Prakash Pandalai

Impact of Maximal Cytoreductive Surgery Plus Regional Heated Intraperitoneal Chemotherapy (HIPEC) on Outcome of Patients With Peritoneal Carcinomatosis of Gastric Origin: Results of the GYMSSA Trial

A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi‐modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis.

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

BackgroundPancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease.A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy.Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer.Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer.DesignThis is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer.Trial RegistrationClinicalTrials.gov ID: NCT01294358

Expanding surgical treatment of pancreatic cancer: the role of regional chemotherapy.

Objectives Pancreatic cancer is a lethal disease that offers little chance of long-term survival for patients with unresectable tumors. Surgery remains the most effective means of attaining prolonged survival, yet its role remains limited. Regional chemotherapy has been described for patients with pancreatic cancer, including reports of objective tumor regression allowing for tumor resection in previously unresectable cases. However, comprehensive data have not been reviewed to date. Methods A review of the literature from 1995 to 2010 was performed to analyze the results of regional chemotherapy administered to patients with advanced pancreatic cancer. Reports of individual cases, postoperative regional therapy, and treatment of mixed tumor types were excluded. Results Twenty-one reports of 895 total patients with pancreatic cancer were reviewed. Greater than 95% of the patients had stage III or IV adenocarcinoma. Objective response rates ranged from nil to 58%, with associated median survivals of 4 to 22 months. Low-grade gastrointestinal and hematologic toxicities were not uncommon. Conclusions Regional chemotherapy can be administered safely to patients with pancreatic cancer but with unclear benefit. Advanced pancreatic tumors converted to resectable status by the use of regional chemotherapy may improve patient survival.

A complicated case of vascular Pythium insidiosum infection treated with limb-sparing surgery

INTRODUCTION Pythiosis is a serious life- and limb-threatening infection endemic to Thailand, but rarely seen in the Western hemisphere. Here, we present a unique case of vascular pythiosis initially managed with limb-sparing vascular bypass grafts complicated by a pseudoaneurysm in our repair. PRESENTATION OF CASE The patient is a 17 year-old Jamaican male with severe aplastic anemia. He sustained a minor injury to his left leg while fishing in Jamaica, which evolved to become an exquisitely tender inguinal swelling. His physical exam and imaging were significant for arteriovenous fistula with limb ischemia. Pathology obtained during surgery for an extra-anatomic vascular bypass showed extensive invasion by Pythium insidiosum. He later developed a pseudoaneurysm at the site of proximal anastomosis and required urgent intervention. DISCUSSION This patient presented with a rare, but classic case of vascular pythiosis, which was unrecognized at the time of presentation. A variety of therapeutic modalities have been used to treat this disease, including antibiotics, antifungals, and immunotherapy, but the ultimate management of vascular pythiosis is surgical source control. CONCLUSION A high index of suspicion in susceptible patients is needed for timely diagnosis of vascular pythiosis to achieve optimal source control.

Treatment of High-risk Venous Thrombosis Patients Using Low-dose Intraclot Injections of Recombinant Tissue Plasminogen Activator and Regional Anticoagulation

Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk.

Su1981 Endoscopic Evaluation of Families With Hereditary Diffuse Gastric Cancer: A Prospective Cohort Study

Introduction: Individuals with E-cadherin gene (CDH1) mutation and a family history of hereditary diffuse gastric cancer (HDGC) are recommended to undergo total gastrectomy or annual endoscopic surveillance. Although data is limited, prior reports have suggested that endoscopic surveillance may be ineffective in detecting microscopic disease or malignancy. Aims: To evaluate current recommendations and advance current knowledge on the utility of endoscopic surveillance in patients with CDH1 mutation. Methods: As part of a protocol evaluation at the National Institutes of Health Clinical Center for subjects with confirmed CDH1 gene mutation, patients underwent gastrointestinal evaluation. Endoscopic (high-definition white-light esophagogastroduodenoscopy (EGD), colonoscopy, and wireless capsule endoscopy (WCE)) data, mucosal biopsies, and gastric explant pathology results were collected and analyzed. Results: 24 subjects from 4 families with confirmed CDH1 mutation were evaluated. Prior to elective total gastrectomy in 17 (71%) subjects or elective surveillance in 7 (29%), EGD and colonoscopy were performed in 24 (100%) and 21 (87%) subjects, respectively. The median age at evaluation was 31.5 years and 42% were male. On EGD, the most common finding was gastric polyps (58%) in the gastric body (93%), and only one biopsy revealed evidence of adenocarcinoma. Themost common histopathologic findings included chronic gastritis (54%) and fundic gland polyps (25%). On explant evaluation, 47% of gastrectomy specimens revealed adenocarcinoma, and 17.6% showed adenomatous polyps with high-grade dysplasia (HGD). In those with adenocarcinoma, gastric ulcers and polyps were found in 3/8 (37.5%) subjects, independently. In those with adenomatous polyps with HGD, polyposis was found in all subjects. 11/24 (45.8%) subjects underwent WCE with no remarkable finding. Polyps were found on colonoscopy in 48% of subjects, of which 70% had tubular adenomas (2 with HGD, both >50 years old) and 20% had >5 polyps (both >50 years old). Conclusion: This study expands on the scant knowledge regarding a gastroenterologists role in the management of patients with Ecadherin (CDH1) gene mutation. EGD surveillance appears to have minimal utility given the lack of correlation between endoscopic and pathologic findings, and prophylactic gastrectomy should remain mainstay of management. Given the colonoscopic findings in this study, the utility of earlier colon cancer screening in these patients should be further explored.

Surgery for li fraumeni syndrome: Pushing the limits of surgical oncology

Objectives:Li Fraumeni syndrome is an autosomal dominant cancer syndrome due to a germline mutation in the p53 tumor suppressor gene. It results in multiple primary neoplasms in children and adults. A common question when faced with a Li Fraumeni patient who develops multiple primary cancers and/or recurrences is what is the proper treatment? Data suggests that ionizing radiation exposure increases the incidence of second malignancies in the Li Fraumeni population. Therefore, how much surgery can a cancer patient tolerate and still derive benefit from it? Methods:We describe a representative case of a 54-year-old female with Li Fraumeni syndrome with an enlarging adrenocortical hepatic metastasis, a new primary ampullary cancer, and an extensive surgical history. Results:We performed a simultaneous pancreaticoduodenectomy and repeat partial hepatectomy. Conclusions:We propose that surgery is underutilized in metastatic solid organ familial cancers in general, and argue that an aggressive surgical approach should be considered in a multidisciplinary manner for patients with Li Fraumeni syndrome and recurrent tumors. However, because of the rarity of this familial cancer there is a paucity of evidence to support this approach, therefore a review of the literature is presented.