Hepatic resection for metastatic colorectal cancer.

One-hundred thirty-one primary hepatic resection for colorectal secondary tumors were performed at Rush-Presbyterian-St. Luke's Medical Center between 1975 and 1993. Perioperative mortality occurred in five patients (3.8%). Twenty-three patients had minor morbidities (18%); major morbidity occurred only in the five patients who died. Curative resections were performed in 107 patients. Overall actuarial survival at 2, 3, and 5 years was 62, 42, and 25 per cent, respectively. Patients with extrahepatic disease (5-year survival, 0% vs 27%; P = 0.049) and positive resection margins (0% vs 30%; P < 0.001) had significantly poorer survival. Among the curative resections, patients who had metachronous hepatic resections did significantly better than those who underwent synchronous colon and hepatic resections (35% vs 13%; P = 0.002). This survival benefit persisted when comparison was restricted to patients with synchronous metastases. Age, sex, race, number of lesions, site of colon primary resection, blood transfusion, disease-free interval, and extent of resection had no effect on survival. All patients who are acceptable surgical risks with potentially resectable metastatic colorectal cancer confined to the liver should undergo exploration. Assessment of resectability should include intraoperative ultrasound in all patients to maximize the probability of tumor clearance.

Survival after repeat hepatic resection for recurrent colorectal hepatic metastases.

BACKGROUND: This is a retrospective clinical study done to examine survival of patients undergoing repeat hepatic resection for recurrent colorectal hepatic metastases. METHODS: The records of 131 patients undergoing hepatic resection for metastatic colorectal cancer were reviewed. Curative resection was performed in 107 of these patients. Thirty-one experienced recurrences confined to the liver. Thirteen (13 of 107, 12%) of them underwent resection and make up the study population. RESULTS: The eight men (62%) and five women (38%) had a median age of 60 years (range, 32 to 75 years). In 30% of patients recurrence developed near the original resection site. In 70% the recurrences were remote from the original site. The patients underwent a total of six wedge resections, two left lateral segmentectomies, three right lobectomies, and two trisegmentectomies. Average blood loss was 2995 cc; average hospital stay was 17.2 days. Morbidity was 23% (3 of 13); mortality was 8% (1 of 13). Four patients died of recurrent disease, with a mean disease-free survival of 9.7 months (median, 7.5 months; range, 3 to 21 months) and mean total survival of 39 months (median, 24 months; range, 8 to 99 months). One of these patients had a second recurrence resected at month 21 and lived an additional 78 months. Seven patients were alive with no evidence of disease, with a mean follow-up time of 34.9 months (median, 14 months; range, 1 to 186 months). Actual 5-year survival was 23% (3 of 13). Actual disease-free 5-year survival was 15% (2 of 13). CONCLUSIONS: In properly selected patients morbidity, mortality, and survival after repeat resection are similar to those after initial resection.

The dilemma of delayed cellulitis after breast conservation therapy.

OBJECTIVE: To determine the clinicopathologic characteristics of patients with breast cancers in whom delayed breast cellulitis developed after conservation therapy (lumpectomy, axillary dissection, and radiation). BACKGROUND: Breast cellulitis developing after conservation therapy represents a difficult diagnostic and management dilemma because determination of its origin may be necessary before further treatment decisions can be made. METHODS: In this retrospective evaluation of 184 sequential patients with breast cancers who underwent conservation therapy, 10 study patients (5%) in whom breast cellulitis developed 3 or more months after surgery were compared with the 174 patients in whom cellulitis did not develop. RESULTS: There was no significant difference in clinicopathologic characteristics of the study patients compared with control patients. The cellulitis resolved in 5 patients (50%) and persisted from 4 months to more than 1 year in 5 patients (50%). The cellulitis recurred in 1 patient who responded to repeated therapy. The 5 patients with persistent cellulitis underwent biopsies, and recurrent cancer was found in 1 patient. Recurrent cancer did not develop in the patients whose cellulitis resolved within 4 months with a minimum follow-up of 24 months. CONCLUSIONS: Delayed-onset cellulitis occurs in a small percentage of patients with breast cancers treated by conservation therapy. The cellulitis may take several weeks to clear, and/or it may recur or persist. If the condition persists after 4 months of therapy, a biopsy should be performed to rule out recurrent cancer.

A 15-year review of esophagectomy for carcinoma of the esophagus and cardia.

OBJECTIVE: To evaluate the effect of surgical approach and adjuvant therapy on patients with carcinoma of the esophagus and/or cardia. DESIGN: Retrospective analysis of 157 consecutive patients who underwent esophagectomy. SETTING: A private university medical center and its affiliated community hospital. PATIENTS: One hundred twenty men and 37 women (mean age, 61.7 years) with carcinoma of the esophagus and/or cardia that was surgically treated between 1978 and 1993. INTERVENTIONS: Three approaches were used for resection: Transhiatal esophagectomy (THE) (n = 67), transthoracic esophagectomy (TTE) (n = 71), and abdominal-only esophagectomy (AOE) (n = 19). Sixty-five patients received adjuvant radiotherapy and chemotherapy. MAIN OUTCOME MEASURES: Surgical mortality, morbidity, and survival and the effect of adjuvant therapy. RESULTS: The overall surgical mortality rate was 7.6%: 12.7% with the TTE, 4.5% with the THE, and 0% with the AOE approach. A significantly increased incidence of adult respiratory distress syndrome (P < .001) and empyema (P < .001) was seen with the TTE approach. The average intraoperative blood loss (P = .08) and the median intensive care unit stay (P = .26) and hospital stay (P = .40) were decreased with the THE and AOE approaches when compared with the TTE approach without significance. The overall median survival time was 17 months, with a 5-year survival rate of 21%. There was no significant difference in survival by pathologic stage between approaches. The addition of adjuvant therapy did not affect the overall median survival time or the 5-year survival rate. Node-positive patients did benefit from adjuvant radiotherapy and chemotherapy, with increased median survival times from 7 to 15 months and a 5-year survival rate from 0% to 15% (P = .01). CONCLUSIONS: The THE and AOE approaches have fewer early complications than does TTE. Both THE and TTE have equal long-term survival rates. Adjuvant therapy provides increased survival to node-positive patients with carcinoma of the esophagus and/or cardia.

Malignant cystosarcoma phyllodes.

UNLABELLED: This study reviewed 26 women who had resection of a malignant cystosarcoma phyllodes. Clinical presentations were palpable mass, 25; pain, 11; and ulceration, 2. Definitive surgical therapy was radical mastectomy (RM), 2; modified radical mastectomy (MRM), 14; total mastectomy (TM), 4; and partial mastectomy (PM), 6. Tumors ranged in size from 1-20 cm (median, 7 cm). Eight patients developed recurrent disease after 10-45 months. Local recurrence was more likely after TM and PM than after MRM and RM (P < 0.05). Patients who developed local recurrence only were treated by wide re-excision, and all such patients are alive with no evidence of disease at 5-25 years. Only one of 16 patients undergoing axillary dissection had involved lymph nodes. Four patients whose tumors ranged from 5-8 cm and who underwent one RM and three MRM developed systemic recurrence; all died of their disease after 15-48 months. CONCLUSION: 1) Although there is a higher local recurrence after PM and TM as compared with MRM and RM for malignant cystosarcoma phyllodes, the local recurrence can be treated with wide excision without affecting long-term survival; 2) systemic recurrence was not related to size or extent of resection; 3) axillary dissection does not predict for or prevent recurrence.

Therapy of disseminated malignant melanoma with recombinant alpha 2b-interferon and piroxicam: clinical results with a report of an unusual response-associated feature (vitiligo) and unusual toxicity (diffuse pulmonary interstitial fibrosis).

Fifteen patients with disseminated malignant melanoma were treated with recombinant alpha 2b-interferon (20 mU/m2 intravenously 5 days per week for 4 weeks and then 10 mU/m2 subcutaneously tiw) and piroxicam (10 mg a day orally for 10 days prior to beginning interferon and daily thereafter). Two complete responses of soft tissue disease and stabilization of disease in two other patients were obtained. One complete response was associated with the development of vitiligo. One patient who had entered complete remission was removed from the study because of diffuse pulmonary interstitial fibrosis, believed due to therapy. The combination of alpha 2b-interferon and piroxicam offers no clinical advantage over the use of alpha 2b-interferon alone.

Synchronous, metachronous, and multiple hepatic resections of liver tumors originating from primary gastric tumors.

BACKGROUND: The role of hepatic resection for noncolorectal gastrointestinal malignancies involving the liver is not well defined. To address this issue we studied our experience with resection of liver tumors arising from primary gastric malignancies. METHODS: A retrospective study of 195 patients who underwent a total of 207 liver resections identified 12 patients with primary gastric cancer who underwent 16 resections for liver involvement. There were 10 adenocarcinomas and two leiomyosarcomas. We examined the type of hepatic surgery, the status of residual disease, and the primary histologic findings. Morbidity, mortality, and actual survival rates were recorded. RESULTS: Thirty-day operative mortality was 8.3% (1 of 12). Hospital mortality was 25% (3 of 12). Operative morbidity occurred in three of nine survivors (33%). Synchronous en bloc resection (n = 3) of stomach and liver for adenocarcinoma produced two long-term survivors (no evidence of disease for 10 and 13 years). Mean survival after synchronous discontinuous resection (n = 4) was 8 months (range, 2 to 17 months). Metachronous resection for adenocarcinoma (n = 3) produced one long-term survivor (74 months), and one patient with recurrent leiomyosarcoma underwent a total of five liver resections and survived 64 months. CONCLUSIONS: For adenocarcinoma, en bloc resection of contiguous liver involvement produced long-term survivors. Synchronous resection of discontinuous metastases did not. Metachronous resection of isolated disease and multiple resections of recurrent isolated disease may have value in carefully selected patients.

Diverse multidrug-resistance-modification agents inhibit cytolytic activity of natural killer cells.

Multidrug resistance (MDR) is the phenomenon in which cultured tumor cells selected for resistance to one chemotherapeutic agent simultaneously acquire resistance to several apparently unrelated drugs. MDR in tumor cells is associated with the over-expression of P-glycoprotein, an ATP-dependent cell-membrane transport molecule. P-glycoprotein is also expressed in several normal tissues but its physiological role(s) is unknown. We recently observed that a hierarchy of MDR-like activity exists among human peripheral blood lymphocytes in the order CD8 > CD4 > CD20 (cytotoxic/suppressor T cells, helper T cells and B cells respectively). In this study, we report that natural killer (NK) cells also express MDR-like activity. This activity could be inhibited with verapamil or solutol HS-15, two agents that reverse MDR in tumor cells. These, and four additional reversing agents, were used to investigate the possible role of P-glycoprotein in NK cells. We observed that at 10% of their IC50, five of six reversing agents inhibited NK-cell-mediated cytotoxicity; at higher (but non-toxic) doses, all six agents were inhibitory. These data suggest that NK-cell-mediated cytotoxicity may require the functional expression of an efflux molecule similar or identical to P-glycoprotein.

Multidrug resistance activity in human lymphocytes.

The multidrug resistance gene (mdr1) is a member of the recently described ATP binding cassette (ABC) superfamily of transporters. Family members include: (1) the cystic fibrosis transmembrane conductance regulator gene; (2) the hlyB gene of bacteria, and (3) the histocompatibility antigen modifier (HAM) gene. The level of expression of mdr1 correlates with multidrug resistance (MDR), the ability of cells to efflux otherwise toxic doses of several chemotherapeutic agents. MDR activity is also associated with the efflux of cationic lipophilic compounds such as the fluorescent dye rhodamine 123. Recently it was reported that normal lymphocytes efflux rhodamine 123, suggesting that these cells possess MDR-like activity due to the expression of mdr1. In this study, using two-color flow cytometric analysis, we observed that the ability to efflux rhodamine 123 was heterogeneous among human lymphocyte subsets in the order of CD8 greater than CD4 greater than CD2O. Rhodamine 123 efflux and accumulation in lymphocytes was sensitive to the known MDR reversing agents, verapamil and Solutol HS 15. Collectively, these data suggest that an MDR-like transport system is present in normal lymphocytes and may be important for trafficking of molecules involved in lymphocyte function.

Major chest wall resection for recurrent breast carcinoma.

Local recurrence of breast cancer is a relatively common entity. Occasionally, the management of such recurrences necessitates full-thickness chest wall resection. Although the chance for cure in such circumstances is small, achieving local control remains a desirable goal to maintain comfort and hygiene. This study evaluates the utility and morbidity of full-thickness chest wall resection in the control of symptomatic local recurrence of breast carcinoma. Twelve patients, undergoing such resections, were identified from hospital records. The resections included an average of three ribs (range, two to five) and, in seven cases, part or all of the sternum. A variety of rigid and soft tissue chest wall reconstructive techniques were utilized. Of the 11 patients available for follow-up, ten reported good overall function postoperatively. There were no postoperative deaths and only one patient developed a major complication requiring prolonged hospital stay. The patients spent an average of 6.6 hours in surgery, 14.6 hours intubated, and 20 days in the hospital. There were ten patients available for long-term follow-up. At the time of this study, 70 per cent were still alive, with or without disease, with a mean survival of 27 months (range, 3-71 months). Forty per cent were alive, disease-free, with a mean survival of 36 months (range, 3-71 months). This series demonstrates low morbidity, improved quality of life, and the possibility of long-term, disease-free survival after full-thickness chest wall resection for recurrent breast carcinoma.

Major abdominal operations in acquired immunodeficiency syndrome.

Twenty-one major abdominal operations performed on 20 patients with Acquired Immunodeficiency Syndrome (AIDS) were reviewed. Fourteen operations were for therapeutic indications, eight were emergent. The array of pathology encountered included opportunistic infection with Mycobacterium avium intracellulare, Cytomegalovirus, Cryptosporidium, abdominal tuberculosis, lymphoma, Kaposi's sarcoma, AIDS-related immune thrombocytopenia, perforated appendicitis and colonic pseudo-obstruction. Hospital mortality was 20 per cent. Major morbidity occurred in 15 per cent of patients and was more common following emergency operations. Preoperative demographic, hematologic, or nutritional parameters examined or the presence of single-organ system dysfunction did not predict outcome. Fifty-three per cent of hospital survivors are alive with a nine-month median postoperative follow-up. It is concluded that major abdominal procedures in patients with AIDS should not be withheld due to fear of excessive morbidity or mortality. General surgeons are involved in the evaluation and treatment of increasing numbers of patients with HIV infection. Appropriate management requires recognition of a wide range of surgical pathology and attention to details of safe intraoperative conduct.

Chitosan: evaluation of a new hemostatic agent.

Topically applied chitosan fails to improve the control of bleeding in a liver laceration model when compared to pressure alone in both normal and heparinized rats, and both chitosan and pressure alone are significantly less effective in controlling bleeding than the application of thrombin. In addition, our histologic results suggest that there may be an increased inflammatory response by the healing liver following topical application of chitosan.

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Prognostic significance of DNA aneuploidy in stage I cutaneous melanoma.

The prognostic significance of DNA aneuploidy was studied restrospectively in 177 Stage I cutaneous melanomas. DNA content was determined by flow cytometry of propidium iodide-stained nuclei recovered from formalin-fixed, paraffin-embedded material. Of 162 evaluable histograms, 124 were diploid, 35 aneuploid, and 3 tetraploid. Aneuploidy strongly correlated with established predictors of unfavorable prognosis, namely, thickness p less than .005, level p less than 0.005, ulceration p less than 0.005, and presence of vertical growth phase p less than 0.02. Overall, aneuploidy was strongly correlated with recurrence (p less than 0.005) and shorter disease-free survival (p less than 0.0001). Aneuploidy was an independent predictor of recurrence for tumors less than 1.5 mm thick (p less than 0.0001) and greater than or equal to 3 mm thick (p = 0.031). For melanomas 1.5-2.9 mm thick, aneuploid tumors had a 27% higher recurrence rate than diploid tumors (63% vs. 36%). This was not statistically significant (p = 0.247). In a multivariate analysis of common predictors stratified by thickness, DNA aneuploidy was the most significant independent parameter (p less than 0.002). DNA content appears to be an important stratification parameter for Stage I cutaneous melanoma.

Gallium-67 scanning for malignant melanoma.

Melanoma is characterized by a tendency to metastasize widely throughout the body and its relative affinity for gallium-67. Because of the ability of this nuclide to image tumor sites in numerous organ systems, it has been used to detect metastases in patients with malignant melanoma. The effectiveness of this technique, however, has been controversial. This article documents the retrospective analysis of results from 296 gallium-67 scintiscans from 222 patients with melanoma. Patients were placed in two groups. The low suspicion group (148 patients undergoing 191 scans) consisted of patients with no evidence of disease; the gallium scans were performed solely for screening purposes. There were 175 true-negative scans, nine true-positive scans (eight of the nine were positive only at the untreated primary site), three false-negative scans, and four false-positive scans. Therefore, in only one patient (0.5%) did a "screening" gallium scan reveal disease that was not expected. The high suspicion group (85 patients undergoing 105 scans) consisted of patients with established evidence of metastatic disease; the gallium scan was performed to confirm those findings and to search for involvement of other organ systems. Of these scans, ten were true-negative, 73 true-positive, 21 false-negative, and one false-positive. In this group the 20% false-negative results indicate that gallium scanning is considerably less sensitive than the combination of clinical and standard radiographic assessment. It was concluded that gallium-67 scintiscanning of patients with melanoma, whether for screening or evaluation of patients with known metastases, provides little information that affects clinical staging or therapeutic design. Therefore, the technique is of limited value for routinely investigating the extent of disease.

Proton NMR examination of tumor cells of high or low metastatic potential.

Three rat 13762NF mammary adenocarcinoma clones and cell lines of different metastatic potentials (MTLn3, MTC, and MTPa) were studied for their proton nuclear magnetic resonance spectral characteristics as intact cells in vitro and after chloroform/methanol, neuraminidase, or ethanol treatments. The intact-cell spectral characteristics of the highly metastatic tumor cell clone MTLn3 were clearly distinguished from the less metastatic clone MTC or the parental MTPa cell line on the basis of spectral peaks in the range of 0.9 to 1.45 p.p.m. broad peaks near 2.0 p.p.m., and peaks in the range of 2.75 to 3.2 p.p.m. Glycoproteins are among the molecules known to have resonances in these upfield spectral regions, and these tumor cell subpopulations have previously been shown to possess characteristic quantitative differences in cell surface, metastasis-associated glycoproteins. Treatment of the cells with neuraminidase or ethanol, or extraction with chloroform/methanol increased spectral detail and also revealed characteristic differences in spectral peaks between the tumor cell subpopulations. The identity of the cellular components responsible for these spectral characteristics are unknown, but some clearly arise from differences in the extractable lipids present in the tumor cell subpopulations. Further study will be required to determine if the spectral differences described in this preliminary report are directly related to the known biochemical characteristics of the highly metastatic clone, and if the observations have general relevance to metastatic potential or are a singular feature of these cells. However, these initial results suggest that manipulation of factors which allow unmasking of spectral detail combined with the use of prescribed tumor cell subpopulations may aid in using proton NMR to identify and define biochemical or structural differences related to the metastatic potential of tumor cells.

Management of acute rectal problems in leukemic patients.

In the interval 1944-1983, 54 patients with leukemia and acute rectal pathology were seen at our institution, including: 25 patients with perirectal abscesses and/or fistulas (PF/F), 16 patients with acutely prolapsed or thrombosed hemorrhoids, 11 patients with anal fissures with or without hemorrhoids, and 2 patients with perianal excoriations. In the past, concerns have been raised about development of septicemia secondary to diagnostic or therapeutic instrumentation. In only 4 of 54 cases did the clinical course clearly suggest digital examination or instrumentation of the rectum may have caused bacteremia though 13 of 54 patients had positive blood cultures for gram negative organisms at some time during their course of which 7 were clearly coliform. Most (42/54) patients were treated initially by sitz baths, suppositories, and stool softeners and/or antibiotics. We observed five patients only and treated two by radiotherapy. Eleven patients required surgical intervention for thrombosed hemorrhoids and perirectal abscess and/or fistulas. Eight other patients with PA/F drained spontaneously. Poor healing after surgical or spontaneous drainage was documented in only one case. This study suggests that sitz baths, suppositories, antibiotics, and judicious surgical drainage (where needed) form the core of therapy for these patients.