Barbara J. Maclean

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 primarycarcinoma. 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.

Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy

OBJECTIVE The purpose of this study was to evaluate the regional pancreatectomy as surgical therapy for ductal adenocarcinoma of the pancreas and to evaluate potential prognostic factors. SUMMARY BACKGROUND DATA Regional pancreatectomy was developed as a more adequate surgical procedure for pancreatic cancer in an attempt to improve the cure rate for this highly lethal disease. Few studies have evaluated large numbers of patients treated with this technique, and in recent years the emphasis has been on more limited surgery for pancreatic cancer. METHODS Fifty-six patients with ductal adenocarcinoma of the pancreatic head were treated by regional subtotal or total pancreatectomy. Clinical and pathologic parameters were reviewed and potential prognostic factors were compared statistically. The three patients who died within 30 days of the operation were excluded from the survival analysis. RESULTS Primary tumor size was the strongest determinant of prognosis. The mean tumor size was 3.9 cm (range, 1-7 cm). Eighty-five percent of patients had peripancreatic soft tissue invasion microscopically, and 58% had regional lymph node metastasis. Kaplan-Meier survival curves indicated a 33% 5-year survival for patients with tumor 2.5 cm or less in diameter (n=12) and 12% for patients with larger tumors (n=39). No patient with a tumor larger than 5 cm survived more than 5 years. Mean tumor size was not significantly associated with lymph node metastases, but 5 of 12 patients (42%) with primary tumor < or =2.5 cm had lymph node metastases. Twenty-four percent of patients with negative lymph nodes and 14% with positive lymph nodes survived 5 years. The difference was not statistically significant (p=0.3), but this is likely related to sample size. The 30- day operative mortality was 5.3%. The most common complications were infection, gastrointestinal bleeding, and gastric stasis. CONCLUSIONS After regional pancreatectomy, tumor size is the strongest predictor of prognosis. A multi- institutional randomized prospective trial of regional pancreatectomy versus pancreaticoduodenectomy is warranted in previously untreated, noninfected cases.

Major hepatic resection for neoplasia: personal experience in 108 patients.

One hundred eight patients have undergone major hepatic resection by the senior author during the eight year period April 1970 to April 1978. Primary liver cancer was present in 36; metastatic colorectal cancer in 25, miscellaneous metastatic cancers in 15, hepatoblastoma in 5, gallbladder cancer in 4, and bile duct cancer in 3. Benign tumors, principally giant hemangioma, were resected in 20 additional patients. The 30 day operative mortality rate was 9% overall. Prior to 1975, 41 of the resections were done using the vascular isolation perfusion technique. The operative mortality rate of 17% for this technique is a reflection of early experience and the advanced stage of disease of many patients. The operative mortality for the standard resection has been only 4%. Subphrenic abscess has developed in only 13% of patients during the past three years. Postoperative hospitalization has been shortened, being a median of 13 days. The resectability rate for malignant disease was 33%. Forty-six per cent of the resections were performed with curative intent. Fifty-four per cent were palliative, performed in individuals with regional spread or distant metastasis. After curative surgery, three year survival was 88% for individuals with primary liver cancer and 72% with metastatic colorectal cancer. After palliative resection, the rates were 31 and 0%, respectively. The three year survival rate is 46% overall, being 81% for the curative resection group and 18% for the palliative group. Tumor markers proved useful in monitoring patients after hepatic resection.

Adverse effect of pregnancy on melanoma. A reappraisal

The influence of pregnancy on the prognosis of cutaneous melanoma in women of childbearing age was examined in a retrospective review of 251 surgically treated cases. There was no statistical difference in survival at five years, free of disease, for Stage I melanoma between nulliparous, parous nonpregnant, and pregnant women. For Stage II melanoma, however, a significantly lower survival rate was observed for pregnant patients (29%) and parous women who had experienced activation of the lesion in a previous pregnancy (22%), as compared with that of nulliparous patients (55%) and other patients in the parous group (51%); p < 0.05. This discrepancy in survival, together with the observed higher frequencies of Stage II cases, melanomas occurring on the trunk, and symptoms such as bleeding, ulceration, irritation, and elevation of the lesion, strongly suggest an adverse influence of pregnancy on women with Stage II melanoma.

The seventies evolution in liver surgery for cancer.

During the past decade, one of the major changes in the field of oncology has been in the surgical approach to primary and secondary cancer of the liver. As a result of data and experience gained in liver transplantation programs and with the application of vascular surgical principles, resectability rates have been increased. The present rate of 32% has been achieved with an overall 30‐day operative mortality rate of 9%. More sophisticated intraoperative and postoperative supports have been essential in achieving these results. The median operating time is now 4′3/4 hours in length. Complications are minimal. The median postoperative hospital stay is now 13 days.

Women 35 years of age or younger have higher locoregional relapse rates after undergoing breast conservation therapy

BACKGROUND The use of breast conservation therapy (BCT) in young women with invasive breast cancer is controversial. To examine this important issue, rates of locoregional recurrence and overall survival after BCT were compared in two subsets of women--those < or = 35 years of age at time of surgery and their older counterparts. STUDY DESIGN We examined records of 290 women with invasive breast cancer treated with BCT (local excision and axillary dissection) at Memorial Sloan-Kettering Cancer Center between 1984 and 1993. These included 87 patients < or = 35 years of age at time of surgery and 203 randomly selected patients > 35 years of age. Followup was obtained from physician charts or patient interviews, or both. Complete data on clinicopathologic factors, recurrence, and survival were available on 280 patients. RESULTS Median followup from time of operation was 8.0 years for the entire group. Mean tumor size was 2.0 cm for women < or = 35 years and 1.8 cm for those > 35 (p = 0.07). Involved nodes were found in 48% of the young patients and 36% of the older patients (p = 0.08). Within our study group (n = 280), 274 patients received radiotherapy. Women < or = 35 years of age had significantly higher rates of locoregional recurrence and lower rates of overall survival than their older counterparts (p < 0.05). On multivariate analysis, these results were independent of tumor size and nodal status. A history of locoregional relapse, however, was not associated with a higher rate of death from disease in the entire cohort or in either age group. CONCLUSIONS Patients < or = 35 years of age undergoing BCT for invasive breast cancer are at higher risk for locoregional recurrence and death from disease. The higher mortality rate, however, does not appear to be a direct result of locoregional relapse. Additional study is required to verify these findings. Currently, young age does not exclude patients from BCT in our practice. But, we include this data as part of the informed consent process.

Selection of the Optimum Surgical Treatment of Stage I Melanoma By Depth of Microinvasion: Use of the Combined Microstage Technique (clark-breslow)

The methods of histologic staging of primary Stage I melanoma and the relation to lymph node metastases and survival after surgery was evaluated in 151 patients with extremity melanoma only. Microstaging by depth of invasion showed a better prognostic correlation than by histologic typing (into superficial spreading, or nodular melanoma). A correlation existed between depth of invasion (Clarks levels) and incidence of nodal metastases at elective node dissection. This incidence of nodal metastases at elective node dissection. This incidence was 5% at Level II, 4% at Level III, 25% at Level IV and 75% at Level V. The measured depth of invasion added prognostic insight to each Clarks level; the minimal invasion at which nodal metastases occurred was 0.6 mm for Level II, 0.9 mm for Level III, 1.5 mm for Level IV and over 4 mm for Level V. The 5 year disease-free survival after surgery was 100% for Clark Level II, 88% for Level III, 66% for Level IV and 15% for Level V. There was a direct relation between the measured depth of invasion and survival and mortality from disease at 5 years. Mortality from disease at 5 years could be directly equated with 10 times microinvasion in mm. Microstaging by direct measurement gave a better prognostic correlation than was found using Clarks levels for more deeply invading melanoma. At this time there is suggestive evidence that patients with certain higher risk lesions may do significantly better with wide excision and elective node dissection than with wide excision alone. These high risk lesions include Clark Level III to V, lesions measuring 0.9 mm or greater and all nodular melanomas.

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 intra-operative 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.

Biostatistical basis of elective node dissection for malignant melanoma.

During the years 1954 through 1964, 259 individuals with primary malignant melanoma had an elective node dissection. Microscopic metastases were found in 15% of these patients. The presence of only a microscopic focus of involvement gave a 10-year cure rate of 67%; metastasis larger than a microscopic focus in a single node, 50%; and more than one node, 15%. One hundred forty-five individuals were treated by wide excision alone with 18% subsequently requiring a therapeutic lymphadenectomy with a ten-year cure of only 6%. A prospective study was then initiated which was concerned with efficacy of selection of patients for elective node dissection. Clarks level of invasion was determined for 258 patients treated since January 1972. The depth of invasion of the primary lesion was found to correlate directly with the absence of lymph node metastases, extent of nodal involvement, and rate of recurrence. It is concluded that the concept of elective node dissection is valid.

Twenty-two year experience with periampullary carcinoma at Memorial Sloan-Kettering Cancer Center.

The resectability rate was high (84 per cent) for patients with periampullary cancer. The incidence of lymph node metastases was also high, being 50 per cent for those with small tumors (2 cm or less). The 5 year cure rate was 67 per cent for patients with negative nodes but 0 per cent for those with positive nodes.