Dilip Parekh

Does an infected peripancreatic fluid collection or abscess mandate operation

OBJECTIVE To assess the treatment of peripancreatic fluid collections or abscess with percutaneous catheter drainage (PCD). SUMMARY BACKGROUND DATA Surgical intervention has been the mainstay of treatment for infected peripancreatic fluid collections and abscesses. Increasingly, PCD has been used, with mixed results reported in the literature. METHODS A retrospective chart review of 1993 to 1997 was performed on 82 patients at a tertiary care public teaching hospital who had computed tomography-guided aspiration for suspected infected pancreatic fluid collection or abscess. Culture results, need for subsequent surgical intervention, length of stay, and death rate were assessed. RESULTS One hundred thirty-five aspirations were performed in 82 patients (57 male patients, 25 female patients) with a mean age of 40 years (range 17-68). The etiologies were alcohol (41), gallstones (32), and other (9). The mean number of Ransons criteria was four (range 0-9). All patients received antibiotics. Forty-eight patients had evidence of pancreatic necrosis on computed tomography scan. Cultures were negative in 40 patients and positive in 42. Twenty-five of the 42 culture-positive patients had PCD as primary therapy, and 6 required subsequent surgery. Eleven patients had primary surgical therapy, and five required subsequent surgery. Six patients were treated with only antibiotics. The death rates were 12% for culture-positive patients and 8% for the entire 82 patients. CONCLUSIONS Historically, patients with positive peripancreatic aspirate culture have required operation. This series reports an evolving strategy of reliance on catheter drainage. PCD should be considered as the initial therapy for culture-positive patients, with surgical intervention reserved for patients in whom treatment fails.

Renal cell carcinoma metastatic to the pancreas: a single-institution series and review of the literature.

OBJECTIVES To present a series of 5 patients with solitary metastatic renal cell carcinoma (RCC) to the pancreas after radical nephrectomy at our institution and review the published reports of this rare event. METHODS A retrospective review of the records of 5 patients with histologically confirmed RCC metastatic to the pancreas after radical nephrectomy was performed. A total of 5 patients (4 men, 1 woman) with a median age of 56 years (range 54 to 68) underwent radical nephrectomy for primary RCC. The pathologic stage was Robson I (n = 3) or Robson III (n = 2), with a left-sided tumor occurring in 3 patients and a right-sided tumor in 2 patients. The median interval from nephrectomy to the diagnosis of the pancreatic metastasis was 12 years (range 4 to 15). All patients were symptomatic at presentation, including weight loss (n = 3), abdominal pain (n = 3), early satiety (n = 1), steatorrhea (n = 1), and/or hemosuccus pancreaticus (n = 1). RESULTS All pancreatic metastases were hypervascular on imaging studies, and surgical removal was accomplished by pancreaticoduodenectomy (n = 3), partial pancreatectomy (n = 1), or subtotal pancreatectomy (n = 1). One patient died of disseminated disease 12 months after pancreatic resection. Two other patients had recurrences in the lung (n = 1) at 5 months or the pancreas/liver (n = 1) at 48 months. Both of these patients underwent a second resection and were disease free at 2 and 12 months afterward. The two remaining patients were disease free at 7 and 24 months after pancreatic resection. CONCLUSIONS RCC is an unpredictable tumor that may demonstrate very late metastases even from early-stage lesions. Aggressive surgical management of isolated pancreatic lesions offers a chance of long-term survival.

Gene therapy of metastatic pancreas cancer with intraperitoneal injections of concentrated retroviral herpes simplex thymidine kinase vector supernatant and ganciclovir

OBJECTIVE The objective of this study was to determine the efficacy of intraperitoneal (IP) injections of a new concentrated herpes simplex thymidine kinase (HS-tk) retroviral vector and ganciclovir (GCV) for peritoneal metastases from pancreas cancer. SUMMARY BACKGROUND DATA Metastatic pancreas cancer is fatal. Gene therapy may provide a novel approach for this disease. Gene therapy with adeno- or retroviral-mediated transfer of the HS-tk gene into tumor cells renders the cells susceptible to GCV. Intratumoral or intracavity injections of retroviral vectors have been ineffective in previous studies. METHODS Pancreatic cancer B x PC3 cells (3 x 10(7)) were injected into the tail of pancreas in nude mice. Mice received IP injections of a concentrated HS-tk vector (5 x 10(7)) cfu/mliters) or a control vector (G1Na) without the tk gene for 10 days and GCV (100 mg/kg) for 14 days. To determine whether the vector would survive in the milieu of the peritoneal cavity, the authors examined the effects of ascitic fluid on the vector. Pancreas cancer cells were transduced in vitro with HS-tk vector in presence of media or ascitic fluid and treated with GCV. RESULTS Highly significant reductions in the mass of metastatic peritoneal tumor deposits were found in HS-tk-treated group (124 +/- 27 mg; n = 11) compared with G1Na vector controls (910 +/- 168 mg; n = 8; p < 0.0001). Results of polymerase chain reaction analysis demonstrated integration of the vector in the tumors, and on immunohistochemistry, expression of the TK protein was seen in the number of surviving colonies (representing nontransduced cells) were similar in both groups, suggesting that the vector effectively transduced tumor cells bathed in the ascitic fluid. CONCLUSIONS Results demonstrate that IP administration of concentrated retroviral HS-tk vectors is effective treatment for pancreas cancer metastatic to the peritoneal cavity; furthermore, the vector is active in the presence of ascitic fluid. Intraperitoneal retroviral HS-tk may provide a novel approach to treatment of metastatic pancreas cancer.

Gene therapy for primary and metastatic pancreatic cancer with intraperitoneal retroviral vector bearing the wild-type p53 gene

BACKGROUND Metastatic pancreatic cancer is uniformly fatal because no effective chemotherapy is available. Mutations in the p53 tumor suppressor gene are found in up to 70% of pancreatic adenocarcinomas. We examined the efficacy of a retroviral vector containing the wild-type p53 gene on metastatic pancreatic cancer in a nude mouse model. METHODS Bxpc3 human pancreatic cancer cells were transduced with either a retroviral p53 vector or an LXSN empty vector. Cells were examined for incorporation of tritiated thymidine to determine the effect of p53 retroviral transduction on DNA synthesis, and a TACS2 assay for apoptosis was performed. The functional activity of p53 in transduced cells was assessed by Western blot analysis with an antibody to WAF1/p21. In vivo effects of intraperitoneal injections of the p53 vector were examined in a nude mouse model of peritoneal carcinomatosis. RESULTS Cells treated with the p53 vector exhibited a 59% to 85.5% reduction in cell number compared with the control cells (P < .05). p53-treated cells demonstrated decreased incorporation of tritiated thymidine (12.7% +/- 0.7% vs 17.5% +/- 1.4%; P = .002), increased staining for apoptosis, and increased expression of the WAF1/p21 protein. Treatment of nude mice with the retroviral p53 vector resulted in a significant inhibition of growth of the primary pancreatic tumor, as well as the peritoneal tumor deposits, compared with the LXSN control vector. CONCLUSIONS Intraperitoneal delivery of a retroviral p53 vector may provide a novel treatment approach for peritoneal carcinomatosis from pancreatic cancer.

EUS-guided fine-needle tattooing for preoperative localization of early pancreatic adenocarcinoma

A 67-year-old woman was evaluated for recurrent pancreatitis. She had no other significant medical history, and her carbohydrate antigen 19-9, amylase, and lipase levels were normal. An initial pancreatic protocol CT showed normal results. A linear EUS examination revealed a poorly defined 5-mm hypoechoic solid area in the pancreatic body close to the portal confluence (Fig. 1). EUS-guided FNA (EUS-FNA) of this area revealed cells suspicious for adenocarcinoma. The patient decided to undergo a laparoscopic resection of the pancreatic lesion. A repeated pancreatic protocol CT failed to localize the lesion. On the day before her planned laparoscopic pancreatic resection, a repeated EUS again revealed the subtle 5-mm hypoechoic area in the pancreatic body. EUS-FNT was performed by slowly injecting, with a 22-gauge needle (Echo-Tip; Cook Endoscopy, Winston–Salem, NC), 2 mL of a sterile carbon-based ink (SPOT; GI Supply, Camp Hill, Pa) into an area of normal pancreatic parenchyma 2 cm toward the head of the pancreas relative to this mass (Fig. 2). There were no acute complications, such as bleeding, abdominal pain, fever, or pancreatitis at the time of the injection. The patient received preprocedural and postprocedural oral ciprofloxacin. At a laparoscopy, there was no evidence of inflammation or bleeding around the easily recognized tattooed area. Intraoperative evaluation failed to identify the pancreatic body tumor. By using the tattooed area as the most medial aspect, the patient underwent, uneventfully, a laparoscopic distal pancreatic resection. A pathologic evaluation of the resected pancreas revealed a 5-mm intraductal papillary mucinous neoplasm (IPMN) with carcinoma in situ, 2 cm from the surgical resection plane (Fig. 3). The patient was continuing to do well 12 months after surgery. She had no evidence of recurrent pancreatitis, IPMN, or pancreatic cancer.

The Minimally Invasive Approach to Surgical Management of Pancreatic Diseases

Laparoscopic pancreas surgery has undergone rapid development over the past decade. Although acceptability among traditional surgeons has been low, emerging specialty centers are reporting excellent outcomes for advanced and complex operations, such as pancreaticoduodenectomy. A note of caution is necessary: These outstanding results are from skilled surgeons, many of whom are pioneers in the field, who have overcome the learning curve over many years of innovation. As the procedures gain wider practice, outcomes need to be carefully watched because many of these procedures are extremely demanding technically. Although many have suggested that controlled, randomized studies comparing laparoscopic pancreatic resections with open resections are necessary to establish the efficacy of laparoscopic procedure, the cumulative data on the safety and efficacy of the laparoscopic procedure argues against such an approach. The logistic difficulties of conducting such studies will be considerable given patient preferences, the need for multicenter studies, and the rapid adoption of the laparoscopic procedure among experienced pancreatic surgeons. A more reasonable approach to truly evaluate the safety of these procedures is the establishment of a national registry that can measure progress of the field and record outcomes in the wider, nonspecialty community. Hepatobiliary training programs should also establish a minimal standard of training for many of the advanced procedures, such as the pancreaticoduodenectomy, so that the benefit of laparoscopic surgery can be made available outside of just a few specialty centers.

Development of systemic immunologic responses against hepatic metastases during gene therapy for peritoneal carcinomatosis with retroviral HS-tk and ganciclovir

Gene therapy with retroviral mediated gene transfer of the herpes simplex thymidine kinase (HS-tk) gene into a tumor mass confers sensitivity of the tumor cells to ganciclovir (GCV). Tumor-specific immunologic responses may develop following treatment of the primary tumor with retroviral HS-tk and GCV. In the present study we assessed whether GCV treatment of HS-tk transduced colon cancer (TK+) implanted in the peritoneal cavity induced a systemic antitumor response that would inhibit growth of a second wild-type (TK−) tumor implanted in the live. DHDK12 rat colon cancer cells were transduced in vitro with the retroviral HS-tk vector and established as a permanent cell line (TK+ cells). TK+ or TK− DHDK12 cells (6×106 cells) were injected intraperitoneally on day 0 into BD-IX rats. On day 10, TK− cells (3×106 cells) were injected into the liver in all the groups. The animals were then treated with GCV (150 mg/kg) for 13 days. TK+ peritoneal tumors underwent significant regression during therapy with GCV (0.05±0.004 g; n=7) compared to wild-type (TK−) tumors (2.2±0.7 g; n=6) (P<0.05). The volume to TK− tumors in the liver was significantly lower in GCV-treated rats with TK+ peritoneal tumors (12.5±8.3 mm3) compared to rats with TK− peritoneal tumors (96.7±18.1 mm3) (P<0.05). Histology of the liver tumors in the TK+ groups showed a dense monocytic infiltrate with fibrosis and only occasional viable tumor cells. Gene therapy with retroviral HS-tk vectors may provide a novel approach to treatment of gastrointestinal cancer by both direct cytotoxicity and an indirect mechanism that may included enhanced immunologic responses against disseminated disease.

Laparoscopic Hand-Assisted Parenchymal-Sparing Resections for Presumed Side-Branch Intraductal Papillary Mucinous Neoplasms

BACKGROUND The diagnosis of side-branch intraductal papillary mucinous neoplasms (IMPNs) is increasingly more common, but their appropriate management is still evolving. We recently began performing laparoscopic hand-assisted enucleation or duodenal-sparing pancreatic head resection for these lesions with vigilant postoperative imaging. MATERIALS AND METHODS Seventeen patients with pancreatic cystic lesions were included in this single-center retrospective review from January 1, 2008 to March 30, 2013. Indication for surgical intervention was growth in size of the cyst, symptoms, cyst size >3 cm, and/or presence of a mural nodule. Twelve patients underwent laparoscopic hand-assisted enucleation, and 5 patients underwent laparoscopic hand-assisted pancreatic head resection. RESULTS The mean age of patients was 64 years old. The most common presenting symptom was abdominal pain. The indication for surgical intervention was growth in the cyst or symptoms in the majority of patients. Fourteen lesions were in the head/uncinate, two were in the pancreatic body, and one was in the tail. Final pathology was consistent with side-branch IPMN in 13 patients (1 with focal adenocarcinoma). Three patients had serous cysts, and 1 had a mucinous cyst. Three patients developed pancreatic leaks, which were controlled with intraoperative placed drains, whereas 1 patient required additional drain placement. Median time from surgery to latest follow-up imaging is over 2 years. No patients have developed recurrent cysts or adenocarcinoma. CONCLUSIONS Duodenal-sparing pancreatic head resection or pancreatic enucleation for patients with presumed side-branch IPMN is a safe and efficacious option, in terms of both operative outcomes and postoperative recurrence risk.

Surgical Management of Chronic Pancreatitis.

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.