Michael P. Vezeridis

Pelvic resection of recurrent rectal cancer : Technical considerations and outcomes

PURPOSE Pelvic recurrence of rectal cancer is an ominous event for the patient and a formidable challenge to the managing surgeon. We reviewed the results of abdominosacral resection to manage these patients and correlated outcome (survival and recurrence) with known prognostic factors. METHODS An abdominosacral resection was performed on 61 patients with pelvic recurrence (53 with curative intent and 6 for palliation; 2 had extended pelvic resection). Of the 53 patients (32 males; average age, 59 years) previous resection included abdominoperineal resection in 27 patients, abdominoperineal resection plus hepatic lobectomy in 2 patients, low anterior resection in 19 patients, plus trisegmentectomy in 1 patient, and advanced primary cancers in 4 patients. Initial primary stage was Dukes B (64 percent) and Dukes C (36 percent). All had been irradiated (3,000-6,500 in 50 patients, 8,300 and 11,000 in 2 patients, and unknown dose in 3 patients). Preoperative carcinoembryonic antigen was elevated (>5 ng/ml) in 54 percent. Extent of resection: high sacral resection S-1-S2 was done in 32 patients, midsacrum in 14 patients, and low S-4-S-5 in 6 patients. Twenty-eight patients (60 percent) required partial or complete bladder resection with or without adjacent viscera, and all had internal iliac and obturator node dissection. RESULTS There were four postoperative (within 60 days) deaths, 8 percent in curative groups (5.4 percent overall). Major complications included prolonged intubation (20 percent), sepsis (34 percent), posterior wound infection or flap separation (38 percent). The survival rate in the curative group (49 postoperative survivors) was 31 percent at five years, with 13 patients surviving beyond five years. Seven of these patients survived from 5 to 21 years, whereas six patients recurred again and died within 5.5 to 7.5 years after abdominosacral resection. Disease-free survival rate at five years was 23 percent. Recent reconstruction with large composite myocutaneous gluteal flaps in 5 patients permitted complete sacral wound coverage, resulting in earlier ambulation and reduced hospital stay. CONCLUSIONS Abdominosacral resection permits removal of pelvic recurrence of rectal cancer that is fixed to the sacrum and is associated with long-term survival in 31 percent of patients. Recent technical advances have improved the short-term outcome and have made the procedure more feasible for surgical teams familiar with these techniques.

Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery.

Objective:Anemia and operative blood loss are common in the elderly, but evidence is lacking on whether intraoperative blood transfusions can reduce the risk of postoperative death. Methods:We analyzed retrospective data from 239,286 patients 65 years of older who underwent major noncardiac surgery in 1997 to 2004 at veteran hospitals nationwide. Propensity-score matching was used to adjust for differences between patients who received intraoperative blood transfusions (9.4%) and those who did not, and data were used to determine the association between intraoperative blood transfusion and 30-day postoperative mortality. Results:After propensity-score matching, intraoperative blood transfusion was associated with mortality risk reductions in patients with preoperative hematocrit levels of <24% (odds ratio: 0.60, 95% CI: 0.41–0.87), and in patients with hematocrit of 30% or greater when there is substantial (500–999 mL) blood loss (odds ratio: 0.35, 95% CI: 0.22–0.56 for hematocrit levels between 30%–35.9% and 0.78, 95% CI: 0.62–0.97 for hematocrit levels of 36% or greater). When operative blood loss was <500 mL, transfusion was not associated with mortality reductions for patients with hematocrit levels of 24% or greater, and conferred increased mortality risks in patients with preoperative hematocrit levels between 30% to 35.9% (odds ratio 1.29, 95% CI: 1.04–1.60). Conclusions:Intraoperative blood transfusion is associated with a lower 30-day postoperative mortality among elderly patients undergoing major noncardiac surgery if there is substantial operative blood loss or low preoperative hematocrit levels (<24%). Transfusion is associated with increased mortality risks for those with preoperative hematocrit levels between 30% and 35.9% and <500 mL of blood loss.

Giant condyloma acuminatum (Buschke-Lowenstein tumor) of the anorectal and perianal regions

PURPOSE: Giant condyloma acuminatum or Buschke-Loewenstein tumor of the anorectal and perianal regions is an uncommon entity that has not been extensively reviewed. We analyzed 42 known cases of giant condyloma acuminatum in the English literature and reviewed their behavior and management. METHODS: All reported cases of giant condyloma acuminatum in the English literature were selected. The relevant clinicopathologic features of this uncommon entity were examined and discussed. RESULTS: These tumors are generally large with the propensity to ulcerate and infiltrate into deeper tissues. The hallmark of the disease is the high rate of recurrence (66 percent) and malignant transformation (56 percent). No distant metastases have been reported. The overall mortality was 20 percent, all occurring in patients with recurrences. Fifty percent of the patients who were initially treated with radical surgery developed recurrences. The average duration of disease was longer in patients with recurrences than in patients without recurrences (9.6 yearsvs.2.8 years). The median number of recurrences was two (range, one to seven) recurrences, and the median time before first recurrence was ten months. Recurrences were treated by radical surgery in 17 patients and chemoradiotherapy ± local excision in 5 patients. Follow-up information for the remaining five patients was not available. The cure rate in the radical surgery group was 61 percent compared with 25 percent in the chemoradiotherapy ± local excision group. CONCLUSIONS: Giant condyloma acuminatum of the anorectal and perianal regions is a highly aggressive tumor with the propensity for recurrences and malignant transformation, but without metastatic potential. A high rate of recurrence is seen in patients with long duration of the disease. Salvage of patients with recurrences can be achieved successfully with radical surgery.

Is surgical management compromised in elderly patients with breast cancer

OBJECTIVE The suggestion that breast cancer management is compromised in elderly patients had prompted our review of the results of policies regarding screening and early detection of breast cancer and the adequacy of primary treatment in older women (> or = 65 years of age) compared to younger women (40 to 64 years of age). SUMMARY BACKGROUND DATA Although breast cancer in elderly patients is considered biologically less aggressive than similar staged cancer in younger counterparts, outcome still is a matter of stage and adequate treatment of primary cancer. For many reasons, physicians appear reluctant to treat elderly patients according to the same standards used for younger patients. There is even government-mandated alterations in early detection programs. Thus, since 1993, Medicare has mandated screening mammography on a biennial basis for women older than 65 year of age compared to the current accepted standard of yearly mammograms for women older than 50 years of age. Using State Health Department and tumor registry data, the authors reviewed screening practice and management of elderly patients with primary breast cancer to determine the effects of age on screening, detection policies (as reflected in stage at diagnosis), treatment strategies, and outcome. METHODS Data were analyzed from 5962 patients with breast cancer recorded in the state-wide Tumor Registry of the Hospital Association of Rhoda Island between 1987 and 1995. The focus of the data collection was nine institutions with established tumor registries using AJCC classified tumor data. Additional data were provided by the State Health Department on screening mammography practice in 2536 women during the years 1987, 1989, and 1995. RESULTS The frequency of mammographic screening for all averaged 40% in 1987, 52% in 1987, and 63% in 1995. In the 65-year-old and older patients, the frequency of screening was 34% in 1987, 45% in 1989, and 48% in 1995, whereas in the 40- to 49-year-old age group, the frequency of mammography was 47% in 1987, 61% in 1989, and 74% in 1995 (p < 0.001). There was a lower detection rate of preinvasive cancer in the 65-year-old and older patients, 8.8% versus 13.7% in patients within the 40- to 64-year-old age group (p < 0.001). There was a higher percentage of treatment by limited surgery among elderly patients with highly curable Stage IA and IB cancer with 26.6% having lumpectomy alone versus 9.4% in the younger patients. Five-year survival in that group was significantly worse (63%) than in patients treated by mastectomy (80%) or lumpectomy with axillary dissection and radiation (95%, < 0.001). A similar effect was seen in patients with Stage II cancer. CONCLUSIONS Breast cancer management appears compromised in elderly patients (older than 65 years of age). Frequency of mammography screening is significantly less in elderly women older than 65 years of age. Early detection of preinvasive (curative cancers) is significantly less than in younger patients. The recent requirement by Medicare of mammography every other year may further reduce the opportunity to detect potentially curable cancers. Approximately 20% of patients had inferior treatment of favorable stage early primary cancer with worsened survival. Detection and treatment strategy changes are needed to remedy these deficiencies.

Oncogene protein co-expression. Value of Ha-ras, c-myc, c-fos, and p53 as prognostic discriminants for breast carcinoma.

ObjectiveA refinement of prognostic variables using traditional pathologic markers integrated with oncogene proteins, enzymes, and hormonal factors may enhance the ability to predict for recurrence or survival in patients with mammary carcinoma. Although various oncogenes and oncogene products have been identified in human breast carcinoma, their relationship to disease outcome remains controversial. MethodsUsing the monoclonal antibodies cS93.1, 9E1.0,F235–1.7.1, and PAb 1801 against each oncogene protein studied, the avidin-biotin complex immunoperoxidase method provided immunohistochemical staining of bound oncogene protein for c-fos, c-myc, Ha-ras, and p53, respectively. Analyses were made on archival pathology tissues of 85 breast cancer patients (stages I, IIA, and IIB). Forty patients (47%) had recurrence of disease; 45 remained free of local-regional or distant disease at mean follow-up of 48 months (range 6–180 months). Molecular biological data were merged with clinicopathologic demographics 1) to determine the frequency of single or co-expression of oncogenes in this patient population; 2) to evaluate the value of these molecular protein markers to predict probability of recurrence; and 3) to determine worth of the studied oncogenes to correlate with traditional clinical pathologic parameters and overall survival. ResultsIn this study, oncogene expression had statistical correlation for recurrence with increasing co-expression: one oncogene 17.2%, two oncogenes 56.3%, three or four oncogenes, 100% (p = 0.001). Increasing oncogene or co-oncogene expression correlated with statistically significant reduction in disease-free and overall survival; with no expression of oncogenes, disease-free survival was 30 (SE ± 5.7) months and overall survival was 56.4 (SE ± 4.57) months. With expression of three oncogenes, disease-free survival was 12 (SE ± 1.23) months (p = 0.0018) and overall survival was 23.4 (SE ± 3.38) months (p = 0.0025). In univariate Wilcoxon analysis, oncogene expression was the most significant variable to determine survival (p = 0.035); in multivariate analysis, age and oncogene co-expression each emerged as the most significant variables for overall survival. For the proportional hazards regression model, oncogene co-expression was significant (p = 0.0104, risk-ratio 1.914) and correlated with age and tumor size as significant variables. Ha-ras and c-fos both, emerged as important individual oncogene proteins

Current perspectives on repeat hepatic resection for colorectal carcinoma : A review

BACKGROUND Recurrence occurs in 65% to 85% of patients after initial hepatectomy for metastases from colorectal cancer. Approximately one half of these have liver metastases, and in 20% to 30% only the liver is involved. Opportunity for resection is frequently limited because of diffuse liver disease or extrahepatic extension, and only 10% to 25% of these patients have conditions amenable to resection. This current review is focused on the rationale, indications, and results of resection of hepatic metastases from colorectal cancer. METHODS The major series of liver resection were reviewed, and the cases of repeat resections were culled out. In addition to standard clinical parameters, the indications and timing after initial resection and the survival and subsequent recurrence after repeat resection were recorded. RESULTS A comprehensive review of the 28 series showed that the mean interval between the first and second liver varied from 9 to 33 months and was about 17.5 months in the two largest series. The median survival in series reporting 10 or more patients was 19 months (mean, 24 months), which is comparable to data in single resection series. In the large French Association series containing 1626 patients with single resections and 144 patients with two resections, the 5-year survival was 25% and 16%, respectively. The recurrence rate after repeat resection is high (greater than 60%), and one half are in the liver. The prognostic factors favoring repeat resection are variable, but they include absence of extrahepatic extension of tumor and a complete resection of the liver metastases. CONCLUSIONS Repeat hepatic liver resection for metastatic colorectal cancer in carefully selected patients appears warranted in view of reasonable survival expectations, which approach that of single liver resection. Risk of recurrence is high, however, suggesting the need for rigorous preoperative and intraoperative assessment and postoperative adjuvant therapy

Squamous-cell carcinoma of the colon and rectum

Six cases of squamous-cell carcinoma of the colon or rectum (one of the colon and five of the rectum) treated at Roswell Park Memorial Institute during the last 20 years are reported in this paper, and the literature on the subject is reviewed. The pathogenetic theories proposed for explanation of the origin of this rare malignancy are discussed. The clinical features of the disease are presented and the role of endoscopy in diagnosis is stressed. The importance of surgery as the primary treatment modality is emphasized. The role of other modalities in the treatment of this disease is discussed.

Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.

BackgroundNumerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database.MethodsSeventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed.ResultsOf 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN.ConclusionsThese results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.

In vivo selection of a highly metastatic cell line from a human pancreatic carcinoma in the nude mouse.

A cell line with high metastatic capacity to the liver was established by sequential passages of a human pancreatic cancer cell line through the nude mouse liver. A subline, L3.5, established after five passages of the fast‐growing variant (FG) of the human pancreatic cancer COLO 357 through the nude mouse liver produced extensive hepatic metastases in 100% of experimental animals when injected into the spleen. The incidence of pulmonary metastases decreased from 43% for FG to 9% for L3.5. The L3.5 cell line showed aggressive growth with almost complete replacement of the hepatic parenchyma in one third of the mean time required for the development of macroscopic metastases of FG in the liver after splenic injections of tumor cells. This study indicates that the nude mouse provides a good model for in vivo selection of metastatic cells from human pancreatic cancer. The L3.5 cell line will be valuable in the study of human pancreatic cancer metastasis, particularly in the area of survival and growth of metastatic cells in the microenvironment of the liver.

Homocysteine and lipid metabolism in atherogenesis: effect of the homocysteine thiolactonyl derivatives, thioretinaco and thioretinamide.

In order to study the relation of homocysteine and lipid metabolism to atherogenesis, rabbits were fed a synthetic atherogenic diet and treated with parenteral thioretinaco (N-homocysteine thiolactonyl retinamido cobalamin), thioretinamide (N-homocysteine thiolactonyl retinamide) or homocysteine thiolactone hydrochloride. All three substances were found to increase dietary atherogenesis. Thioretinaco and thioretinamide increase total homocysteine of serum, but there is no effect of parenteral homocysteine thiolactone hydrochloride on serum homocysteine. The synthetic diet with corn oil significantly lowers serum homocysteine, compared either to baseline chow diet or to the synthetic diet with butter. Atherogenesis is correlated with total homocysteine, total cholesterol and LDL + VLDL cholesterol, and serum homocysteine is correlated with total cholesterol, LDL + VLDL, and HDL cholesterol in the total sample. Both synthetic diets elevate serum cholesterol, triglycerides and LDL + VLDL, but not HDL, compared to baseline values. Thioretinamide causes significant elevation of cholesterol and LDL + VLDL, compared to controls. The results show that increased dietary saturated fat and cholesterol cause deposition of lipids within the arteriosclerotic plaques produced by homocysteine, converting fibrous to fibrolipid plaques. Facilitation of atherogenesis is attributed to the effect of homocysteine on artery wall, either from parenteral homocysteine or from the increased synthesis of homocysteine from methionine, produced by thioretinaco and thioretinamide.