in the EE/DRSP group and 29.2%, 15.7%, 14.0%, 23.1%, and 0.0% in the DNG group at Y1, Y2, Y3, Y4, and Y5, respectively. The discontinuation rates were 1.7%, 1.7%, 4.0%, 0.0%, and 7.4% at Y1, Y2, Y3, Y4, and Y5, respectively, in the EE/DRSP group and 10.4%, 3.3%, 4.0%, 3.8%, and 0.0% at the same times in the DNG group. The recurrence rates were less than 4% in both the groups.Conclusions: The side effects of commonly prescribed postoperative hormone treatments were relatively mild, and the occurrence of side effects decreased with continuous administration. Further, the long-term use of postoperative hormone treatments is likely to prevent recurrence of endometriosis after surgery.

Effectiveness and Safety of a Modified Technique of Transvesical Obturator Nerve Block to Avoid Adductor Contractions during Transurethral Resection of Bladder Tumors

<b><i>Introduction:</i></b> The aim of the study was to evaluate the effectiveness of a modified transvesical obturator nerve block (ONB) in the prevention of obturator nerve reflex and consecutive bladder perforations (BPs) during transurethral resection of bladder tumors (TURBTs). <b><i>Materials and Methods:</i></b> A retrospective analysis of all patients resected in 2014–2015 due to a bladder tumor of the lateral walls, including a follow-up period until December 2018, was performed. Two groups were defined: in the first group, all patients underwent TURBT with a modified transvesical ONB. The second group underwent conventional TURBT with intermittent resection. Primary endpoints were the rates of adductor contractions and BPs. <b><i>Results:</i></b> Ninety-four out of 1,145 resected patients presented with tumors on the lateral wall of the bladder and a complete dataset including a long-term follow-up. Thirty-six patients were treated in the ONB group, and 58 patients comprised the control group. The median age in the 2 groups was 70.8 and 71.8 years in the first and second groups, respectively. Adductor spasms were reported in 8.33 versus 25.86% (<i>p</i> = 0.057) and perforation in 2.78 versus 17.24% (<i>p</i> = 0.047) in groups 1 and 2, respectively. After a median follow-up of 32.5 months, there was no significant difference in recurrence rates (52.78 vs. 51.72%, <i>p</i> = 0.672). In a subgroup analysis, lower perforation rates were recorded for the ONB group in patients with tumors &#x3c;3 cm (0/30 vs. 8/46, <i>p</i> = 0.076) and in patients with unifocal tumors (0/12 vs. 5/23, <i>p</i> = 0.141). <b><i>Discussion/Conclusion:</i></b> The simplified approach of transvesical ONB demonstrated in this study appears to be an inexpensive, safe, effective, and simple-to-use technique.

Local Recurrence of Primary Cardiac Leiomyosarcoma After Resection: A Rare Case

Introduction: Leiomyosarcoma (LMS) is a fatal tumor, though primary cardiac is very rarely encountered. In this report, we evaluated the surgical and medical management of primary cardiac LMS, which is a sporadic tumor.Case Presentation: A 60-year-old female patient was examined for pulmonary edema after penicillin allergy in May 2019, while transthoracic echocardiography (ECHO) revealed an appearance compatible with a 5x3.5 cm mass in the right atrium. In addition, transesophageal ECHO showed a 7x4.6 cm foreground mass compatible with a myxoma in the right atrium (RA). The patient was then operated on emergency. Besides, an adjuvant ifosfamide-mesna-doxorubicine (IMA) protocol was planned to be given to the patient after local radiotherapy.Conclusions: In this report presented, we made RT and chemotherapy treatment plans in the case of recurrence without R0 surgery. Recurrence rates of up to 50% can occur in LMS, and systemic chemotherapy can be applied after relapse

Downregulated Expression of miRNA-130a-5p Aggravates Hepatoma Progression via Targeting PTP4A2

Background. Hepatoma is a leading cause of death worldwide, with high metastasis and recurrence rates. The aberrant expression of miRNA-130a-5p is involved in the development and progression of various cancers. However, there are no studies investigating the role of miRNA-130a-5p in hepatoma. The present study is aimed at clarifying the functional role of miRNA-130a-5p in hepatoma progression. Methods. The expression levels of miRNA-130a-5p in hepatoma tissues and cell lines were detected by qRT-PCR assays. Bioinformatic analysis, gain-/loss-of-function experiments, and luciferase activity assays were conducted to verify whether miRNA-130a-5p is targeted by protein tyrosine phosphatase 4A2 (PTP4A2). The functions of miRNA-130a-5p and PTP4A2 in hepatoma were determined by cell proliferation assays. Results. The expression of miRNA-130a-5p was downregulated in hepatoma tissues and was related to poor prognosis. However, the expression level of PTP4A2 was contradictory to that of miRNA-130a-5p, and PTP4A2 upregulation could aggravate hepatoma progression. The ectopic overexpression of PTP4A2 promoted hepatoma cell proliferation in vitro, which could be reversed by miRNA-130a-5p. Conclusions. Our study implies that miRNA-130a-5p, which is downregulated in hepatoma tissues, can suppress hepatoma cell proliferation via targeting PTP4A2.