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Biomedical subjects

R P DeMatteo

Publications and source records attributed to R P DeMatteo.

At least 19 recordsLinked to original sources

Segment-oriented approach to liver resection.

Segment-oriented liver resection is a distinct surgical approach and represents the virtuosity of hepatic surgery. It is unique in the finesse of its execution and in its oncologic efficacy and safety. The varied combinations of segmentectomy allow greater flexibility and opportunity for liver surgeons to extirpate the equally diverse nature and location of intrahepatic pathologic conditions. The technique promotes tumor clearance while con-serving uninvolved parenchyma.

Dissection↗

The role of staging laparoscopy in hepatobiliary malignancy: prospective analysis of 401 cases.

BACKGROUND: Patients with potentially resectable hepatobiliary malignancy are frequently found to have unresectable tumors at laparotomy. We prospectively evaluated staging laparoscopy in patients with resectable disease on preoperative imaging. METHODS: Staging laparoscopy was performed on 410 patients with potentially resectable hepatobiliary malignancy. The preoperative likelihood of resectability was recorded. Data on preoperative imaging, operative findings, and hospital course were analyzed. RESULTS: Laparoscopic inspection was complete in 291 (73%) patients. In total, 153 patients (38%) had unresectable disease, 84 of whom were identified laparoscopically, increasing resectability from 62% to 78%. On multivariate analysis, a complete examination, preoperative likelihood of resection, and primary diagnosis were significant predictors of identifying unresectable disease at laparoscopy. The highest yield was for biliary cancers, and the lowest was for metastatic colorectal cancer. In patients with unresectable disease identified at laparoscopy, the mean hospital stay was 3 days, and postoperative morbidity was 9%, compared with 8 days and 27%, respectively, in patients found to have unresectable disease at laparotomy. CONCLUSIONS: Laparoscopy spared one in five patients a laparotomy while reducing hospital stay and morbidity. Targeting laparoscopy to patients at high risk for unresectable disease requires consideration of disease-specific factors; however, the surgeons' preoperative impression of resectability is also important.

Aged↗

A clinical scoring system predicts the yield of diagnostic laparoscopy in patients with potentially resectable hepatic colorectal metastases.

BACKGROUND: Laparoscopy may identify occult metastatic disease and prevent unnecessary laparotomy in some patients with potentially resectable colorectal liver metastases but is unnecessary in the majority of individuals who undergo resection. The objectives of the current study were to assess the impact of laparoscopy after extensive preoperative imaging and to determine whether a preoperative clinical risk score can identify those patients most likely to benefit from the procedure. METHODS: Between December 1997 and July 1999, 103 consecutive patients with potentially resectable colorectal liver metastases underwent laparoscopy prior to planned laparotomy and partial hepatectomy. Surgical findings, length of hospital stay, and hospital charges were analyzed. Patients were assigned a clinical risk score (CRS) based on five factors related to the primary tumor and the hepatic disease. The likelihood of finding occult unresectable disease and the yield of laparoscopy were analyzed with respect to the CRS. RESULTS: Seventy-seven patients (75%) underwent resection. Laparoscopy identified 14 of 26 patients with unresectable disease, 10 of whom were spared an unnecessary laparotomy. In patients who underwent biopsy only, the laparoscopic identification of unresectable disease shortened the hospital stay (1.2 +/- 0.6 days vs. 5.8 +/- 2.3 days; p = 0.0001) and reduced the total hospital charges by 55% (P = 0.0001). The CRS predicted the likelihood of occult unresectable disease, which was 12% in those with a score < or = 2 but increased to 42% in those with a score > 2 (P = 0.001). If laparoscopy were used only in high risk patients (CRS > 2), 57 laparoscopies would have been avoided and the net savings doubled. CONCLUSIONS: With extensive preoperative imaging, the vast majority of patients with potentially resectable hepatic colorectal metastases do not benefit from laparoscopy. However, in the minority of patients with occult unresectable disease, laparoscopy prevents unnecessary laparotomy and reduces hospital stay and the total hospital charges. The CRS, previously shown to predict survival after hepatic resection, identifies those high risk patients most likely to benefit from laparoscopy and may improve resource utilization.

Aged↗

Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma.

Replication-competent, attenuated herpes simplex viruses (HSV) have been demonstrated to be effective oncolytic agents in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the utility of combining these two approaches, two oncolytic HSV vectors (NV1034 and NV1042) were designed to express the murine GM-CSF and murine IL-12 genes, respectively. These cytokine-carrying variants were compared with the analogous non-cytokine-carrying control virus (NV1023) in the treatment of murine SCC VII squamous cell carcinoma. All three viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. SCC VII cells infected by NV1034 and NV1042 effectively produced GM-CSF and IL-12, respectively. In an SCC VII subcutaneous flank tumor model in immunocompetent C3H/HeJ mice, intratumoral injection with each virus caused a significant reduction in tumor volume compared with saline injections. The NV1042-treated tumors showed a striking reduction in tumor volume compared with the NV1023- and NV1034-treated tumors. On subsequent rechallenge in the contralateral flank with SCC VII cells, 57% of animals treated with NV1042 failed to develop tumors, in comparison with 14% of animals treated with NV1023 or NV1034, and 0% of naive animals. The increased antitumor efficacy seen with NV1042 in comparison with NV1023 and NV1034 was abrogated by CD4(+) and CD8(+) lymphocyte depletion. NV1042 is a novel, attenuated, oncolytic herpesvirus that effectively expresses IL-12 and elicits a T lymphocyte-mediated antitumor immune response against murine squamous cell carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of cancer.

Animals↗

Gastrointestinal stromal tumors and leiomyosarcoma of the abdomen and retroperitoneum: a clinical comparison.

INTRODUCTION: The present study was undertaken to define the clinical differences between leiomyosarcomas (LMS) occurring within the abdomen and retroperitoneum and gastrointestinal stromal tumors (GIST). METHODS: It was a retrospective, single-institution review of patients treated for intra-abdominal and retroperitoneal GIST and LMS from July 1, 1982 through August 1, 1999. RESULTS: A total of 561 patients, 239 with GIST and 322 with LMS, were identified. Patients with GIST were older, with a median age of 58 years versus 54 years in the LMS group (P < .01). The majority of patients with GIST were male (58%), whereas 68% of LMS patients (excluding gender-specific sites) were female (P < .01). The 5-year disease-specific survival for GIST and LMS were 28% and 29%, respectively. The presentation status and ability to achieve a complete surgical resection were the main independent predictors of outcome for both GIST and LMS. Local and distant recurrence was common in both. The pattern of distant recurrence differed: 50% of all first-site GIST recurrences involved the liver, whereas 30% of all LMS first-site recurrences involved the lungs. CONCLUSIONS: Although the two patient populations appear to be distinct, their clinical courses are similar. The pattern of distant spread follows the known patterns of hematogenous dissemination. Complete surgical resection is the cornerstone of treatment for primary GIST and LMS and in selected patients with local and distant recurrence.

Age Factors↗

What is the yield of intraoperative ultrasonography during partial hepatectomy for malignant disease?

BACKGROUND: Previous studies have shown that intraoperative ultrasonography (IOUS) during hepatic resection for malignancy changes the operative plan or identifies occult unresectable disease in a large proportion of patients. This study was undertaken to reassess the yield of IOUS in light of recent improvements in preoperative staging. STUDY DESIGN: Patients with potentially resectable primary or metastatic hepatic malignancies subjected to exploration, bimanual palpation of the liver, and IOUS were evaluated prospectively. Intraoperative findings were recorded, and preoperative imaging studies were reanalyzed by radiologists blinded to the intraoperative findings. The extent of disease based on preoperative imaging was compared with the intraoperative findings. RESULTS: From October 1997 until November 1998, 111 patients were evaluated. At exploration, a total of 77 new findings or findings different than suggested on the imaging studies were identified in 61 patients (55%), the most common of which was additional hepatic tumors (n = 37). Thirty-five of 77 (45%) new findings were identified by IOUS alone and 10 (13%) by palpation alone; the remainder were identified by both palpation and IOUS. Forty-seven of 61 patients (77%) underwent a complete resection despite new intraoperative findings, with a modification (n = 28) or no change (n = 19) in the planned operation. Twenty-one patients (19%) had new findings identified only on IOUS. Thirteen of these patients underwent resection with no change in the operative plan, six underwent a modified resection and two were considered to have unresectable disease based solely on the findings of IOUS. CONCLUSIONS: In patients with hepatic malignancies submitted to a potentially curative resection, new intraoperative findings or findings different than suggested on preoperative imaging studies are common. But resection with no change in the operative plan or a modified resection is still possible in the majority of patients despite such findings. The findings on IOUS alone rarely lead to a change in the operative plan.

Aged↗

Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes.

Intrahepatic cholangiocarcinoma (IHC) is a rare primary hepatic tumor of bile duct origin for which resection is the most effective treatment. But resectability, outcomes after resection, and recurrence patterns have not been well described. Patients with IHC were identified from a prospective database. Demographic data, tumor characteristics, and outcomes were analyzed. From March 1992 to September 2000, 53 patients with hepatic tumors underwent exploration and were found to have pure IHC on pathologic analysis. Patients with mixed hepatocellular and cholangiocarcinoma tumors were excluded. At exploration, 20 patients were unresectable for an overall resectability rate of 62% (33 of 53). Median survival for patients submitted to resection was 37.4 months versus 11.6 months for patients undergoing biopsy only (p = 0.006; median followup for surviving patients, 15.6 months). Actuarial 3-year survival was 55% versus 21%, respectively. Factors predictive of poor survival after resection included vascular invasion (p = 0.0007), histologically positive margin (p = 0.009), or multiple tumors (p = 0.003). After resection, 20 of 33 patients (61%) recurred at a median of 12.4 months. Sites of recurrence included the liver (14), retroperitoneal or hilar nodes (4), lung (4), and bone (2). The median disease-free survival was 19.4 months, with a 3-year disease-free survival rate of 22%. Factors predictive of recurrence were multiple tumors (p = 0.0002), tumor size (p = 0.001), and vascular invasion (p = 0.01). About two-thirds of patients who appeared resectable on preoperative imaging were amenable to curative resection at the time of operation. Although complete resection improved survival, recurrence was common. The majority of recurrences were local or regional, which may help guide future adjuvant therapy strategies.

Actuarial Analysis↗

Peritoneal washings are not predictive of occult peritoneal disease in patients with hilar cholangiocarcinoma.

BACKGROUND: Evaluation of peritoneal cytology provides valuable staging information in patients with gastric and pancreatic adenocarcinoma, but its usefulness in patients with extrahepatic cholangiocarcinoma is unclear. The aim of this study was to evaluate the predictive value of peritoneal cytology in patients with potentially resectable hilar cholangiocarcinoma. This study evaluated a possible association between positive peritoneal cytology and percutaneous transhepatic biliary drainage, which is commonly used in these patients and may result in peritoneal biliary leakage and peritoneal seeding. STUDY DESIGN: From October 1997 through June 2000 26 patients with hilar cholangiocarcinoma underwent staging laparoscopy immediately before planned open exploration and resection. Peritoneal washings were obtained during laparoscopic examination before any biopsies were taken. Cytologic analysis was performed using the Papanicolau technique. RESULTS: There were 18 men and 8 women, with a median age of 69 years (range 42 to 81 years). The most common presenting symptom was jaundice (n = 19). Previous biliary drainage was performed in 23 patients: 9 percutaneous and 14 endoscopic. Metastatic disease was suspected preoperatively in six patients, three to the liver, two to the peritoneum, and one to regional lymph nodes, all of which were confirmed at laparoscopy. Laparoscopy identified five additional patients with metastatic disease. Peritoneal cytology was positive for malignant cells in two patients, both of whom had gross peritoneal metastases. Nine other patients had metastatic disease to distant sites within the abdomen, but none had positive cytology. Overall, six patients had metastatic disease to the peritoneal cavity, only one of whom had undergone earlier percutaneous biliary drainage. CONCLUSIONS: Peritoneal cytology was not predictive of occult metastatic disease. Laparoscopic staging identified some patients with unresectable hilar cholangiocarcinoma, but analysis of peritoneal cytology provided no additional information. There was no association between percutaneous transhepatic biliary drainage and peritoneal tumor seeding.

Adult↗

Management of 155 patients with benign liver tumours.

BACKGROUND: Benign hepatic tumours continue to represent a diagnostic and therapeutic challenge. This study evaluates the indications and results of resection compared with observation in patients with benign hepatic tumours. METHODS: Patients with a primary diagnosis of benign liver tumour were identified from a prospective database and evaluated retrospectively. RESULTS: From January 1992 to June 1999, 155 patients with benign hepatic tumours were evaluated. The diagnoses included haemangioma (n = 97), focal nodular hyperplasia (FNH) (n = 42), hepatic adenoma (n = 12) and cystadenoma (n = 4). Sixty-eight patients (44 per cent) underwent resection because of symptoms (n = 36), inability to exclude a malignancy (n = 31) or enlargement on serial imaging (n = 11). The operative morbidity and mortality rates were 21 per cent and zero respectively. Thirty patients had a preoperative percutaneous needle biopsy, 19 of which were either incorrect or indeterminate. Overall, 39 of 42 patients with symptoms attributed to the tumour were asymptomatic after resection and 18 of 21 patients with symptoms considered unrelated to the tumour were asymptomatic after a period of observation and/or treatment of unrelated conditions (median follow-up 16 months). CONCLUSION: When indicated, resection of benign liver tumours can be performed safely. Symptomatic patients with a small FNH or haemangioma can be observed because their symptoms are unlikely to be related to the liver tumour. Percutaneous needle biopsy rarely changes management.

Adult↗

Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma.

OBJECTIVE: To analyze resectability and survival in patients with hilar cholangiocarcinoma according to a proposed preoperative staging scheme that fully integrates local, tumor-related factors. SUMMARY BACKGROUND DATA: In patients with hilar cholangiocarcinoma, long-term survival depends critically on complete tumor resection. The current staging systems ignore factors related to local tumor extent, preclude accurate preoperative disease assessment, and correlate poorly with resectability and survival. METHODS: Demographics, results of imaging studies, surgical findings, pathology, and survival were analyzed prospectively in consecutive patients. Using data from imaging studies, all patients were placed into one of three stages based on the extent of ductal involvement by tumor, the presence or absence of portal vein compromise, and the presence or absence of hepatic lobar atrophy. RESULTS: From March 1991 through December 2000, 225 patients were evaluated, 77% of whom were seen and treated within the last 6 years. Sixty-five patients had unresectable disease; 160 patients underwent exploration with curative intent. Eighty patients underwent resection: 62 (78%) had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative histologic margins). Negative histologic margins, concomitant partial hepatectomy, and well-differentiated tumor histology were associated with improved outcome after all resections. However, in patients who underwent an R0 resection, concomitant partial hepatectomy was the only independent predictor of long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a concomitant hepatic resection and none had tumor-involved margins; 3 of these 9 patients remained free of disease at a median follow-up of 88 months. The rates of complications and death after resection were 64% and 10%, respectively. In the 219 patients whose disease could be staged, the proposed system predicted resectability and the likelihood of an R0 resection and correlated with metastatic disease and survival. CONCLUSION: By taking full account of local tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately predicts resectability, the likelihood of metastatic disease, and survival. Complete resection remains the only therapy that offers the possibility of long-term survival, and hepatic resection is a critical component of the surgical approach.

Adult↗

Results of hepatic resection for sarcoma metastatic to liver.

OBJECTIVE: To evaluate the outcome of patients with liver metastases from sarcoma who underwent hepatic resection at a single institution and were followed up prospectively. SUMMARY BACKGROUND DATA: The value of hepatic resection for metastatic sarcoma is unknown. METHODS: There were 331 patients with liver metastases from sarcoma who were admitted to Memorial Hospital from 1982 to 2000, and 56 of them underwent resection of all gross hepatic disease. Patient, tumor, and treatment variables were analyzed to assess outcome. RESULTS: Of the 56 patients who underwent complete resection, 34 (61%) had gastrointestinal stromal tumors or gastrointestinal leiomyosarcomas. Half of the patients required an hepatic lobectomy or extended lobectomy. There were no perioperative deaths in the completely resected group, although 3 of the 75 patients who underwent exploration (4%) died. The postoperative 1-, 3-, and 5-year actuarial survival rates were 88%, 50%, and 30%, respectively, with a median of 39 months. In contrast, the 5-year survival rate of patients who did not undergo complete resection was 4%. On multivariate analysis, a time interval from the primary tumor to the development of liver metastasis greater than 2 years was a significant predictor of survival after hepatectomy. CONCLUSIONS: Complete resection of liver metastases from sarcoma in selected patients is associated with prolonged survival. Hepatectomy should be considered when complete gross resection is possible, especially when the time to the development of liver metastasis exceeds 2 years.

Adult↗

The role of adjuvant therapy after liver resection for colorectal cancer metastases.

Intrahepatic recurrence is common after major resection for colorectal cancer (CRC) metastases to the liver. In this review, the available data on different adjuvant therapies from systemic chemotherapy to regional approaches by direct perfusion of chemotherapeutic agents via the hepatic artery and portal vein will be discussed. Intraperitoneal administration of chemotherapy is another form of regional therapy. Novel approaches with immunotherapy and trials of neoadjuvant therapy in association with resection of CRC hepatic metastases have also been reported. The purpose of this review is to outline these various strategies and their role in combination with resection of CRC liver metastases. Although improved hepatic disease-free survival has been demonstrated with some strategies, overall survival is minimally affected and recurrence of metastatic disease at distant sites is still a major problem. Therefore, future directions should incorporate the use of new systemic agents effective against CRC metastases. Identification of subgroups through clinical features, molecular markers, proteins, or specific tumor properties may also help to individualize treatment.

Antineoplastic Agents↗

Survival after resection of multiple hepatic colorectal metastases.

BACKGROUND: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined. METHODS: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed. RESULTS: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4-20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median = 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival. CONCLUSIONS: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.

Adult↗

Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.

OBJECTIVE: To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively. SUMMARY BACKGROUND DATA: A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven. METHODS: Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival. RESULTS: Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver. CONCLUSIONS: GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.

Actuarial Analysis↗

Surgical treatment of malignant liver tumours.

Surgical resection is the mainstay of treatment for malignant liver tumours and offers the only chance of cure. Advances in radiological imaging, surgical technique and peri-operative management have enabled liver resection to be performed safely. Partial hepatectomy is indicated for the treatment of hepatocellular carcinoma and hepatic metastases from colorectal cancer. In addition, it may be utilized for selected patients with liver metastases from other primary tumours. Total hepatectomy with transplantation may be of benefit in some patients with unresectable neuroendocrine metastases or small hepatocellular carcinomas. The role of cryosurgery has not been precisely defined, and it needs to be compared with other palliative therapies such as ethanol injection and hepatic artery embolization.

Carcinoma, Hepatocellular↗

Imaging of hepatobiliary neoplasms.

Improvements in imaging have markedly improved the ability to detect hepatobiliary masses. The radiologic features of a lesion when considered in the context of the medical history, physical findings, and laboratory data can often provide a diagnosis. Investigative modalities can accurately stage hepatobiliary tumors and determine their resectability so that the patient may be offered appropriate therapeutic interventions. This article summarizes the essential imaging techniques and their application to common hepatobiliary neoplasms.

Angiography↗

Immunologic barriers to hepatic adenoviral gene therapy for transplantation.

Adenoviral gene transfer has potential use to attenuate the immunogenicity of hepatic allografts. However, the clinical application of adenoviral gene therapy is currently impeded by the potent host immune response to the virus that limits the duration of its effects. In these studies, we identify the cellular and humoral immune responses to recombinant adenovirus in the liver of mice and define the immunologic barriers to the successful application of this technology to transplantation. The immunobiology of recombinant adenovirus was studied in mouse liver using vectors containing the lacZ and alkaline phosphatase marker genes. The duration of transgene expression was studied in various immunodeficient mice to determine the mechanism of viral clearance. Adoptive transfer of serum to B lymphocyte deficient mice and neutralizing antibody assays were used to define the antiviral humoral response. Hepatic adenoviral transgene expression was prolonged in animals deficient in CD4+ or CD8+ T cells indicating their importance in viral clearance. Unexpectedly, mice lacking B lymphocytes also had delayed elimination of virus suggesting that B cells play a role in the primary immune response. Effective repeat gene transfer was blocked by adenoviral-specific neutralizing antibody. Therefore, a T lymphocyte response results in viral elimination after a primary intravenous inoculation of recombinant adenovirus and a potent humoral response inhibits effective repeat adenoviral gene transfer. The immunogenicity of the vector must be overcome for adenoviral gene therapy to have therapeutic application for hepatic transplantation.

Adenoviridae↗

Effect of adenoviral early genes and the host immune system on in vivo pancreatic gene transfer in the mouse.

Gene transfer technology may provide a novel approach to treatment for pancreatic diseases. Recombinant adenovirus achieves efficient gene transfer in vivo. In this study, a murine model of adenoviral-mediated pancreatic gene transfer was developed, and the factors responsible for adenoviral elimination were investigated. Three days after direct pancreatic injection of a replication-defective adenovirus containing the lacZ transgene, a high proportion (76.8 +/- 6.7%) of pancreatic cells expressed beta-galactosidase, the gene product. Gene expression was absent by 28 days posttransduction. In immunodeficient mice, beta-galactosidase expression persisted with 20.0 +/- 6.0% of pancreatic cells staining positive 60 days after viral transduction. To test whether early viral proteins are the antigenic components responsible for the potent antiviral immune response, normal mice were injected with different adenoviral vectors containing early gene deletions. Vectors containing deletions in early region 2 or 4 expressed beta-galactosidase at 28 days. Presently available adenoviral vectors engineered to avoid this response offer minimal improvements in transgene duration. Further vector modifications or alternative strategies are needed to achieve stable pancreatic adenoviral transgene expression.

Adenoviridae↗