A CT-based radiomics nomogram involving the cystic fluid area for differentiating appendiceal mucinous neoplasms from appendicitis with intraluminal fluid.

OBJECTIVE: To develop and validate a radiomics nomogram based on computed tomography (CT) to distinguish appendiceal mucinous neoplasms (AMNs) from appendicitis with intraluminal fluid (AWIF). METHOD: A total of 211 patients from two medical institutions were retrospectively analysed, of which 109 were pathologically confirmed as having appendicitis with concomitant CT signs of intraluminal fluid and 102 as having AMN. All patients were randomly assigned to a training (147 patients) or validation cohort (64 patients) at a 7:3 ratio. Radiomics features of the cystic fluid area of the appendiceal lesions were extracted from nonenhanced CT images using 3D Slicer software. Minimum redundancy maximum relevance and least absolute shrinkage and selection operator regression methods were employed to screen the radiomics features and develop a radiomics model. Combined radiomics nomogram and clinical-CT models were further developed based on the corresponding features selected after multivariate analysis. Lastly, receiver operating characteristic curves, and decision curve analysis (DCA) were used to assess the models' performances in the training and validation cohorts. RESULTS: A total of 851 radiomics features were acquired from the nonenhanced CT images. Subsequently, a radiomics model consisting of eight selected features was developed. The combined radiomics nomogram model comprised rad-score, age, and mural calcification, while the clinical-CT model contained age and mural calcification. The combined model achieved area under the curves (AUCs) of 0.945 (95% confidence interval [CI]: 0.895, 0.976) and 0.933 (95% CI: 0.841, 0.980) in the training and validation cohorts, respectively, which were larger than those obtained by the radiomics (training cohort: AUC, 0.915 [95% CI: 0.865, 0.964]; validation cohort: AUC, 0.912 [95% CI: 0.843, 0.981]) and clinical-CT models (training cohort: AUC, 0.884 [95% CI: 0.820, 0.931]; validation cohort: AUC, 0.767 [95% CI: 0.644, 0.863]). Finally, DCA showed that the clinical utility of the combined model was superior to that of the clinical CT and radiomics models. CONCLUSION: Our combined radiomics nomogram model constituting radiomics, clinical, and CT features exhibited good performance for differentiating AMN from AWIF, indicating its potential application in clinical decision-making.

Natural history and growth prediction model of pancreatic serous cystic neoplasms.

OBJECTIVE: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. METHODS: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. RESULTS: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. CONCLUSION: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.

Recurrent mucinous cystic neoplasm of the mesentery in a young nullipara mimicking as ovarian carcinoma.

INRODUCTION: Mucinous cystic neoplasms are rare tumors. They may originate from either ovaries, pancreas, or other intra-abdominal sites, but rarely from the mesentery. CASE HISTORY: A 22-year-old nulliparaous woman, who had undergone laparascopic bilateral cystectomy for recurrent ovarian mass, presented with pain in abdomen, backache, and menstrual irregularities. Provisionally diagnosed as ovarian carcinoma, she underwent bilateral salpingo-oophorectomy and sigmoid colectomy. However, the histopathological examination revealed mucinous cystic neoplasm of the mesentery. DISCUSSION: Thus, complete resection of the cysts with meticulous gross and histopathological examination remains the gold standard to differentiate mucinous cystic neoplasm (MCN) of the mesentery from its mimics, especially malignant counterparts, enabling clinicians to adequately manage such patients. Here, we present a case of recurrent MCN of mesentery (mesocolon), mimicking as ovarian carcinoma confirmed on histopathological examination, in a young adult.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study.

BACKGROUND: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. METHODS: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed. RESULTS: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively). CONCLUSION: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.

Recurrent GATA3 P409Afs*99 Frameshift Extension Mutations in Sweat-gland Carcinoma With Neuroendocrine Differentiation.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) was recently proposed as a new cutaneous adnexal neoplasm with neuroendocrine differentiation; however, its genetics are not well known. Herein, we performed clinicopathologic and genetic analyses of 13 SCAND cases and 5 control cases of endocrine mucin-producing sweat gland carcinoma (EMPSGC). The SCAND group included 11 males and 2 females with a median age of 68 years (range, 50 to 80 y). All SCAND lesions occurred in the ventral trunk or genital area. Of the 13 SCAND cases, 9 and 5 exhibited lymph node and distant metastases, respectively. Three (23.1%) patients with SCAND died of the disease. In contrast, neither metastasis nor mortality was confirmed in the EMPSGC cases. Immunoexpression of the androgen receptor, c-Myb, and MUC2 was limited in SCAND, whereas EMPSGC frequently expressed these immunomarkers. GATA3 P409Afs*99 extension mutations were detected in 7 (53.8%) of the 13 SCAND cases, using Sanger or panel sequencing. All 7 SCAND cases with GATA3 mutations were located in the genital, inguinal, or lower abdominal regions, whereas 5 of the other 6 SCAND cases were located in the anterior upper to mid-trunk. No GATA3 mutations were detected in the EMPSGC cases (0/5, 0%). These clinicopathologic and genetic findings support SCAND as a tumor entity distinguishable from EMPSGC. In addition, the characteristic frameshift extension mutations in GATA3 contribute to the establishment of the tumor-type concept of SCAND.

Racial disparities in rates of invasiveness of resected intraductal papillary mucinous neoplasms in the United States.

BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.

Diagnosis and treatment of patients with suspected mucinous cystic neoplasms of the liver: a retrospective cohort study.

PURPOSE: Mucinous cystic neoplasms of the liver (MCN-L) are hepatic cysts with a low malignant potential. The recent European Association for the Study of the Liver (EASL) guidelines provide guidance on the imaging features and surgical management of MCN-L, yet are hampered by a lack of studies adhering to the revised World Health Organization (WHO) criteria. This study attempted to validate the new 2022 EASL-guidelines in a retrospective cohort study of patients who underwent surgery for suspected MCN-L. METHODS: Patients undergoing surgery for suspected MCN-L in a single center between 2010 and 2020 were included. Imaging features were assessed according to the EASL guidelines and were compared to final pathological diagnoses, according to the WHO criteria. RESULTS: In total, 35 patients were included. In three patients, there were no worrisome imaging features, yet final pathological diagnosis showed MCN-L. Contrarily, six patients with worrisome imaging features did not have MCN-L. Five patients were diagnosed with MCN-L on final pathology. The sensitivity of the EASL-guidelines for the diagnosis of MCN-L was 40% (95%CI: 5.3-85%) and the specificity was 80% (95% CI: 61-92%). CONCLUSION: Although the new EASL-guidelines provide some guidance, they could not reliably distinguish MCN-L from other cysts in our series. Thus, preoperative diagnosis of MCN-L remains challenging and we should be careful in selecting surgical strategies based on these criteria.

The Role of Intraoperative Pancreatoscopy in the Surgical Management of Intraductal Papillary Mucinous Neoplasms: A Scoping Review.

OBJECTIVES: Most patients with intraductal papillary mucinous neoplasms (IPMNs) are diagnosed with a solitary lesion; however, the presence of skip lesions, not appreciable on imaging, has been described. Postoperatively, these missed lesions can continue to grow and potentially become cancerous. Intraoperative pancreatoscopy (IOP) may facilitate detection of such skip lesions in the remnant gland. The aim of this scoping review was to appraise the evidence on the role of IOP in the surgical management of IPMNs. MATERIALS AND METHODS: Studies reporting on the use of IOP during IPMN surgery were identified through searches of the PubMed, Embase, and Scopus databases. Data extracted included IOP findings, surgical plan modifications, and patient outcomes. The primary outcome of interest was the utility of IOP in surgical decision making. RESULTS: Ten studies reporting on the use of IOP for IPMNs were identified, representing 147 patients. A total of 46 skip lesions were identified by IOP. Overall, surgical plans were altered in 37% of patients who underwent IOP. No IOP-related complications were reported. CONCLUSIONS: The current literature suggests a potential role of integration of IOP into the management of patients with IPMNs. This tool is safe and feasible and can result in changes in surgical decision making.

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol.

AIMS: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. METHODS: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). RESULTS: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). CONCLUSION: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

Variations in subtle cystic tumors of the atrioventricular node: Five autopsy cases.

Cystic tumor of the atrioventricular node (CTAVN) is the most common primary cardiac tumor cause of sudden death but is rarely found during forensic autopsy. We present five autopsy cases of sudden death from undiagnosed CTAVN. The tumors varied in their histological appearance, which may be related to their variation in clinical presentation. Some of the cases had been diagnosed with epilepsy before death; it seems that syncopal attacks caused by CTAVN may be misdiagnosed as epilepsy. When performing forensic autopsy, CTAVN should be considered in the differential diagnosis of sudden death. Careful examination of the cardiac conduction system is important in every sudden death case regardless of age.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs).

BACKGROUND: Main-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. METHODS: We performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000-2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. RESULTS: 33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. CONCLUSIONS: Postoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

Radiomics model versus 2017 revised international consensus guidelines for predicting malignant intraductal papillary mucinous neoplasms.

OBJECTIVES: To evaluate a CT-based radiomics model for identifying malignant pancreatic intraductal papillary mucinous neoplasms (IPMNs) and compare its performance with the 2017 international consensus guidelines (ICGs). MATERIALS AND METHODS: We retrospectively included 194 consecutive patients who underwent surgical resection of pancreatic IPMNs between January 2008 and December 2020. Surgical histopathology was the reference standard for diagnosing malignancy. Using radiomics features from preoperative contrast-enhanced CT, a radiomics model was built with the least absolute shrinkage and selection operator by a five-fold cross-validation. CT and MR images were independently reviewed based on the 2017 ICGs by two abdominal radiologists, and the performances of the 2017 ICGs and radiomics model were compared. The areas under the curve (AUCs) were compared using the DeLong method. RESULTS: A total of 194 patients with pancreatic IPMNs (benign, 83 [43%]; malignant, 111 [57%]) were chronologically divided into training (n = 141; age, 65 ± 8.6 years; 88 males) and validation sets (n = 53; age, 66 ± 9.7 years; 31 males). There was no statistically significant difference in the diagnostic performance of the 2017 ICGs between CT and MRI (AUC, 0.71 vs. 0.71; p = 0.93) with excellent intermodality agreement (k = 0.86). In the validation set, the CT radiomics model had higher AUC (0.85 vs. 0.71; p = 0.038), specificity (84.6% vs. 61.5%; p = 0.041), and positive predictive value (84.0% vs. 66.7%; p = 0.044) than the 2017 ICGs. CONCLUSION: The CT radiomics model exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. CLINICAL RELEVANCE STATEMENT: Compared with the radiologists' evaluation based on the 2017 international consensus guidelines, the CT radiomics model exhibited better diagnostic performance in classifying malignant intraductal papillary mucinous neoplasms. KEY POINTS: • There is a paucity of comparisons between the 2017 international consensus guidelines (ICGs) and radiomics models for malignant intraductal papillary mucinous neoplasms (IPMNs). • The CT radiomics model developed in this study exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. • The radiomics model may serve as a valuable complementary tool to the 2017 ICGs, potentially allowing a more quantitative assessment of IPMNs.

HER2/ ERBB2 Immunohistochemical Expression and Copy Number Status in Ovarian Mucinous Tumors.

Primary mucinous ovarian carcinoma (MOC) is a rare ovarian epithelial cancer, which is often refractory to chemotherapy. HER2-targeting therapy is being increasingly considered in gynecologic malignancies. Although there have been limited studies examining the HER2 status of such tumors, the criteria for HER2 expression scoring have not been standardized for MOC as it has for other sites. This study aimed to survey immunohistochemical HER2 expression patterns in MOC and its precursor, mucinous borderline tumor in correlation with fluorescence in situ hybridization (FISH). Immunohistochemistry (IHC) for HER2 was performed on 12 cases of MOC and 15 mucinous borderline tumors, including 7 with intraepithelial carcinoma. HER2 expression was quantified using the gastric/gastroesophageal carcinoma protocol. Cases were considered 3+ if the tumor cells displayed strong complete or basolateral/lateral membranous staining in ≥10% of tumor cells. Cases (2+) had weak to moderate staining in ≥10% of tumor cells. Cases (1+) had faint staining in ≥10% of tumor cells. Cases considered 0 had no staining or faint staining in <10% of tumor cells. HER2 expression was also quantified with the endometrial serous carcinoma protocol, which uses a 30% tumor cell positivity cutoff. FISH for HER2 was performed on all 3+ and 2+ and a subset of 1+ cases. Of the MOC cases, 25% were 3+ and 1 mucinous borderline tumor with intraepithelial carcinoma had 3+ staining. All 3+ IHC MOC cases had >30% basolateral membranous staining. HER2 amplification was confirmed by FISH on all 3+ IHC cases and in one 2+ IHC case of MOC. Up to 25% of mucinous ovarian tumors showed HER2 IHC overexpression with an excellent correlation between IHC and FISH using the HER2 scoring protocol for either gastric/gastroesophageal carcinoma or uterine serous carcinoma.

The Deception of Pancreas Cyst Surveillance: A Case Study.

Pancreatic cysts are a growing pandemic around the world. Intrapapillary mucinous neoplasms are the most common type of pancreatic cysts and given their premalignant nature, guidelines recommend surveillance. This case study and discussion addresses the five existing guidelines published to help clinicians manage patients with intraductal papillary mucinous neoplasms and illustrates how, despite guidelines and close surveillance, intraductal papillary mucinous neoplasms can transform into pancreatic adenocarcinoma.