Jonathan S. Moulton

Total pancreatectomy and autologous Islet cell transplantation as a means to treat severe chronic pancreatitis

Autologous islet cell transplantation after near-total or total pancreatic resection can alleviate pain in patients with severe chronic pancreatitis and preserve endocrine function. From February 2000 to February 2003, a total of 22 patients, whose median age was 38 years, underwent pancreatectomy and autologous islet cell transplantation. Postoperative complications, metabolic studies, insulin usage, pain scores, and quality of life were recorded for all of these patients. The average number of islet cells harvested was 245,457 (range 20,850 to 607,466). Operative data revealed a mean estimated blood loss of 635 ml, an average operative time of 9 hours, and a mean length of hospital stay of 15 days. Sixty-eight percent of the patients had either a minor or major complication. Major complications included acute respiratory distress syndrome (n = 2), intra-abdominal abscess (n = 1), and pulmonary embolism (n = 1). There were no deaths in our series. All patients demonstrated C-peptide and insulin production indicating graft function. Forty-one percent are insulin independent, and 27% required minimal amount of insulin or a sliding scale. All patients had preoperative pain and had been taking opioid analgesics; 82% no longer required analgesics postoperatively. Pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.

Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Prevalence and Predictors of Severity as Defined by Atlanta Criteria Among Patients Presenting with Acute Pancreatitis

Introduction Effective triage of patients with acute pancreatitis is dependent on the ability to accurately predict a severe course. Predictors (e.g., APACHE II score of >8) have been tested against wide-ranging definitions of severity (prevalence, 15%–40%). To ensure uniformity in defining a severe course of acute pancreatitis, the Atlanta symposium of 1992 adopted all-encompassing criteria (local complications, systemic complications, need for surgery, or death). Aims To assess the prevalence of each Atlanta criteria for severe acute pancreatitis and to determine the sensitivity, specificity, and positive and negative predictive values of the APACHE II score as a predictor of these criteria for severe acute pancreatitis. Methodology We reviewed records of patients admitted to the University of Cincinnati Medical Center (Cincinnati, OH, U.S.A.) between 1994 and 1998 with acute pancreatitis. Exclusion criteria included referral from an outside hospital, immunocompromised state, and chronic pancreatitis. Results Seventy-four consecutive patients met our inclusion criteria. Ten patients (13.5%) had a severe course. Seven patients developed only local complications. Three patients had systemic complications. Pancreatic surgical intervention was required in four patients. No deaths occurred. An APACHE II score of >8 exhibited 50% sensitivity and 69% specificity (positive predictive value, 20%; negative predictive value, 89%). All patients with systemic complications and two of seven patients with only local complications had an APACHE II score of >8. Conclusions The prevalence of severity among our nonreferred patients with acute pancreatitis was less than previously reported. The APACHE II scoring system exhibited reasonable sensitivity in predicting systemic complications and/or the need for surgery, with a low positive predictive value. This most certainly is a function of the low pretest probability of severe pancreatitis. Future studies attempting to identify predictive systems that triage patients in a more cost-effective manner should restrict their analysis to Atlanta criteria other than local complications.

Efficacy of intrapleural tissue-type plasminogen activator in the treatment of loculated parapneumonic effusions.

PURPOSE To assess the feasibility and effectiveness of intrapleural recombinant tissue-type plasminogen activator (r-tPA) in the treatment of loculated parapneumonic effusions (PPEs). MATERIALS AND METHODS A single-arm prospective study of 25 consecutive patients with loculated PPEs was analyzed. All patients received 6-mg doses of intrapleural r-tPA on a defined schedule via a thoracostomy tube. The volume of output from the tubes was recorded and analysis of the fluid composition performed. Follow-up was both clinical and radiographic, with all patients undergoing pre- and postprocedural computed tomography. RESULTS Eighteen of the 25 patients (72%) required no additional intervention and had a complete clinical and radiographic response with the fibrinolytic therapy. Seven patients (28%) were treated with video-assisted thoracoscopic surgery, but no patient required thoracotomy for total decortication. There were no hemorrhagic complications. CONCLUSIONS Intrapleural r-tPA is effective in the treatment of loculated PPEs. It can be performed safely and in some patients may avoid the need for additional surgical intervention.

The radiologic assessment of acute pancreatitis and its complications

This review summarizes the role of radiologic tests, especially CT, in the diagnosis and assessment of acute pancreatitis and its complications. Consideration of the underlying pathologic changes of complicated pancreatitis and their radiographic correlates allows identification of the presence, extent, and nature of local complications. This information can be crucial in making appropriate management decisions. Based on these data, general guidelines for the appropriate use of CT in acute pancreatitis can be formulated. Patients with clinically mild pancreatitis in whom the diagnosis is secure probably do not require imaging as long as they respond appropriately to conservative management. In patients with clinically severe pancreatitis, early CT should be performed to evaluate the extent and nature of local complications. If radiographic changes are mild and the patient responds to conservative management, no further imaging is needed. If the patient does not respond appropriately or clinically worsens, follow-up CT should be performed, seeking delayed complications. Patients in whom the initial CT shows severe pancreatitis and peripancreatic inflammatory changes should be followed with serial CT to assess resolution. Initially, serial CT should be performed every 1-2 weeks, or sooner if clinically indicated. If at any time there is clinical suspicion of infection, aggressive use of FNA is indicated. The decision to intervene, whether for infectious or sterile complications of pancreatitis, must still be made on clinical grounds. CT can be helpful in choosing the appropriate means of intervention.

Primary hepatic pheochromocytoma

We report a case of a single intrahepatic pheochromocytoma in the absence of an adrenal lesion and no evidence of metastatic disease. The patient had strong clinical and biochemical evidence of a pheochromocytoma. A CT scan was abnormal but nondiagnostic for pheochromocytoma. An 123I-metaiodobenzyl guanidine (MIBG) scan was falsely negative, but an MRI scan showed a definitive hepatic abnormality. After confirmation of endocrine activity by venous sampling, the tumor was surgically removed. The patients symptoms have resolved and her plasma catecholamine levels as well as her 24-h urine catecholamine excretion have normalized. The case shows an unusual location of an isolated pheochromocytoma and provides an example of a false negative I-123 MIBG scan.

Primary Malignant Fibrous Histiocytoma of the Heart Treated With Orthotopic Heart Transplantation

A24-year-old white man presented with dyspnea and fatigue. Physical examination revealed hepatosplenomegaly. A chest roentgenogram showed small pleural effusions without infiltrates. Ultrasound examination revealed ascites of the abdomen and pelvis and echogenic liver vessels that suggested congestive heart failure. A nuclear magnetic resonance image of the chest (Fig 1A⇓) showed a 4×6-cm mass occupying the right ventricle. The mass filled the apex and obstructed the right ventricular cavity. A computerized tomogram (Fig 1B⇓) localized the mass to the anterior and inferior right ventricular wall. For treatment, the tumor was debulked to reduce right ventricle obstruction. …

Multiple focal nodular hyperplasia of the liver in a 21-year-old woman.

Focal nodular hyperplasia (FNH) is a relatively common condition, the diagnosis of which is now regularly made with diagnostic imaging. Cases of multiple FNH (more than four lesions) are rare, however, and the presence of numerous lesions may complicate the workup and diagnosis. We recently treated a young woman with multiple FNH. We report this case to highlight the clinical issues presented by this rare variant of a common benign hepatic disease.

Trp53 Mutants Drive Neuroendocrine Lung Cancer through Loss-of-Function Mechanisms with Gain-of-Function Effects on Chemotherapy Response

Lung cancer is the leading cause of cancer-related deaths with small-cell lung cancer (SCLC) as the most aggressive subtype. Preferential occurrence of TP53 missense mutations rather than loss implicates a selective advantage for TP53-mutant expression in SCLC pathogenesis. We show that lung epithelial expression of R270H and R172H (R273H and R175H in humans), common TRP53 mutants in lung cancer, combined with RB1 loss selectively results in two subtypes of neuroendocrine carcinoma, SCLC and large cell neuroendocrine carcinoma (LCNEC). Tumor initiation and progression occur in a remarkably consistent time frame with short latency and uniform progression to lethal metastatic disease by 7 months. R270H or R172H expression and TRP53 loss result in similar phenotypes demonstrating that TRP53 mutants promote lung carcinogenesis through loss-of-function and not gain-of-function mechanisms. Tumor responses to targeted and cytotoxic therapeutics were discordant in mice and corresponding tumor cell cultures demonstrating need to assess therapeutic response at the organismal level. Rapamycin did not have therapeutic efficacy in the mouse model despite inhibiting mTOR signaling and markedly suppressing tumor cell growth in culture. In contrast, cisplatin/etoposide treatment using a patient regimen prolonged survival with development of chemoresistance recapitulating human responses. R270H, but not R172H, expression conferred gain-of-function activity in attenuating chemotherapeutic efficacy. These data demonstrate a causative role for TRP53 mutants in development of chemoresistant lung cancer, and provide tractable preclinical models to test novel therapeutics for refractory disease. Mol Cancer Ther; 16(12); 2913–26. ©2017 AACR.

Routine use of U-tube drainage for necrotizing pancreatitis: a step toward less morbidity and resource utilization.

BACKGROUND A U-tube drainage catheter (UTDC) is a novel intervention for necrotizing pancreatitis, with multiple benefits: bidirectional flushing, greater interface with large fluid collections, less risk of dislodgement, and creation of a large-diameter fistula tract for potential fistulojejunostomy. We report the first clinical experience with UTDC for necrotizing pancreatitis. METHODS From 2011 to 2014, all patients undergoing UTDC for necrotizing pancreatitis at our institution were identified. Clinical variables including patient, disease, and intervention-specific characteristics as well as long-term outcomes populated our dataset. RESULTS Twenty-two patients underwent UTDC for necrotizing pancreatitis; the median follow-up was 10.2 months. Necrotizing pancreatitis was most commonly owing to gallstones (n = 9; 41%), idiopathic disease (n = 5; 23%), and alcohol abuse (n = 4; 18%). During the course of UTDC and definitive operative therapy (when required), patients had median hospital stays of 31 days, 6 interventional radiology procedures, and 6 CT scans. Operative intervention was not necessary in 9 patients (41%). Among the other 13 patients, 4 patients underwent distal pancreatectomy/splenectomy, 8 had a fistulojejunostomy performed, and 1 underwent both procedures. CONCLUSION UTDC for necrotizing pancreatitis patients is associated with effective drainage and low morbidity/hospital resource utilization. With skilled interventional radiologists and multidisciplinary coordination, this technique is a valuable means of minimizing morbidity for patients with necrotizing pancreatitis.