Spiros P. Hiotis

Phase I/II Trial of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy and Surgery for Locoregionally Advanced Pancreatic Cancer

BackgroundWe used a novel combination of induction chemotherapy with gemcitabine (GEM) and cisplatin (CDDP), followed by concurrent chemoradiotherapy (CCRT) with the same agents in patients with locoregionally advanced pancreatic cancer. Surgery or additional chemotherapy followed on the basis of response.MethodsPatients with borderline resectable or locally advanced pancreatic cancer received induction weekly with GEM (1000xa0mg/m2) or CDDP (30xa0g/m2). Patients without progression of disease then underwent surgery or CCRT, including four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy. After CCRT, patients deemed resectable underwent surgery; patients with disease that remained unresectable and that did not progress received additional GEM/CDDP for 2xa0months.ResultsA mean 76% of intended GEM dose and 75% of CDDP dose was delivered during induction (nxa0=xa026). There were three incidences of grade 4 toxicity (fever or neutropenia). After induction, five patients progressed and one patient underwent resection. Eighteen patients received CCRT, and three patients underwent resection. After CCRT, disease of 10 patients progressed, and in 5 patients, it remained unresectable without progression, and the patient received additional GEM/CDDP. Dose-limiting toxicity was at dose level IV (thrombocytopenia). Median overall and disease-specific survival was 13xa0months.ConclusionGEM/CDDP induction chemotherapy followed by CCRT is well tolerated and rendered the disease of 4 of 26 patients resectable in this study. The recommended phase II dose for GEM and CDDP in combination with full-dose radiotherapy (5040 cGy) is 300xa0mg/m2 and 10xa0mg/m2 weekly for 5xa0weeks. Median survival in this group was 13xa0months. This neoadjuvant combined modality approach is both feasible and active; further studies are warranted.

Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for gastric cancer

Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased R0 resection rate. Potential disadvantages include increased surgical complications. This study assesses postoperative morbidity and mortality by comparing patients undergoing gastrectomy with and without neoadjuvant chemotherapy. From October 1998 to July 2002, a total of 34 patients with locally advanced gastric cancer were placed on a phase II neoadjuvant chemotherapy protocol consisting of two cycles of CPT-11 (75 mg/m2) with cisplatin (25 mg/m2). Demographic, clinical, morbidity, and mortality data were compared for these patients (CHEMO) versus 85 patients undergoing gastrectomy without neoadjuvant chemotherapy (SURG). The CHEMO patients were more likely to be less than 70 years of age (P ≦ 0.01), have proximal tumors (P ≦ 0.01), and undergo proximal gastrectomy (P ≦ 0.025). Fifty-two percent of SURG patients had T3/T4 tumors compared to 19% of CHEMO patients, consistent with tumor downstaging. The R0 resection rate was similar (80%). Morbidity was 41% in CHEMO patients and 39% in SURG patients. There were five postoperative deaths (4.4%), two in the CHEMO group and three in the SURG group (P = NS). It was concluded that neoadjuvant chemotherapy with CPT-11 and cisplatin is not associated with increased postoperative morbidity compared to surgery alone. CPT-11-based neoadjuvant chemotherapy should be tested further in combined-modality treatment of gastric cancer.

Multiorgan resection for gastric cancer: intraoperative and computed tomography assessment of locally advanced disease is inaccurate.

Multiorgan resection of locally advanced gastric cancer has previously been associated with increased morbidity. This study was performed to determine the actual prevalence of pathologic T4 disease in multiorgan gastric resection specimens excised for presumed clinical T4 gastric cancer. A prospective oncology database was queried to identify gastric cancer patients who underwent en bloc multiorgan resection for clinical T4 lesions. Four hundred eighteen patients with gastric cancer underwent gastrectomy between 1990 and 2002. Multiorgan resection was performed in 21 of 418 (5%) patients. Multiorgan resection was not associated with a significant increase in morbidity or mortality. Pathologically confirmed T4 disease was present in only 8 of 21 (38%) patients; the pathologic T stage in all remaining patients was T3 (13 [62%]). Fifteen patients were evaluated by preoperative computed tomography scan. Preoperative computed tomography was inaccurate in assessing T4 lesions, with a positive predictive value of only 50%. Multiorgan resection was safely performed in patients with locally advanced gastric cancer. Pathologic T4 disease was present in only one third of multiorgan resections performed for en bloc excision of locally advanced gastric cancer. Improved methods for intraoperative assessment of disease extension to adjacent viscera should be investigated.

Non‐invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice

Background: Maintenance of complex transgenic colonies and labour‐intensive techniques pose significant challenges in work involving mouse models for hepatocellular carcinoma (HCC). Other animal models of unusual species are generally impractical for research purposes.

Diagnostic laparoscopy in the evaluation of the viral hepatitis patient with potentially resectable hepatocellular carcinoma

BACKGROUNDnDespite significant recent improvements in liver imaging, preoperative evaluation of the potentially resectable patient with viral Hepatitis and Hepatocellular Carcinoma (HCC) is often inaccurate. Diagnostic laparoscopy may change management for patients with under-appreciated nodular cirrhosis or intrahepatic metastases, preventing unnecessary open exploration. The purpose of this study is to determine the effectiveness of routine laparoscopy as a separate procedure prior to resection in the evaluation of patients with potentially resectable HCC.nnnMETHODSnPatients with potentially resectable HCC were evaluated preoperatively with routine blood tests and axial imaging. All study patients also underwent diagnostic laparoscopy with laparoscopic ultrasonography. Laparoscopy was performed in an inpatient hospital setting, with 23 hour stays in most cases.nnnRESULTSnAmong 65 patients evaluated with Hepatocellular Carcinoma between July 2001 and November 2003, 20 patients with potentially resectable disease were evaluated by diagnostic laparoscopy. All patients had viral Hepatitis: 16 with Hepatitis B and 4 with Hepatitis C. All study patients had cirrhosis; 18 classified as Childs-Pugh A and 2 as Childs-Pugh B. Diagnostic laparoscopy changed the management in 9/20 (45%) cases. Management was changed because of severe nodular cirrhosis in 4 cases, inaccurate assessment of intrahepatic metastases in 2 cases, inability to identify an HCC in 1 case, peritoneal carcinomatosis in 1 case, and inability to tolerate induction to general anesthesia in 1 case.nnnDISCUSSIONnDiagnostic laparoscopy is useful in the evaluation of the potentially resectable patient with HCC. Information obtained from laparoscopy may change the clinical management in up to 45% of cases.

Liver and Biliary Tract

You are asked to see a 32-year-old intensive care unit patient in the medical service who is febrile and lethargic with a history, according to her husband—a selfproclaimed recluse—of shaking chills and who needs evaluation and possible management. With the exception of hospitalization for childbirth (youngest child is 1 year old), the patient has no known medical problems. On physical examination, the patient is jaundice and has right upper quadrant tenderness. There is no rebound tenderness. The patient was recently started on pressors to achieve hemodynamic stability. Pertinent positive laboratory results include an alkaline phosphatase level of 600, a total bilirubin level of 6 (direct −4.5), and a white blood cell count of 15,000. The patient has been receiving full-spectrum antibiotics for 36 hours. Which of the following recommendations should your acute care surgical consultation render?