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Methods: We performed a retrospective study of 44 patients who underwent right or extended right hepatic lobectomy to determine the incidence and significance of hypophosphatemia after major hepatic resection., Results: The postoperative serum phosphate level (measured as inorganic phosphorus) dropped in all 44 patients studied. Profound hypophosphatemia (less than 1.0 mg/dl) was significantly (p less than 0.001) associated with the frequent development of major postoperative complications (cardiorespiratory, five cases; infections, four cases; hemorrhage, one case; and liver failure, one case). Factors such as extent of liver resection, blood loss, blood or plasma transfusion, postoperative bilirubin level, and preexisting liver diseases showed no significant correlation with the nadir inorganic phosphorous level. Use of aluminum-containing antacids caused a further drop of the serum values (p less than 0.05). Early phosphorous replacement showed a significant protective effect (p less than 0.05), with higher serum levels and fewer major complications., Conclusions: These observations affirm the importance of frequent monitoring and replacement of phosphate after major hepatic resection.

Recent studies suggest an improved survival in patients who undergo radical lymph node dissection for the curative treatment of gastric carcinoma. We have undertaken a retrospective review to compare morbidity and mortality between patients who underwent radical lymph node dissection and those who underwent resections of lesser scope. Of the surgically related events compared, only the amount of postoperative abdominal drainage was significantly different in the group that underwent radical lymph node dissection Forty-four percent of patients who underwent radical lymph node dissection and 35% of patients who underwent a procedure of lesser scope developed a major complication. There was also no significant difference in the postoperative death rate, with a total of two 30-day in-hospital deaths (1.1%). Our observations indicate that radical lymph node dissection can be performed as safely as lesser operations for gastric carcinoma, and should not be avoided because of the fear of complications.

The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay.

Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation.

The treatment options for recurrent extremity sarcoma following conservative surgery and irradiation are limited. Amputation is the treatment of choice offered for the majority of these patients. In a selected group of patients with recurrent sarcoma, we have investigated the role of brachytherapy along with function-preserving resection. From 1979 to 1988, 40 patients underwent resection and brachytherapy for recurrent extremity sarcoma. There were 23 males and 17 females. All of the patients received function-preserving resection and an afterloading temporary tumor bed implant. A median dose of 4500 cGy was delivered with a range from 3000 to 4800 cGy. The median follow-up was 36 months with a range of 12 to 120 months. The actuarial local control at 5 years is 68%. Five patients (12.5%) developed complications such as wound ulceration (4) and femoral fracture (1) requiring surgery. Five patients developed local failure and an additional two patients had both local and distant failure. All of the failures occurred in patients with more than two prior recurrences. This review suggests that brachytherapy can be used as an effective treatment option in selected patients with recurrent extremity sarcoma following prior surgery and irradiation with satisfactory limb preservation. The data also suggest that higher local control rates can be achieved with early brachytherapeutic intervention.

A retrospective study of early gastric cancer (60 patients) was performed to evaluate its diagnosis and treatment. Ninety-five per cent of patients presented with nonspecific gastrointestinal symptoms and 53.3% had been treated for presumed benign disease for up to 48 months before diagnosis. Fiberoptic endoscopy detected these lesions more accurately than radiologic examination. The disease-free 5-year survival rate after resection was 76.4%. Survival showed no significant correlation with sex, tumor site, macroscopic appearance, extent of gastric resection, or histopathologic type. Tumors larger than 1.5 cm in diameter, invasion of submucosa, or lymph node metastasis resulted in significantly lower survival rates. Three of eight patients with nodal metastasis survived 5 or more years, including one who had second-echelon deposits. A high index of suspicion may permit more frequent detection. Extended lymphadenectomy (R2) is recommended to achieve the highest possible cure rate.

We performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity. Twelve factors, including splenectomy, were associated with a poor prognosis by univariate analysis. Multivariate analysis identified six of these factors, but not splenectomy, as independently predictive of death due to gastric cancer. The apparent adverse effect of splenectomy was due to its association with other significant risk factors. Postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not (45% vs 21%); patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group (75% vs 47%). We conclude that splenectomy has no direct influence on survival, but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor.

We reviewed the clinical records and pathologic material of 176 adults with primary soft tissue sarcomas treated at Memorial Sloan-Kettering Cancer Center between 1950 and 1985. Seventy-two patients (41%) had low-grade sarcomas and 104 (59%) had high-grade sarcomas. All but 18 patients underwent some form of excision as initial therapy. Adjuvant radiotherapy and chemotherapy combined with surgical excision showed no significant effect. A significantly increased risk of treatment failure was associated with large tumor size, positive surgical margins, bone involvement, local recurrence, metastatic spread, and high histologic grade. Except for recurrence, the p value by univariate analysis in the log-rank test for comparison of survival according to these clinical and pathologic characteristics was p less than 0.0001. Although the overall survival was 75% at 2 years, 55% at 5 years, and 46% at 10 years, only 20% of the patients with high-grade sarcomas were alive 10 years after treatment. Most patients with rhabdomyosarcoma, high-grade peripheral nerve tumor, and high-grade fibrous histiocytoma and all patients with high-grade angiosarcoma died of disease less than 5 years after diagnosis. New therapeutic strategies are needed to improve the survival of adult patients with high-grade soft tissue sarcomas of the head and neck.

While there is debate in the literature concerning the tolerance of neurovascular structures to external beam radiation, the tolerance of these tissues to interstitial radiation has never been established. To evaluate the dose of radiation and its effect on early and late toxicity of neurovascular structures, a retrospective review of our experience was undertaken. Between 1975 and 1987, 299 patients with extremity sarcomas underwent limb-sparing surgery and tumor bed Iridium-192 interstitial implantation at Memorial Sloan-Kettering Cancer Center. Forty-five patients (15%) of this group were found to have locally advanced tumors involving major neurovascular structures. Of these patients, 64% had high grade lesions. Eleven percent had evidence of gross residual disease on these structures, and an additional 58% had microscopic residual disease at or close to the margins of resection. After loading catheters were placed directly upon the neurovascular structures in the exposed tumor bed and a median dose of 4400 cGy was delivered to the target volume. Eight patients had previous radiation to the treated field and 13 patients received postoperative radiation. With a median follow-up of 4 years, the 5-year actuarial disease-free survival was 69% and the 5-year actuarial freedom from in-field failure was 79%. The 5-year actuarial incidence of distant metastases was 30%. Eighty-four percent of the patients maintained long-term preservation of limb function without the need for amputation. Four patients (9%) ultimately developed evidence of radiation neuritis 6-20 months post therapy. All four patients had received additional radiation with cumulative doses exceeding 9000 cGy to the neurovascular bundle. We conclude that combined surgical resection and interstitial radiation for locally advanced sarcomas with neurovascular involvement can provide excellent local control with preservation of limb and neurovascular function without significant toxicity.

From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.

The therapeutic value of extensive gastric resection and regional lymphadenectomy in the curative treatment of gastric adenocarcinoma is controversial. We undertook a retrospective study of 210 patients treated with curative intent from 1960 to 1980. A multivariate survival analysis using the Cox model revealed five significant variables predictive of death from gastric cancer--two inherent pathologic factors: (1) nonpyloric site and (2) metastases in more than three lymph nodes, and three treatment factors that could often be controlled by the surgeon: (3) microscopic positive gastric resection margin, (4) inadequate lymphadenectomy, and (5) total gastrectomy. These observations reaffirm the value of wide gastric resection and adequate lymphadenectomy but argue against a general policy of elective total gastrectomy in the curative treatment of gastric carcinoma.

A technique of esophagogastrectomy is described in which a single gastrotomy permitted insertion of an end-to-end circumferential stapler for esophagogastric anastomosis, a transgastric pyloromyectomy, and placement of a gastrostomy tube. A transgastric pyloromyectomy was easy to perform and functioned adequately. The stapler could be advanced via the gastrotomy into the mediastinum or the upper thorax for the anastomosis. The placement of a gastrostomy tube obviated the need for prolonged use of a nasogastric tube, thus removing a major cause of discomfort. Use of this technique in 20 patients simplified the operative procedure and the postoperative care.

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.

Sixty-four adult patients with soft-tissue sarcomas received adjuvant chemotherapy with a six-drug combination regimen after surgery. Seventy percent remain free of disease with a median follow-up of 50 months. Only seven patients have died of their disease, all within the first 24 months after surgery. Most patients experienced severe nausea and vomiting secondary to the actinomycin D and dacarbazine parts of the protocol, and three patients experienced frank Adriamycin cardiomyopathy. Toxicity from this combination was otherwise mild. The 58% recurrence rate of 12 patients who discontinued therapy early because of nausea was significantly greater than the 23% rate for those who completed or relapsed on therapy (P = 0.01). Adjuvant chemotherapy should be considered after surgery for patients with soft-part sarcomas, especially those with high-grade tumors that have a considerable risk of recurrence.

A retrospective study was made of 38 myosarcomas of the small and large intestines (34 leiomyosarcomas and 4 malignant leiomyoblastomas). Endoenteric, small, and noninvasive tumors were successfully treated by simple wedge excision, cautery snare removal, or segmental bowel resection with a high 5-yr cure rate of 86% (12/14). Exo-enteric tumors often invaded adjacent structures or perforated into the peritoneal cavity. Extensive resection procedures, including pancreaticoduodenectomy, abdominoperineal resection, and pelvic exenteration salvaged only 13% (2/16) of these patients. Three clinicopathologic factors adversely affected prognosis: i) tumor size greater than 5 cm in diameter, ii) extra-intestinal invasion or free perforation, and iii) high histopathologic grade of malignancy. The presence of none, one, two, or three of these adverse factors gave decreasing 5-yr survival rates of 100, 44, 31, and 0%, respectively. These observations suggest use of a multimodal treatment program that may minimize treatment failure from local as well as distant disease.

The high operative mortality of major hepatic resection for tumor can be improved by a technic of resection using complete vascular isolation and hypothermic perfusion of the liver. Complete clamping of the portal vein, vena cava, and hepatic artery was necessary and well tolerated. Major physiologic, biochemical, and coagulation changes, however, can occur with this technic that requires close monitoring by the anesthesiologist. With astute observation and prompt corrective measures when indicated, these changes can be minimized to enable a safe and smooth resection to be carried out.

A clinicopathologic study was made of 32 soft-tissue sarcomas of the anterior abdominal wall (ten desmoid tumors and 22 fully malignant sarcomas). Direct invasion of the costal margin or the iliac crest was observed in both types, whereas transperitoneal invasion and metastasis developed characteristically with fully malignant sarcomas. Wide monobloc resection of the abdominal wall, including, where necessary, resection of adjacent bony parts and reconstruction with a prosthetic mesh, satisfactorily controlled local disease in nine of ten patients with desmoid tumor, and in three of four patients with primary operable, fully malignant sarcoma. Adjunctive therapy with radiation and chemotherapy may improve the outcome in patients with recurrent or high-grade sarcomas, but adequate monobloc resection of the primary tumor remains the most important therapeutic objective.

Today, the presence of a hepatic tumor can be diagnosed with considerable accuracy by means of isotope scans, arteriogram and ultrasonic imaging. Its localization to one lobe or other lobes is also generally achievable but with less accuracy because it is not yet possible to visualize the interlobar fissure by a noninvasive technique. Exploratory laparotomy with a view to resection is the preferred approach if the patient is in good general condition. Percutaneous biopsy of a hepatic lesion should be avoided unless laparotomy is not contemplated. Resection is the mainstay of therapy for all forms of hepatic malignant tumors and is the only modality that gives some prospect of cure. The prohibitively high operative mortality rate of former years, mostly due to hemorrhage, has gradually decreased with improved understanding of hepatic anatomy and innovations in surgical technique. By means of adequate vascular control and, if necessary, parenchymal cold perfusion, major resections of difficult and bulky lesions can now be accomplished with safety. Systemic chemotherapy with single agents, intra-arterial infusion chemotherapy and hepatic dearterialization have each been found to be of modest therapeutic value in a variable proportion of patients with diffuse unresectable cancer of the liver. The results of current experience indicate that the response rate is not high and long term control of tumor is rare. Multiple drug combinations with or without infusion therapy or dearterialization are being tried in many centers. Therapeutic strategy and end results for the different forms of benign and malignant neoplasms of the liver are discussed.

Malignant soft-tissue tumors of the abdominal wall consist of desmoid tumors and nondesmoid soft-tissue sarcomas. These neoplasms tend to invade adjacent musculoaponeurotic and bony structures. Transperitoneal organ invasion can also occur with devastating sequelae, especially after an incomplete excision. Extirpation with the full-thickness of the abdominal wall is required except for small, superficial lesions. A wide-margin resection, including any adherent viscus, segments of adjacent ribs, and iliac or pubic crest, offers the best assurance of local control. Adjunctive radiotherapy can be given when the margin of resection is unavoidably limited, but an effective radiation dose can be difficult to administer, due to the sensitivity of underlying intestines. Metastases develop frequently with high-grade sarcomas; adjuvant chemotherapy may be tried in these patients, but its value remains unproven.

Sarcomas (fleshy tumors) were distinguished from carcinoma (crab leg tumors) at the time of Hippocrates. Sarcomas are related embryologically to leukemias and lymphomas because all are thought to be malignancies of mesodermal embryologic origin. Neurosarcomas, however, are an exception, since they arise from tissue of neuroepidermal origin. Malignant sarcomas of the soft tissue represent an unusual primary malignant tumor. These lesions are characterized by their diversity in the histologic appearance and in their biologic behavior, as well as in anatomical origin. Currently there are approximately 7,400 newly diagnosed bone and soft tissue sarcomas, and approximately 4,200 deaths per year in the United States.1 The incidence of sarcomas varies by histologic type in various age groups. Embryonal rhabdomyosarcoma in the orbit peaks in the 4-year-old, and in the urinary tract in adolescence.2 Osteosarcoma has peak incidence in the teenage years, and Ewing's sarcoma develops between the ages of 15 and 30. Other sarcomas such as malignant fibrous histiocytoma and chondrosarcoma generally occur in patients aged more than 55 years. The incidence of osteosarcoma in whites and nonwhites is equal; Ewing's sarcoma is predominantly a disease of Caucasians.3 The relatively infrequent occurrence of these tumors plus their diverse histology and diverse presentations have made it difficult for any one institution to have enough patients to directly compare, in a randomized prospective fashion, one treatment with another in order to determine the optimal primary therapy. The purpose of this monograph is to review recent concepts in terms of pathology, surgery, radiation therapy, chemotherapy, and multimodality therapy.

A retrospective study was made of 106 locally and regionally advanced epidermoid carcinomas of the trunk and extremity treated from 1949 to 1970. Forty-six of the tumors had a known cause, of which radiation exposure was the most common. In addition to axillary and inguinal nodal metastases, these cancers also manifested intransit, epitrochlear and popliteal lymphatic metastatic disease. Surgical treatment consisted of wide monobloc resection for the majority of the primary neoplasms, amputation being necessary for tumors fixed to skeletal or neurovascular structures. Clinically enlarged regional lymph nodes were subjected to biopsy, but elective regional node dissection did not offer therapeutic benefit. Patients with biopsy proved nodal metastases were treated by either radical nodal dissection or high exarticulation, with similar results. Actuarial five year survival rates after definitive surgical treatment were 71 per cent for patients with regional node-negative and 57 per cent for those with regional node-positive tumors. Local and regional recurrences of tumors were frequent in patients who had deep seated tumors of the trunk and postsacral region, or bulky nodal disease, despite pathologically negative resection margins. Uncontrolled recurrent tumor with sepsis and compromise of vital organ function was the most common cause of death. Radiation therapy achieved partial regression of the tumor in eight patients and complete regression in one of 15 patients. A critical analysis is made of the various clinicopathologic factors which affect prognosis, and the possible means of improving the results of treatment are discussed.