Resected Tumor Research Articles

Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.

Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower-grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery. We established a prospective, multi-institutional cohort of men with Grade Group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes and polygenic risk. Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis. In a cohort of low-grade prostate cancer patients, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance. Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.

Rhabdomyosarcoma of the skull with EWSR1 fusion and ALK and cytokeratin expression: a case report.

Rhabdomyosarcoma (RMS) comprises of heterogeneous group of neoplasms that occasionally express epithelial markers on immunohistochemistry (IHC). We herein report the case of a patient who developed RMS of the skull with EWSR1 fusion and anaplastic lymphoma kinase (ALK) and cytokeratin expression as cytomorphologic features. A 40-year-old man presented with a mass in his forehead. Surgical resection was performed, during which intraoperative frozen specimens were obtained. Squash cytology showed scattered or clustered spindle and epithelioid cells. IHC revealed that the resected tumor cells were positive for desmin, MyoD1, cytokeratin AE1/ AE3, and ALK. Although EWSR1 rearrangement was identified on fluorescence in situ hybridization, ALK, and TFCP2 rearrangement were not noted. Despite providing adjuvant chemoradiation therapy, the patient died of tumor progression 10 months after diagnosis. We emphasize that a subset of RMS can express cytokeratin and show characteristic histomorphology, implying the need for specific molecular examination.

Effect of Da Vinci robotic transanal minimally invasive surgery for rectal neoplasms

Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.

ThP5.8 - Familial hepatocellular carcinoma: a model for studying preventive and therapeutic measures

Abstract Aims Limited attention has been given to the role of primary genetic factors in hepatocellular carcinoma (HCC) especially as familial clusters of HCC are mostly described in areas of endemic hepatitis B virus (HBV) infection. The aim of the study was to review the literature on familial hepatocellular carcinoma (FHCC) and give evidence to suggest that FHCC may be a good model for studying preventive and therapeutic measures for HCC Methods Electronic searches of the Medline (PubMed) data base were performed to identify original published case studies on familial HCC. Results 16 case studies on FHCC were reported between 1965-2016. Even in the presence of HBV infection, FHCC seemed statistically unlikely to occur by chance. Genetic contributions may explain healthy and unhealthy HBsAg carriers, the male sex being predominantly affected, and HBV being directly oncogenic and causing HCC in the absence of cirrhosis in the younger patients. The highest risk of HCC occurs when a hereditary component is acting in concert with environmental factors such as HBV infection through epigenomic alterations. A family history of HCC increases the risk of FHCC independently of hepatitis due to a multifactorial inheritance including DICER 1 germline mutation and altered liver zonation. Epigenetic studies on monozygotic twins with HCC will identify the susceptible loci which can be used therapeuticallym. FHCC is a prognostic factor for improved survival in early resectable tumours with no/minimal cirrhosis. Conclusions HCC lacks a strong hereditary component but HCC-prone families of the familial type may provide a powerful model for studying preventive and therapeutic measures.

Investigation of High Frequency Irreversible Electroporation for Canine Spontaneous Primary Lung Tumor Ablation.

In this study, the feasibility of treating canine primary lung tumors with high-frequency irreversible electroporation (H-FIRE) was investigated as a novel lung cancer treatment option. H-FIRE is a minimally invasive tissue ablation modality that delivers bipolar pulsed electric fields to targeted cells, generating nanopores in cell membranes and rendering targeted cells nonviable. In the current study, canine patients (n = 5) with primary lung tumors underwent H-FIRE treatment with an applied voltage of 2250 V using a 2-5-2 µs H-FIRE waveform to achieve partial tumor ablation prior to the surgical resection of the primary tumor. Surgically resected tumor samples were evaluated histologically for tumor ablation, and with immunohistochemical (IHC) staining to identify cell death (activated caspase-3) and macrophages (IBA-1, CD206, and iNOS). Changes in immunity and inflammatory gene signatures were also evaluated in tumor samples. H-FIRE ablation was evident by the microscopic observation of discrete foci of acute hemorrhage and necrosis, and in a subset of tumors (n = 2), we observed a greater intensity of cleaved caspase-3 staining in tumor cells within treated tumor regions compared to adjacent untreated tumor tissue. At the study evaluation timepoint of 2 h post H-FIRE, we observed differential gene expression changes in the genes IDO1, IL6, TNF, CD209, and FOXP3 in treated tumor regions relative to paired untreated tumor regions. Additionally, we preliminarily evaluated the technical feasibility of delivering H-FIRE percutaneously under CT guidance to canine lung tumor patients (n = 2). Overall, H-FIRE treatment was well tolerated with no adverse clinical events, and our results suggest H-FIRE potentially altered the tumor immune microenvironment.

Management of patients with adrenal myelolipoma: experience from a tertiary referral centre.

Adrenal myelolipomas are rare, benign, tumours of the adrenal cortex. This study reports the experience of a tertiary adrenal surgery referral centre's approach to the management of patients with adrenal myelolipoma. A retrospective observational cohort study was conducted on all adult patients (> 18years age) diagnosed with adrenal myelolipoma from January 1, 2014, to December 30, 2022. Demographics, imaging characteristics, histological diagnosis (where applicable) and follow-up data were compared between patients undergoing surgery and those referred to surveillance. Indications for operative intervention were recorded at the time of multidisciplinary team discussion, consisting of surgeons, endocrinology physicians, radiologists, pathologists and specialist nursing representatives. Of the 522 patients with an adrenal lesion discussed in adrenal tumour meeting between 2014 and 2022, n = 15 (2.8%) were diagnosed with adrenal myelolipoma. Of the 15 patients, 4 underwent adrenalectomy at first presentation (27%), while 1 patient underwent adrenalectomy after interval follow-up. Indications for operative intervention were as follows: 'indeterminate lesion' (n = 3), 'abdominal pain and size (> 4cm)' (n = 1) and 'mass effect on adjacent organs' (n = 1). The mean rate of lesion growth in patients referred for surveillance (n = 10) was 0.13cm/year. Histology confirmed adrenal myelolipoma as the diagnosis in all resected tumours. For patients with adrenal myelolipoma, the presence of symptoms and/or indeterminate features on imaging may be more clinically useful indications for operative intervention over size alone. The surveillance of adrenal myelolipomas, even in patients with adrenal lesions > 4cm, is a safe clinical strategy, provided the imaging characteristics are benign and patients remain asymptomatic.

Lung Microbial and Host Genomic Signatures as Predictors of Prognosis in Early-Stage Adenocarcinoma.

Risk of early-stage lung adenocarcinoma recurrence after surgical resection is significant, and the postrecurrence median survival is approximately 2 years. Currently, there are no commercially available biomarkers that predict recurrence. In this study, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. In 91 patients with early-stage (stage IA/IB) lung adenocarcinoma with extensive follow-up, we used 16s rRNA gene sequencing and host RNA sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. Of 91 subjects, 23 had tumor recurrence over 5-year period. In tumor samples, lung adenocarcinoma recurrence was associated with enrichment in Dialister and Prevotella, whereas in unaffected lung samples, recurrence was associated with enrichment in Sphingomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with lung adenocarcinoma recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment in Stenotrophomonas geniculata and Chryseobacterium was positively correlated with upregulation of IL2, IL3, IL17, EGFR, and HIF1 signaling pathways among the host transcriptome. In tumor samples, enrichment in Veillonellaceae (Dialister), Ruminococcaceae, Haemophilus influenzae, and Neisseria was positively correlated with upregulation of IL1, IL6, IL17, IFN, and tryptophan metabolism pathways. Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC = 0.83). This study suggests that lung adenocarcinoma recurrence is associated with distinct pathophysiologic mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

Simultaneous Detection of Collagen I Alpha II and Cytokeratin 19 mRNA by Multiplex qPCR in Liquid Biopsy in Diagnosis of Patients with Resectable Solid Tumors.

The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden's J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

Oncocytic Lipoadenoma of the Parotid Gland against a Background of Multifocal Oncocytic Hyperplasia: Report of a Rare Case

ABSTRACT Oncocytic lipoadenoma is an extremely rare benign salivary gland tumor with only few cases reported in the literature. We herein report a case of oncocytic lipoadenoma originating in the parotid gland of a 65-year-old man. The tumor presented as a slowly growing asymptomatic right-sided parotid gland mass. On MRI, right parotid showed a 40 × 32 × 20 mm well-encapsulated, neoplastic mass in the superficial lobe. On core biopsy, differentials considered were nodular oncocytosis and oncocytoma. Subsequently, superficial parotidectomy was performed. The resected tumor was encapsulated, yellowish brown, and homogenous. Microscopically, it was composed of oncocytoma-like epithelial component admixed with mature adipocytes, each contributing to 50% of the mass. Adjacent salivary gland showed multiple foci of oncocytosis. Differential diagnosis includes lipomatous tumors as well as neoplastic and non-neoplastic oncocytic lesions of the salivary gland. The present case of oncocytic lipoadenoma against a background of multifocal oncocytic hyperplasia has been reported for its rarity.

351. CONVERSION SURGERY FOR PATIENTS WITH ESOPHAGEAL CANCER AFTER ICI TREATMENT

Abstract Background As more and more immuno checkpoint inhibitor (ICI) agents are used in clinical practice for the treatment of esophageal cancer these days, we are becoming more likely to see a patient with initially unresectable but currently resectable tumor through the treatment with ICIs. Little is known about such conversion surgery for esophageal cancer. So, we here report our experiences. Subjects and Methods The patients who underwent esophageal cancer surgery after the treatment with ICI from 2020 to 2023 who had initially been diagnosed as unresectable were enrolled. Electronic medical records were retrospectively reviewed to collect clinicopathological findings. Result There were 15 eligible cases; 12 male and 3 female, median age 70 (51-81). Histology was SCC in all cases; 7 primary, 7 recurrent and 1 residual tumors. Involved distant metastatic organ was lymph node in 4 cases, liver in 4 cases, and lung in 1 case. Involved recurrent organ was lymph node in all the 7 recurrent cases. Clinical response to ICI treatment was detected in 12 cases (PD in 3 cases). R0 resection was achieved in 14 cases and pCR was detected in 3 cases. No irAE-suspected event was detected in all cases during postoperative course. Conclusion Since the patients' background, number and duration of the ICI treatment, treatment history before the conversion surgery were miscellaneous, it is still hard to lead conclusive statement on the conversion surgery for esophageal cancer after ICI treatment. So, it is necessary to keep going to experience conversion surgery cases for esophageal cancer to assess its efficacy.

Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: a case report and a review of the literature.

Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.

Non-cutaneous soft tissue tumors and pseudotumors in the foot and ankle reported in Brazilian services

Objectives: Review the histological types of non-cutaneous soft tissue tumors and pseudotumors that affect the foot and ankle,reported in Brazilian health services.Methods: An integrative review of the literature from the Scielo and PubMed platforms, based on the descriptors “Soft Tissue Tumors,”“Pseudotumors,” “Foot, “Ankle,” and “Brazil.” Those who answered the following research question: “What are the non-cutaneous softtissue tumors and pseudotumors in the foot and ankle reported in Brazilian health services?” were included. The combination of eachauthor’s analysis contributed to reducing possible biases.Results: Six articles were selected, yielding 23 reports of tumors and pseudotumors, which were subsequently categorized intomalignant and benign tumors. There were five benign findings: three benign tumors, two giant cell tumors, one fibromatosis, andtwo pseudotumors classified as synovial chondromatosis. Eighteen malignant findings were reported: seven unspecified soft tissuesarcomas, four synovial sarcomas, three myxofibrosarcomas, one fibrosarcoma, one liposarcoma, one undifferentiated pleomorphicsarcoma and one papillary intralymphatic angioendothelioma.Conclusion: In the last ten years, more reports of malignant than benign tumors have been reported. However, this finding does notnecessarily reflect the Brazilian epidemiological reality, as it may represent a view in which resected benign tumors and pseudotumorsare often not sent for anatomopathological study or reported in the literature. Level of evidence I; Prognostic studies - investigating the effect of a patient characteristic on the outcome of disease

Anesthesia for an infant with congenital mediastinal mass: a case report

BackgroundGiant anterior mediastinal masses in infants are one of the most challenging cases faced in pediatric anesthesia practice. They can pose unique challenges for resection such as cardiovascular collapse on induction of anesthesia and injury to surrounding structures that maybe compressed or displaced. Principles that must be followed and kept in mind during removal of giant mediastinal mass include appropriate diagnostic imaging to define mass extent, airway control during induction, a multidisciplinary team approach including cardiothoracic for sternotomy, cannulation to institute cardiopulmonary bypass, otolaryngology for rigid bronchoscopy, preservation of neurovascular structure, and complete resection whenever possible. Our patient had a mass that weighed twice his whole body weight.Case presentationHere we present a 3-month-old Middle Eastern infant weighing 3.2 kg with a large congenital teratoma who presented to the emergency room with cyanosis and respiratory distress. During his hospital course, he underwent three procedures, two of them under light-to-moderate sedation: a diagnostic computer tomography scan followed by mass content drainage by interventional radiology (Figs. 1, 2). On the third day, he had a thoracotomy with complete tumor resection under general anesthesia with the help of an epidural for pain control (Fig. 3). The resected tumor weighed 2.5 kg, which was equal to twice the patient’s total body weight (Fig. 4). After the surgery, he was extubated in the operating room and discharged home 3 days later.Fig. 1Anterior–posterior chest x-ray showing the anterior mediastinal mass (AMM)Fig. 2Cross-section computed tomography (CT) showing large anterior mediastinal mass (AMM)Fig. 3Gross anatomy of the tumor before resectionFig. 4Gross anatomy of the removed tumorConclusionAnterior mediastinal mass patients can be challenging for the anesthesiologist. They need meticulous thorough perioperative assessment to determine the extent of compression on major intramediastinal structures and to predict the complications. Planning by multidisciplinary team and discussion with the family is important. These types of cases should be preferably operated on by an experienced team in a well-equipped operation room in tertiary care institutes.

Peri-Tumoural Lipid Composition and Hypoxia for Early Immune Response to Neoadjuvant Chemotherapy in Breast Cancer.

The deregulation of monounsaturated, polyunsaturated, and saturated fatty acids (MUFAs, PUFAs, SFAs) from de novo synthesis and hypoxia are central metabolic features of breast tumour. Early response markers for neoadjuvant chemotherapy (NACT) are critical for stratified treatment for patients with breast cancer, and restoration of lipid metabolism and normoxia might precede observable structural change. In this study, we hypothesised that peri-tumoural lipid composition and hypoxia might be predictive and early response markers in patients with breast cancer undergoing NACT. Female patients with breast cancer were scanned on a 3T clinical MRI scanner at baseline and Cycle1, with acquisition of lipid composition maps of MUFAs, PUFAs, and SFAs, and hypoxia maps of effective transverse relaxation rate R2*. The percentage change in lipid composition and hypoxia at Cycle1 was calculated with reference to baseline. Tumour-associated macrophages were analysed based on immunostaining of CD163 from biopsy and resection, with the percentage change in the resected tumour calculated across the entire NACT. We found no significant difference in lipid composition and R2* between good and poor responders at baseline and Cycle1; however, the correlation between the percentage change in MUFAs and PUFAs against CD163 suggested the modulation in lipids with altered immune response might support the development of targeted therapies.

Distinguishing follicular-type thyroid carcinomas from their benign counterparts, a study of 104 consecutively resected and needle-biopsied tumors

Distinguishing follicular-type thyroid carcinomas from their benign counterparts, a study of 104 consecutively resected and needle-biopsied tumors

Mixed hepatocellular carcinoma and high-grade neuroendocrine neoplasm with ambiguous histopathological features: a case report.

Well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC) are distinct entities with different biological behavior. However, difficult cases showing equivocal morphology have been reported in some organs. Herein, we report a case of primary hepatic neuroendocrine neoplasm (NEN) with ambiguous histopathological features admixed with conventional hepatocellular carcinoma (HCC). A 70-year-old man with untreated chronic hepatitis B underwent left medial sectionectomy because of two incidental liver masses. On pathological examination, one of the resected tumors had intermingling NEN and HCC components. The NEN component consisted of relatively uniform tumor cells proliferating in trabecular, cord-like, or solid patterns with peripheral nuclear palisading. The tumor cells were immunopositive for synaptophysin, chromogranin A, cluster of differentiation 56 (CD56), and focally hepatocyte paraffin 1. p53 showed wild-type expression. The Ki-67 labeling index was 27% at the hot spot. Eleven months after the surgery, he died of a cerebral hemorrhage without evidence of recurrent liver cancer. The intermediate degree of differentiation and the modest proliferative activity can challenge the distinction between NEC and NET G3. While the coexisting HCC indicates NEC rather than NET in a pathogenetic viewpoint, such ambiguous tumor may not be as aggressive as typical NECs.

Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.

Advancing Pancreatic Cancer Surgical Treatments and Proposal of New Approaches.

Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems-the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition-assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center's neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy's Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes.

Are there features that can predict the unresectability of pleural mesothelioma?

The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM. Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling. Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879). Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM. A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments. About half of pleural mesothelioma patients are reported to receive an incorrect disease stagepreoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.