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1.
World J Surg Oncol ; 22(1): 99, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38627808

ABSTRACT

BACKGROUND: Colorectal peritoneal metastases (CRPM) are present in 10-20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. METHODS: A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. RESULTS: Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. CONCLUSION: Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/secondary , Hyperthermic Intraperitoneal Chemotherapy , Colorectal Neoplasms/pathology , Cytoreduction Surgical Procedures , Retrospective Studies , Quality of Life , Neoplasm Recurrence, Local/pathology , Combined Modality Therapy , Survival Rate , Antineoplastic Combined Chemotherapy Protocols
2.
Int Immunopharmacol ; 130: 111769, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38442584

ABSTRACT

Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Hyperthermia, Induced , Liver Neoplasms , Membrane Proteins , Nucleotidyltransferases , Picibanil , Radiofrequency Ablation , Toll-Like Receptor 4 , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/pathology , Picibanil/pharmacology , Picibanil/therapeutic use , Retrospective Studies , Toll-Like Receptor 4/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Animals , Mice , Cell Line, Tumor , Mice, Inbred C57BL , Male
3.
Magy Onkol ; 68(1): 86-88, 2024 Mar 14.
Article in Hungarian | MEDLINE | ID: mdl-38484379

ABSTRACT

We compared the clinical outcomes of second breast conserving therapy (2ndBCT) versus salvage mastectomy (sMT) for the treatment of ipsilateral breast tumour recurrences (IBTR). 195 patients who presented with an IBTR after previous breast conserving treatment were salvaged either with re-excision and perioperative interstitial brachytherapy (n=39) or sMT (n=156). A total dose of 5×4.4Gy was delivered to the tumour bed, on 3 consecutive days. The median follow-up time was 59 and 56 months. During follow-up 4 (10.2%) and 28 (17.9%) second local recurrences occurred after 2ndBCT and sMT, respectively. There were no significant differences between treatments in 5-year oncological outcomes (local and regional recurrence-free survival, disease- and metastasis-free survival, cancer-specific and overall survival). After 2ndBCT, the rate of good to excellent cosmesis was 70%. 2ndBCT is a safe and feasible option for the management of IBTR, resulting similar 5-year oncological outcomes and better cosmetic results compared to sMT.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Mastectomy , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Mastectomy, Segmental/methods , Combined Modality Therapy
4.
Sci Rep ; 14(1): 4270, 2024 02 21.
Article in English | MEDLINE | ID: mdl-38383712

ABSTRACT

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Humans , Retrospective Studies , Bayes Theorem , Neoplasm Recurrence, Local/pathology , Colonic Neoplasms/pathology , Rectal Neoplasms/pathology , Prognosis , Neoplasm Staging , Colorectal Neoplasms/pathology
5.
Ann Surg Oncol ; 31(4): 2368-2377, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38172447

ABSTRACT

BACKGROUND: Peritoneal sarcomatosis (PS) is a rare tumor with limited therapeutic options. Bidirectional intraoperative chemotherapy (BDIC) using intravenous ifosfamide and doxorubicin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is an emerging treatment for peritoneal malignancies. PATIENTS AND METHODS: Patients with PS who underwent CRS/BDIC using intravenous ifosfamide and HIPEC from January 2017 to July 2021 were retrospectively analyzed. The last follow-up date was May 2022. RESULTS: A total of 29 patients were included. Overall survival (OS) rates at 6, 12, 24, and 48 months after CRS/BDIC were 93.1%, 89.2%, 81.4%, and 73.3%, respectively. As of May 2022, 6 patients (20.6%) had died, including four (13.8%) with a proven recurrent tumor and two with incomplete tumor resection [completeness of cytoreduction (CC)-2 or CC-3]. Of the 20 patients (68.9%) with CC-0 or CC-1, 7 had locoregional tumor recurrence without distant metastasis, whereas the other 13 were alive with no evidence of recurrent tumor in May 2022. Disease recurrence rates were 15% at 6 months and 35% at 12, 24, and 48 months after CRS/BDIC. Clavien-Dindo class ≥ IIIa complications developed in 9 patients (31.0%) with no deaths. Leukopenia occurred in 5 patients (17.2%) and thrombocytopenia in 12 patients (41.3%); these hematologic abnormalities resolved. A total of 9 (31.0%) patients developed nephrotoxicity; all recovered except one, who progressed to chronic kidney disease. CONCLUSIONS: CRS/BDIC using intravenous ifosfamide and doxorubicin-based HIPEC is a potentially effective treatment for PS and has an acceptable rate of complications.


Subject(s)
Hyperthermia, Induced , Hyperthermic Intraperitoneal Chemotherapy , Humans , Ifosfamide , Combined Modality Therapy , Cytoreduction Surgical Procedures , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/pathology , Doxorubicin , Survival Rate
6.
Asia Pac J Clin Oncol ; 20(2): 228-233, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36656047

ABSTRACT

PURPOSE: To evaluate the efficiency and safety of combined local bladder hyperthermia and intravesical chemotherapy (IVC) for the treatment of patients with pT1 stage bladder cancer. METHOD: A total of 189 patients with pT1 who underwent transurethral resection of bladder cancer (TURBT) were retrospectively reviewed. After TURBT, the patients with low-grade urothelial carcinoma (UC) were treated with either an IVC with pirarubicin (THP) protocol or chemo-thermotherapy (CHT) with THP protocol, whereas patients with high-grade UC were treated with either an intravesical immunotherapy (IVI) with bacillus Calmette-Guerin (BCG) protocol or CHT protocol, patients' characteristics, tumor biological features, and follow-up data were analyzed and compared between CHT and IVC group in low-grade UC, CHT, and IVI group in high-grade UC, respectively. RESULTS: The median follow-up time was 24 months. In patients with low-grade UC, the median recurrence free survival (RFS) interval and costs of treatment in CHT group were significantly higher than those in IVC group (p = .01, p < .001, respectively), CHT was associated with higher RFS compared with IVC by Kaplan-Meier analysis, and three patients in IVC group upgraded to high grade when tumor recurred, whereas no cases were found upgraded in CHT group, p = .38. In patients with high-grade UC, tumor recurrence rates at 12 (p = .004) and 24 months (p = .004) after TURBT, rate of complications (p = .04)-especially for hematuresis (p = .03) and irritation symptoms (p = .04)-the median costs of treatment (p < .001) in CHT group were significantly lower than those in IVI group, RFS interval, health-related quality of life) at 12 and 24 months after TURBT in CHT group was significantly higher than those in IVI group (p < .001, p = .002, and p < .001, respectively), and CHT was associated with higher RFS compared with IVI by Kaplan-Meier analysis. The rate of patients upstaged to pT2 in CHT group seemed lower than that in IVI group, but there was no significantly statistical difference (14.3% vs. 24%, p = .58). CONCLUSION: CHT has a beneficial prophylactic effect in patients with pT1 bladder cancer, especially in patients with high-grade UC, which is much more effective and safer than BCG, meanwhile it costs less compared with BCG.


Subject(s)
Carcinoma, Transitional Cell , Hyperthermia, Induced , Urinary Bladder Neoplasms , Humans , BCG Vaccine/adverse effects , Carcinoma, Transitional Cell/pathology , Hyperthermia, Induced/adverse effects , Neoplasm Invasiveness , Neoplasm Recurrence, Local/pathology , Quality of Life , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Neoplasm Staging
7.
JAMA Oncol ; 10(1): 79-86, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37943566

ABSTRACT

Importance: In March 2023, the National Comprehensive Cancer Network endorsed watch and wait for those with complete clinical response to total neoadjuvant therapy. Neoadjuvant therapy is highly efficacious, so this recommendation may have broad implications, but the current trends in organ preservation in the US are unknown. Objective: To describe organ preservation trends among patients with rectal cancer in the US from 2006 to 2020. Design, Setting, and Participants: This retrospective, observational case series included adults (aged ≥18 years) with rectal adenocarcinoma managed with curative intent from 2006 to 2020 in the National Cancer Database. Exposure: The year of treatment was the primary exposure. The type of therapy was chemotherapy, radiation, or surgery (proctectomy, transanal local excision, no tumor resection). The timing of therapy was classified as neoadjuvant or adjuvant. Main Outcomes and Measures: The primary outcome was the absolute annual proportion of organ preservation after radical treatment, defined as chemotherapy and/or radiation without tumor resection, proctectomy, or transanal local excision. A secondary analysis examined complete pathologic responses among eligible patients. Results: Of the 175 545 patients included, the mean (SD) age was 63 (13) years, 39.7% were female, 17.4% had clinical stage I disease, 24.7% had stage IIA to IIC disease, 32.1% had stage IIIA to IIIC disease, and 25.7% had unknown stage. The absolute annual proportion of organ preservation increased by 9.8 percentage points (from 18.4% in 2006 to 28.2% in 2020; P < .001). From 2006 to 2020, the absolute rate of organ preservation increased by 13.0 percentage points for patients with stage IIA to IIC disease (19.5% to 32.5%), 12.9 percentage points for patients with stage IIIA to IIC disease (16.2% to 29.1%), and 10.1 percentage points for unknown stages (16.5% to 26.6%; all P < .001). Conversely, patients with stage I disease experienced a 6.1-percentage point absolute decline in organ preservation (from 26.4% in 2006 to 20.3% in 2020; P < .001). The annual rate of transanal local excisions decreased for all stages. In the subgroup of 80 607 eligible patients, the proportion of complete pathologic responses increased from 6.5% in 2006 to 18.8% in 2020 (P < .001). Conclusions and Relevance: This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy. Given the National Comprehensive Cancer Network endorsement of watch and wait, the increasing trends in organ preservation, and the nearly 3-fold increase in complete pathologic responses, international professional societies should urgently develop multidisciplinary core outcome sets and care quality indicators to ensure high-quality rectal cancer research and care delivery accounting for organ preservation.


Subject(s)
Organ Preservation , Rectal Neoplasms , Adolescent , Adult , Female , Humans , Male , Middle Aged , Chemoradiotherapy , Neoadjuvant Therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Pathologic Complete Response , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome , Watchful Waiting
8.
Otolaryngol Head Neck Surg ; 170(1): 132-140, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37622529

ABSTRACT

OBJECTIVE: To identify socioeconomic factors influencing the presentation and outcomes of cutaneous head and neck squamous cell carcinoma (cHNSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center with comprehensive cancer center. METHODS: Patients treated for cHNSCC at a single institution between 2008 and 2022 were included. Demographic, socioeconomic data and disease characteristics were obtained from medical record abstraction. Outcome measures included tumor stage, number of distinct primaries, recurrence, and disease-related death. χ2 and Mann-Whitney tests were implemented to evaluate clinicopathologic distributions across disease stages. Survival analyses were performed using Cox regression and Kaplan-Meier analysis. RESULTS: A total of 346 patients met the inclusion criteria. The median age at presentation and length of follow-up was 70.8 and 3.1 years, respectively. The majority of the cohort was white, male, and English-speaking. 13.3% of patients were underinsured and 27.5% were immunosuppressed. Patients who presented with advanced disease were more likely to be underinsured (21.7% vs 9.6%, P = .006) and have a history of homelessness (8.5% vs 2.1%, P = .014). Immunosuppressed patients were more likely to be underinsured (P = .009). Insurance status (1.97 [1.06-3.66], P = .032) and immune status (2.35 [1.30-4.26], P = .005) were independently associated with worse recurrence-free survival. CONCLUSION: Socioeconomic factors that influence access to care, such as insurance status, are associated with cHNSCC disease stage and disease recurrence. These factors may impose barriers that delay diagnosis and treatment. This may result in worse disease-related outcomes and greater treatment-associated morbidity for certain patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Skin Neoplasms , Humans , Male , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Carcinoma, Squamous Cell/pathology , Retrospective Studies , Skin Neoplasms/pathology , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/pathology , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Insurance Coverage
9.
Br J Nutr ; 131(2): 276-285, 2024 01 28.
Article in English | MEDLINE | ID: mdl-37642137

ABSTRACT

The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.


Subject(s)
Amino Acids, Branched-Chain , Ascites , Humans , Ascites/chemically induced , Ascites/metabolism , Ascites/pathology , Amino Acids, Branched-Chain/therapeutic use , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Liver/metabolism , Dietary Supplements , Body Weight
10.
Int J Surg ; 110(1): 45-52, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37800569

ABSTRACT

BACKGROUND: The benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for colorectal cancer with peritoneal metastasis (CPM) remain controversial. R0 resection without peritoneal stripping might be as effective as CRS plus HIPEC. The authors aimed to compare the long-term oncological outcomes of patients with CPM and peritoneal cancer index (PCI) scores less than or equal to 6 who underwent R0 resection in Japan with those who underwent CRS plus HIPEC in Korea. MATERIALS AND METHODS: This international, retrospective cohort study was conducted in Korea and Japan using a prospectively collected clinical database. Patients who underwent surgery from July 2014 to December 2021 for CPM with a PCI score of less than or equal to 6 and completeness of the cytoreduction score-0 were included. The primary outcome was relapse-free survival (RFS), and the secondary outcomes were overall survival, peritoneal RFS (PRFS), and postoperative outcomes. RESULTS: The 3-year RFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 35.9% versus 6.9% ( P <0.001); 31.0% versus 6.7% ( P =0.040) after propensity score matching. The median PRFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 24.5 months versus 17.2 months ( P =0.017). The 3-year overall survival and postoperative complications did not significantly differ between the two groups. CONCLUSIONS: RFS and PRFS rates were significantly prolonged after CRS plus HIPEC, whereas postoperative complications and length of hospital stay were not increased. Therefore, curative CRS plus HIPEC may be considered a treatment strategy for selected patients with resectable CPM and low PCI scores.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Cytoreduction Surgical Procedures/adverse effects , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/drug therapy , Hyperthermic Intraperitoneal Chemotherapy , Retrospective Studies , Japan , Neoplasm Recurrence, Local/pathology , Colorectal Neoplasms/pathology , Postoperative Complications/drug therapy , Republic of Korea , Survival Rate , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
11.
Pediatr Radiol ; 54(1): 157-169, 2024 01.
Article in English | MEDLINE | ID: mdl-38019284

ABSTRACT

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.


Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Child , Humans , Craniopharyngioma/diagnostic imaging , Craniopharyngioma/surgery , Craniopharyngioma/pathology , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Prognosis , Magnetic Resonance Imaging/methods , Hypothalamus/diagnostic imaging , Hypothalamus/pathology , Edema
12.
Clin Cancer Res ; 30(2): 344-355, 2024 01 17.
Article in English | MEDLINE | ID: mdl-37955629

ABSTRACT

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Hypopharyngeal Neoplasms , Laryngeal Neoplasms , Larynx , Humans , Hypopharyngeal Neoplasms/drug therapy , Hypopharyngeal Neoplasms/pathology , Organ Preservation , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/pathology , Fluorouracil , Laryngectomy , Neoplasm Recurrence, Local/pathology , Larynx/pathology , Cisplatin , Induction Chemotherapy , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/pathology , Treatment Outcome
13.
Phytother Res ; 38(1): 131-146, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37821355

ABSTRACT

Neuroblastoma and glioblastoma are primary malignant tumors of the nervous system, with frequent relapse and limited clinical therapeutic drugs. The failure of their treatment is due to the tumor cells exhibiting cancer stem-like cells (CSLCs) properties. Octamer binding transcription factor 4 (Oct4) is involved in mediating CSLCs, our previous work found that Oct4-driven reprogramming of astrocytes into induced neural stem cells was potentiated with continuous sonic hedgehog (Shh) stimulation. In this study, we aimed to study the importance of Oct4 and Shh combination in the stemness properties induction of neuroblastoma and glioblastoma cells, and evaluate the anti-stemness effect of dauricine (DAU), a natural product of bis-benzylisoquinoline alkaloid. The effect of Oct4 and Shh co-activation on cancer stemness was evaluated by tumor spheres formation model and flow cytometry analysis. Then the effects of DAU on SH-SY5Y and T98-G cells were assessed by the MTT, colony formation, and tumor spheres formation model. DAU acts on Oct4 were verified using the Western blotting, MTT, and so on. Mechanistic studies were explored by siRNA transfection assay, Western blotting, and flow cytometry analysis. We identified that Shh effectively improved Oct4-mediated generation of stemness in SH-SY5Y and T98-G cells, and Oct4 and Shh co-activation promoted cell growth, the resistance of apoptosis. In addition, DAU, a natural product, was found to be able to attenuate Oct4/Shh co-activated stemness and induce cell cycle arrest and apoptosis via blocking AKT/ß-catenin signaling in neuroblastoma and glioblastoma, which contributed to the neuroblastoma and glioblastoma cells growth inhibition by DAU. In summary, our results indicated that the treatment of DAU may be served as a potential therapeutic method in neuroblastoma and glioblastoma.


Subject(s)
Benzylisoquinolines , Biological Products , Glioblastoma , Neuroblastoma , Tetrahydroisoquinolines , Humans , Glioblastoma/drug therapy , Glioblastoma/pathology , Hedgehog Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Neuroblastoma/drug therapy , Neuroblastoma/metabolism , Neuroblastoma/pathology , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Benzylisoquinolines/pharmacology , Neoplastic Stem Cells , Cell Proliferation , Apoptosis , Biological Products/pharmacology
14.
Ann Surg Oncol ; 31(1): 614-621, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37872456

ABSTRACT

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.


Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Hyperthermic Intraperitoneal Chemotherapy , Cytoreduction Surgical Procedures , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced/adverse effects , Peritoneal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Appendiceal Neoplasms/pathology , Adenocarcinoma, Mucinous/pathology , Retrospective Studies , Survival Rate
15.
J Surg Oncol ; 129(4): 793-801, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38151831

ABSTRACT

INTRODUCTION: Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS: Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS: Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively.  Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION: Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Follow-Up Studies , Hepatectomy , Colorectal Neoplasms/pathology , Blood Transfusion, Autologous , Retrospective Studies , Liver Neoplasms/secondary , Neoplasm Recurrence, Local/pathology , Prognosis
16.
Curr Oncol ; 30(11): 9996-10006, 2023 Nov 18.
Article in English | MEDLINE | ID: mdl-37999146

ABSTRACT

Patients with low-grade appendiceal mucinous carcinomas (LAMNs) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have a favorable prognosis. However, a subgroup of patients presents a clinically aggressive course with disease progression despite receiving treatment. The purpose of this study is to report the experience of clinically aggressive LAMN patients treated by the same team, and to present a review of the literature. The cases of four patients with clinically aggressive LAMNs were reviewed. Clinical and histopathological characteristics were re-examined. Recurrences and the time of recurrence, as well as the survival time, were recorded. These patients were four men with clinically aggressive LAMNs treated with CRS plus HIPEC. One of them underwent CC-0 surgery, two underwent CC-1 surgery, and one underwent CC-3 surgery. All patients received systemic chemotherapy after surgery. Recurrence was recorded in three of the patients within 4-23 months after the initial treatment. Two of the patients underwent secondary CRS. Three patients died of disease recurrence within 13-23 months, and one is alive with a disease relapse at 49 months after his initial surgery. LAMNs were identified in both the initial specimens and the specimens obtained during reoperation. The prognosis of LAMN patients treated with CRS plus HIPEC is favorable. A small number of patients present a clinically aggressive course that is unresponsive to any treatment. Molecular and genetic studies are required to identify this group of LAMN patients who have an unfavorable prognosis.


Subject(s)
Appendiceal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Humans , Male , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/surgery , Combined Modality Therapy , Hyperthermia, Induced/adverse effects , Neoplasm Recurrence, Local/pathology , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/surgery , Pseudomyxoma Peritonei/etiology
17.
In Vivo ; 37(6): 2768-2775, 2023.
Article in English | MEDLINE | ID: mdl-37905618

ABSTRACT

BACKGROUND/AIM: We aimed to compare the clinicopathological outcomes in patients with locally advanced rectal cancer after short- or long-course concurrent chemoradiotherapy (CCRT) followed by delayed surgery. PATIENTS AND METHODS: The records of 94 patients with cT3-4N0-2M0 rectal cancer who received CCRT between 2010 and 2017 were reviewed. Short-course radiotherapy (RT) was delivered with a median total dose of 25 Gy in five fractions (n=27), and long-course RT was delivered with a median total dose of 50.4 Gy in 28 fractions (n=67). The following concurrent chemotherapy regimens were administered: 5-fluorouracil plus leucovorin in 58 and capecitabine in 24; in 12 cases agents were unknown. The median interval between CCRT and surgery was 8 weeks. Adjuvant chemotherapy was administered after surgery in 80 patients (5-fluorouracil plus leucovorin, n=54; capecitabine, n=9; other, n=14; and unknown, n=3). Propensity-score matching analysis was conducted. RESULTS: The median follow-up duration was 4.3 years. There were no statistically significant differences between the short- and long-course RT groups in sphincter preservation (85.2% vs. 92.5%, p=0.478), pathological complete remission (18.5% vs. 14.9%, p=0.905), downstaging (44.4% vs. 26.9%, p=0.159), and negative circumferential resection margin (92.6% vs. 89.6%, p=0.947) rates. No differences were found in survival outcomes between the short- and long-course groups at 3 years (overall survival: 91.8% vs. 88.1%, p=0.790; disease-free survival, 75.2% vs. 72.5%, p=0.420; locoregional relapse-free survival, 90.5% vs. 98.4%, p=0.180; and distant metastasis-free survival, 79.6% vs. 73.5%, p=0.490). Similar results were observed after PSM. CONCLUSION: Clinically, short-course CCRT may be a feasible alternative to long-course CCRT in patients with locally advanced rectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Rectal Neoplasms , Humans , Capecitabine , Leucovorin , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoadjuvant Therapy/methods , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Chemoradiotherapy/methods , Rectal Neoplasms/pathology , Fluorouracil
18.
Bratisl Lek Listy ; 124(11): 827-832, 2023.
Article in English | MEDLINE | ID: mdl-37874805

ABSTRACT

OBJECTIVES: The aim of our study is to determine whether mapping the lymphatic drainage and diagnostic excision of lymph nodes from lateral neck compartment is able to detect ultrasound unknown metastases in this compartment early and thus favorably affect the prognosis of patients with papillary thyroid cancer (PTC). BACKGROUND: Lymph node involvement in the lateral neck compartment is seen in 30-60 % of patients with PTC at the time of diagnosis and affects the prognosis of patients in terms of disease recurrence. METHODS: From June 2012 to December 2016, 154 patients with no evidence of lateral nodal involvement on imaging studies were treated with total thyroidectomy and central comparment neck dissection. A volume of 0.2 ml of Patent Blue dye was applied in the upper half of the thyroid gland with subsequent exposure of lymphatic drainage in the lateral compartment and 2-3 sentinel lymph nodes (SLN) were removed for frozen section (Group 1). In case of metastatic involvement, a lateral comparment neck dissection was performed. The reference groups were composed of a set of patients without detected lymphatic drainage (Group 2) and a set of patients who underwent lateral compartment neck dissection for preoperatively detected metastases in the lymph nodes (Group 3). The biochemical, structural and overall persistence of the disease at the time of administration of adjuvant radioiodine ablation was evaluated. RESULTS: The SLN identification rate was 95.45 %. In Group 1, a total of 32 patients had a positive SLN. Out of these, 24 patients had positive SLNs based on the analysis of frozen section, while in 8 patients, the positive diagnosis was confirmed through definitive histology. The comparison of data from the entire follow-up period in all three groups of patients revealed statistically significant differences in persistence of disease, namely in favor of Group 1. The percentage of reoperations for persistence and recurrence of disease was significantly lowest in Group 1 (2.04 %) compared to Groups 2 and 3 (6.94 % and 45.45 % respectively). CONCLUSION: The method is safe and sensitive for detecting unknown lymph node metastases in the lateral neck compartment, and may facilitate a decision to perform accurate surgical treatment of patients with PTC (Tab. 4, Fig. 2, Ref. 38).


Subject(s)
Carcinoma, Papillary , Sentinel Lymph Node , Thyroid Neoplasms , Humans , Thyroid Neoplasms/surgery , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Iodine Radioisotopes , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Sentinel Lymph Node Biopsy/methods , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymph Nodes/pathology , Thyroidectomy/methods , Neck Dissection/methods
19.
Nagoya J Med Sci ; 85(3): 639-647, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37829486

ABSTRACT

We evaluated the efficacy and safety of an endoscope-embedded transvaginal laser hyperthermia system for superficial cervical cancer that remained in the cervix after radiotherapy. We developed an innovative endoscope-embedded hyperthermia system consisting of a diode laser device, a temperature control unit, an endoscope control unit, and a transvaginal probe. Superficial lesions of recurrent or residual cervical cancer on the uterine cervix or vaginal wall after radiotherapy were eligible for this study. A total of four cases of three patients were eligible for this treatment. Case 1: The post-chemoradiotherapy residual tumor of a patient with stage IIB squamous cell carcinoma of the cervix was treated with the device. Two months after the laser hyperthermia treatment, the tumor's disappearance was confirmed. Case 2: A post-hysterectomy persistent tumor on the vaginal stump of a patient with stage IIB adenocarcinoma of the cervix was subjected to the laser hyperthermia treatment. Two months after the treatment, the stump's cytology was false positive. Case 3: As in case 2, this patient's recurrence in the anterior vaginal wall was subjected to laser hyperthermia treatment, but the tumor's growth was not controlled. Case 4: A tumor at the vaginal margin was identified during a salvage hysterectomy in a patient with stage IIB squamous cell carcinoma of the cervix who underwent chemoradiotherapy. After laser hyperthermia treatment, the tumor's disappearance was confirmed. Our new endoscope-embedded laser hyperthermia system can be a candidate for treating residual superficial cervical cancer after radiotherapy by accurately capturing superficial lesions.


Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Hyperthermia, Induced , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/pathology , Adenocarcinoma/pathology , Hysterectomy , Endoscopy, Gastrointestinal , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Retrospective Studies
20.
Sci Rep ; 13(1): 16362, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37773315

ABSTRACT

Current treatment for glioblastoma includes tumor resection followed by radiation, chemotherapy, and periodic post-operative examinations. Despite combination therapies, patients face a poor prognosis and eventual recurrence, which often occurs at the resection site. With standard MRI imaging surveillance, histologic changes may be overlooked or misinterpreted, leading to erroneous conclusions about the course of adjuvant therapy and subsequent interventions. To address these challenges, we propose an implantable system for accurate continuous recurrence monitoring that employs optical sensing of fluorescently labeled cancer cells and is implanted in the resection cavity during the final stage of tumor resection. We demonstrate the feasibility of the sensing principle using miniaturized system components, optical tissue phantoms, and porcine brain tissue in a series of experimental trials. Subsequently, the system electronics are extended to include circuitry for wireless energy transfer and power management and verified through electromagnetic field, circuit simulations and test of an evaluation board. Finally, a holistic conceptual system design is presented and visualized. This novel approach to monitor glioblastoma patients is intended to early detect recurrent cancerous tissue and enable personalization and optimization of therapy thus potentially improving overall prognosis.


Subject(s)
Glioblastoma , Humans , Animals , Swine , Glioblastoma/diagnostic imaging , Glioblastoma/therapy , Glioblastoma/pathology , Neoplasm Recurrence, Local/pathology , Prostheses and Implants , Prognosis , Combined Modality Therapy
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