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Hepato-Pancreato-Biliary (HPB) malignancies constitute a highly aggressive group of cancers that have a dismal prognosis. Patients not amenable to curative intent surgical resection are managed with systemic chemotherapy which, however, confers little survival benefit. Antibody-Drug Conjugates (ADCs) are tripartite compounds that merge the intricate selectivity and specificity of monoclonal antibodies with the cytodestructive potency of attached supertoxic payloads. In view of the unmet need for drugs that will enhance the survival rates of HPB cancer patients, the assessment of ADCs for treating HPB malignancies has become the focus of extensive clinical and preclinical investigation, showing encouraging preliminary results. In the current review, we offer a comprehensive overview of the growing body of evidence on ADC approaches tested for HPB malignancies. Starting from a concise discussion of the functional principles of ADCs, we summarize here all available data from preclinical and clinical studies evaluating ADCs in HPB cancers.
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Neoplasias del Sistema Biliar , Inmunoconjugados , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Inmunoconjugados/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
Retroperitoneal ganglioneuroma (RGN) is a rare benign tumor that arises from the retroperitoneal sympathetic ganglia composed of mature Schwann cells, ganglion cells and nerve fibers. These tumors can occur anywhere along the paravertebral sympathetic plexus and occasionally from adrenal medulla. Although they grow in excessive size, they may cause compression to adjacent organ or structures thus giving rise to symptoms. Resecting RGN's is a challenging endeavor, as they tend to encase neighboring vessels to their site of origin. The reported case is a 43-year-old male who presented with lumbar pain that increased progressively in intensity over the last 6 months. Preoperative investigations revealed a large tumor with encasement of the origins of the superior mesenteric artery and bilateral renal arteries. The tumor was completely resected and the final pathology confirmed the diagnosis of RGN.
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OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1âyear in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.
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Benchmarking/normas , Neoplasias de los Conductos Biliares/cirugía , Hepatectomía/normas , Tumor de Klatskin/cirugía , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Asia/epidemiología , Neoplasias de los Conductos Biliares/epidemiología , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Tumor de Klatskin/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Pancreatic fistula (PF) remains the primary source of morbidity after distal pancreatectomy (DP). There is currently no optimal stump closure technique to reduce PF rates. We present a novel technique for pancreatic stump closure using Clip Ligation of the duct and Associated Suturing of Pancreas (CLASP). Five patients (three females) with a median age of 65 years underwent DP and splenectomy for pancreatic body or tail tumour using the CLASP technique. Four of those operations were done laparoscopically. Only one patient developed grade A PF. No other postoperative complications were noticed. The mean length of stay was 5.4 days. The CLASP technique was applicable in both laparoscopic and open distal pancreatectomy. The key points include mobilisation of the pancreatic body from the retroperitoneum and division of the parenchyma with energy device. The technique of pancreatic stump closure involves the isolation of the pancreatic duct (PD), application of a double ligaclip on the proximal duct, division of the PD and finally suturing of the pancreatic stump. The CLASP technique is an effective and safe alternative technique to the current traditional methods of pancreatic stump closure.
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Abdomen/cirugía , Colectomía , Hepatectomía , Hipertensión Portal/cirugía , Hepatopatías/cirugía , Pancreaticoduodenectomía , Derivación Portosistémica Quirúrgica , Enfermedad Crónica , Colectomía/efectos adversos , Hepatectomía/efectos adversos , Humanos , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Hepatopatías/complicaciones , Hepatopatías/diagnóstico , Hepatopatías/fisiopatología , Pancreaticoduodenectomía/efectos adversos , Presión Portal , Derivación Portosistémica Quirúrgica/efectos adversos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Gallbladder duplication can present a clinical challenge primarily due to difficulties with diagnosis and identification. Recognition of this anomaly and its various types is important since it can complicate a gallbladder disease or a simple hepatobiliary surgical procedure. The case report of a 63-year-old woman who presented with cholangitis and underwent a successful laparoscopic management of symptomatic gallbladder duplication is described, emphasizing several important considerations. Using ERCP, MRCP and 3D reconstructions the two cystic ducts with one common bile duct were identified. A review of the literature in referral of this variant, its anatomical classifications and significance to clinical and surgical practice is included. In conclusion, gallbladder anomalies should be anticipated in the presence of a cystic lesion reported around the gallbladder when evaluating radiologic studies. In case of surgery, preoperative diagnosis is essential to prevent possible biliary injuries or reoperation if accessory gallbladder has been overlooked during initial surgery. Laparoscopic cholecystectomy remains feasible for intervention can be safely done and awareness is necessary to avoid complications or multiple procedures.
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Colangitis/etiología , Enfermedades de la Vesícula Biliar/congénito , Vesícula Biliar/anomalías , Enfermedad Aguda , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética/métodos , Colangitis/diagnóstico , Colecistectomía Laparoscópica/métodos , Diagnóstico Diferencial , Femenino , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/cirugía , Enfermedades de la Vesícula Biliar/complicaciones , Enfermedades de la Vesícula Biliar/diagnóstico , Humanos , Imagenología Tridimensional , Persona de Mediana EdadRESUMEN
BACKGROUND: Both pre- and postconditioning have been shown to protect the liver parenchyma from ischemia/reperfusion (I/R) injury during hepatectomy by altering the production of NO. However, to date there is no study to compare their effect on the inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) gene expression, who are the main modulators in the pathway of NO during the acute phase of I/R injury. METHODS: We designed a prospective experimental cohort comprising of three groups (sham group-SG, preconditioning-PrG and postconditioning group-PoG) and consisting of 10 animals per group. All animals underwent extended hepatectomy (70%) under prolonged warm ischemia either after preconditioning or followed by postconditioning or without any protective maneuver (SG). Following reperfusion blood samples and liver biopsies were obtained at the start of reperfusion (0 hours), at 6 and 12 hours post reperfusion. iNOS and eNOS gene expression was assessed on liver tissue by polymerase chain reaction (PCR); in addition, the extent of hepatocellular injury was histologically assessed. RESULTS: At the beginning of reperfusion iNOS expression was significantly reduced in the PoG in comparison to the SG (Kruskal-Wallis test, P=0.012; Mann-Whitney U test, P<0.0005 Bonferroni correction) and continued to remain at low levels until 6 hours post reperfusion (Kruskal-Wallis test, P=0.01; Mann-Whitney U test, P<0.0005-Bonferroni correction) This difference was eliminated by 12 hours. No significant differences were found in the expression of eNOS between groups and within time measurements. Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were found increased at the start of reperfusion; their levels continued to increase by 6 hours in all groups, however only in the PoG the increase attended statistical significance at 12 hours after reperfusion. ALT levels presented only minor alterations during the course of reperfusion. The PrG was found to have more intense hepatocellular injury at the start of reperfusion than the PoG however, that appeared to gradually settle by 12 hours in contrast to PoG where the hepatocellular injury continued to deteriorate. CONCLUSIONS: PoG appeared to decrease iNOS overexpression more effectively than PrG in comparison to animals who have undergone no protective maneuver (SG). However, PrG was more effective than PoG in ameliorating the hepatocellular injury observed at 12 hours after the ischemic insult.
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Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.
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Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Seudoobstrucción Intestinal/etiología , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
An inflammatory pseudotumor of the liver is a rare tumor-like lesion consisting of an inflammatory infiltrate that often can mimic a malignant liver neoplasm. The cause of an inflammatory pseudotumor of the liver is unknown, but it has been reported to be associated with different comorbid conditions most likely inflammatory or infectious in origin. We present an 83-year-old female who presented with a symptomatic gallstones disease and an incidental finding of inflammatory pseudotumor mimicking intrahepatic cholangiocarcinoma in preoperative liver imaging. Differentiating a pseudotumor from hepatic space-occupying neoplasms is crucial since it is one of the most important tumor-mimicking lesions. The imaging findings of this rare tumor can pose diagnostic difficulties because of the amount of fibrosis and cellular infiltration. If malignancy has been excluded, patients can be treated conservatively with steroids and non-steroidal anti-inflammatory drugs. However, complete surgical resection has been the modality of treatment for most of the cases with an indeterminate diagnosis.
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BACKGROUND: The aim of the study was to evaluate the safety and efficacy of extending a previous endoscopic sphincterotomy (ES) in patients with retained or recurrent common bile duct (CBD) stones. METHODS: Between 2001 and 2013, extension of a previous ES, for known or suspected CBD stones, was performed in 118 patients (m/f, 53/65) with a median age of 74 (range: 31-91) years (group A). During the same period, ES was performed in 1064 patients with suspected or known choledocholithiasis (group B). The efficacy and complications of the extension (group A) were analyzed and a comparison was made between groups regarding complications. RESULTS: Bile duct cannulation was straightforward in all patients in group A, while it was considered difficult in 49% of patients in group B. Complete clearance was achieved in 76/97 patients (78%) with CBD stones, after a mean of 1.18 attempts per patient. Mechanical lithotripsy was required in 10% of patients. After extension, immediate bleeding occurred in 24 patients (20%), which stopped spontaneously in 9 (37%) and endoscopic hemostasis was required in the remainder. Complications were more frequent in group B (5.3% vs. 0.8%, P=0.031), but there was no significant difference for any individual complication. Immediate bleeding was more common in group B (29% vs. 20%, P=0.035), but there was no difference in clinical bleeding. CONCLUSION: Extension of a previous ES seems to be a simple, effective and safe technique, allowing stone clearance in nearly 80% of patients; it is thus recommended in patients with CBD stones after ES.
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An appendiceal mucocele is a dilatation of the appendix and it is the result of benign or malignant diseases, which cause the obstruction of the appendix and the consequent accumulation of mucus secretion. The preoperative diagnosis is difficult due to non-specific clinical manifestations of the disease. We present a case of an 83-year-old female patient with a history of breast cancer that was referred to our hospital for an evaluation of a right adnexal mass discovered during her yearly follow-up. The patient underwent an exploratory laparotomy with a provisional diagnosis of a right adnexal mass. A perioperative, appendiceal mucocele was diagnosed. She underwent a formal appendectomy and histopathology of the specimen revealed a low-grade mucinous neoplasm. Appendiceal mucinous neoplasms represent a rare form of pathology among all appendectomy specimens. A preoperative diagnosis is difficult due to the lack of specific symptoms and it is often misdiagnosed as an adnexal mass. The perforation of the appendix and subsequent extravasation of its contents into the abdominal cavity may lead to pseudomyxoma peritonei, which has a very poor prognosis if not treated properly.
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Biliary mucinous cystic neoplasms of the liver are rare cystic tumors comprising less than 5% of the liver cystic neoplasms. These tumors demonstrate a female predominance and entail a risk of malignant transformation. We present a 56-year-old female patient with a multiloculated liver cystic lesion measuring 22 cm who underwent a cystectomy with en bloc resection of the liver segments II, III, and cholecystectomy. Serum cancer antigen 19.9 was 4,122.00 U/ml, supporting the diagnosis of a biliary cystic tumor. The cytology of the cystic fluid was negative for malignancy and intracystic fluid cancer antigen 19.9 level was measured over 12,000.00 U/l. The patient is free of recurrence at one-year follow up. Although a rare entity, the biliary mucinous cystic neoplasms should be considered in the differential diagnosis in the patients with liver cystic tumors. The appropriate management with complete surgical resection with negative margins is recommended given the risk of recurrence and malignant transformation.
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Positron emission tomography-computed tomography (PET/CT) improves the diagnostic interpretation of fluorine-18 fluorodeoxyglucose (18F-FDG ) PET and CT in oncologic patients and has an impact on both diagnostic and therapeutic aspects of patient management. However, false positive findings from the PET/CT imaging should be taken into consideration as they mislead physicians into improper therapeutic actions. We present a 48-year-old female patient with a history of left colectomy for colorectal cancer and subsequent liver metastasectomy. After one year of follow-up, she presented with a highly suspicious lesion in the liver, which was confirmed on PET/CT as a metastatic liver tumor. Consequently, the patient underwent surgical excision of the tumor, and the definitive histological diagnosis showed a granulomatous tissue with giant cells and foreign body tissue reaction. Based on this report, we briefly review the dangerous pitfalls from radiological and PET/CT imaging concerning the preoperative diagnostic workup examination, as they may significantly alter the treatment plan in oncologic patients.
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BACKGROUND: Ingestion of caustic substances is a medical emergency in both the adult and pediatric population and is associated with high morbidity and mortality. The extent of injuries after ingestion of caustic substances depends on the nature, amount, and concentration of the agent and on the exposure time. Acutely, caustic substances may cause massive hemorrhage and gastrointestinal tract perforation; the most markedly affected cases require urgent surgical treatment. Patients surviving the initial event may present with aorto-enteric or gastrocolic fistulae, esophageal strictures, dysphagia, and increased risk of esophageal cancer as long term sequelae. CASE REPORT: The features of three cases of caustic ingestion are reported to demonstrate significantly different complaints presented at the emergency department. Two patients had free gastric perforation, one at presentation, and one delayed. The third patient presented with late severe strictures of the esophagus and pylorus. The outcomes of the three patients are discussed in detail along with the most current management strategies. CONCLUSIONS: Among adults, ingestion of caustic substances is usually associated with more severe lesions due to the increased amount of ingested substance, as compared with pediatric patients. The most serious presentation is that of visceral perforation, most commonly of the stomach and rarely of the esophagus. Management involves urgent resuscitation with correction of fluid and electrolyte and acid-base abnormalities and immediate surgical exploration in those patients with signs of perforation. Once the perioperative period is managed successfully, the long-term results can be satisfactory. Managing of strictures or else reconstructive procedures must be well timed to allow for psychological and nutritional rehabilitation.
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Quemaduras Químicas/complicaciones , Cáusticos/toxicidad , Estenosis Esofágica/inducido químicamente , Estómago/lesiones , Administración Oral , Adulto , Anciano , Servicio de Urgencia en Hospital , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Introduction and Aim. With the implementation of multimodal analgesia regimens, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are often administered for optimal pain control and reduction of opioid use. The aim of the study was to examine the effects of lornoxicam, a NSAID, on anastomotic healing employing an animal model. Materials and Methods. A total of 28 Wistar rats were randomly assigned in two groups. All animals underwent ascending colonic transection followed by an end-to-end hand sewn anastomosis. Group 1 received intraperitoneally lornoxicam before and daily after surgery. Group 2 received intraperitoneally an equal volume of placebo. Half of the animals in each group were euthanized on the 3rd pod and the remaining on the 7th pod. Macro- and microscopic indicators of anastomotic healing were compared using a two-tailed Fisher exact test. Results. The lornoxicam group significantly decreased fibroblast in growth and reepithelization of the mucosa at the anastomotic site on the 3rd pod and significantly increased occurrence of deep reaching defects, necrosis, and microabscess on the 7th pod. Conclusion. Lornoxicam administration during the perioperative period adversely affects histologic parameters of intestinal anastomotic healing. These effects of lornoxicam administration were not found to induce significant increase of anastomotic dehiscence in the rat model.
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When confronting a biliary stricture, both benign and malignant etiologies must be carefully considered as a variety of benign biliary strictures can masquerade as hilar cholangiocarcinoma (CCA). Therefore, patients could undergo a major surgery despite the possibility of a benign biliary disease. Approximately 15% to 24% of patients undergoing surgical resection for suspected biliary malignancy will have benign pathology. Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract, which can cause obstructive jaundice and can pose a difficult diagnostic task. We present a rare case of a young woman who was referred to our hospital with obstructive painless jaundice due to a biliary stricture at the confluence of the hepatic bile ducts, with a provisional diagnosis of cholangiocarcinoma. Though, during her work up she was found to have EC, an extremely rare benign cause of biliary stricture, which is characterized by a dense eosinophilic infiltration of the biliary tree causing stricturing, fibrosis, and obstruction and which is reversible with short-term high-dose steroids. Despite its rarity, EC should be taken into consideration when imaging modalities demonstrate a biliary stricture, especially if preoperative diagnosis of malignancy cannot be made, in the setting of peripheral eosinophilia and the absence of cardinal symptoms of malignancy.
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Colangitis/inducido químicamente , Colangitis/diagnóstico , Constricción Patológica/fisiopatología , Eosinofilia/diagnóstico , Eosinofilia/fisiopatología , Adulto , Conductos Biliares , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
Morel-Lavallée lesions are cystic lesions occurring between the subcutaneous tissue and the underlying layer of a fascia. The most frequent mechanism of occurrence is posttraumatic, usually after degloving injuries. The chain of events leading to the occurrence of this lesion is the formation of a potential space between the subcutaneous tissue and the firmly attached deep fascia, which in turn fills with blood and/or lymph and/or necrotic fat, secondary to disruption of the capillaries. We present a case of a 74-year-old male patient with a cystic lesion of the lateral surface of his left thigh increasing in size over a period of six months. Despite the meticulous history acquisition, we were unable to reveal any alleged mechanism of injury of the area. The patient underwent an MRI which revealed an ovoid cyst. The patient underwent surgical excision of the cyst. The pathology examination revealed a simple cyst, lined by a fibrous capsule and filled with serosanguineous fluid, thus confirming the diagnosis. The patient made a full recovery and since has been asymptomatic.
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Merkel cell carcinoma (MCC) is a rare skin malignancy associated with sun exposure and considered as a Neuroendocrine Tumor due to its characteristic histologic features. However there is increasing number of reports of Unknown Primary MCC's (UPMCC). Although initially UPMCC was considered a variant of known primary MCC, there is growing evidence that it could represent a different clinical entity. We present the case of a 60 year-old male patient who was referred to our department for surgical management of lymph node disease for UPMCC. The patient had undergone excisional biopsy of an inguinal lump, which was found to be an infiltrated lymph node by MCC. The patient underwent full imaging staging including a PET/CT, which failed to identify a primary site, and revealed only intra-abdominal lymph node disease. The patient underwent extended retroperitoneal and inguinal lymph node dissection and remains free of recurrence 16 months postoperatively.
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CONTEXT: Chronic inflammatory vasculitis, namely Wegener's granulomatosis, is an autoimmune disease predominantly affecting the respiratory tract and rarely the mucosa of the upper or lower gastrointestinal tract. We report two cases of isolated pancreatic manifestation of Wegener's granulomatosis, mimicking a tumor. CASE REPORTS: Two patients, a 57-year-old man and a 68-year-old woman, presented with isolated lesions thought to be pancreatic adenocarcinoma and both underwent surgical resection. On pathology, the lesions were found to be a granulomatous vasculitis and were considered to represent isolated pancreatic Wegener's granulomatosis, in the absence of other clinical features of the disease. CONCLUSIONS: Benign diseases such as Tuberculosis may mimic pancreatic tumours diagnosed on cross-sectional imaging. Wegener's granulomatosis should be included in the differential diagnosis of an isolated pancreatic mass, in the absence of other cardinal symptoms for malignancy, due to the extensive surgery and risks involved in resection of pancreas.