Preoperative assessment of lymph nodal metastases with [68Ga]Ga-DOTATOC PET radiomics for improved surgical planning in well-differentiated pancreatic neuroendocrine tumours.

PURPOSE: Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention. METHODS: Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models' bACC, SN, SP, PPV and NPV were collected and compared (Kruskal-Wallis, Mann-Whitney). RESULTS: LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*). CONCLUSION: In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.

Single-Center Retrospective Study Comparing Double Vein Embolization via a Trans-Jugular Approach with Liver Venous Deprivation via a Trans-Hepatic Approach.

PURPOSE: To compare safety, technical and clinical outcomes of double vein embolization (DVE) via a trans-jugular approach with liver venous deprivation (LVD) via a trans-hepatic approach. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on patients undergoing simultaneous portal and hepatic veins embolization in view of a major hepatectomy (June 2019-November 2022). Hepatic vein embolization was performed either by transjugular plug (DVE) or by transhepatic plug followed by glue injection (LVD). Inclusion criteria were availability of pre-procedural CT scan, and availability of CT scans acquired 10 days and 25 days post-procedure. Comparative data included complication rate, fluoroscopy time, dose area product (DAP), Future Liver Remnant volume and function increase (FLR-V and FLR-F increase, respectively) and clinical outcomes. RESULTS: Thirty-six patients (n = 14 DVE; n = 22 LVD) were included. No baseline significant differences were observed among the two groups. One grade-3 complication (2.8%) was observed in the LVD group; one case of technical failure (2.8%) was observed in the DVE group. Fluoroscopy time and DAP were similar between DVE and LVD (29 ± 17.7 vs. 25 ± 8.2 min, p = 0.97; 105.1 ± 63.5 vs. 143.4 ± 79.5 Gy·cm2, p = 0.15). No differences arose at either time-point in FLR-V increase (46.7 ± 23.1% vs. 48.2 ± 28.2%, 52.9 ± 30.9% vs. 53.2 ± 29%, respectively, p = 0.9). FLR-F increase also did not differ significantly (62.8 ± 55.2 vs. 67.4 ± 57.5, p = 0.9). No differences in drop-out rate from surgery were observed. (28.6% vs. 27.3%, p = 0.93). One case of grade-B post-hepatectomy liver failure (2.8%) was observed in the LVD group. CONCLUSION: LVD via transhepatic approach and DVE via transjugular approach seem equally safe and effective. Level of Evidence Level 3, Retrospective Cohort Study.

Comparing Liver Venous Deprivation and Portal Vein Embolization for Perihilar Cholangiocarcinoma: Is It Time to Shift the Focus to Hepatic Functional Reserve Rather than Hypertrophy?

Purpose: Among liver hypertrophy technics, liver venous deprivation (LVD) has been recently introduced as an effective procedure to combine simultaneous portal inflow and hepatic outflow abrogation, raising growing clinical interest. The aim of this study is to investigate the role of LVD for preoperative optimization of future liver remnant (FLR) in perihilar cholangiocarcinoma (PHC), especially when compared with portal vein embolization (PVE). Methods: Between January 2013 and July 2022, all patients diagnosed with PHC and scheduled for preoperative optimization of FTR, through radiological hypertrophy techniques, prior to liver resection, were included. FTR volumetric assessment was evaluated at two distinct timepoints to track the progression of both early (T1, 10 days post-procedural) and late (T2, 21 days post-procedural) efficacy indicators. Post-procedural outcomes, including functional and volumetric analyses, were compared between the LVD and the PVE cohorts. Results: A total of 12 patients underwent LVD while 19 underwent PVE. No significant differences in either post-procedural or post-operative complications were found. Post-procedural FLR function, calculated with (99m) Tc-Mebrofenin hepatobiliary scintigraphy, and kinetic growth rate, at both timepoints, were greater in the LVD cohort (3.12 ± 0.55%/min/m2 vs. 2.46 ± 0.64%/min/m2, p = 0.041; 27.32 ± 16.86%/week (T1) vs. 15.71 ± 9.82%/week (T1) p < 0.001; 17.19 ± 9.88%/week (T2) vs. 9.89 ± 14.62%/week (T2) p = 0.034) when compared with the PVE cohort. Post-procedural FTR volumes were similar for both hypertrophy techniques. Conclusions: LVD is an effective procedure to effectively optimize FLR before liver resection for PHC. The faster growth rate combined with the improved FLR function, when compared to PVE alone, could maximize surgical outcomes by lowering post-hepatectomy liver failure rates.

Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors.

PURPOSE: To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery. METHODS: This retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE. RESULTS: Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040). CONCLUSION: SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.

Combining Laparoscopic Liver Partitioning and Simultaneous Portohepatic Venous Deprivation for Rapid Liver Hypertrophy.

Future liver remnant (FLR) volume is an important indicator of the risk of posthepatectomy liver failure (PHLF) and limits the feasibility of major hepatectomies. A case series of 5 patients treated with a novel approach is presented. Laparoscopic liver partitioning was combined with subsequent liver venous deprivation (embolization of both the portal and the hepatic veins). Baseline average FLR was 28.8%. All procedures were successfully performed without major complications. Mean 1-, 2- and 4-week hypertrophy of the FLR were 35%, 40.3%, and 46.4%, respectively. Four patients underwent planned surgery after a mean interval of 28 days. Of these, 2 patients achieved sufficient FLR volume and function after 2 weeks and underwent surgery before the 4-week volumetric analysis. One patient did not undergo surgery because of intraoperative diagnosis of peritoneal metastases. No cases of PHLF were observed at 5-day follow-up.

PET/MRI for Staging the Axilla in Breast Cancer: Current Evidence and the Rationale for SNB vs. PET/MRI Trials.

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

High-risk early-stage oral tongue squamous cell carcinoma, when free margins are not enough: Critical review.

Oral tongue squamous cell carcinoma (OTSCC) is a quite peculiar disease from an anatomical and biological standpoint. An increasing amount of literature highlights the existence of a small subset of T1-T2N0 OTSCC, properly resected on a margin-dependent basis, which conversely proved higher than expected rates of loco-regional/distant failure and disease-specific mortality. These specific high-risk tumors might not have a margin-dependent disease and could possibly benefit from a more aggressive upfront loco-regional treatment, especially addressing the so-called T-N tract. Widespread adoption of a histopathological risk model would allow early recognition of these high-risk diseases and, consequently, intensification of the traditional treatment strategies in that specific niche. We reviewed the available knowledge trying to shed light on the potential determinants of the dismal prognosis of these high-risk OTSCC, with special reference to the role of overlooked T-N tract involvement and possible alternatives in terms of elective neck management and risk stratification.

Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis. METHODS: Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio-guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field. RESULTS: A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow-up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease-free survivals in a patient with positive and negative inguinal sentinel nodes. CONCLUSIONS: In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.

Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients.

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.

Sentinel node biopsy after primary systemic therapy in node positive breast cancer patients: Time trend, imaging staging power and nodal downstaging according to molecular subtype.

BACKGROUND: The management of axilla after Primary Systemic Therapy (PST) for breast cancer is a highly debated field. Despite the proven axillary downstaging occurring after PST, there is still some degree of reluctance in applying sentinel node biopsy (SNB) in the neoadjuvant setting. PATIENTS AND METHODS: We performed a retrospective analysis on 181 PST patients with axillary positive nodes at presentation treated between 2005 and 2017 at San Raffaele Hospital in Milan. The aim was to observe the application time trend of SNB, to determine the imaging staging power and the axillary downstaging according to molecular subtypes. RESULTS: Median follow-up after surgery was 32.5(IQR: 12-59) months. After PST, 119 (65.7%) patients had no clinically palpable nodes, 72 (39.7%) converted to N0 on final imaging and 34 (18.8%) underwent SNB with an increasing application trend. Axillary-US showed the highest accuracy (69.3%) in re-staging axilla after PST. Staging power of preoperative testing varied with tumour biology: Positive Predictive Value was higher in Luminal A (80% for clinical examination and 100% for axillary-US) and Luminal B (72% and 70.5%) tumours, whilst Negative Predictive Value was higher in HER2 positive (100% and 93.3%), and triple negative (71.4% and 93.3%) tumours. Ninety five (52.5%) patients experienced axillary downstaging after PST, by molecular subtype 15% (3/20) in Luminal A, 46.4% (45/97) in Luminal B, 90.9% (20/22) in HER2+ and 70.3% (26/37) in triple negative breast tumours. CONCLUSION: SNB application after PST for breast cancer in node positive patients at presentation is increasing. Pre-operative axillary imaging and tumour biology help identify patients who might be candidates for SNB as a single staging procedure.

Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease.

Objective: [18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Methods: Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Results: Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal < 3). Serum IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P < 0.05 for all comparisons). Conclusions: 18F-FDG uptake of IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation.

Targeted radionuclide therapy: frontiers in theranostics.

The concept of targeted radionuclide therapy (TRT) relies on the use of injected nuclear medicine as treating agents, targeted at the cellular or molecular level. The growth of the interest in TRT was stimulated by the advances in radionuclide production and labeling as well as by the improvement in the knowledge of appropriate and specific molecular targets. In recent years, different studies on TRT were focused on the evaluation of radionuclide compounds able to combine imaging of the disease with TRT, in a theranostic approach. This approach is of particular interest towards the personalization of treatments, allowing both the baseline characterization of oncological pathologies and treatment optimization by correct dosimetric calculation as well as therapy monitoring. This paper presents a review of recent literature on TRT, with a particular focus on clinical applications promoting such a theranostic approach, showing the impact of the synergy of diagnostic imaging and therapeutics.

Biomarkers from in vivo molecular imaging of breast cancer: pretreatment 18F-FDG PET predicts patient prognosis, and pretreatment DWI-MR predicts response to neoadjuvant chemotherapy.

OBJECTIVE: Human cancers display intra-tumor phenotypic heterogeneity and recent research has focused on developing image processing methods extracting imaging descriptors to characterize this heterogeneity. This work assesses the role of pretreatment 18F-FDG PET and DWI-MR with respect to the prognosis and prediction of neoadjuvant chemotherapy (NAC) outcomes when image features are used to characterize primitive lesions from breast cancer (BC). MATERIALS AND METHODS: A retrospective protocol included 38 adult women with biopsy-proven BC. Patients underwent a pre-therapy 18F-FDG PET/CT whole-body study and a pre-therapy breast multi-parametric MR study. Patients were then referred for NAC treatment and then for surgical resection, with an evaluation of the therapy response. Segmentation methods were developed in order to identify functional volumes both on 18F-FDG PET images and ADC maps. Macroscopic and histogram features were extracted from the defined functional volumes. RESULTS: Our work demonstrates that macroscopic and histogram features from 18F-FDG PET are able to biologically characterize primitive BC, and define the prognosis. In addition, histogram features from ADC maps are able to predict the response to NAC. CONCLUSION: Our work suggests that pre-treatment 18F-FDG PET and pre-treatment DWI-MR provide useful complementary information for biological characterization and NAC response prediction in BC.

Prospective comparison of MR with diffusion-weighted imaging, endoscopic ultrasound, MDCT and positron emission tomography-CT in the pre-operative staging of oesophageal cancer: results from a pilot study.

OBJECTIVE: To compare the diagnostic performance of MR and diffusion-weighted imaging (DWI), multidetector CT, endoscopic ultrasonography (EUS) and 18F-FDG (fluorine-18 fludeoxyglucose) positron emission tomography CT (PET-CT) in the pre-operative locoregional staging of oesophageal cancer. METHODS: 18 patients with oesophageal or Siewert I tumour (9 directly treated with surgery and 9 addressed to chemo-/radiotherapy before) underwent 1.5-T MR and DWI, 64-channel multidetector CT, EUS and PET-CT before (n = 18) and also after neoadjuvant treatment (n = 9). All images were analysed and staged blindly by dedicated operators (seventh TNM edition). Two radiologists calculated independently the apparent diffusion coefficient from the first scan. Results were compared with histopathological findings. After the population had been divided according to local invasion (T1-T2 vs T3-T4) and nodal involvement (N0 vs N+), sensitivity, specificity, accuracy, positive- and negative-predictive values were calculated and compared. Quantitative measurements from DWI and PET-CT were also analysed. RESULTS: For T staging, EUS showed the best sensitivity (100%), whereas MR showed the highest specificity (92%) and accuracy (83%). For N staging, MR and EUS showed the highest sensitivity (100%), but none of the techniques showed adequate results for specificity. Overall, MR showed the highest accuracy (66%) for N stage, although this was not significantly different to the other modalities. The apparent diffusion coefficient was different between surgery-only and chemo-/radiotherapy groups (1.90 vs 1.30 × 10-3 mm2 s-1, respectively; p = 0.005)-optimal cut off for local invasion: 1.33 × 10-3 mm2 s-1 (p = 0.05). Difference in standardized uptake value was also very close to conventional levels of statistical significance (8.81 vs 13.97 g cm-3, respectively; p = 0.05)-optimal cut off: 7.97 g cm-3 (p = 0.44). CONCLUSION: In this pilot study, we have shown that MR with DWI could enrich the current pre-operative work-up for oesophageal cancer and could be used for T and N staging. However, larger studies will need to be carried out before introducing this technique in the standard diagnostic pathway, in order to understand if MR with DWI could change its management and replace more costly or invasive tests such as PET-CT or EUS. Advances in knowledge: This pilot study represents the first effort where the four techniques have been prospectively compared together for oesophageal cancer staging. The combination of MR and DWI could provide important, additional information for staging and initial treatment decision-making.

Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patient's serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients. CASE SUMMARY: A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV. CONCLUSION: The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD.

Prone 18F-FDG PET/CT changes diagnostic and surgical intervention in a breast cancer patient: some considerations about PET/CT imaging acquisition protocol.

We report a case study demonstrating the value of prone positioning in positron emission tomography (PET) of a woman with diagnosed breast cancer (BC) addressed to lumpectomy. Surgeon required (18)F-fluorodeoxiglucose ((18)F-FDG) PET study for staging and assessment of lymphnode involvement/metastasis prior to lumpectomy: a whole-body supine study and a prone acquisition of breast. Supine study revealed one lesion, while prone study revealed two lesions. Prone PET findings changed diagnosis and therapeutic intervention for patient who was subsequently subjected to quadrantectomy.

Response to chemotherapy in gastric adenocarcinoma with diffusion-weighted MRI and (18) F-FDG-PET/CT: correlation of apparent diffusion coefficient and partial volume corrected standardized uptake value with histological tumor regression grade.

PURPOSE: To assess whether changes in diffusion-weighted MRI (DW-MRI) and (18) F-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT), correlate with treatment response to neoadjuvant therapy (NT), as expressed by tumor regression grade (TRG), from locally advanced gastric adenocarcinoma (GA). MATERIALS AND METHODS: Seventeen patients underwent both DW-MRI and (18) F-FDG-PET/CT scans before and after the end of NT. Apparent diffusion coefficient (ADC) and mean standardized uptake value (SUV) corrected for partial volume effect (PVC-SUVBW-mean ) were evaluated and compared with histopathological TRG. RESULTS: Pre- and post-NT and percentage changes for ADC and PVC-SUVBW-mean were assessed. Post-NT ADC and ΔADC showed a significant inverse correlation with TRG (r = -0.71; P = 0.0011 and r = -0.78; P = 0.00020, respectively) and significant differences in their mean values were found between responders (TRG 1-2-3) and nonresponders (TRG 4-5) (P = 0.0009; P = 0.000082, respectively). No correlations with TRG were found for pre-NT ADC and for all PVC-SUVBW-mean values as well as between ΔADC and Δ PVC-SUVBW-mean . CONCLUSION: DW-MRI seems more accurate than (18) F-FDG-PET/CT and ADC modifications may represent a reproducible tool to assess tumor response for GA.

Sentinel node biopsy in squamous-cell carcinoma of the anal canal.

BACKGROUND: Radiochemotherapy is the standard treatment for patients with carcinoma of the anal canal. Therefore, a surgical specimen is not usually obtained. Inguinal lymph node metastases cannot be accurately predicted by either clinical examination or imaging techniques. In this study, we applied the sentinel node technique in patients with anal canal squamous-cell carcinoma to determine whether this provided more reliable staging of tumors. METHODS: From May 2007 to May 2009, we enrolled 11 patients (7 women) with a mean age 65 (range 39-80) years with squamous-cell carcinoma of the anal canal and clinically and radiologically negative groin lymph nodes. The patients were staged with endorectal ultrasound, computed tomographic scan, magnetic resonance imaging of the pelvis, and positron emission tomography. There were two T1, four T2, and five T3 tumors (International Union Against Cancer classification). Lymphoscintigraphy with peritumoral 99mTc colloid injection was performed 16 to 18 h before surgery. During the surgery, patent blue dye was injected peritumorally, and the sentinel inguinal node was identified by a handheld gamma probe and dye visualization. RESULTS: The sentinel lymph node was detected in all 11 patients by scintigraphy; in 9 cases, the lymph node was in the inguinal region. All of these patients underwent radioguided node biopsy, and a total of 12 lymph nodes were removed. The average diameter of the resected nodes was 8 (range 4-20) mm. No serious complications occurred. In three patients, metastases were identified in the lymph node. CONCLUSIONS: Sentinel node biopsy is a more accurate method than clinical or radiological techniques to stage the disease of patients with anal carcinoma.

Sentinel node mapping during laparoscopic distal gastrectomy for gastric cancer: technical notes.

BACKGROUND: With increasing experience, sentinel node navigation has been applied even to gastric cancer. Sentinel lymph nodes are identified by injecting lymphatic tracer dye and radioisotope-labeled particles around a gastric tumor into the submucosa endoscopically. The aim of this video was to demonstrate the feasibility of laparoscopic sentinel node navigation (SLN) in gastric cancer. METHODS: A 71-year-old man with a diagnosis of gastric cancer was admitted to the authors' department. The preoperative workup demonstrated a uT1 node-negative gastric cancer. The patient was scheduled for laparoscopic distal gastrectomy with SLN. The day before surgery, the patient was submitted to endoscopy. During the procedure, the radiotracer (technetium-99) was injected at four points around the tumor. The operation was performed with the patient in the Lloyd-Davies position using four trocars. After opening of the gastrocolonic ligament, the patient underwent an intraoperative endoscopy, and blue dye (patent blue) was injected at four points around the tumor. The lymphatic basin was identified with the probe and the blue dye. The sentinel node then was identified. No pickup technique was used. A standard laparoscopic gastrectomy with intracorporeal anastomosis was concluded successfully. Through a supraumbilical incision, the specimen was extracted. The sentinel node was dissected at the bench table after the operation. RESULTS: The pathologic report demonstrated a gastric carcinoma, namely, pT1, pN1 (Sentinel node (Sn), 1/36), G3 gastric cancer. Only the sentinel node was positive, containing a micrometastasis. The patient's postoperative course was uneventful. CONCLUSIONS: Sentinel node navigation with a double tracer during laparoscopic gastrectomy for cancer is feasible. Nevertheless, it is mandatory to standardize the method of SLN identification to increase the diagnosis of lymph node metastases.