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Pathology Jun 2024KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC...
KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.
PubMed: 38918148
DOI: 10.1016/j.pathol.2024.04.002 -
Surgery Jun 2024Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of...
Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study).
BACKGROUND
Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival.
METHODS
Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed.
RESULTS
In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00).
CONCLUSION
A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.
PubMed: 38918108
DOI: 10.1016/j.surg.2024.05.010 -
Chinese Medical Journal Jun 2024
PubMed: 38915227
DOI: 10.1097/CM9.0000000000003185 -
International Journal of Gynecological... Jun 2024Targeted anti-HER2 therapy has been recently added to the standard treatment recommendations in endometrial serous carcinoma. Current eligibility requires testing for...
Targeted anti-HER2 therapy has been recently added to the standard treatment recommendations in endometrial serous carcinoma. Current eligibility requires testing for HER2 overexpression and/or gene amplification by immunohistochemistry and by fluorescence in situ hybridization. However, clinical trials have also demonstrated the efficacy of anti-HER2 drugs against activating ERBB2/HER2 mutations in a variety of solid tumor types, and fam-trastuzumab deruxtecan is now approved by the US Food and Drug Administration for HER2-mutant non-small cell lung cancer. This study aimed at evaluating the detailed clinical, histomorphological, immunohistochemical, and molecular characteristics of gynecologic malignancies with ERBB2/HER2 mutations. We identified 16 tumors with 19 ERBB2/HER2 mutations in our departmental archives: 11 endometrial primaries, 2 endocervical adenocarcinomas, 1 ovarian mucinous adenocarcinoma, 1 tubo-ovarian undifferentiated carcinoma, and 1 high-grade endometrioid adenocarcinoma of Mullerian origin. ERBB2/HER2 mutations most often involved the tyrosine kinase domain (52.6%), and the most frequent specific mutation was R678Q (31.6%), involving the juxtamembrane domain. More than half (54.5%) of endometrial carcinomas and half of all tumors were MMR-deficient, resulting from MSH6 loss in all but 2 tumors. None of the tumors (0%) were POLE-mutated, while 18.8% were TP53-mutated. HER2 IHC was negative (score 0 or 1+) in 12 tumors (67%) and equivocal (score 2+) in 4 tumors (33%), whereas none of the tumors were scored as HER2 3+. Score 2+ was associated with R678Q, L755S, I767M mutations, and ERBB2/HER2 rearrangement with a breakpoint in exon 23. Concurrent ERBB2/HER2 amplification was identified in 2 endometrial carcinomas, with HER2/CEP17 ratios of 3.1 and 3.5. We also queried the cBioportal database, which revealed 70 ERBB2/HER2-mutant gynecologic tumors with a total of 77 ERBB2/HER2 mutations, most often involving the active site of the tyrosine kinase domain (n=36; 46.8%), and the most common specific mutation was S310F (n=20; 26%), located in the extracellular domain. Our results provide important details regarding the clinicopathological and molecular associations of potentially actionable ERBB2/HER2 mutations in endometrial carcinoma and other gynecological cancer types and contribute to addressing clinical treatment needs and improving pathology testing recommendations in the future.
PubMed: 38914011
DOI: 10.1097/PGP.0000000000001050 -
Frontiers in Oncology 2024Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid...
Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid surgery. We retrospectively searched for the patients with implants of thyroid tumor after surgery from our database prior to August 2023. The clinical and pathological data were reviewed. Six female patients with a mean age of 33.6 ± 13.3 years were enrolled in this study. There was a rare case with mucinous adenocarcinoma, three follicular thyroid carcinoma, and two papillary thyroid carcinoma. The case with primary enteric adenocarcinoma of thyroid with subcutaneous implantation was first reported. The patient with mucinous adenocarcinoma received six courses of TP regimen chemotherapy. Five cases received radioactive iodine therapy. After a mean of 69.5 months of follow-up, one case recurred in the lateral region, and no metastasis or recurrence happened in the other five cases. Although the implantation after thyroid surgery is uncommon, the cases serve as a reminder to take greater care to avoid implantation.
PubMed: 38912068
DOI: 10.3389/fonc.2024.1412466 -
World Journal of Clinical Cases Jun 2024The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly...
The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly disease. Premalignant lesions such as Intraductal Papillary Mucinous Neoplasms or Mucinous Cystic Neoplasms of the pancreas are detectable on imaging exams and this permits their management prior their invasive development. Pancreatic intraepithelial neoplasms (PanIN) are the most frequent precursors of pancreatic adenocarcinoma (PDAC), and its particular type PanIN high-grade represents the malignant non-invasive form of PDAC. Unfortunately, PanINs are not detectable on radiologic exams. Nevertheless, they can associate indirect imaging signs which would rise the diagnostic suspicion. When this suspicion is established, the patient will be enrolled in a follow-up strategy that includes performing of blood test and serial imaging test such as computed tomography or magnetic resonance imaging, which will cost in the best-case scenario a burden of healthcare systems, and potential mortality in the worst-case scenario when the patient underwent resection surgery, worthless when there is no moderate or high grade dysplasia in the final histopathology. This issue will be avoid having at its disposal a diagnostic technique capable of detecting high-grade PanIN lesions, such is the cytology of pancreatic juice obtained by nasopancreatic intubation. Herein, we review the possibility of detection of early malignant lesions before they become invasive PADC.
PubMed: 38898835
DOI: 10.12998/wjcc.v12.i17.2935 -
Cancers May 2024Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The...
Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN.
AIMS
This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN.
METHODS
Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN ( = 217) as well as PDAC ( = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes.
RESULTS
Invasive IPMN was significantly smaller in size ( < 0.001) and of a lower tumor grade ( < 0.001), with fewer lymph node metastases ( < 0.001), lymphangiosis ( < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN.
CONCLUSIONS
Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.
PubMed: 38893136
DOI: 10.3390/cancers16112016 -
Cancers May 2024Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade,...
BACKGROUND
Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade, now accounting for 10% of all new CRC diagnoses. Average-onset colorectal cancer (AO-CRC) has shown a steady decline in its incidence and related mortality over the past 20 years. The disparities in outcomes and overall survival (OS) between EO-CRC and AO-CRC are controversial. Our study compared OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified the associated factors.
METHODS
Data on patient characteristics, tumor characteristics, incidence, and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 years with a confirmed diagnosis of all histological subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site codes. mEO-CRC and mAO-CRC were compared. OS distributions and CCS were analyzed using the Kaplan-Meier method and log-rank test to assess differences. A Cox regression model was used to assess the associations between variables.
RESULTS
mEO-CRC constituted 17.79% of the cases, whereas 82.21% had mAO-CRC. Most patients with mEO-CRC were 45-49 years old (47.66%), male (52.16%) and White (72.57%) and had adenocarcinoma histology (87.30%). Left colon tumors were most prevalent in both groups (40.26%) but were more prevalent in mEO-CRC patients than in mAO-CRC patients (49.63% vs. 38.23%, < 0.001). Patients with mEO-CRC had higher OS ( < 0.001) and CSS ( < 0.001) than those with mAO-CRC. Patients with mEO-CRC also had significantly better median overall survival (30 months vs. 18 months, < 0.001). The factors associated with worse OS included mAO-CRC ( < 0.001), mucinous adenocarcinoma ( < 0.001), male sex ( = 0.003), and a lack of surgical intervention ( < 0.001).
CONCLUSIONS
Most patients with mEO-CRC fall within the range of 45 to 49 years of age. Patients with mEO-CRC were more likely to receive cancer-directed therapy (including chemotherapy and radiotherapy) and had better OS and CSS than those with mAO-CRC. This is likely attributable to the better performance status, fewer comorbidities, and better tolerance to cancer-directed therapy in mEO-CRC patients. The factors associated with worse OS and CSS were age > 50 years, mucinous adenocarcinoma, male sex, and no surgical treatment.
PubMed: 38893124
DOI: 10.3390/cancers16112004 -
Pancreas Jul 2024Endoscopic ultrasound (EUS) is an excellent diagnostic tool that provides high-resolution images of pancreatic cystic lesions. However, its role in the diagnosis of...
OBJECTIVES
Endoscopic ultrasound (EUS) is an excellent diagnostic tool that provides high-resolution images of pancreatic cystic lesions. However, its role in the diagnosis of malignant intraductal papillary mucinous neoplasm (IPMN) remains limited and unclear. We aimed to determine the usefulness of this modality for such diagnosis.
METHODS
Overall, 246 patients who underwent EUS for IPMN after computed tomography (CT)/magnetic resonance imaging (MRI) from April 2018 to June 2021 were followed up until March 2022. We assessed the added value of performing EUS after CT or MRI for diagnosing malignant IPMN, using receiver operating characteristic curve analysis. Walls as thick as 2 mm were considered thickened in this study if they were highly uneven.
RESULTS
EUS clearly enhanced accuracy in identifying enhancing nodules and thickened walls. The areas under the receiver operating characteristic curve and corresponding 95% confidence intervals were 0.655 (0.549-0.760) and 0.566 (0.478-0.654) upon CT/MRI but 0.853 (0.763-0.942) and 0.725 (0.634-0.817) when observed using EUS. The combination of nodule size, thickened wall, and main duct size yielded the highest area under the receiver operating characteristic curve (0.944 [0.915-0.973]).
CONCLUSIONS
EUS more accurately detects malignant IPMN, as uneven wall thickening and certain nodules cannot be identified with CT/MRI.
Topics: Humans; Endosonography; Male; Female; Aged; Middle Aged; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Pancreatic Neoplasms; Pancreatic Intraductal Neoplasms; ROC Curve; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous; Aged, 80 and over; Retrospective Studies; Adult; Reproducibility of Results
PubMed: 38888840
DOI: 10.1097/MPA.0000000000002329 -
BMC Gastroenterology Jun 2024Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in...
BACKGROUND
Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS
A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS
Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION
MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Dilatation, Pathologic; Aged; Common Bile Duct; Pancreatic Intraductal Neoplasms; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous
PubMed: 38886637
DOI: 10.1186/s12876-024-03291-y