Biomedical subjects

J G Fortner

Publications and source records attributed to J G Fortner.

At least 37 records · Page 2Linked to original sources

PubMed1989

"Radical" abdominal cancer surgery: current state and future course.

Biologically driven cancer surgery is essential for the best care of the cancer patient. Modern technology and support have improved the safety and operative results of radical surgery. Better understanding of tumor biology with technical advances permit rational, en bloc resection of the primary cancer and regional lymphatic drainage with better cure rates. The author has operated on 1103 patients with liver tumors since 1970. The liver tumors were resected in 415 patients, with major hepatic resections being done in 359. Since 1979, the author carried out 62 regional pancreatectomies. Thirty-three were for stage 1 or 2 adenocarcinomas of the head of the pancreas. The 5-year actual survival was 31 per cent. There has been similar improvement in treating ampullary and periampullary cancer, gallbladder cancer, or extrahepatic bile duct cancer. These data show significant improvement in the results of treating cancer by radical or biologically driven surgery. Abdominal cancer is not a generalized disease until late in its course.

Biliary Tract Neoplasms↗

PubMed1988

Primary lymphoma of the liver.

Nine adult white men ranging in age from 27 to 76 (mean, 55 years) were treated for primary hepatic lymphoma between 1972 and 1986 at the Memorial Sloan-Kettering Cancer Center. Six patients presented with right upper quadrant or epigastric pain or discomfort, and three patients complained of fatigue and lethargy. Fever and night sweats were evident in two, and two patients had lost weight. One patient was asymptomatic; the liver mass was detected during the work-up for cancer of the prostate. Seven patients on whom computerized tomography was performed all had solitary masses in the liver although in three of them tumor had extended into both lobes as noticed at surgery. One had additional porta hepatic lymph node metastasis. Eight patients underwent an exploratory laparotomy; four had hepatic resection, and four had wedge biopsies of unresectable liver tumor. One patient had a percutaneous needle biopsy of the liver. Eight patients received combination chemotherapy. Six patients are alive, five of whom are in initial complete remission. All three patients who died had persistent or recurrent disease in the liver. The results of therapy and surgery to date in these and in other cases in the literature are encouraging.

Adult↗

PubMed1988

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

Adult↗

PubMed1988

Recurrence of colorectal cancer after hepatic resection.

Survival estimates of 95, 65, and 49 percent at 1, 3, and 5 years, respectively, after hepatic resection in 77 patients when all gross metastatic cancer was removed compare favorably with the series of Wagner et al [20] of untreated, apparently comparable patients. In the present series, recurrent disease was evident after hepatic resection, most commonly in the lungs; the liver; and locally, in that order. About half of the 45 patients with a second recurrence were operated on, and the recurrence was completely removed in roughly half of these patients. A median survival estimate of 31 months (range 1 to 67 months) after complete removal of the second recurrence was better than the survival estimate of 14 months (range 1 to 18 months) for those in whom the recurrence could not be removed (p less than 0.01). An elevated carcinoembryonic antigen level as the only indicator of recurrence after hepatic resection has proved to be an ominous prognostic sign.

Adolescent↗

PubMed1986

Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard).

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.

Adult↗

PubMed1986

Total pancreatectomy increases the metabolic response to glucagon in humans.

To evaluate the impact of glucagon deficiency on the response to glucagon replacement, we infused physiological doses of glucagon (1.25 ng/kg X min) into 9 totally pancreatectomized (PX) diabetic patients (C-peptide, undetectable) 1) for 24 h during their usual diet and insulin regimen and/or 2) for 6 h in a fasted insulin-withdrawn state. During both glucagon infusions, plasma glucagon rose from 46 +/- 2 (+/- SE) pg/ml (0-10% 3500 mol wt glucagon) to 112 +/- 9 pg/ml. In the 24-h study (n = 4), glucagon significantly increased mean 24-h glucose levels (272 +/- 27 mg/dl; P less than 0.05) and glycosuria (29 +/- 5 g/day; P less than 0.01) compared to preinfusion (158 +/- 14 mg/dl and 4 +/- 4 g/day, respectively) and postinfusion (200 +/- 35 mg/dl and 3 +/- 2 g/day) control periods. Blood ketones did not change. The 24-h glucagon infusion significantly lowered the fasting levels of the glucogenic amino acids aspartate (43%; P less than 0.01), threonine (46%; P less than 0.05), serine (46%; P less than 0.02), glycine (47%; P less than 0.01), and methionine (34%; P less than 0.02). Fasting alanine levels decreased from 835 +/- 236 to 393 +/- 66 microM (P less than 0.05). The 6-h glucagon infusion caused a 101 +/- 14 mg/dl maximal plasma glucose increment in PX (n = 8) vs. 33 +/- 11 in 5 insulin-withdrawn type I diabetic patients serving as controls (P = 0.022). Furthermore, when glucagon was infused at a higher rate (3 ng/kg X min) in 12 additional type I diabetic patients, the mean maximal plasma glucose increment (54 +/- 15 mg/dl) was still less than half that in PX, despite a 3-fold higher infusion plasma glucagon level (326 +/- 37 pg/ml). The 6-h glucagon infusion caused a significant decrease in the concentrations of glucogenic amino acids in the glucagon-deficient patients, but not in the type I diabetic patients. We conclude that 1) glucagon replacement in the PX patient markedly alters blood glucose and glucogenic amino acids, but not ketone levels; and 2) the metabolic response to glucagon is considerably more pronounced in PX patients than in type I diabetic patients. These data suggest that glucagon responsiveness is enhanced in the chronic hormone-deficient state.

Adult↗

PubMed1986

Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance.

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Glucagon immunoreactivity and chromatographic profiles in pancreatectomized humans. Paradoxical response to oral glucose.

The nature and origin of plasma immunoreactive glucagon (IRG) after pancreatectomy in humans remains controversial. Low plasma IRG levels and heterogeneity hamper accurate assessment. We studied plasma IRG levels and profiles in 12 patients 2-57 mo after a total pancreatectomy (with antrectomy and duodenectomy) for cancer (N = 9) or chronic pancreatitis (N = 3). After oral glucose, plasma IRG (with the COOH-terminal-specific 30K glucagon antibody) rose from 59 +/- 7 to a peak of 113 +/- 17 pg/ml at 60-120 min. Chromatographic profiles revealed four distinct IRG fractions. In every patient a plasma IRG fraction of 9000-15,000 Mr, detectable basally, increased markedly after oral glucose and accounted for the rise in total IRG observed in plasma. Nine of the 12 pancreatectomized subjects had no detectable 3500-Mr glucagon and the remaining 3 had very low levels. For the group as a whole, 3500-Mr IRG comprised 1-2% of the total recovered IRG. Two patients were also studied before pancreatectomy: suppressibility of glucagon (Mr 3500) was evident. After surgery this paradoxical response to oral glucose was demonstrated. Reproducibility of these responses was confirmed in two patients studied twice over 2 yr. Diabetic controls without pancreatectomy did not show this response. The absence or marked reduction of pancreatic glucagon was confirmed in five of the pancreatectomized patients after intravenous arginine or oral protein. Normal basal plasma IRG and profiles, oral glucose suppressibility, and arginine stimulation were present in five control patients with unresectable pancreatic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence.

The Registry of Hepatic Metastases has collected data on consecutive patients from 24 institutions who have undergone hepatic resection for colorectal carcinoma metastases. Patterns of recurrence were examined in a subgroup of 607 patients who had undergone curative resection of isolated hepatic metastases. Forty-three percent of these patient have had recurrences in the liver and 31% have had recurrences in the lung (either alone or in combination with other organs). A multivariate analysis showed that patients with positive pathologic margins or bilobar metastases were at an increased risk of having a recurrence in the liver (68% and 64%, respectively). We conclude that: hepatic resection effectively controls hepatic tumor in a substantial number of patients, adjuvant therapy after hepatic resection should be directed at both the lung and liver to significantly increase survival, and patients with positive pathologic margins or bilobar metastases are at an increased risk for hepatic recurrence.

Clinical Trials as Topic↗

PubMed1985

Technique of regional subtotal and total pancreatectomy.

The technique of regional pancreatectomy as detailed is divided into five phases. The procedure includes en bloc regional lymph node dissection, peripancreatic soft tissue resection, and resection with reconstruction of the pancreatic segment of portal vein. The pancreatic resection can be subtotal or total.

Hepatic Artery↗

PubMed1985

Selective use of wide excision with elective lymph node dissection for malignant melanoma.

One hundred and eighty individuals with clinically negative regional lymph nodes are the basis of this study. One hundred and ten of these underwent an elective lymph node dissection. The incidence of histologically positive lymph nodes was 0 percent, 17 percent, and 42 percent for those with thin, intermediate thickness and deeply invasive lesions. Of these 25 patients with histologically positive lymph nodes, the metastases were micro in size (less than or equal to 2 mm) in 75 percent of the intermediate thickness group compared with 38 percent of the deeply invasive group. At the present time, the size of lymph node metastases appears to correlate with disease-free estimates: at 2 years, the disease-free estimates are 70 percent for those with micro metastases and 24 percent for those with macro metastases. Therapeutic success is influenced greatly by the number of circulating cancer cells challenging the host's defense mechanism. The large cell mass of clinically evident metastatic disease would appear to present most patients with an uncontrollable number.

Female↗

PubMed1984

Treatment of primary undifferentiated sarcoma of the liver with surgery and chemotherapy.

Primary undifferentiated sarcoma of the liver is a rare tumor with survival reliant on total excision of the tumor. The authors report such a tumor, initially nonresectable, in a 7-year-old girl whose tumor was successfully excised following treatment with cisplatin and Adriamycin (doxorubicin). The light and electron microscopic details of this patient's tumor are presented.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1984

Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection.

In the United States, there are an estimated 5000 to 6000 new patients annually who might be candidates for major hepatic resection to treat their recurrent colon cancer. Since 1971, the program reported here has evaluated various factors that might influence the curative potential of such an approach. Sixty-five patients had a major hepatic resection from March 1971 through May 1982. Using a stepwise proportional hazard analysis, all data that had been stored in CLINFO (a data analysis system by Bolt, Beranek and Newman; Boston, MA) were evaluated for the effect of multiple variables on the survival of patients with resected hepatic metastases. Twenty-seven had a right hepatic lobectomy; 14 had extended right hepatectomy with one having the caudate lobe also removed; ten had left lobectomy, nine had left lateral segmentectomy; and five had a major hepatic resection with three-dimensional wedge excision of a metastatic deposit in the contralateral lobe. The 30-day operative mortality rate was 7% (4/58) for patients undergoing the standard major hepatic resection. It was 14% for seven patients in whom the isolation-hypothermic perfusion technique was used early in the series. In ten patients, wedge excision only was required to remove the tumor. Stage I disease is defined as tumor confined to the resected portion of the liver without invasion of major intrahepatic vessels or bile ducts. Stage II disease is regional spread and Stage III disease is metastasis to lymph nodes or extraregional sites. The 3-year survival estimate was 66% for the 37 patients with Stage I disease. The 3-year survival estimate for 13 patients with Stage II disease was 58%. Five of the nine patients with Stage III disease are presently alive from 3 to 23 months; one of the other four died at 35 months of disease. The stage of liver disease was the most significant variable in this survival analysis (p = 0.02); Dukes' classification of colorectal primary was significant at p less than 0.05. Those factors found not to be significant determinants of survival were: number of metastatic hepatic deposits, site of colon primary, age, sex, preoperative liver function tests, and CEA.

Adult↗

PubMed1984

Multivariate analysis of a personal series of 247 patients with liver metastases from colorectal cancer. II. Treatment by intrahepatic chemotherapy.

One hundred and seventeen patients with colorectal hepatic metastases had insertion of catheters for infusional chemotherapy. The two-year survival estimate of patients with less than 50% hepatic replacement and no other adverse factors was 37%. Nine of 39 patients in this group are alive at 24 months. The catheters were placed into the hepatic artery (HA), 23; into the portal venous system (PV), 18; into both HA and PV, 64; or into an accessory HA following ligation, 12. Fifty-nine patients had ligation of the common HA also. The 30-day postoperative mortality rate was 1.7% (2/117) and morbidity was 37.6%. The majority of complications were related to fever (61%, 27/44). Over the past 2 years, 87% of patients have been discharged within 10 days following surgery. Preoperative CEA ranged from 0.5-12,150 ng/ml (median 165 ng/ml); 93% (78/84) had plasma CEA levels exceeding 5 ng/ml. All patients had careful intraoperative staging: per cent hepatic replacement (PHR) ranged from 5-95% (median 60%); portal, celiac, or periaortic lymph node metastases were observed in 31% (36/117). Initial intrahepatic chemotherapy programs consisted of either CAMF (9 patients), MAFL (60 patients), BFS (22 patients), continuous infusion FUDR (14 patients), or miscellaneous drugs (4 patients). Median survival time of 109 evaluable patients was 11.5 months. The effect of 20 variables on the observed survival time was analyzed using a multivariate proportional hazard model. Three variables were found to have influenced survival: PHR emerged as the most significant, p = 0.000001. Increased PHR was associated with decreased survival time. Lymph node metastases and prior chemotherapy were prognostic factors also, p = 0.0006 and p = 0.03, respectively. No patient with PHR greater than 80% lived more than 8 months. Utilization of these variables would appear to be necessary for accurate stratification and evaluation of future chemotherapy trials in patients with colorectal hepatic metastases.

Adult↗

PubMed1984

Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Tumor staging and results.

Regional pancreatectomy refers to an en bloc removal of a tumor in or adjacent to the pancreas with an adequate soft tissue margin and with its regional lymphatic drainage. The pancreatic segment of portal vein is part of the en bloc resection with venous reconstruction by end-to-end anastomosis without a graft. This operation, called a Type I regional pancreatectomy, may utilize either a total or subtotal removal of the pancreas. Localized arterial involvement by a neoplasm necessitates adding a segmental resection of the artery with vascular reconstruction, a Type II procedure. Sixty-one patients have had this procedure from 1972 through 1982. They are a subset of the 270 patients with cancer of the pancreas, ampullary and periampullary regions, duodenum, or terminal portion of the common bile duct who were treated by the author during this period. The 61 consist of 35 patients who had an infiltrating duct adenocarcinoma of the pancreas and 21 who had other kinds of malignant tumors. In addition, four were classified as having pancreatitis and a fifth patient had a pseudolymphoma. The resectability rate is about 30%. The present operative mortality rate is 8%. Approximately one-third of the patients are alive; 43% of the 21 patients with malignant tumors other than infiltrating duct adenocarcinoma of the pancreas are alive with a median survival time of 40 months (3-92 months). Forty-three per cent were Stage I but more than half were T3 or T4 lesions. Twenty-five per cent of patients with Stages II or III are alive. Twenty per cent of patients with infiltrating duct carcinoma of the pancreas are presently alive, 28% died of recurrent disease, and 26% died of other causes; more than 90% of these patients had advanced stage disease (Stage II or III).

Adenocarcinoma↗

PubMed1983

Regional pancreatectomy for cancer of the pancreas, ampulla and other related sites.

Regional pancreatectomy refers to an en bloc removal of a tumor in or adjacent to the pancreas with an adequate soft tissue margin and with its regional lymphatic drainage. The pancreatic segment of portal vein is part of the en bloc resection with venous reconstruction by end-to-end anastomosis without a graft. This operation, called a Type I regional pancreatectomy, may utilize either a total or subtotal removal of the pancreas. Localized arterial involvement by a neoplasm necessitates adding a segmental resection of the artery with vascular reconstruction, a Type II procedure. Sixty-one patients have had this procedure from 1972 through December 1982. Thirty-four patients had an infiltrating duct adenocarcinoma of the pancreas, 22 had other malignant tumors, 4 were classified as having pancreatitis, and a fifth had a pseudolymphoma. The resectability rate is about 30 per cent. The present operative mortality rate is 4 per cent by 30 days and 8 per cent after 30 days. One-third of the patients are presently alive; 45 per cent of the 22 patients with malignant tumors other than infiltrating duct adenocarcinoma of the pancreas are alive with a median survival time of 391/2 months ranging from 3 to 92 months. More than 80 per cent of patients with infiltrating duct adenocarcinoma of the pancreas had advanced stage of the disease (T3 or T4 and Stage II or III cancers); twenty-one per cent are presently alive, 29 per cent died of recurrent disease, and 24 per cent died of other causes. The optimal treatment for patients with cancers in the region of the head of the pancreas is a regional subtotal pancreatectomy Type I or Type II followed by adjuvant chemotherapy.

Antineoplastic Agents↗

PubMed1983

Preoperative chemotherapy and surgical resection in the management of posterior paraspinal tumors. Report of three cases.

Three patients with posterior paravertebral tumors are presented to illustrate the value of preoperative chemotherapy prior to surgical resection. All three had massive tumors adjacent to the spine, extending over several vertebral segments, with myelographic evidence of epidural involvement in one patient. Tissue diagnosis by incisional biopsy confirmed the diagnosis of extraosseous osteogenic sarcoma in one, extraosseous Ewing's sarcoma in the second, and embryonal rhabdomyosarcoma in the third. All patients were treated with chemotherapy preoperatively. Marked regression in tumor size was noted, and surgical excision of the tumor along with involved segments of spine was easily accomplished. Histological examination following surgery revealed completely necrotic tumor in two patients. Preoperative chemotherapy for fully malignant tumors offers the following advantages: 1) extremely bulky and otherwise unresectable tumors can be reduced in size to enable complete surgical resection; 2) systemic chemotherapy is instituted earlier in the course of disease to prevent more effectively the appearance of metastases; and 3) the information gained regarding the sensitivity of the tumor to a particular chemotherapy regimen allows postoperative adjuvant chemotherapy to be used on a more rational basis.

Adolescent↗

PubMed1983

Sensitivity of xenografts of human pancreatic adenocarcinoma in nude mice to heat and heat combined with chemotherapy.

The sensitivity of two human pancreatic adenocarcinomas (Capan-1 and Capan-2) to heat and heat combined with chemotherapy was studied using xenografts of the tumors in the foot of athymic nude mice. Heat was applied by immersion of the tumor in a water bath at 43.5 degrees for 1 hr. A single i.p. dose of mitomycin C, cisplatin, 5-fluorouracil, or 0.9% NaCl solution was given at 1 hr prior to treatment. Heat treatment alone significantly suppressed tumor growth (p less than 0.001), with 35% of the tumors showing complete regression. Combined treatment using heat plus chemotherapy yielded significantly greater suppression of tumor growth (p less than 0.05) with mitomycin for both tumors and with cisplatin or 5-fluorouracil for Capan-1. Combined treatment also gave higher rates of complete tumor regression: 55 and 64%, respectively, for Capan-1 and Capan-2 as compared with 18 and 47% for the respective tumors treated by heat alone. These observations suggest that human pancreatic carcinomas are sufficiently sensitive to heat combined with chemotherapeutic treatment to warrant a clinical trial of these modalities.

Adenocarcinoma↗