Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma: New hopes on the horizon.

In this editorial, we comment on the article by Wang et al. This manuscript explores the potential synergistic effects of combining zanubrutinib, a novel oral inhibitor of Bruton's tyrosine kinase, with high-dose methotrexate (HD-MTX) as a therapeutic intervention for primary central nervous system lymphoma (PCNSL). The study involves a retrospective analysis of 19 PCNSL patients, highlighting clinicopathological characteristics, treatment outcomes, and genomic biomarkers. The results indicate the combination's good tolerance and strong antitumor activity, with an 84.2% overall response rate. The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL, particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B. Furthermore, the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring. In essence, the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL. The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes. While the findings suggest promise, the study's limitations should be considered, and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Ultrastructural differences between synovial sarcoma and solitary fibrous tumor: comparative study in adult patients from the National Cancer Institute of Mexico.

Synovial sarcoma (SS) and solitary fibrous tumor (SFT) are entities with considerable morphological and immunohistochemical similarities that sometimes show a non-confirmatory profile (TLE1 negative, CD34 and focal or negative STAT6 and lack of specific fusion IHC markers), in which the utility ultrastructure is unknown. A cross-sectional, retrospective, analytical, nonexperimental study was carried out by the Department of Pathology of the National Cancer Institute of Mexico (INCan) e from January 1, 2009 to December 31, 2018. With 17 SFT cases with diffuse or focal CD34 and STAT6 positivity and 18 cases of SS with positive FISH molecular test t(X:18) breakapart were studied by electron microscopy of fresh glutaraldehyde fixed or paraffin-embedded tissue. The ultrastructural findings with a significant difference present in the SS were tandem tight junctions, desmosomes and abundance of dilated rough endoplasmic reticulum (RER) cisternae (p < 0.001, 0.003, and 0.001, respectively); while in the (SFT) the presence of abundant glycogen, basal lamina, long and slender cytoplasmic processes, pinocytic vesicles, hemidesmosomes, and/or dense plaques, collagen skein, and microvilli-like buds (p = 0.028, 0.005, and <0.001 for the last five). We then infer that the five distinctive markers of the SFT are the collagen skeins intermingled with cellular processes in a shape of "squid can," and the pinocytic vesicles as they were not observed in any case of SS. Conversely, tandem junctions were not found in any SFT case. Although the presence of multivesicular buds in the SFT was not significant, it had not been previously described.

Synovial sarcoma with ossification and calcification with SS18 immunochemical expression and rearrangement by fluorescent in situ hybridization / Sarcoma sinovial con osificación y calcificación, con expresión de SS18 por inmunohistoquímica y reordenamiento de SS18 por hibridación in situ fluroescente

Synovial sarcoma is a soft tissue tumor of uncertain origin. Generally, it is a monophasic spindle cell neoplasm that can have glandular-like structures. Ossification and presence of calcification is a rare phenomenon with only a few reported cases. We present the case of a young male with a synovial sarcoma of the right foot. Histology revealed prominent deposits of tumoral osteoid and coarse calcifications. The diagnosis was confirmed by the expression of SS18 by immunohistochemistry and the demonstration of the rearrangement of the SS18 gene by fluorescent in situ hybridization. We reviewed the literature for synovial sarcoma with prominent ossification or calcification, and to the best of our knowledge, this is the first case with expression of SS18 by immunohistochemistry. The main differential diagnoses are osteosarcoma (both primary of bone and extraosseous) and sclerosing epithelioid fibrosarcoma.(AU)

El sarcoma sinovial (SS) es un tumor de partes blandas de origen incierto. Generalmente es una neoplasia monofásica de células fusiformes que puede tener estructuras de tipo glandular. La osificación y la presencia de calcificaciones es un fenómeno raro, con pocos casos reportados. A continuación presentamos el caso de un hombre joven con un sarcoma sinovial del pie derecho que en la histología mostró depósitos de osteoide tumoral y calcificaciones gruesas. El diagnóstico fue confirmado por la expresión de SS18 por inmunohistoquímica y la demostración del reordenamiento del gen SS18 por hibridación in situ fluorescente. Revisamos la literatura referente a sarcoma sinovial con osificación o calcificación prominente, y este es el primer caso con expresión de SS18 por inmunohistoquímica. Los principales diagnósticos diferenciales son con osteosarcoma (tanto primario de hueso como extraóseo) y fibrosarcoma epitelioide esclerosante (sclerosing epithelioid fibrosarcoma [SEF]).(AU)

A fucoidan plant drink reduces Helicobacter pylori load in the stomach: a real-world study.

Background: Helicobacter pylori (Hp) infection is highly prevalent globally and is predominantly managed by antibiotics. Recently, the anti-adhesive, antioxidant, antitoxin, immunomodulatory, anti-coagulant, and anti-infective activities of fucoidan, a polysaccharide extracted from brown seaweeds, have been widely studied, and the results showed promise. Fucoidan has the potential to be utilized in Hp eradication therapy. Our present clinical study was designed to evaluate the efficiency of Lewuyou®, a fucoidan plant drink (FPD) in eradicating Hp in humans. Methods: This multi-center, clinical study was conducted between October 2020 and July 2021. Hp infection was confirmed by urea breath test (UBT). A total of 122 patients with confirmed Hp infection were enrolled; after exclusion of incomplete data, 85 eligible patients (37 males and 48 females aged 20-81 years) were included in the final analysis. FPD (50 mL per vial) was orally administered twice daily for a 4-week cycle, and 41 patients completed an 8-week cycle. Results: No adverse event (AE) was reported in all 122 participants who had consumed FPD. The Hp eradication rate and clearance rate were 77.6% (66/85) and 20.0% (17/85), respectively, after 4 weeks of FPD consumption and 80.5% (33/41) and 26.8 (11/41) , respectively, after 8 weeks of consumption. Conclusions: The 4- and 8-week protocols of FPD consumption were safe and effective at reducing Hp load on the gastric mucosa, with Hp eradicated in the majority of participants.

Synovial sarcoma with ossification and calcification with SS18 immunochemical expression and rearrangement by fluorescent in situ hybridization.

Synovial sarcoma is a soft tissue tumor of uncertain origin. Generally, it is a monophasic spindle cell neoplasm that can have glandular-like structures. Ossification and presence of calcification is a rare phenomenon with only a few reported cases. We present the case of a young male with a synovial sarcoma of the right foot. Histology revealed prominent deposits of tumoral osteoid and coarse calcifications. The diagnosis was confirmed by the expression of SS18 by immunohistochemistry and the demonstration of the rearrangement of the SS18 gene by fluorescent in situ hybridization. We reviewed the literature for synovial sarcoma with prominent ossification or calcification, and to the best of our knowledge, this is the first case with expression of SS18 by immunohistochemistry. The main differential diagnoses are osteosarcoma (both primary of bone and extraosseous) and sclerosing epithelioid fibrosarcoma.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.

Prognostic significance of tumour budding in Merkel cell carcinoma.

Prognostic factors in Merkel cell carcinoma (MCC) are scarce. Tumour budding (TB) has been shown to have a prognostic role in different cancers but has not been explored in MCC. We aimed to determine if TB influences survival in MCC. We performed a retrospective evaluation of 45 cases of MCC in a cancer centre. This included a survival analysis involving TB in patients with MCC, and we searched for variables associated with TB. The mean age of the patients was 69 years. Histologically, the average Breslow was 11.36 mm, and the mean mitotic rate was 31.9 mitoses/mm2. The diagnosis was made in clinical stages I and II in 40% of cases, 22.2% in stage III, and 37.8% in stage IV. Tumour budding was low ( 10 buds/0.785 mm2) in 24.4%. There were no clinical or pathological features associated with high TB. Among the prognostic factors for 5-year survival, we found that tumour size and clinical stage were statistically associated with survival (p = 0.031 and 0.021), but TB was not. No clinical or pathological characteristics of MCC are associated with any degree of TB. Tumour budding does not influence overall survival.

Efficacy and safety of self-expanding metal stents in patients with inoperable esophageal cancer: a real-life study.

Background: Dysphagia is the most frequent symptom in patients diagnosed with esophageal cancer. Self-expanding metal stents (SEMS) are the current palliative treatment of choice for dysphagia in patients with non-curable esophageal cancer. This study aimed to evaluate the efficacy and adverse events (AEs) of different types of SEMS for palliation of dysphagia. Methods: We performed a retrospective cohort study of patients with advanced esophageal cancer and SEMS placement for dysphagia palliation in a tertiary care center. The primary outcome was the clinical success defined as an improvement in dysphagia (reduction of at least 2 points in the Mellow-Pinkas scoring system for dysphagia) after SEMS placement. Results: Between January 1999 and May 2020, 295 patients with esophageal cancer were identified. Among them, 75 had a SEMS placement for dysphagia palliation. The mean age of the patients was 61.3 years (standard deviation: 13.4), 69 patients (92%) were men, and the mean Mellow-Pinkas scoring for dysphagia pre- and post-SEMS placement were 3.1 and 1.4 (change from baseline -1.7), respectively. Technical success and clinical success were achieved in 98.6% and 58.9%, respectively. AEs were identified in 35/75 patients (46.7%), and SEMS migration was the most frequent AE in 22/75 patients (29.3%). There were no significant differences in improvement in dysphagia (p = 0.054), weight changes (p = 0.78), and AE (p = 0.73) among fully covered SEMS (fc-SEMS) and partially covered SEMS (pc-SEMS). The median follow-up was 89 days (interquartile range: 29-221). Conclusion: SEMS placement was associated with a rapid improvement in dysphagia, high technical success, and a modest improvement in dysphagia with no major AE among fc-SEMS and pc-SEMS.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer.

BACKGROUND: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent. METHODS: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS). RESULTS: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031). CONCLUSIONS: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

INTRODUCTION: Appropriate size of resection margins in acral melanoma is not clearly established. OBJECTIVE: To investigate whether narrow-margin excision is appropriate for thick acral melanoma. METHODS: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). RESULTS: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). CONCLUSION: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

INTRODUCCIÓN: La extensión apropiada de los márgenes de resección en el melanoma acral no está claramente establecida. OBJETIVO: Investigar si la escisión con margen estrecho es adecuada en el melanoma acral grueso. MÉTODOS: Se estudiaron 306 pacientes con melanoma acral. Conforme a la extensión del margen quirúrgico (de 1 a 2 cm y > 2 cm), se analizaron los factores asociados a la recurrencia y la supervivencia. RESULTADOS: De 306 pacientes, 183 fueron mujeres (59.8 %). La mediana del grosor de Breslow fue 6 mm; 224 casos (73.2 %) fueron de tipo ulcerados, 154 pacientes (50.3 %) tenían enfermedad en estadio clínico III, 137 en II (44.8 %) y 15 en IV (4.9 %). Todos los casos presentaron margen negativo, con una mediana de 31.5 mm. Un grosor de Breslow de 7 mm (p = 0.001) y la etapa clínica III (p = 0.031) se asociaron a recurrencia; los factores asociados a la supervivencia fueron el índice de Breslow (p = 0.047), la ulceración (p = 0.003), la etapa clínica avanzada (p < 0.001) y el uso de adyuvancia (p = 0.003). CONCLUSIÓN: Un margen de resección de 1 a 2 cm no afectó la recurrencia tumoral ni la supervivencia en los pacientes con melanoma acral.

Prognosis of polypoid melanoma: a comparative study with non-polypoid melanomas.

Polypoid melanoma is considered an exophytic and frequently non-pigmented variant of nodular melanoma with an adverse prognosis; however, very few studies have been published about it with contradictory results. Therefore, our objective was to determine the prognostic value of this configuration in melanomas. A transversal retrospective study of 724 cases was analyzed according to the main configuration (polypoid vs. non-polypoid) regarding their clinicopathologic characteristics and survival analysis. Of the 724 cases, 35 (4.8%) met the definition of polypoid melanoma; such cases, compared with non-polypoid melanomas, were associated with a high Breslow thickness (7 mm vs. 3 mm), 68.6% had a Breslow >4 mm; showed different clinical stages of presentation, and presented more ulceration (77.1 vs. 51.4%). In the 5-year overall survival (OS) analysis, polypoid melanoma is associated with a lower 5-year OS, together with lymph node metastasis, Breslow thickness, clinical stage, mitoses per mm 2 , vertical growth phase, ulceration, and state of the surgical margins; however, in the multivariate analysis, the factors that remained independent predictors of death were the Breslow thickness groups, the clinical stage, the presence of ulceration, and the state of the surgical margins. Polypoid melanoma was not an independent predictor of OS. We found a prevalence of 4.8% of polypoid melanomas, which showed a worse prognosis than non-polypoid melanomas, explained by a higher proportion of ulcerated cases, greater Breslow thickness, and ulceration. However, polypoid melanoma was not an independent predictor of death.

Tasa de recurrencia e implicación del margen quirúrgico en la supervivencia del paciente con melanoma acral. ¿Es necesario un margen amplio? / Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

Resumen Introducción: La extensión apropiada de los márgenes de resección en el melanoma acral no está claramente establecida. Objetivo: Investigar si la escisión con margen estrecho es adecuada en el melanoma acral grueso. Métodos: Se estudiaron 306 pacientes con melanoma acral. Conforme a la extensión del margen quirúrgico (de 1 a 2 cm y > 2 cm), se analizaron los factores asociados a la recurrencia y la supervivencia. Resultados: De 306 pacientes, 183 fueron mujeres (59.8 %). La mediana del grosor de Breslow fue 6 mm; 224 casos (73.2 %) fueron de tipo ulcerados, 154 pacientes (50.3 %) tenían enfermedad en estadio clínico III, 137 en II (44.8 %) y 15 en IV (4.9 %). Todos los casos presentaron margen negativo, con una mediana de 31.5 mm. Un grosor de Breslow de 7 mm (p = 0.001) y la etapa clínica III (p = 0.031) se asociaron a recurrencia; los factores asociados a la supervivencia fueron el índice de Breslow (p = 0.047), la ulceración (p = 0.003), la etapa clínica avanzada (p < 0.001) y el uso de adyuvancia (p = 0.003). Conclusión: Un margen de resección de 1 a 2 cm no afectó la recurrencia tumoral ni la supervivencia en los pacientes con melanoma acral.

Abstract Introduction: Appropriate size of resection margins in acral melanoma is not clearly established. Objective: To investigate whether narrow-margin excision is appropriate for thick acral melanoma. Methods: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). Results: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). Conclusion: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

Prognosis of Mesorectal Tumor Deposits in Patients with Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision.

BACKGROUND: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colon cancer. However, there is no information of their survival impact in rectal cancer with neoadjuvant chemoradiotherapy (n-CRT). METHODS: Retrospective study in 223 patients with rectal cancer with n-CRT. A survival analysis of factors associated with decreased overall survival (OS) including TDs was performed. RESULTS: From 223 patients, 131 (58.7%) were men, mean age 59.8 (± 13.06) years, and 42 (18.8%) of them revealed TDs. Survival analysis of TDs showed no association with mortality. Factors associated with decreased 5-year OS were the histologic grade (p = 0.42), perineural invasion (p = 0.001), and mesorectal quality (p = 0.067). Perineural invasion (HR = 2.335, 95% CI = 1.198-4.552) remained as independent factor in the multivariate analysis. CONCLUSIONS: TDs were not associated with mortality in rectal cancer patients treated with n-CRT. Factors associated with decreased survival were inadequate mesorectal quality and perineural invasion.

Solid and papillary neoplasm of the pancreas (SPNP): a case report.

Background: Solid and papillary neoplasm of the pancreas (SPNP) is a rare pancreatic tumor, well known for its predilection for young women and large volume. The tumor has a favorable prognosis and differentiating it from other pancreatic tumors with aggressive behavior is necessary. Case Description: We present the case of a 34-year-old female without relevant background. She presented with abdominal pain and by fine needle biopsy was diagnosed as ductal carcinoma. During the evaluation, an abdominal ultrasound revealed a pancreatic growth that was "bulky, solid, with irregular margins, in homogeneously hypoechoic, with anechoic areas of necrosis, located lateral to the tail of the pancreas and medial to the upper pole of the left kidney and the lower splenic pole". The patient was admitted, and surgery was performed. At the laparotomy, a tumor of 15 cm in diameter was detected. The tumor was located in the tail of the pancreas, was well encapsulated, and of solid consistency. Caudal pancreatectomy with a splenectomy was carried out. The final pathology diagnosis was a SPNP. Conclusions: In the presence of a large abdominal mass of pancreatic relevance, even in older women, the possibility of having an SPNP should always be evaluated. Given the low malignancy potential of this tumor and the excellent prognosis with radical surgical treatment, the preoperative diagnosis should always be particularly accurate. Surgical resection is recommended as the treatment of choice.

Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription.

Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a transmembrane receptor that has a complex role in cancer, acting either to promote or inhibit tumor progression in different tumor types. The effect of ROR2 on gastric cancer is unclear. Methods: Immunohistochemistry was used to investigate the role of ROR2 in the prognosis of gastric cancer. Transwell assay and a BALB/c nude mice pulmonary metastasis model were used to ascertain the role of ROR2 in promoting metastasis in vitro and in vivo. A protein expression array, chromatin immunoprecipitation (ChIP) assay, and luciferase reporter assay were employed to search for the target genes of ROR2. Results: ROR2 was found to be upregulated in gastric cancer tissues, which was correlated with poor disease-free survival (DFS) and overall survival (OS) in gastric cancer patients. Moreover, ROR2 promoted gastric cancer cell migratory and invasive behaviors in vitro and metastasis in vivo. Further research showed that ROR2 promoted gastric cancer metastasis via upregulation of matrix metalloproteinase 3 (MMP3). Analyses of clinical data indicated that high expression of ROR2 was correlated with a high expression of MMP3. Further study showed that ROR2 activated c-JUN by translocating phosphorylated JNK1/2 into the nucleus, and c-JUN interacted directly with the MMP3 promoter, leading to enhanced MMP3 transcription. Conclusions: We report for the first time that ROR2 is upregulated in gastric cancer, promotes metastasis, and is associated with poor prognosis in gastric cancer. The findings suggest that ROR2 may be a promising prognostic predictor for gastric cancer. Silencing the JNK1/2-c-JUN pathway, thereby inhibiting MMP3 expression, may serve as a promising strategy to inhibit gastric cancer progression.

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Prognostic significance of tumor budding in melanoma.

Cutaneous melanoma is an aggressive neoplasm with growing incidence and continuous research is undertaken for novel prognostic factors. This current research aims to determine if tumor budding is an independent factor that correlates with the survival of patients with melanoma. A total of 742 cases of melanoma were evaluated. A receiver operating curve (ROC) was performed to analyze tumor budding impact on survival, identifying a cutoff point associated with death. Subsequently, two groups of participants were created based on that result. Participants within the two groups were compared for clinicopathologic characteristics and survival analysis. Also, a multivariate analysis was performed. Of the total, 447 (60.2%) melanomas occurred in women and 295 in men. The mean age was 57.5 years + 15.75. The most common location was in acral areas (68.2%) followed by trunk (16.7%) and head and neck (15.1%). At presentation, 142 cases (19.1%) presented as stage I, 307 (41.4%) as stage II, 269 (36.3%) as stage III, and 24 (3, 2%) in stage IV. Regarding tumor budding, 586 (79%) cases showed tumor budding (at least one bud in 0.785 mm 2 ), with a median of 5. From the ROC curve, 4.5 tumor buds/0.785 mm 2 was the best cutoff point for correlation with death, grouping the series in low budding (0-4 buds/0.785 mm 2 ) and high budding ( > 5 buds/0.785 mm 2 ). Cases with high tumor budding were associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death. High tumor budding was associated with a significant decrease in 5-year overall survival (94.4% vs. 55.5%, P < 0.001). In the multivariate analysis, the factors remaining as independent predictors of survival were acral location, clinical stage IV, recurrence during clinical follow-up, and high tumor budding. High tumor budding (>5 buds in 0.785 mm 2 ) independently correlates with 5-year overall survival rates and is associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death.