Pancreatic ductal adenocarcinoma complete regression after preoperative chemotherapy: Surgical results in a small series.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) becomes a systemic disease from an early stage. Complete surgical resection remains the only validated and potentially curative treatment; disappointingly only 20% of patients present with a resectable tumour. Although a complete pathological regression (pCR) after the preoperative chemotherapy could intuitively lead to better outcomes and prolonged survival some reports highlighted significant rates of recurrence. CASES PRESENTATION: We describe three cases of pCR following preoperative chemotherapy for PDAC. The first two cases received neoadjuvant mFOLFIRINOX and PAX-G scheme for borderline resectable PDAC. Recurrence appeared 9 and 12 months after surgery. Although both patients started adjuvant therapy straight after the diagnosis of recurrence, the disease rapidly progressed and led them to death 12 and 15 months after surgery. The third case was characterized by germline BRCA2 mutation. The patient presented with PDAC of the body, intrapancreatic biliary stenosis and suspected peritoneal metastasis. One year later, after first and second-line chemotherapy, she underwent explorative laparoscopy and total spleno-pancreatectomy without evidence of viable tumour cells in the surgical specimen. At six months she is recurrence-free. CONCLUSIONS: Very few reports describe a complete pathological response following preoperative chemotherapy in pancreatic cancer. We observed three cases in the last three years with disappointing oncological results. Further investigations are needed to predict PDAC prognosis in pCR after chemotherapy.

Emergency Presentation of Gastric Ectopic Pancreas.

Ectopic pancreas is a rare embryological abnormality apparently not in association with others. Stomach and duodenum are the most common organs involved. Symptoms are nonspecific. Patients may complain of dyspepsia, abdominal pain or intestinal obstruction. Malignant evolution of ectopic pancreatic cells has been reported. Diagnosis can be very challenging due to the rarity of the disease and the absence of specific symptoms and radiological findings. We report two cases of young-adult men admitted to the emergency department due to acute upper gastro-intestinal and pancreatic symptoms. In both cases, during upper gastrointestinal endoscopy no mucosal vegetations were found. Endoscopic ultrasonography revealed gastric lesions originating from the muscularis propria, with a pattern suspected but not conclusive for malignancy. Fine needle aspiration was inconclusive in both cases. The patients underwent abdominal computed tomography, that showed gastric masses originating from the antrum and the lesser curvature of the stomach, with enlarged locoregional lymph nodes. According to the patients' symptoms, family history, radiological and cytological findings, the patients were scheduled for an explorative laparoscopy. In both cases, gastric ectopic pancreas was found. Clinical presentation of ectopic pancreas is heterogeneous and the diagnosis can be challenging, especially in an emergency setting. Endoscopic ultrasonography and fine needle aspiration can be useful for the diagnosis and clinical staging, but they can be unspecific. Diagnostic-therapeutic laparoscopy should be considered in symptomatic patients.

Craniovertebral junction instability as an extension of cocaine-induced midline destructive lesions: case report.

With the increasingly widespread illicit use of cocaine, a broad spectrum of clinical pathologies related to this form of drug abuse is emerging. The most frequently used method of administration of powdered cocaine is intranasal inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal tract are common. Habitual nasal insufflations of cocaine can cause mucosal lesions. If cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate and can mimic other diseases such as tumors, infections, and immunological diseases. In the literature currently available, involvement of the craniovertebral junction in the cocaine-induced midline destructive lesions (CIMDLs) has never been reported. The present case concerns a 44-year-old man who presented with long-standing symptoms including nasal obstruction, epistaxis, dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in light of the patient's history and the findings on physical and endoscopic examinations, imaging studies, and laboratory testing. Involvement of the craniovertebral junction in the destructive process was evident. For neurosurgical treatment, the authors considered the high grade of atlantoaxial instability, the poorly understood cocaine-induced lesions of the spine and their potential evolution overtime, as well as cocaine abusers' poor compliance. The patient underwent posterior craniovertebral fixation. Understanding, classifying, and treating cocaine-induced lesions involving the craniovertebral junction are a challenge.

Primary treatment response rather than front line stem cell transplantation is crucial for long term outcome of peripheral T-cell lymphomas.

Outcome of systemic peripheral T-cell lymphomas (PTCL) is unsatisfactory and no controlled clinical study guides the therapy. Phase II studies suggest to consolidate response achieved after front-line treatment with stem cell transplant (SCT). We retrospectively evaluate the impact of front-line SCT consolidation in a single Center cohort of 209 patients treated during the last two decades. Median age was 49 years (range 15-85) with a prevalence of male sex (61%), advanced stage (68%) while IPI was >2 in 44%. Primary treatment was MACOP-B (39%) CHO(E)P (39%), intensive regimens (18%) or others (4%). Complete response to primary treatment (i.e. before SCT) was 60% (5% partial remission). Forty-four patients further proceeded to SCT while 92 did not receive consolidation. Outcome of primary responders was good, with a 3-year overall survival of 74% (82% in ALCL ALK+ and 69% for the other histologies). By multivariate analysis a better overall survival was significantly associated with IPI<2 (P=0.001), primary response (P=0.000), and ALCL ALK+ (P=0.012). The multivariate analysis performed on responders, showed that only IPI was predictive of a better survival while ALCL ALK+ and undergoing SCT were not. Response to primary treatment rather than post-remission programs is the crucial determinant of PTCL outcome.

Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have recently been identified as a therapeutic option in several clinical conditions. Whereas bone marrow (BM) is considered the main source of MSC (BM-MSC), the invasive technique required for collection and the decline in allogeneic donations call for alternative sources. Human umbilical cord (UC) represents an easily available source of MSC (UC-MSC). METHODS: Sections of full-term UC were transferred to cell culture flasks and cultured in 5% human platelet lysate (PL)-enriched medium. Neither enzymatic digestion nor blood vessel removal was performed. After 2 weeks, the adherent cells were harvested (P1), replated at low density and expanded for two consecutive rounds (P2 and P3). RESULTS: We isolated and expanded MSC from 9/9 UC. UC-MSC expanded with a mean fold increase (FI) of 42 735 ± 16 195 from P1 to P3 in a mean of 29 ± 2 days. By processing the entire cord unit, we theoretically could have reached a median of 9.5 × 10(10) cells (ranging from 1.0 × 10(10) to 29.0 × 10(10)). UC-MSC expressed standard surface markers; they contained more colony-forming unit (CFU)-fibroblast (F) and seemed less committed towards osteogenic, chondrogenic and adipogenic lineages than BM-MSC. They showed immunosuppressive properties both in vitro and in an in vivo chronic Graft versus Host disease (cGvHD) mouse model. Both array-Comparative Genomic Hybridization (CGH) analysis and karyotyping revealed no chromosome alterations at the end of the expansion. Animal studies revealed no tumorigenicity in vivo. CONCLUSIONS: UC constitute a convenient and very rich source of MSC for the production of third-party 'clinical doses' of cells under good manufacturing practice (GMP) conditions.

Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients.

AIM: To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS: Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defined as 15 buds/high-power field. RESULTS: Tumor buds and K-RAS mutation both correctly classified 68% of patients. All patients with K-RAS mutation (n = 7) or high-grade tumor budding (n = 11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P = 0.008)]. CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

Interleukin-2 immunotherapy action on innate immunity cells in peripheral blood and tumoral tissue of pancreatic adenocarcinoma patients.

BACKGROUND AND AIMS: Innate immunity cells play a crucial role in host anticancer defense: cancer patients with high levels of natural killer (NK) cells and eosinophils have a better prognosis. Recombinant interleukin-2 (rIL-2) immunotherapy stimulates innate immunity cells. This study aims to evaluate the toxicity of pre- and postoperative rIL-2 treatment and the effects on innate immunity both in peripheral blood and in cancer tissue of patients with resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Seventeen patients received high dose rIL-2 preoperative subcutaneous administration and two low dose postoperative cycles. We evaluated NK cell and eosinophil count in blood and in pancreatic surgical specimens. RESULTS: Toxicity was moderate. In the early postoperative period, blood NK cells and eosinophils significantly increased compared to basal values (p < 0.02). Histopathological analysis did not find significant intratumoral infiltration of NK cells nor of eosinophils. CONCLUSIONS: Preoperative high dose rIL-2 administration is able to counteract surgery-induced deficiency of NK cells and eosinophils in peripheral blood in the early postoperative period, although it cannot overcome local mechanisms of immune tumor escape in cancer tissue. The amplification of innate immunity, induced by immunotherapy, may improve the control of metastatic cells spreading in the perioperative period.

Prolonged survival of a patient affected by pancreatic adenocarcinoma with massive lymphocyte and dendritic cell infiltration after interleukin-2 immunotherapy. Report of a case.

Several studies have shown that there is a paucity of immune cells within the stroma of pancreatic adenocarcinoma, a very aggressive cancer with a median survival of about 18 months. A 65-year-old man presented with jaundice. Abdominal ultrasound revealed intra- and extrahepatic bile duct dilatation and a 45-mm diameter hypoechoic solid mass within the pancreatic head; a computed tomography scan excluded vascular infiltration and metastatic lesions. The patient received immunotherapy consisting of 6,000,000 IU human recombinant interleukin-2 administered subcutaneously twice a day for 3 consecutive days. Thirty-six hours after the last dose, he underwent a pylorus-preserving pancreatoduodenectomy. Because of the presence of high-grade dysplasia detected by intraoperative histological examination of a distal section, a spleen preserving total pancreatectomy was performed. The postoperative course was uneventful. The patient died 32 months after surgery because of local recurrence. Histopathology showed G3 pancreatic ductal adenocarcinoma infiltrating the anterior and posterior peripancreatic tissue, duodenal wall and intrapancreatic common bile duct, with sarcoma-like foci and a component of intraductal tumor involving the common bile duct. In the distal pancreas, widespread foci of pancreatic intraepithelial neoplasia (PanI2-3) were found. The Ki-67 proliferation index was 16%. TNM staging was pT3 pN1 R1. Sections were immunostained for the T-lymphocyte marker CD3 and for the dendritic cell marker CD1a. Intratumoral infiltration was high for CD1a+ cells and mild for CD3+ cells. Preoperative immunotherapy with interleukin-2 may contribute to massive stromal infiltration of immune cells in pancreatic adenocarcinoma. This may prolong the survival even in the presence of negative prognostic factors (age >65 years, tumor diameter >20 mm, R1, tumor grade G3).

A case of pancreatic heterotopy of duodenal wall, intraductal papillary mucinous tumor and intraepithelial neoplasm of pancreas, papillary carcinoma of kidney in a single patient.

We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure.