Anastomotic bleeding from invaginated pancreaticogastrostomy following pancreatoduodenectomy: incidence, risk factors, treatment and prevention.

BACKGROUND: Meta-analysis of 10 randomized prospective trials demonstrated a higher risk of postoperative bleeding from pancreaticogastrostomy (PG) compared with pancreatojejunostomy following pancreatoduodenectomy (PD). This study evaluated the incidence, risk factors, and treatment of anastomotic bleeding from invaginated PG. METHODS: We retrospectively evaluated all consecutive PDs performed between April 1, 2011 and December 31, 2022 using invaginated PG by the double purse-string technique. Multivariate analysis identified risk factors for anastomotic PG bleeding. RESULTS: During the study, 695 consecutive patients with a median age of 66 years underwent PD; the majority was performed for ductal pancreatic adenocarcinomas. Simultaneous vascular resections were performed in 328 patients. Postoperative mortality was 4.1%. Bleeding from PG occurred in 33(4.6%) patients at a median interval of 5 days (range, 1-14) from surgery, leading to reoperation in 21(63%). PG bleeding-related mortality was 9.0%. Multivariate analyses identified a soft pancreatic texture and Wirsung duct > 3 or ≤ 3 mm (Class C and D, respectively, of the ISGPS) (odds ratio [OR]: 2.17, 95% confidence interval [95% CI]: 1.38-3.44; P = 0.0009) and wrapping of the invaginated pancreas (OR: 0.37, 95% CI: 0.17-0.84; P = 0.01) as independent risk factors for PG bleeding. CONCLUSIONS: In a large volume setting, anastomotic bleeding from invaginated PG occurred in ~ 5% of patients and was associated with soft pancreatic parenchyma and small wirsung duct. The reduced rate of PG bleeding observed with wrapping of the invaginated pancreatic stump warrants further evaluation in a prospective randomized study.

Preoperative pancreatic radiologic characteristics predict pancreatic-specific complications before pancreaticoduodenectomy: the pancreatic acinar radiologic score.

BACKGROUND: High acinar pancreatic contents are associated with a higher rate of postpancreatectomy acute pancreatitis and pancreatic fistula formation (POPF). Predicting acinar contents preoperatively might identify those at high risk of developing postoperative complications. METHODS: A multivariable analysis was performed to identify radiological factors associated with high pancreatic acinar content at histology in patients undergoing pancreaticoduodenectomy. Clinical and radiological variables identified were used to build a composite score predicting low, moderate, and high acinar pancreatic contents. RESULTS: Pancreatic density, wirsung caliber, and pancreatic thickness on preoperative CT-scan predicted acinar contents. These three variables predicted low, moderate, and high acinar content in 94 (26%), 122 (33.6%), and 147 (40.5%) patients, respectively. Patients with high radiological acinar scores compared with patients with intermediate-low risk scores were more frequently male (73.4% vs. 54.1%; p = 0.0003), obese (14% vs. 6%; p = 0.01), and had a statistically significant higher rate of pancreatic-specific complications (23.8% vs. 8.33%; p = 0.01), POPF (12.9% vs. 4.63%; p = 0.005) and pancreaticogastrostomy bleeding (10.8% vs. 4.17%; p = 0.01). CONCLUSION: A simple radiological score combining pancreatic thickness, density, and wirsung caliber at CT scan preoperatively predicts patients with pancreatic parenchyma that are at higher risk of postoperative pancreatic-specific complications.

Pancreatectomy After Neoadjuvant FOLFIRINOX Chemotherapy: Identifying Factors Predicting Long-Term Survival.

INTRODUCTION: We aimed to evaluate the long-term outcomes of the association of neoadjuvant chemotherapy with pancreatectomy with vascular resection in patients with locally advanced pancreatic cancer. METHODS: Clinical data from patients who underwent pancreatic resection after neoadjuvant FOLFIRINOX were retrospectively reviewed. Cox analyses were used to identify factors prognostic of overall survival (OS). RESULTS: FOLFIRINOX protocol was administered pre-operatively with a median number of nine cycles (range 2-18) in 98 patients. Types of resections included pancreaticoduodenectomy (n = 53), total pancreatectomy (n = 17), and distal spleno-pancreatectomy (n = 28). Venous resection and arterial resections were performed in 85 (86.7%) and 64 patients (65.3%), respectively. The overall 90-day mortality and morbidity rates were 6.1% (n = 6) and 47% (n = 47), respectively. The median OS was 31.08 months after surgery. OS rates at one, three, five, and 10 years were 82%, 47%, 28%, and 21%, respectively. According to the type of vascular resection, median OS and 5-year survival rates were exclusive venous resection (31.08 months; 23%) and arterial resections (24.7 months; 27%). Multivariate Cox analysis found lymph node involvement, venous invasion, and total pancreatectomy as independent prognostic factors for OS. According to the presence of 0 or 1-3 risk factors, 5-year survival (85% vs 16%) and median overall survival rates (not reached versus 24.7 months, respectively) were statistically significantly different (p < 0.0001). CONCLUSIONS: A multimodal treatment, including neoadjuvant FOLFIRINOX combined with pancreatectomy with venous and arterial resection, achieves long term survival rates in patients with locally advanced disease. Surgery, in experienced centers, should be integrated into the treatment of patients with locally advanced pancreatic adenocarcinomas.

Uterine sarcomas and rare uterine mesenchymal tumors with malignant potential. Diagnostic guidelines of the French Sarcoma Group and the Rare Gynecological Tumors Group.

The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine sarcomas, as well as soft tissue sarcomas, can be distinguished into complex genomic sarcomas and simple genomic sarcomas. Leiomyosarcoma and pleomorphic type undifferentiated uterine sarcoma belong to the first group. Low-grade and high-grade endometrial stromal sarcomas, NTRK, COL1A1::PDGFB, ALK, RET, ROS1 associated sarcomas, and SMARCA4 deficient uterine sarcoma belong to the second group. Leiomyosarcoma is the most common uterine sarcoma followed by endometrial stromal sarcomas. Three different histologic subtypes of leiomyosarcomas are recognized with distinct diagnostic criteria and different clinical outcomes, the myxoid and epithelioid leiomyosarcomas being even more aggressive than the fusiform type. The distinction between low-grade and high-grade endometrial stromal sarcoma is based first on morphology and immunohistochemistry. The detection of fusion transcripts helps in the diagnosis. Definitely recognized as a separate entity, uterine PEComa is a rare tumor whose diagnostic criteria are being recently defined. Uterine PEComa has a specific algorithm stratifying the tumors into uncertain malignant potential and malignant tumors. Embryonal rhabdomyosarcomas of the uterine cervix are not restricted to children but can also be observed in adult women and are almost always DICER1 mutated, unlike embryonal rhabdomyosarcoma of the vagina which are DICER1wild-type, and adenosarcoma which can be DICER1 mutated but with less frequency. As sarcomas associated with fusion transcripts involving the NTRK, ALK, COL1A1::PDGFB genes can benefit from targeted therapy, systematic detection are now relevant especially for patients with high risk of relapse or in recurrent setting. The integration of molecular data with dedicated expert pathology review for histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

64CuCl2 PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice.

64CuCl2 is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of 64CuCl2 in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. 18F-FDG was used as a comparator. Twenty-two animals were imaged 7-9 days following 4T1-cell implantation inside mammary glands. Dynamic 64CuCl2 µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning 18F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor 64CuCl2 accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle 64CuCl2 accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The 18F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. 64CuCl2 PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.

[Splenic rupture revealing metastasis of a yolk sac tumor]. / Rupture splénique révélant une métastase d'une tumeur du sac vitellin.

We report a rare entity in adults with an exceptional secondary complication. This is a case of a splenic localization of a yolk sac tumor responsible for a splenic rupture in a 52-year-old man.

Prognostic significance of residual lymphovascular invasion after resection of locally advanced and borderline resectable pancreatic adenocarcinomas treated by neoadjuvant chemotherapy.

BACKGROUND: The current study aimed to identify histological prognostic factors after resection of locally advanced (LA) and borderline (BL) pancreatic adenocarcinomas treated by neoadjuvant chemotherapy (NC). METHODS: A retrospective review was performed of patients with LA and BL adenocarcinomas operated after NC between January 2010 and April 2018. Prognostic factors for survival were assessed by multivariate Cox analysis. RESULTS: Of the 84 patients, 29 had BL and 55 had LA pancreatic adenocarcinomas. Seventy-five patients underwent synchronous venous resection and 57 underwent arterial resection. The median overall survival from surgery was 21.10 months (BL 23-LA 21) (95% CI: 14.8-30.3) with 1-, 3-, and 5-year overall survival rates of 73%, 32%, and 20%, respectively. Multivariate analysis identified lymphovascular invasion (LVI) as an independent prognostic factor for overall survival (HR: 2.32, 95% CI: 1.28-4.22; p = 0.004). Patients without LVI (n = 37) had superior median overall and 5-year survival rates (31.0 months [40 from diagnosis]; 39%) compared to patients with LVI (n = 47; 14.4 months [22 from diagnosis]; 7%). The absence of residual LVI was associated with major pathologic response rates (p < 0.05). CONCLUSION: The persistence of LVI at pathology after resection of LA and BL treated by neoadjuvant chemotherapy predicts poor response and limited long-term survival.

Solid pseudopapillary tumour should be part of differential diagnosis of focal pancreatic lesions with increased 18 F-FDOPA uptake.

OBJECTIVE: To assess the specificity of increased 18 F-dihydroxyphenylalanine (18 F-FDOPA) uptake in patients who underwent PET/CT for suspicion of isolated pancreatic neuroendocrine tumour (pNET). False-positive results mimicking a pNET have been investigated. MATERIAL AND METHODS: Carbidopa-assisted 18 F-FDOPA PET/CT scans performed in patients with suspicion of localized pNET were retrieved. Only patients with a definitive diagnosis were retrospectively included. When available, the histopathological result after pancreatic surgery was the gold standard. In other cases, the diagnosis was based on endoscopic ultrasonography (EUS)/cytology and/or on concordant imaging results of at least two of the following: contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). RESULTS: Forty-four among 731 patients were selected. Among these, 36 patients (82%) were surgically treated, revealing pNET (n = 28), solid pseudopapillary tumour (SPT) (n = 4), adenocarcinoma (n = 2), serous cystadenomas (n = 1) and solitary fibrous tumour (n = 1) cases. An additional three cases of pNET were diagnosed by EUS/cytology. In the remaining five patients, a consensus was reached on follow-up imaging results: pNET (n = 1), serous cystadenoma (n = 2) and undetermined/no pNET (n = 2). Both specificity and negative predictive value of 18 F-FDOPA PET/CT for localized pNET were 67%. Surprisingly, all four false-positive results were SPTs showing intense 18 F-FDOPA uptake and negative SRS. There was no significant difference in 18 F-FDOPA uptake intensity between PET-positive pNETs and SPTs. CONCLUSION: 18 F-FDOPA PET/CT is not specific for pNET in patients with localized pancreatic lesions. SPT could mimic pNET and should be part of differential diagnosis in such a clinical situation. If these results are confirmed in a broader population, the imaging pattern 18 F-FDOPA PET-positive/SRS-negative lesions might be considered as the imaging phenotype of SPT.

Outcomes of Simultaneous Resection of Small Bowel Neuroendocrine Tumors with Synchronous Liver Metastases.

BACKGROUND: This study evaluated the short- and long-term outcomes of synchronous resection of liver metastases (LM) from small bowel neuroendocrine tumors (SB-NET). METHODS: A retrospective review of patients undergoing resection for LMs from SB-NETs from January 1997 and December 2018 was performed. RESULTS: There were 44 patients with synchronous SB-NET and LMs. Perioperative and 90-day mortality values were zero, and the morbidity rate was 27%. The median overall survival (OS) was 128.4 months (CI 95% 74.0-161.5 months) with 1-, 3-, 5-, and 10-year survival rates of 100%, 83%, 79%, and 60%, respectively. Not achieving surgical treatment for LM was the unique independent factor for survival (HR 6.50; CI 95% 1.54-27.28; p = 0.01) in patients with unresected LMs having OS and 10-year survival rates (42 months, 33%) versus patients undergoing liver resection (152 months, 66%)(p = 0.0008). The recurrence rate was 81.8% and associated with longer OS and 5-year survival rates when limited to the liver [223 months (61%) vs 94 months (87%)]. CONCLUSIONS: Simultaneous resection of SB-NETs with synchronous LMs was safe and associated with considerable long-term survival even in the presence of bilobar disease. However, recurrence after resection was common (81%) but associated with longer survival rates when limited to the liver.

GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): A novel CTNNB1 rearrangement.

Mutations of CTNNB1 have been implicated in tumorigenesis in many organs. However, tumors harboring a CTNNB1 translocation are extremely rare and this translocation has never been reported in a uterine mesenchymal neoplasm. We report a novel translocation t(2;3)(p25;p22) involving the GREB1 (intron 8) and CTNNB1 (exon 3) in a uterine tumor resembling ovarian sex cord tumor (UTROSCT), which exhibited extrauterine metastasis. The translocation detected by RNA-sequencing was validated by RT-PCR, and resulted in nuclear expression of ß-catenin. Juxtapositioning with GREB1, which is overexpressed in response to estrogens, resulted in overexpression of a truncated and hypophosphorylated nuclear ß-catenin in the primary and recurrent tumors. This accumulation of nuclear ß-catenin results in a constitutive activation of the Wnt/ß-catenin signaling pathway with a major oncogenic effect. The CTNNB1 gene fusion, promoted by an estrogen-responsive gene (GREB1), could be a potential driver of tumorigenesis in this case and a therapeutic target with adapted inhibitors. RT-PCR and immunohistochemistry performed on 11 additional UTROSCTs showed no CTNNB1 fusion transcript or nuclear ß-catenin immunoreactivity.

Macrovascular venous invasion of pancreatic neuroendocrine tumours: impact on surgical outcomes and survival.

BACKGROUND: This study evaluates the impact of macrovascular venous invasion (MVI) on surgical and survival outcomes of pancreatic neuroendocrine tumours (PNETs). METHODS: We retrospectively reviewed data of 125 patients operated for PNETs. Operative, pathological,and survival outcomes were compared between PNETs with and without MVI. RESULTS: Macrovascular venous invasion was detected in 25 of 125 PNETs (20%) presenting as tumour thrombi (n = 12) or venous wall invasion (n = 13). MVI was associated with larger tumours, a higher rate of lymph node involvement, less differentiated tumours, and a higher rate of perineural invasion. Resection of PNETS with MVI more often necessitated combined hepatic, venous and multivisceral resections, had a higher rate of intraoperative blood transfusion (p = 0.04) but similar morbidity (44% vs. 42%) and mortality (0 vs. 1%) as PNETs without MVI. PNETs with MVI had a lower median overall survival rate (60 vs. 149 months; p = 0.03). Multivariate analysis revealed that PNETs of the pancreatic head, synchronous liver metastases and higher tumour grade were prognostic factors for overall survival. CONCLUSIONS: MVI is found in more advanced PNETs. Resection of PNETs with MVI is characterized by increased transfusion rate and reduced overall survival.

Head-to-head comparison between 18F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas.

PURPOSE: Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of 18F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. METHODS: Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both 18F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further 18F-FDOPA PET/CT and/or MRA. RESULTS: 18F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. 18F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. 18F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, 18F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. CONCLUSION: 18F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that 18F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when 68Ga-labeled somatostatin analogues are not available.

Feasibility and reliability of pancreatic cancer staging using a new confocal non-fluorescent microscopy probe: a double-blind study in rats.

BACKGROUND: Surgical management of pancreatic cancer depends on tumor resectability and staging. Lymph node (LN) metastases represent an important decision-making factor when it comes to surgical treatment. AIMS: To evaluate a new in vivo, endoscopic confocal microscopy (CM) system not requiring fluorescence markers, for detection and staging of pancreatic cancer in rats. METHODS: A confocal system consisting of a confocal scanning laser operating in reflection mode and a dedicated rigid Hopkins rod-lens endoscope were used for in vivo imaging in a rat model of pancreatic ductal adenocarcinoma. A double-blind study compared CM to standard histology in (1) the detection of tumors in rat bearing cancer (n = 11) and controls (n = 6), and (2) in the detection of local nodal involvement at 3 and 6 weeks after tumor induction. RESULTS: CM detected all pancreatic tumors with 100 % sensitivity and specificity and identified 15 metastatic LNs with an average adenocarcinoma nodule diameter of 2.3 mm (range from 1 to 4.2 mm) out of the 66 examined. CM demonstrated a sensitivity of 87.5 % and a specificity of 98 % in LN detection. The Spearman's rank correlation/rho calculator was of 0.87. CM demonstrated a negative predictive value of 96.1 % and a positive predictive value of 93.3 % in the detection of metastatic LNs. CONCLUSIONS: Interpretation of confocal images has a high concurrence rate with histopathology examination for primary tumor and lymphatic involvement detection making it a promising technique for in vivo real-time detection and staging of pancreatic cancer. Larger studies are warranted to confirm these preliminary results.

[The RENAPE network: towards a new healthcare organization for the treatment of rare tumors of the peritoneum. Description of the network and role of the pathologists]. / Réseau RENAPE : vers une nouvelle organisation des soins pour le traitement des tumeurs rares du péritoine. Description du réseau et rôle des pathologistes.

As part of the national 2009-2013 Cancer Plan, and with the support of the National cancer Institute and the French ministry of health, the National network for the treatment of rare peritoneal malignancies (RENAPE) has been organized. Its main objective is to optimize the framework for the healthcare management and treatment of rare peritoneal malignancies. This specific organization covers the whole national territory including clinical expert and specialized structures and should lead to an appropriate treatment based on expertise and proximity. Within the RENAPE network, the RENA-PATH group gathers the pathologists actively involved in the management of rare peritoneal malignancies. The actions of RENA-PATH are focused primarily on the harmonization of pathological diagnostic criteria, reporting of new cases in the RENAPE registry and histology reviewing.

[Peritoneal pseudomyxoma: an overview emphasizing pathological assessment and therapeutic strategies]. / Mise au point sur le pseudomyxome péritonéal. Aspects anatomo-pathologiques, et implications thérapeutiques.

Pseudomyxoma peritonei is a clinical entity characterized by a gelatinous ascite associated with mucinous tumor deposits spreading on peritoneal surface and potentially invading abdominal organs. It is considered as a tumor process linked, in most of cases, to a mucinous appendiceal neoplasm. Pseudomyxoma peritonei may benefit from a therapeutic strategy combining cytoreductive surgery and intra-peritoneal chemotherapy, which has led to a major prognosis improvement. Different classifications are available and the last one corresponds to the WHO 2010 version, which individualizes pseudomyxoma peritonei in two classes: low grade and high grade mucinous carcinoma. The very low frequency of this entity and its specific therapeutic strategy need specific health care centres, as well as physicians and pathologists collaborating through dedicated networks. The aim of this article is to summarize the pathology, causes, mechanisms and therapeutic approaches of pseudomyxoma peritonei, as well as their interfaces with dedicated networks.

[Peritoneal malignant mesothelioma: review and recent data]. / Mésothéliome malin péritonéal : mise au point et données actuelles.

Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.