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Stefano Crippa

Publications and source records attributed to Stefano Crippa.

At least 19 recordsLinked to original sources
PubMed2025

Optimized GMP-grade production of non-viral Sleeping Beauty-generated CARCIK cells for enhanced fitness and clinical scalability.

BACKGROUND: Strict adherence to GMP guidelines and regulatory compliance is crucial when transitioning from research to clinical-grade production of ATMPs like CAR T cells. The success of CAR T cell therapy in treating hematological malignancies highlights the need for closed or automated systems to ensure quality and efficacy. Recent evidence also suggests that ex vivo culture conditions can significantly impact CAR T cell functionality. METHODS: We present our optimized methodology for expanding Sleeping Beauty transposon-engineered Chimeric Antigen Receptor-Cytokine-Induced Killer (CARCIK) cells using G-Rex devices and evaluate its impact on CARCIK cell phenotype and T cell fitness. RESULTS: Building on our previously validated protocol, we introduced key simplifications to optimize the CARCIK differentiation process. Delaying the nucleofection step eliminated the need for feeder cells while maintaining efficient CAR expression and high cell viability. Transitioning from T-flasks to G-Rex bioreactors reduced operator hands-on time from 21 to 28 days to 14-17 days and resulted in a less differentiated CARCIK cell product. Metabolic and transcriptional analyses showed that the novel protocol improves CARCIK cell fitness and in vivo efficacy against B-cell lymphoma. The novel method was validated in Good Manufacturing Practices (GMP) conditions at our two Cell Factories and yielded enough numbers of CARCIK-CD19 cells for clinical use. CONCLUSIONS: Optimizing non-viral CARCIK cell production using G-Rex bioreactors and refined timing adjustments has streamlined the workflow, enhanced cell fitness, and resulted in a highly effective therapeutic product with demonstrated in vivo efficacy in mice. These improvements reduced manipulation and contamination risks, while optimizing logistics and space efficiency, facilitating allogeneic CARCIK generation for a current phase I/II clinical trial (NCT05869279) in patients with R/R CD19 + non-Hodgkin Lymphoma (B-cell NHL) and Chronic Lymphocytic Leukemia (CLL), confirming the approach's scalability and clinical potential.

Humans↗
PubMed2006

Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate?

BACKGROUND: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are reported to be less aggressive than the main-duct type. Hence, less aggressive treatment has been proposed for the former. AIM: To evaluate the effectiveness of a follow-up protocol for BD-IPMNs. DESIGN: Prospective study. SETTING: An academic tertiary referral centre. PATIENTS: From 2000 to 2003, 109 patients with BD-IPMNs underwent trans-abdominal ultrasound and magnetic resonance cholangiopancreatography with secretin. Patients who presented malignancy-related parameters (size >3.5 cm, nodules, thick walls, carbohydrate antigen 19.9 level >25 U/l, recent-onset or worsened diabetes) and/or complained of symptoms were submitted to surgery (arm A). All asymptomatic patients without suspicion of malignancy were followed up according to a 6-month clinical-radiological protocol (arm B). MAIN OUTCOME MEASURES: The effectiveness of conservative management of BD-IPMNs. RESULTS: 20 (18.3%) patients underwent surgery (arm A); pathological diagnosis of BD-IPMNs was always confirmed. 89 (81.7%) patients were followed up for a median of 32 months (arm B); of these, 57 (64%) patients had multifocal disease. After a mean follow-up of 18.2 months, 5 (5.6%) patients showed an increase in lesion size and underwent surgery. The pathological diagnosis was branch-duct adenoma in three patients and borderline adenoma in two. CONCLUSIONS: Surgery is indicated in <20% of cases of BD-IPMNs, and, in the absence of malignancy-related parameters, careful non-operative management seems to be safe and effective in asymptomatic patients. Although observation for a longer time is needed to confirm these results, our findings support the guidelines recently recommended by the International Association of Pancreatology.

Adenocarcinoma, Mucinous↗
PubMed2006

Gastric metastasis by lung small cell carcinoma.

Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity.

Carcinoma, Small Cell↗
PubMed2006

Surgical strategy in the treatment of pancreatic neuroendocrine tumors.

Endocrine pancreatic tumors are rare and their surgical treatment is often debated. This review analyzes the management and the different indications in functioning and non-functioning neoplasms. The choice among different procedures is described as well as the role of intra operative ultrasound. Moreover, the different patterns of tumor spread are considered (local, loco-regional and metastatic) along with the indications according to the main controversies relating to cytoreductive surgery, transplantation and multiple endocrine neoplasia type 1 patients.

Cholecystectomy↗
PubMed2006

Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature.

BACKGROUND: Unlike primary pancreatic carcinoma, metastases to the pancreas are rare, and their resection may be performed as palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases. MATERIALS AND METHODS: Between January 1994 and December 2004 13 patients (nine women and four men; median age: 59 years; range: 36-79 years) were admitted to our institution with metastatic lesion to the pancreas. The clinical features of the treatment and results were examined. RESULTS: Primary tumors were renal cell carcinoma (n=5), lobular carcinoma of the breast (n=3), endometrioid carcinoma of the ovary (n=1), colonic adenocarcinoma (n=1), jejunal leiomyosarcoma (n=1), melanoma (n=1), and non-small-cell lung cancer (n=1). The median interval between primary tumor and pancreatic metastases was 36 months (range: 5-192 months). Six patients (46%) were asymptomatic, while the other seven patients presented with jaundice, pain, and duodenal obstruction. Two patients with extrapancreatic disease underwent palliative surgery, and the remaining 11 patients underwent operative procedures that included seven pancreaticoduodenectomy and four distal pancreatectomies with splenectomy. Postoperative mortality was nil, and the morbidity rate was 30%. The two patients who underwent palliative surgery died after 7 and 9 months, respectively. The median survival of the resected patients was 26 months (range: 13-95 months). Five patients died of disease, eight are alive at the time of this report. CONCLUSION: A trend towards improved survival, even if not statistically significant, was observed in the renal carcinoma patients reported here. Surgical resection can be performed safely in selected patients with isolated metastases to the pancreas, achieving long-term survival as well as good palliation.

Adult↗
PubMed2006

Complications after pancreaticoduodenectomy: the problem of current definitions.

Pancreaticoduodenectomy nowadays represents a complex procedure and a challenge for the surgeon. Even though mortality is reported to be below 5% for experienced surgeons, morbidity is still around 30%-50%, often leading to prolongation of hospital stay, demanding postoperative investigations and procedures, and outpatient monitoring of the patients with complications. In the literature there is no agreement on the definitions of postoperative complications following pancreaticoduodenectomy, leading to a wide range of complication rates in different specialist units, particularly regarding the source of every complication, postoperative pancreatic fistula, and others such as delayed gastric emptying. Some authors have demonstrated that applying different definitions in homogeneous, single-center series, the incidence of a complication varied with statistical significance, implying the impossibility of correctly comparing different experiences. It seems essential to organize a Consensus Meeting among expert surgeons to prepare world-wide accepted definitions. The aim of this article is to review the current controversial definitions and to suggest a new clinical-based approach to the problem of the feasibility and reliability of the definitions themselves.

Abdominal Abscess↗
PubMed2005

Colorectal cancer with neuroendocrine differentiation in a child.

Colorectal cancer is extremely rare in children and presents with a poor prognosis because of the delay in diagnosis and lack of histological differentiation. We report a case of a sigmoid colon carcinoma with areas of neuroendocrine cells in a 12-year-old patient without familial occurrence of colorectal cancer. Symptoms at presentation were anaemia, anorexia, abdominal pain and weight loss. The patient was treated with radical resection and adjuvant chemotherapy. One year later, a local recurrence and hepatic metastases were diagnosed and she underwent chemotherapy and surgical resection. Twenty-six months from initial diagnosis she is alive with evidence of disease. The clinical presentation, diagnosis and treatment of the previously reported cases of colorectal cancer in children are also reviewed.

Adenocarcinoma↗
PubMed2005

Palliative management strategies of advanced gastrointestinal carcinoid neoplasms.

BACKGROUND/AIMS: Optimal management of gastrointestinal carcinoid neoplasms that metastasize to the liver is controversial. Although operative resection seems to be the most effective approach to metastatic disease, hepatic metastases are usually multicentric and often non-resectable. We investigated the effectiveness of several forms of palliative tumor cytoreduction followed by administration of somatostatin analogues in advanced carcinoid neoplasms. METHODS: We reviewed our experience with 34 patients with gastrointestinal carcinoid neoplasms. Eighteen patients had metastases and 14 had hormonal symptoms. Twenty-two patients underwent radical surgery, ten with multiple liver metastases were treated with a combination of debulking (resection, radiofrequency ablation, chemoembolization), followed by medical treatment with long-acting octreotide and eventually by radiolabelled somatostatin analogues, and two patients with intractable disease received only biotherapies. RESULTS: The six patients with metastatic disease who underwent radical curative liver resection had a median survival of 52 months, compared with a median survival of 48 months in the ten patients who underwent palliative debulking. Symptomatic improvement was observed in all the patients after debulking procedures. The two patients who underwent only medical treatment died after 9 and 18 months. CONCLUSIONS: Aggressive tumor debulking should be performed in patients with liver metastases already at diagnosis even when complete resection is not feasible because the combination of cytoreductive procedures followed by biotherapies may provide good long-term survival and achieves symptom control in most patients with advanced disease.

Adult↗
PubMed2005

Intraductal papillary mucinous tumors of the pancreas. Surgical treatment: at what point should we stop?

The intraoperative management of the margins of intraductal papillary mucinous tumors (IPMNs) undergoing pancreatic resection is crucial. The surgeon must discontinue the resection whenever the pancreatic margin is negative and, of course, when a total pancreatectomy is indicated.Nevertheless, a wide gray area exists. The real surgical problems are represented by i) IPMNs involving only a segment of the pancreatic gland, thus necessitating intraoperative histological examination of the resection and the decision as to "when to stop the resection"; ii) the intraoperative management of those margins which are neither clearly negative nor clearly positive; iii) the actual indications either for surgery or for follow-up in those patients affected by peripheral IPMNs. In the literature, negative resection margins have a range of between 49 to 81% with a pancreatic recurrence rate of from 0 to 25% in follow-ups ranging from 6 months to 11 years after the first operation. In general, in this disease which mainly involves the head and uncinate process of the gland, decisions are a "balance" between the patient and the disease. In fact, on the one hand, there is the usual elderly patient with possible comorbidities, symptoms and the presence of diabetes; on the other hand, the disease, which usually involves the head and the uncinate process of the gland, tends to grow along the duct and be potentially malignant if carcinoma is not already present.

Adenocarcinoma, Mucinous↗
PubMed2004

Pancreaticoduodenectomy for pancreatic metastases from breast carcinoma.

CONTEXT: Unlike primary pancreatic carcinoma, metastases to the pancreas are rare events and their resection may be performed as a palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases from breast carcinoma. CASE REPORT: Three patients underwent pancreaticoduodenectomy for pancreatic metastases from breast carcinoma between 1990 and 2002. The clinical features of and the results after resection were examined. The presenting clinical symptoms were jaundice, pain and weight loss. In all cases, the pancreatic metastases were solitary lesions located in the head of the pancreas and the intervals between the primary breast carcinoma and the pancreatic metastases were 3, 5 and 7 years. The primary tumor was lobular carcinoma. Metastases were initially misdiagnosed as primary cancers. All patients underwent pancreaticoduodenectomy. One patient died from disseminated metastatic disease 26 months after surgery. The other two patients are alive 37 and 21 months after pancreaticoduodenectomy; the second one has had recurrence of the disease. CONCLUSION: In rare cases, the pancreas may be the presenting site for breast metastases, typically years after treating the primary tumor. Pancreaticoduodenectomy can be performed in the absence of extreme metastatic disease; it can provide worthwhile palliation and improve survival.

Adult↗
PubMed2004

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature.

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.

Gallbladder Neoplasms↗
PubMed2003

Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.

BACKGROUND/AIMS: in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. METHODOLOGY: 40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients. RESULTS: increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days. CONCLUSIONS: it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Open pancreaticogastrostomy after pancreaticoduodenectomy: a pilot study.

Management of the pancreatic stump following pancreaticoduodenectomy (PD) has always been a main source of concern among pancreatic surgeons. The present pilot study describes the reconstructive technique of anterior transgastric pancreaticogastrostomy (PG) after pylorus-preserving PD. Outcome in 50 patients with "soft" residual parenchyma treated with this technique is also reported. The average duration of the intervention was 351 minutes (range, 240-360); only two patients needed intraoperative transfusion with 2 units of blood. The postoperative period involved complications in 15 cases (30%). In particular, four patients developed pancreatic fistulas (8%), which were grade C in three cases (6%) and grade B in one patient (2%). Two patients (4%) presented with enteric fistula from erosion from a drain. Two patients experienced perianastomotic fluid collections associated with delayed gastric emptying (4%) and a clinically silent 5-cm abdominal collection was observed in an additional case. Bleeding of a gastric ulcer was treated in one case and four patients developed bronchopneumonia. None of the complications required a second surgical intervention and there were no deaths. One patient with a symptomatic fluid collection was treated by ultrasound-guided cutaneous drainage. The mean hospitalization time was 11.1 days (range, 8-25 days). The results obtained in this pilot study appear encouraging and merit further analysis in a randomized comparative trial.

Adult↗
PubMedDate not supplied

Gallbladder carcinoid: a case report.

Carcinoids are neuroendocrine tumours that rarely originate in the biliary tract. We report a case of gallbladder carcinoid associated with cholelithiasis extending to hepatic segments IV and V. The mass was detected by ultrasound in a 71-year-old-man investigated for recurrent right upper quadrant pain irradiating to the back and associated with dyspepsia. Cholecystectomy, locoregional lymphadenectomy and 4th and 5th hepatic segment resection were performed. The patient underwent chemotherapy and was also treated with somatostatin analogues. Despite this, he died after 12 months. We stress the rarity and aggressive behaviour of gallbladder carcinoid.

Aged↗
PubMedDate not supplied

[Laparoscopic pancreatic resection: preliminary experience].

The aim of the study was to evaluate the results of laparoscopic pancreatectomy for pancreatic tumours. Four women and three men underwent laparoscopic pancreatectomy and were recruited into the study retrospectively over the period from June 2002 to February 2004. Pancreaticoduodenectomy (n = 4), intermediate pancreatectomy (n = 1) and distal pancreatic resection with splenectomy (n = 2) were successfully performed. Operative mortality was nil. The postoperative morbidity included two low-output pancreatic leaks. Mean operating time, blood loss and hospital stay were 342 minutes, 289 mL and 14 days, respectively. The pathological diagnosis was ductal adenocarcinoma in one, neuroendocrine tumour in five and metastatic melanoma in one. All patients are still well after a median follow-up of 7 months (range: 1-20 months). The patients appear to benefit from laparoscopic pancreatectomy for pancreatic tumours. The minimally invasive approach ensures adequate treatment but requires the expertise of highly skilled laparoscopic surgeons.

Adult↗
PubMedDate not supplied

Preoperative interleukin-2 immunotherapy in pancreatic cancer: preliminary results.

BACKGROUND/AIMS: Cancer patients' immunodeficiency, made worse by surgery, represents a poor prognostic factor for postoperative complications and long-term survival. Interleukin-2 has been shown to contrast the immunodeficiency related to the tumor and surgical treatment. The aim of this study is to evaluate the effectiveness of preoperative immunotherapy with interleukin-2 in pancreatic cancer patients. METHODOLOGY: 19 patients with pancreatic cancer undergoing radical surgery were divided in 2 different groups. Group 1: 9 patients treated with preoperative Interleukin-2 (9 million IU of IL-2 s.c. for 3 consecutive days) followed by pancreaticoduodenectomy after 36 hours; group 2: 10 patients who underwent pancreaticoduodenectomy without any neoadjuvant treatment. Two groups were well matched for age, sex, stage of disease, preoperative tumor markers and preoperative hematological assessment. Inflammatory cells' infiltration on the resected specimens, pre- and postoperative blood lymphocyte counts were evaluated as well as postoperative complications and survival and compared between the groups. RESULTS: Hematological and histological findings showed no significant difference between the 2 groups. Postoperative complications were more frequent in the control than in the treated group (p<0.05). Two-year survival was 33% in the treated group compared with 10% in the control (p<0.05). CONCLUSIONS: Preoperative Interleukin-2 administration seems to achieve a positive effect on postoperative complications and survival in pancreatic adenocarcinoma.

Adenocarcinoma↗