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Biomedical subjects

John F Gibbs

Publications and source records attributed to John F Gibbs.

At least 19 recordsLinked to original sources
PubMed2006

The introducer technique is the optimal method for placing percutaneous endoscopic gastrostomy tubes in head and neck cancer patients.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are often placed in head and neck cancer patients to provide nutritional support, but studies have found the complication rates to be higher than other subsets of patients who undergo PEG placement. Complication rates as high as 50% have been reported, with the bulk of these complications being PEG site issues (i.e., cellulitis, abscess, fascitis, and tumor implantation). Because the pull technique has been the primary technique used, the theory is that the transoral tube passage is the source of the complications in these patients. Alternatively, the introducer technique uses a transabdominal approach to place the device, avoiding any tube contamination by upper aerodigestive organisms or tumor cells. At our institution, this technique has been used exclusively for head and neck cancer patients and this article reports our experience. METHODS: One hundred forty-nine head and neck cancer patients who had a prophylactic PEG tube placed were reviewed from January 1, 1999 to December 31, 2003. The rates of placement success, morbidity, and complications were determined. RESULTS: Successful placement was achieved in 148 (99%) patients without any PEG-related deaths. Overall, 17 complications (11%) occurred, with only one major complication (0.7%) identified. PEG site infections were uncommon with only five cases (3.4%) and all were mild cellulitis. CONCLUSIONS: The introducer technique is the safest method for PEG tube placement in head and neck cancer patients. The overall rate of complications is low and PEG site infectious complications are rare. The introducer technique should be the method of choice for PEG tubes in head and neck cancer patients.

Enteral Nutrition↗
PubMed2006

COX-2 expression in hepatocellular carcinoma is an initiation event; while EGF receptor expression with downstream pathway activation is a prognostic predictor of survival.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is a leading cause of cancer mortality with over 90% of HCC patients succumbing to the disease. Current systemic therapies have had no measurable impact on survival in this disease; however there are small subsets of patients who benefit from systemic therapy who have been difficult to identify. Improvements in patient stratification and the development of biological therapies have resulted from the elucidation of the molecular mechanisms integral to tumor development and progression. Recent studies have found that COX-2 and EGFR are frequently inappropriately expressed in HCC compared to normal liver expression; however the presence of surface receptors does not always mean that the downstream pathway is active. In this study, we investigate the incidence and impact of activated EGFR downstream messengers phosphorylated akt (pakt) and/or phosphorylated MAPK (pMAPK) on survival in patients with HCC. METHOD: Thirty consecutive HCC patients treated at a single institution were retrospectively reviewed. Patient data including age, sex, Child's score, histological type, grade, stage, and survival were analyzed. Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissues using monoclonal antibodies to COX-2, EGF receptor, pMAPK, and pakt. Histoscores were determined for each marker and evaluated for impact in survival, stage, and tumor grade. RESULTS: The median age was 67 years (39-83) and 67% of patients were male. Median survival was 9.8 months (1-47 months) for the whole group. COX-2 and EGFR expression was present in 90 and 67% of the tumors, respectively. Expression of activated downstream EGFR messengers was present in 53% of tumors (pMAPK 41%, pakt 31%). Median survival was significantly better in patients with downstream messenger expression, 24.4 months, compared to no expression, 4.7 months (P = 0.03). These groups were matched in age, stage, and Child's score. CONCLUSION: COX-2 and EGFR expression are commonly seen in HCC. Activated downstream EGFR expression is also common in HCC and is a predictor of improved survival. There may be a therapeutic role for EGFR tyrosine kinase inhibitors in this subset of patients and further investigation is warranted.

Adult↗
PubMed2006

Gallbladder cancer: Defining the indications for primary radical resection and radical re-resection.

BACKGROUND: The role of radical resection for gallbladder cancer is an ongoing area of debate. In this review, we present our experience managing gallbladder cancer at a tertiary center by using an aggressive surgical approach for T2 or greater disease, reserving simple cholecystectomy only for T1 lesions. METHODS: Seventy-six patients with histologically confirmed gallbladder cancer were identified from our cancer registry. Estimated survival distributions were calculated by the Kaplan-Meier method, and comparisons were made by using the log-rank test. The Cox proportional hazards model was used to determine the effect on survival of T stage, nodal status, age, and margins. RESULTS: Sixty-four patients were assessable for this study. Simple cholecystectomy was the only procedure performed in 10 T2 and 15 T3 cases. Radical cholecystectomy was performed as the primary procedure in two T2, two T3, and six T4 cases. Radical re-resection was accomplished in seven T2 and two T3 cases. Excluding the T4 group, there was a significant survival advantage (P = .007) for the radical resection group (n = 13; median survival not yet reached) compared with the simple cholecystectomy group (n = 25; median survival, 17 months; 95% confidence interval, 7-27 months). Analysis of the 13 T2 and T3 patients who underwent radical resections revealed that the radical re-resection group (n = 9) had an overall survival similar to that of the primarily resected group (n = 4). All T2N(+) and T3N(-) patients are still alive and disease free after 5 years of follow-up, whereas none of the T3N(+) or T4 patients survived beyond 24 months. Increasing T stage and age (>65 years) were independent predictors of a poor prognosis. CONCLUSIONS: Radical resection for T2 and T3 disease resulted in a significant survival advantage compared with simple cholecystectomy. Patients who undergo radical re-resection after an incidentally discovered gallbladder cancer experience the same survival benefit as primarily resected patients. Radical resection for T2N(-), T2N(+), and T3N0 cases can achieve long-term survival. Conversely, the prognosis for T3N(+) and T4 patients is poor, and improved outcome for this group will likely depend on the development of multi-institutional neoadjuvant clinical trials that can identify effective systemic regimens.

Adenocarcinoma↗
PubMed2006

Genomic instability of human aberrant crypt foci measured by inter-(simple sequence repeat) PCR and array-CGH.

Aberrant crypt foci (ACF) are the earliest identifiable neoplastic lesions in the colon. Thirty-two ACFs were examined for genomic instability in forms detectable either by inter-(simple sequence repeat) PCR or by array comparative genomic hybridization [array-CGH]. One-fourth of ACFs revealed moderate instability by inter-(simple sequence repeat) PCR; none showed amplifications or deletions on array-CGH. The absence of genomic events detectible by BAC array-CGH indicates early events in colorectal tumor progression are typically smaller than the approximate 150 kb size of a BAC clone insert.

Aged, 80 and over↗
PubMed2006

Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma.

BACKGROUND: Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy. METHODS: We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists. RESULTS: Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival. CONCLUSIONS: p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.

Adenocarcinoma↗
PubMed2006

Type-2 dominant cytokine gene expression following hepatic surgery.

BACKGROUND/PURPOSE: Hemorrhage and ischemic liver injuries associated with hepatic resection are thought to play a role in postoperative complications, possibly through altered cytokine production. The current study was performed to investigate the effects of hepatectomy on cytokine gene expression. METHODS: We collected blood preoperatively, at completion of operation, and on postoperative days 1 and 5 from ten patients undergoing hepatic resection. The peripheral blood mononuclear cells were evaluated with real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression of interleukin-10 (IL-10), proinflammatory cytokines (interferon-gamma [IFNgamma], IL-15, tumor necrosis factor alpha [TNFalpha], and chemokines regulated on activation, normal T expressed and secreted [RANTES], macrophage inflammatory protein 1 alpha [MIP-1alpha], [MIP-1beta]). Wilcoxon Rank and paired t-tests were used for statistical analysis. RESULTS: Immediately following hepatectomy there was a significant (31.4 +/- 60.5-fold; P < 0.05) increase in IL-10 gene expression that was sustained until the first postoperative day. In contrast, there was a significant downregulation (38 +/- 71 eight fold lower than preoperative; P < 0.05) of IFNgamma gene expression on day 1. By postoperative day 5, the changes in gene transcript levels of both IL-10 and IFNgamma had returned to the preoperative baselines. This contrasting change in IL-10 and IFNgamma gene expression in response to hepatic resection was statistically significant (P = 0.02). CONCLUSIONS: Hepatectomy elicits an imbalance towards the immunosuppressive type-2 cytokine profile in the early postoperative period. Measurement of cytokine gene transcripts following hepatic resection may have predictive value for clinical outcome, and deserves further study.

Chemokines↗
PubMed2006

Diagnosing regenerative nodular hyperplasia, the "great masquerader" of liver tumors.

Distinguishing benign tumors and pseudotumors of the liver from malignant tumors is a common clinical problem. Regenerative nodular hyperplasia (RNH) represents one of the more challenging pseudotumors to diagnose, because they can appear clinically indistinguishable from either a primary or a secondary liver malignancy. Even after comprehensive radiologic evaluation and image-guided percutaneous biopsy, the diagnosis of RNH can remain elusive. We reviewed the pathophysiology of RNH and present five cases illustrating the limitations of percutaneous biopsy and the utility of laparoscopic wedge biopsy in establishing the diagnosis. All patients underwent a complete workup that included percutaneous biopsy. Patients with a nondiagnostic percutaneous biopsy underwent a laparoscopic wedge biopsy or anatomical resection. H&E, vimentin, trichrome, and reticulin staining as well as CD34 immunostaining were performed. Five patients were diagnosed with RNH between May 2002 and April 2004. Three had focal nodular disease, whereas the other two had a diffuse multinodular presentation. Percutaneous biopsy definitively made the diagnosis in only one out of the five cases. Laparoscopic wedge biopsy was necessary to accurately make the diagnosis in three cases, whereas the fifth diagnosis was established after an anatomical resection. RNH is a unique pseudotumor of the liver that can present either as a solitary nodule or as a multinodular process. Percutaneous biopsy is associated with limitations in diagnosing RNH, and a more definitive surgical biopsy may be required. When RNH is considered, laparoscopic wedge biopsy is a safe and efficient way to obtain enough tissue to preserve the hepatic architecture required for diagnosis, while avoiding the morbidity of an unnecessary open resection.

Adult↗
PubMed2006

Akt expression may predict favorable prognosis in cholangiocarcinoma.

BACKGROUND: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. METHODS: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. RESULTS: Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. CONCLUSION: Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.

Adult↗
PubMed2005

The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice.

BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. METHODS: We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. RESULTS: Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-XL that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. CONCLUSION: These data suggest that in a clinical setting we will see heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including tumors that are highly sensitive as well as those that are resistant. While much more work is needed to understand the molecular basis for this heterogeneity, it is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased therapeutic efficacy in almost every case and therefore may be a highly effective strategy for controlling human pancreatic cancer validating and expanding upon what has been reported for cell lines.

Journal Article↗
PubMed2005

Long-term management of patients after potentially curative treatment of extremity soft tissue sarcoma: practice patterns of members of the Society of Surgical Oncology.

The optimal strategy for follow-up of extremity soft tissue sarcoma patients after primary treatment with curative intent is not known. The 1592 members of the Society of Surgical Oncology (SSO) were sent a survey to determine their practices. Office visits and chest X-rays were the most frequently performed items for all years. Complete blood count and liver function tests were the most commonly ordered blood tests, but many respondents did not order any blood tests routinely. Imaging studies of the extremities were recommended for most patients during the first postoperative year. Postoperative surveillance strategies after sarcoma treatment vary appreciably among surgeons. Surgeon age, tumor size, tumor grade, and geographic location of the surgeon account for only a modest amount of the variation, suggesting that lack of evidence supporting any particular strategy is the factor responsible for most of the variation. Efforts to provide high-quality evidence on this topic are warranted.

Extremities↗
PubMed2005

Image analysis using the fluorochromasia assay to quantify tumor drug sensitivity.

A method of assessing chemosensitivity of tissue utilizing tissue fluorescence and image analysis was implemented to provide a rapid and quantitative means of assessing the effect of drugs on tissue metabolic activity and proliferative capacity. The fluorescent microscopic image captured by a silicon-intensified target (low-light-detecting) camera and linked to an image- processing unit was measured for fluorescent brightness and tumor image area. An established rodent model served to characterize the system's ability to measure serially the tumor's metabolic activity and growth. Further studies on fresh human tumors were conducted with a novel topoisomerase II inhibitor, NC-190. Tumor image area and fluorescent brightness were measured 24 h pretreatment, 48 h posttreatment, and 48 h post-drug removal. Fifty-five percent (28/51) of fresh human tumors showed sensitivity to 48-h exposure to 10, 30, or 100 microM NC-190. The potential benefit of this technique is the ability to predict the response of tumors to chemotherapeutic agents as a laboratory tool for preclinical drug evaluation and clinically prior to the commencement of therapy.

1,2-Dimethylhydrazine↗
PubMed2005

Pancreatic cancer screening: identifying premalignant disease.

Evaluation of: Canto MI, Goggins M, Yeo CJ et al.: Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin. Gastroenterol. Hepatol. 2(7), 606-621 (2004). Endoscopic ultrasound was utilized in the screening of individuals at high risk for pancreatic cancer. Patients with abnormal endoscopic ultrasound findings were further evaluated with fine-needle biopsy, endoscopic retrograde cholangipancreatography, and computerized tomography scanning. A total of 38 patients were enrolled in this prospective screening program. A total of seven patients were identified with suspicious neoplastic lesions and underwent pancreatic resection. No significant morbidity or mortality resulted from the screening tests or subsequent intervention including surgery. Surgical pathology revealed two neoplastic masses (invasive carcinoma and intraductal pancreatic mucinous neoplasm), three pancreatic intraepithelial neoplastic lesions, and two benign lesions for a diagnostic yield of 13.1% (five of 38). The patient with invasive carcinoma remains disease free over 5 years following surgery. The results of this study suggest a reasonable approach to detecting early neoplastic lesions in asymptomatic individuals. Such early intervention efforts hold much potential in reducing the mortality of this aggressive disease. Further studies are needed to confirm the suggested clinical benefit of screening and to answer questions related to specific screening protocols.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2004

Risk factors associated with earlier age of onset in familial pancreatic carcinoma.

BACKGROUND: An estimated 5-10% of all pancreatic adenocarcinomas have a hereditary association. The objective of the current study was to characterize the clinical and pathologic features of familial pancreatic carcinoma and to determine potential differences in demographics, risk factors, and outcomes between familial and sporadic pancreatic carcinoma populations. METHODS: A retrospective review was performed to identify patients diagnosed with pancreatic carcinoma who had an associated familial disposition. Demographic analyses and assessment of clinical features and treatment outcomes were performed for the familial subgroup, and the results were compared with observations made in the nonfamilial, or 'sporadic', population. RESULTS: Thirty of 826 patients (3.6%) had familial pancreatic carcinoma. Baseline demographics, resectability, and metastases were similar in both the familial cohort and the sporadic cohort. The mean age of onset was slightly lower in the familial cohort (57.6 years, compared with 61 years in the sporadic cohort). However, the familial population had a significantly greater proportion of patients who were diagnosed at age <50 years compared with the sporadic population (36.7% vs. 18.3%; P=0.017). A positive smoking history was more commonly associated with familial pancreatic carcinoma (87% vs. 66%; P=0.06). The overall median survival durations were 7 months and 6 months for the familial group and the sporadic group, respectively. CONCLUSIONS: Patients with familial pancreatic carcinoma present at an earlier age compared with their counterparts who have nonfamilial disease. Smoking may play a significant role in the risk or promotion of pancreatic carcinoma in patients with an inherited predisposition.

Adenocarcinoma↗
PubMed2004

The effectiveness of complete decongestive physiotherapy for the treatment of lymphedema following groin dissection for melanoma.

OBJECTIVE: Groin dissection is performed for the treatment of melanoma and other malignancies. Lymphedema rates as high as 47% have been reported. In 1996, we began using complete decongestive physiotherapy (CDP) in selected patients with lymphedema following groin dissection. Here, we review our results in a small cohort of patients. METHODS: A retrospective review of the medical records of 14 patients, treated with CDP for lymphedema secondary to groin dissection for melanoma was conducted. All patients were treated with CDP at Roswell Park Cancer Institute (RPCI), between 1996 and 2002. Of the 14 patients, 12 underwent groin dissection at RPCI. Response to therapy was measured by limb volume determinations. Patient gender, age, body mass index (BMI), type of operation, type of adjuvant therapy, time to treatment, patient compliance, lymphedema stage, and initial edema were analyzed for association with response to treatment. Incidence was estimated by a review of the operative logs. RESULTS: Fourteen patients were treated with CDP for lymphedema secondary to groin dissection for melanoma, with a median decrease in lymphedema of 60% (range: 35-145%; P = 0.0003). Increased BMI was associated with a decreased response to treatment (P = 0.02). Response to CDP was not effected by time to treatment, patient compliance, lymphedema stage, and initial edema. During this time, 39 groin dissections were done at RPCI. The incidence of lymphedema treated with CDP at RPCI was 31% (12/39; standard error 7.4%). CONCLUSIONS: With a decrease in lymphedema of 60%, CDP may provide relief for patients with lymphedema following groin dissection. Elevated BMI was associated with a decreased response to CDP.

Adult↗
PubMed2004

The prognostic significance of margin width for extremity and trunk sarcoma.

BACKGROUND AND OBJECTIVES: To evaluate the significance of resection margin for soft tissue sarcoma (STS), we determined local recurrence-free interval (LRFI), distant metastases-free interval (DMFI), and overall survival (OS) for primary extremity and truncal STS with clear margins (> or =10 mm), close margins (1-9 mm), and positive margins (0 mm). METHODS: Patients were evaluated via review of charts and tumor specimens. RESULTS: Among 111 patients, tumors were predominantly high grade (86%), > or =5 cm (76%), and deep (81%). A minority of patients received adjuvant radiation (38%) and/or adjuvant chemotherapy (34%). Margin width was > or =10 mm (48%), 1-9 mm (40%), or 0 mm (12%). Margins > or =10 mm were less common for large (P = 0.009) or deep (P = 0.02) tumors. By multivariate analysis, independent factors for LRFI were tumor size (P = 0.04) and margin width (P = 0.03). Independent factors related to DMFI were tumor grade (P = 0.002), size (P = 0.007), and patient age (P = 0.02). Independent factors relating to OS were tumor grade (P = 0.001), size (P = 0.004), and depth (P = 0.03). CONCLUSIONS: Margins > or =10 mm independently predicted longer LRFI and are optimal for extremity STS resection. Adjuvant radiotherapy should be considered for all STS resected with margins <10 mm, and margin width should be considered when reporting and interpreting LR outcomes for these patients.

Chemotherapy, Adjuvant↗