Serplulimab combined with gemcitabine, nab-paclitaxel and stereotactic body radiotherapy as the first-line treatment for patients with metastatic pancreatic adenocarcinoma in China: a multicentre, single-arm, phase II trial (ICSBR) protocol.

INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.

Complete response to chemotherapy in a 6-year survivor of metastatic pancreatic cancer.

A woman in her 40s underwent evaluation for abdominal pain, jaundice and acholic stools and was diagnosed with metastatic pancreatic head adenocarcinoma. She was enrolled in a clinical trial investigating the benefits of ibrutinib with nab-paclitaxel and gemcitabine, and subsequently received modified FOLFIRINOX. Over the course of 6 years on chemotherapy, she experienced complete regression of the pancreatic and liver lesions, as well as normalisation of her tumour markers. She has been off chemotherapy for 6 months with no evidence of disease and normal tumour markers. Despite advances in chemotherapy and surgical options, metastatic pancreatic adenocarcinoma continues to carry a grim prognosis. This case report demonstrates a rare case of a long-term survivor of unresectable metastatic pancreatic adenocarcinoma treated with chemotherapy alone.

[Retroperitoneal schwannoma mimicking colorectal cancer metastases: a false positive result report.] / Schwannoma retroperitoneal simulando metástasis de cáncer colorrectal: reporte de un resultado falso positivo.

Introduction: schwannomas are benign and common soft tissue tumors. They are usually asymptomatic and are discovered for other reasons. Materials: we present the case of an 82-year-old male patient with a recent diagnosis of moderately differentiated adenocarcinoma of the colon and a hypermetabolic periaortic nodule as an incidental finding. Results: percutaneous biopsy of the periaortic nodule confirmed the diagnosis of schwannoma. At one year of follow-up, growth of the schwannoma has been demonstrated. There are no signs of progression of his oncological disease. Conclusions: schwannomas are benign tumors, rarely found in the retroperitoneum and can be sources of false-positive positron emission tomography results.

Introducción: los schwannomas son tumores benignos y frecuentes de las partes blandas. Habitualmente son asintomáticos y son descubiertos por otros motivos. Materiales y métodos: presentamos el caso de un paciente masculino de 82 años con diagnóstico reciente de adenocarcinoma de colon moderadamente diferenciado y con un nódulo periaórtico hipermetabólico como hallazgo incidental. Resultados: la biopsia percutánea del nódulo periaórtico confirmó el diagnóstico de schwannoma. Al año de seguimiento, se ha demostrado crecimiento del schwannoma. No hay signos de progresión de su enfermedad oncológica. Conclusión: los schwannomas son tumores benignos, infrecuentes en el retroperitoneo y pueden ser fuentes de resultados falsos positivos en tomografía por emisión de positrones.

Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.

BACKGROUND/AIM: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. PATIENTS AND METHODS: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. RESULTS: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. CONCLUSION: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.

Metastatic Gastric Adenocarcinoma in the Inguinal Hernia Sac Diagnosed Radiologically: A Case Report.

Macroscopic tumor implants in the hernia sac are a very rare condition. They occur as a result of the implantation of malignant cells in the malignant ascites from the inguinal canal to the hernia sac. In this case report, we share the clinical and radiological findings of the macroscopic tumoral implants in the hernia sac at the level of the inguinal canal and scrotum in a male patient aged 65 years with a history of total gastrectomy for gastric adenocarcinoma and developing malignant ascites six months after the surgery.

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Ascending colon cancer metastasized to the right testicle: a case report.

BACKGROUND: Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient's case of testicular metastasis from colon cancer. CASE PRESENTATION: We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography-computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma. CONCLUSION: Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.

Urachal mixed adenocarcinoma and small cell neuroendocrine carcinoma with widespread metastasis and resistance to chemotherapy: a case report.

Neuroendocrine carcinoma arising from the urachus is extremely rare. We describe a case of a 33-year-old gentleman who presented with hematuria and diagnosed to have a composite adenocarcinoma and small cell neuroendocrine carcinoma arising from the urachus. The patient also had widespread metastasis at the time of presentation, therefore, he was referred for chemotherapy. However, the disease showed progression despite treatment. Recognition of neuroendocrine carcinoma component in urachal tumors, although rare, is very essential as this histologic type carries poor prognosis with aggressive clinical outcome.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Unusual Unique Renal Metastasis of Rectal Carcinoma.

Rectal cancer Is a Common malignant pathology; its usual spread in volves the liver and lungs. The occurrence of renal metastases is exceptional. CT scanning aims to evaluate extension and may incidentally reveal a renal mass, which can be better characterized through MRI and ultrasound. We describe a case of a solitary renal metastasis from rectal cancer and underscore the significant role of imaging in positively diagnosing this uncommon pathology.

Surgical and multimodal treatment of metastatic oesophageal cancer: retrospective cohort study.

BACKGROUND: In contrast to the well-established multimodal therapy for localized oesophageal cancer, the metastatic stage is commonly treated only with systemic therapy as current international guidelines recommend. However, evidence suggesting that multimodal therapy including surgery could benefit selected patients with metastasized oesophageal cancer is increasing. The aim of this study was to investigate the survival of patients diagnosed with metastatic oesophageal cancer after different treatment regimens. METHODS: This was a retrospective single-centre study of patients with adenocarcinoma or squamous cell carcinoma of the oesophagus with synchronous or metachronous metastases who underwent Ivor Lewis oesophagectomy between 2010 and 2021. Each patient received an individual treatment for their metastatic burden based on an interdisciplinary tumour board conference. Survival differences between different treatments were assessed using the Kaplan-Meier method, as well as univariable and multivariable Cox regression models. RESULTS: Out of 1791 patients undergoing Ivor Lewis oesophagectomy, 235 patients diagnosed with metastases were included. Of all of the included patients, 42 (17.9%) only underwent surgical resection of their metastatic disease, 37 (15.7%) underwent multimodal therapy including surgery, 78 (33.2%) received chemotherapy alone, 49 (20.9%) received other therapies, and 29 (12.3%) received best supportive care. Patients who underwent resection or multimodal therapy including surgery of their metastatic burden showed superior overall survival compared with chemotherapy alone (median overall survival of 19.0, 18.0, and 11.0 months respectively) (P < 0.001). This was confirmed in subcohorts of patients with metachronous solid-organ metastases and with a single metastasis. In multivariable analyses, resection with or without multimodal therapy was an independent factor for favourable survival. CONCLUSION: Surgical resection could be a feasible treatment option for metastasized oesophageal cancer, improving survival in selected patients. Further prospective randomized studies are needed to confirm these findings and define reliable selection criteria.

Late port-site metastasis of unexpected gallbladder carcinoma after laparoscopic cholecystectomy: A case report.

INTRODUCTION: Incidental gallbladder carcinoma refers to a discovery of gallbladder cancer during or after cholecystectomy. Late port-site metastasis (PSM) following Laparoscopic cholecystectomy (LC) is rare with an incidence rate of 10.3%. PATIENT CONCERNS: We report a case of a 58-year-old man who presented with a painful abdominal wall mass for 6 weeks. He had a history of LC for symptomatic cholelithiasis, 8 years prior. DIAGNOSIS: Histopathological examination revealed a positive result for metastatic adenocarcinoma from the abdominal wall mass. Moreover, Positron emission tomography (PET) showed a small focus of intense fluorodeoxyglucose (FDG) uptake in the gallbladder bed, which was highly suspicious for malignancy. INTERVENTION: Decision was to proceed with surgery owing to uptake in the gallbladder bed with single-site metastasis to the previous port site. In addition, in the board meeting, an agreement was reached for performing distal pancreatectomy with splenectomy owing to uncertainty of malignancy based on what was discovered during the full metastatic workup. Diagnostic laparoscopy followed by midline laparotomy performed. Radical completion cholecystectomy with lymphadenectomy was done. Followed by complete resection of the anterior abdominal wall. Distal pancreatectomy and splenectomy were then performed. OUTCOME: Pathological diagnosis showed metastatic/invasive, moderately differentiated adenocarcinoma with positive margins on the posterior surface of excised port-site mass. The positive margins necessitated further chemoradiotherapy, followed by adjuvant chemotherapy until lung metastasis was identified. After this, the patient was scheduled for palliative chemotherapy. CONCLUSION: Presence of PSM is often associated with peritoneal metastasis. For this reason, it is advised to evaluate the patient for possible metastasis.

Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.

Surgical Management of Brain Metastasis from Esophageal Cancer: A Systematic Review and Single-Center Experience.

BACKGROUND: Brain metastases from esophageal cancer (BMEC) are rare and aggressive, with limited literature on optimal treatment modalities and a standard of care yet to be established. The objective of this study was to systematically review existing literature and perform a retrospective analysis of our institution's patients to evaluate the influence of different treatment modalities on patient outcomes. METHODS: A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and a retrospective review of our institutional experience with BMEC were both conducted. Data based on mean survival,histology, metastasis location, and treatment modality were abstracted. RESULTS: A total of 48 studies representing 136 patients with BMEC were identified, in addition to the 11 patients treated at our institution. There were a total of 100 males (12 unreported), with a median age of 62.2 at diagnosis in our systematic review, along with 8 males with a median age of 62 in our institutional review. Collectively, survival rates observed based on histology were not similar (squamous cell carcinoma: 9.2 months, adenocarcinoma: 13.4 months), however, based on treatment modalities (surgery: 11.6 months, radiation: 10.4 months, chemotherapy: 12.3 months), and metastasis location (supratentorial: 10.5 months, infratentorial: 9.9 months), the survival times were comparable. CONCLUSIONS: Our review suggests that causes of death were often independent of brain metastases highlighting the need for further studies on early detection and prevention of primary esophageal cancer, as well as improved treatment modalities for BMECs.

Bilateral Adrenal Metastasis of Prostatic Adenocarcinoma on 68 Ga-PSMA PET/CT Imaging.

ABSTRACT: An 84-year-old man with prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT due to PSA recurrence. Foci of 68 Ga-PSMA uptake were observed in bilateral adrenal glands. Adrenal MRI showed metastasis only in the left adrenal gland. Metastatic 68 Ga-PSMA uptake was also observed in the mediastinum and bone. Enzalutamide treatment was started. Follow-up 68 Ga-PSMA PET/CT scan showed regression in both adrenal gland metastases and other metastases.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Hepatoid Adenocarcinoma of the Esophagus with Thyroid Metastasis: A Case Report.

Rare hepatoid adenocarcinomas are highly heterogeneous. In this case, hepatoid adenocarcinoma occurred in both the esophagus and thyroid, and the combination of chemotherapy and immunotherapy may be a promising therapeutic tool for rare tumors. Laryngoscope, 134:3673-3676, 2024.