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Objective: The purpose of the study was to investigate the surgical management of cutaneous melanomas of the hands and feet., Summary Background Data: Prior studies suggest that patients with melanomes > 1-mm thick should be treated with excision with a 2-cm margin and undergo elective lymphadenectomy in selected circumstances. These recommendations are based primarily on data from melanomas of the trunk and extremities. Melanomas of the hands and feet are less common and less well studied. They pose a surgical challenge because primary wound closure often is difficult, and the incidence and management of regional node metastases are unclear., Methods: Charts of patients with melanomas of the hands or feet treated at the Massachusetts General Hospital between 1980 and 1994 were reviewed retrospectively. Local recurrence rates and the incidence of regional node metastases were analyzed as a function of histology, margin of excision, and microscopic thickness of the melanoma., Results: Data from 116 patients (39 men, 77 women) with melanomas of the hands (n = 26) and feet (n = 90) were evaluated. Pathologic diagnoses were: acral lentiginous melanoma (48 patients); subungual melanoma (13 patients), and skin of dorsum of the hand or foot (n = 55). Digital amputation was required in all 13 patients with subungual melanoma to maintain local control; still, nodal metastases developed in 46% of patients within 1 year. Seventy-one percent of patients with acral lentiginous melanoma presented with lesions > or = 1.5 mm, and nodes or systemic disease or both developed in 56% of patients. Acral lentiginous melanoma lesions < 1.5-mm thick were treated principally by excision with a 1-cm margin; a local recurrence or metastases did not develop in any of the patients. None of the patients with melanomas on the dorsum of the hand or foot < 1.5-mm thick had a local recurrence, but regional or systemic disease developed in > 50%. Local control in patients with lesions > 1.5-mm thick frequently required skin grafting or amputation. The majority of patients with melanomas > or = 1.5 mm in thickness undergoing elective lymph node dissection had histologically positive nodes for melanoma., Conclusions: Melanomas of the hands and feet < 1.5-mm thick have a low incidence of nodal metastases and are treated effectively with wide excision of the primary with a 1-cm margin. Thicker melanomas are associated with a > 50% rate of regional or systemic failure. In the absence of metastatic disease, these individuals should undergo local excision with a 2-cm margin and intraoperative lymphatic mapping followed by lymphadenectomy if the sentinel node is positive.

Esophageal replacement remains a challenge. Colon and jejunum provide alternative conduits to replace the lower esophagus when stomach is not suitable. Between 1971 and 1991, 41 patients underwent short-segment interposition of the esophagus with jejunum or colon. Indications were failed antireflux procedures (n = 21), nondilatable stricture (n = 9), achalasia (n = 2), moniliasis (n = 2), Barrett's esophagus with carcinoma in situ (n = 2), hemorrhagic esophagitis after esophagogastrectomy (n = 1), motility disorder (n = 1), instrumental perforation (n = 1), carcinoma (n = 1), and leiomyosarcoma (n = 1). Thirty-one patients (75.6%) had prior surgical procedures. Interposition with colon was performed in 22 patients and with jejunum in 19. Major complications occurred in 45% after colon interposition (10/22) and hospital mortality was 4.5% (1/22). Major complications after jejunal interposition occurred in 31% (6/19) and hospital mortality was 10.5% (2/19). A contained anastomotic leak occurred in 1 patient, perforation of a colon segment in 1, and jejunal graft necrosis in a third. Late functional results in 34 patients with a mean follow-up of 87 months were excellent or good in 26, fair in 5, and poor in 1. Colon interposition failed to improve symptoms in 2 patients with gastrointestinal motility disorders. Six patients underwent manometry and barium food provocation study. Two colon segments and 3 jejunal interpositions were hypoperistaltic or aperistaltic according to manometry. There was 1 case of aperistaltic jejunum with a distended afferent loop. When stomach is not available, successful palliation of swallowing can be accomplished with either jejunum or colon. Surgeons involved in the management of esophageal disease should be familiar with the technical details of both procedures.

In a prospective study of 879 triple-lumen catheters, 219 pulmonary artery catheters, 31 double-lumen and six single-lumen catheters used for the administration of total parenteral nutrition over a 1-year period, the overall complication rate was 12.5 per cent (14.7 complications per 1000 catheter-days) and the catheter-related sepsis rate 4.4 per cent (5.2 per 1000 catheter-days). The probability of development of catheter-related sepsis did not increase with the duration of catheterization. There were no differences in the rate of complications associated with 427 catheters changed by replacement at a new site compared with 159 lines changed over a guidewire. These data support the use of multilumen central venous catheters for the administration of total parenteral nutrition. They suggest that a routine weekly change of line is unnecessary; catheters should be changed only on the development of a complication. When it is required, a catheter should be changed by replacement over a guidewire.

Pressure-controlled perfusion of specimens of surgical hepatic resection produced improved yields of human hepatocytes for studies of long-term cultures. The effect of an extracellular matrix configuration on albumin secretion was evaluated by culture on a single layer of collagen or between double layers of collagen gel with Dulbecco's modified Eagle and Williams E media. Hepatocytes from 12 patients were maintained for more than 30 days, and in five of 12 experiments cells were cultured beyond 2 months. In the double gels the cells demonstrated typical polygonal liver cell morphology and higher albumin secretion (p < 0.01) up to 65 days; in contrast, in the single gels cells spread horizontally, and albumin secretion declined rapidly within 3 weeks. A comparison of media formulations showed that maximum albumin secretion occurred 5 days later but was maintained significantly longer with Dulbecco's medium (p < 0.01). The simple addition of a second layer of gelled collagen forming a collagen sandwich significantly stabilizes and supports the long-term culture of human hepatocytes.

A retrospective analysis of 194 patients who underwent hepatic resection for primary or metastatic malignant disease from January 1962 to December 1988 was undertaken to determine variables that might aid the selection of patients for hepatic resection. Hepatic metastases were the indication for resection in 126 patients. The 5-year survival rate was 17 per cent. For patients with resected metastases from colorectal cancer (n = 104), the survival rate at 5 years was 18 per cent. The 5-year survival rate was 27 per cent when the resection margin was > 5 mm compared with 9 per cent when the margin was < or = 5 mm (P < 0.01). No patient with extrahepatic invasion, lymphatic spread, involvement of the resection margin or gross residual disease survived to 5 years, compared with a 23 per cent 5-year survival rate for patients undergoing curative resection (P < 0.02). The survival rate of patients with poorly differentiated primary tumours was nil at 3 years compared with a 20 per cent 5-year survival rate for patients with well or moderately differentiated tumours (P not significant). The site and Dukes' classification of the primary tumour, the sex and preoperative carcinoembryonic antigen level of the patient, and the number and size of hepatic metastases did not affect the prognosis. The 5-year survival rate for patients with hepatocellular carcinoma (n = 42) was 25 per cent. An improved survival rate was found for patients whose alpha-fetoprotein level was normal (37 per cent at 5 years) compared with those having a raised level (nil at 3 years) (P < 0.01). Involvement of the resection margin, extrahepatic spread and spread to regional lymph nodes were associated with an 8 per cent 5-year survival rate versus 44 per cent for curative resection (P < 0.005). The presence of cirrhosis, the presence of symptoms, and the multiplicity and size of the tumour did not affect the prognosis. The 5-year survival rate of 11 patients with hepatic sarcoma was 25 per cent. No patient with peripheral cholangiocarcinoma survived to 1 year in contrast to patients with hilar cholangiocarcinoma, all four of whom survived for more than 14 months.

To determine the reasons for improved mortality and morbidity rates after major hepatic resection, five variables were analyzed retrospectively in 300 patients operated on over a 27-year period: (1) the indication for surgery, (2) the surgical approach, (3) the urgency with which surgery was performed, (4) the nature of the surgical procedure, and (5) the experience of the surgeon. The operative mortality rate decreased from 19% between 1962 and 1979 to 9.7% between 1980 and 1988 (p less than 0.05). The operative mortality rates for patients undergoing resection for benign hepatic neoplasms was 3.4%; for metastatic tumors, 6.3%; for primary hepatic malignancies, 19%; and for trauma, 33%. Fifty-seven percent of operations before 1980 were performed through a thoracoabdominal exposure as compared with 19% after 1980. Overall a thoracoabdominal exposure of the liver was associated with a 20% mortality rate as compared with 8.6% for operations with abdominal exposure of the liver (p less than 0.02). Elective operations accounted for 65% of hepatic resections before 1980, as compared with 90% after 1980, and were associated with an 8.8% mortality rate as compared with 30.7% for urgent and emergency operations (p less than 0.001). Segmental and wedge resections were associated with a 5.3% mortality rate as compared with 14.7% for major hepatic resections (p less than 0.05), but this difference did not affect overall operative mortality rates because there was no change in the proportion of major hepatic resections after 1980. Surgical experience was not a determinant of operative mortality or morbidity rates in elective operations. Although there was no reduction in the complication rate after 1980, there was a reduction in postoperative stay from 26 days before 1980 to 16 days after 1980 (p less than 0.001). A reduction in the incidence of postoperative sepsis and a change in its management was associated with improved operative mortality rates.

We report the case of a 49-year-old woman with a large renal angiomyolipoma that invaded the liver. In some areas, the tumor had the appearance of a typical angiomyolipoma; however, it also had foci where the spindle cells of the lesion showed marked cytologic atypia and mitotic activity, giving it the appearance of a high-grade sarcoma. Immunohistochemical studies demonstrated expression of vimentin, desmin, and muscle-specific actin by the sarcoma cells; these findings were consistent with leiomyosarcoma. A second, small typical angiomyolipoma was also present in the kidney. In addition, the liver exhibited focal nodular hyperplasia. Three weeks after resection of the primary renal tumor, pulmonary metastases were diagnosed by fine-needle aspiration biopsy. This is the first report of a case of angiomyolipoma with sarcomatous transformation and biopsy-proven metastatic disease.

To determine the preoperative variables affecting the mortality rate and the development of severe complications in patients who have had myocardial revascularization or a valve replacement and who then undergo a noncardiac operation, we retrospectively studied data from 120 such patients over the 5 years from 1982 through 1986. Thirty-six percent of patients had a noncardiac operation during the first month after the cardiac operation. The mortality rate was 11%, and the morbidity rate was 56%. The statistical comparison of the predictive accuracy of postoperative complications of three simple, widely used classifications (American Society of Anesthesiologists physical status, New York Heart Association classification, Massachusetts General Hospital cardiac risk index) demonstrated the superiority of the simplified three-class cardiac risk index (Massachusetts General Hospital-cardiac risk index; predictive accuracy of 84%). In a multivariate discriminant analysis of 21 variables in this population, five variables (myocardial infarction in previous 6 months, S3 gallop or jugular vein distention, arrhythmia on last preoperative electrocardiogram, emergency operation, delay between cardiac and noncardiac operation) were identified as being the most predictive of a postoperative complication. When these variables were used in the function (DF3) obtained by linear discriminant analysis, the prediction accuracy of a postoperative complication reached 83%. Performance of the new models in a prospective validation population remained satisfactory (75% for Massachusetts General Hospital-cardiac risk index three-class index and 72% for DF3). Extensive statistical analysis of our data tested by a validation study provided simple predictive models based on clinical variables easily available even in emergency situations.

To identify specific genetic regulatory mechanisms associated with renal ischemia, we measured the accumulation of Egr-1 and c-fos mRNAs in the mouse kidney after occlusion of the renal artery and reperfusion. At 1 h after right nephrectomy and arterial occlusion of the contralateral kidney for 10 or 30 min, Egr-1 mRNA levels were three to five times greater in these kidneys as compared with those in control animals that had sustained unilateral nephrectomy alone and were much greater than levels in the normal organ. Whether ischemia was imposed for 10 or for 30 min, renal Egr-1 mRNA contents were equivalent and remained elevated after 24 h of reperfusion subsequent to 30 min of ischemia. Although c-fos mRNA also accumulated in response to ischemia and reperfusion, the pattern differed from that of Egr-1 in that c-fos mRNA content varied with the duration of ischemia and was undetectable 24 h after injury. Contralateral nephrectomy was not necessary to see the marked accumulation of Egr-1 and c-fos mRNAs with unilateral ischemia. Reflow was necessary, however, since only minimal sequence accumulation occurred by the end of the ischemic period. After left uninephrectomy alone, Egr-1 mRNA levels in the remaining kidney were maximal 30 min after surgery, but were not detectable thereafter; c-fos mRNA levels did not change after unilateral nephrectomy. Differential expression of early growth-related genes implicated in transcriptional activation may influence tissue recovery after renal ischemia.

During extracorporeal shock wave lithotripsy of gallstones, sonography often shows a swirling pattern of echogenic foci shortly after the application of shock waves. This effect has been thought to represent gallstone fragments in suspension. However, evidence suggests that this finding is in part due to cavitation, a physical phenomenon associated with the formation or movement of gas bubbles in the fluid-filled gallbladder. Condoms filled with degassed water and five human bile specimens were positioned in the focus of an MPL 9000 lithotriptor (Dornier Medical Systems, Munich). A solitary nonradiopaque gallstone was then added to a bile-filled condom, and the sonographic pattern was observed before and after fragmentation. The mean clearance time of the cavitation bubbles was 4 seconds for degassed water and 22 seconds for human bile. Gallstone fragments were distinguished from cavitation bubbles by their prolonged settling time (up to 30 minutes) along the dependent gallbladder wall.

Although pentagastrin has a tropic action on intestinal mucosa in suckling rat pups, and at weaning a rise in gastrin levels coincides with maturation of the intestinal mucosa, direct correlations of serum gastrin levels and intestinal maturation have yet to be made. Ten-day-old rats were subjected either to antrectomy to produce a 43% decrease in serum gastrin levels or to fundectomy to produce a 319% increase over gastrin levels in rumenectomized or normal animals. These changes were not associated with tropic or adaptive changes in jejunal or colonic mucosa as determined by jejunal and colonic DNA content, jejunal sucrase activity, jejunal villous height, or crypt depths in jejunum and colon at the beginning (day 15), middle (day 21), or end (day 27) of the weaning period. To the contrary, an inverse relation was found between serum gastrin levels and both jejunal mucosal DNA content and sucrase activity as an index of maturation.

The potential tropic effect of gastrin in promoting colonic carcinogenesis was tested in rats (n = 133) with 6- to 16-fold variations in endogenous gastrin resulting from antrectomy or fundectomy, followed by 12 injections of 1,2-dimethylhydrazine (10 mg/kg). The incidence and grade of differentiation of resulting tumors, as well as the thickness, content of nucleic acids, and specific activity of DNA in colonic mucosa, were similar in both high-gastrin and low-gastrin animals and were unchanged from data in unoperated control animals receiving only the carcinogen. Long-term changes in endogenous gastrin concentration are not followed by colonic mucosal tropic effects, and gastrin does not act as a cofactor in dimethylhydrazine-induced carcinogenesis at this dosage.

Because the submandibular salivary glands of male mice are rich in growth factors such as epidermal growth factor and nerve growth factor, and because there are sporadic reports of sialadenectomized mice showing growth retardation and endocrine abnormalities, we studied oxidative metabolism and fertility after submandibular sialadenectomy. Despite similar intake of food, male mice (n = 60) deprived of submandibular saliva, either by duct ligation or gland excision, initially weighed 12-13% less than the sham controls and had a slower rate of growth (P less than 0.001). After 5 mo, mice with duct ligation caught up with the sham-operated mice, but the differences compared with submandibular-sialadenectomized mice were still apparent at 32 wk (P less than 0.001). The mean respiratory quotient of submandibular-sialadenectomized and duct-ligated mice was 0.71 instead of 0.88 as in the shams at 10, 20, and 30 wk after operation (P less than 0.01). No effect on fecundity was observed in either male or female mice following submandibular sialadenectomy.

We reviewed photographs of 256 primary cutaneous melanomas to determine the gross morphological correlates of metastases. Seven and a half years after diagnosis, the melanomas with ulceration occupying at least 80% of their surface had the highest rate of metastases (85%), and melanomas without a nodule had the lowest metastatic rate (11%). Melanomas with nodules had a metastatic rate of 62%, and this rate increased in direct proportion to nodule diameter. Even after adjusting for nodule diameter and ulceration, melanomas with single nodules located completely within the confines of an associated plaque had half of the metastatic rate of melanomas with nodules located at the periphery (abutting normal skin). These data suggest that (1) carefully recorded gross pathological data can augment the microscopic pathological data in the determination of prognosis; (2) skin lesions suspected to be melanoma should be photographed; (3) the photograph, if followed by surgical removal of the lesion, should be attached to the pathology report in the patient's permanent medical record; (4) nodule diameter is better correlated with metastases than the total lesion diameter (as traditionally held); and (5) the cytologically malignant melanocytes that constitute the less-raised portion of most melanomas may not be biologically malignant, thus enlarging the precursor concept for malignant melanoma. The TNM staging system for malignant melanoma could be modified to incorporate these data.

Because epidermal growth factor (EGF) can modify cell proliferation in the gastrointestinal tract, effects of EGF were studied on the development of colonic, rectal, and anal neoplasms in male mice treated with 1,2-dimethylhydrazine (DMH) (20 mg/kg/wk for 20 weeks). DMH treatment caused a 13% increase in colonic RNA content, a 16% increase in DNA content, and 28% greater crypt depth. EGF (5 micrograms on alternate days during weeks 20 to 22) administered to DMH-treated mice produced no additional changes in colonic mucosa. At 30 weeks colorectal tumors were present in 13 of 20 mice treated with DMH (mean number of tumors per mouse 2.3 +/- 0.5) and 18 of 24 mice (mean 2.6 +/- 0.7) treated with DMH and EGF. Anal tumors were present in two of 20 DMH-treated mice (mean 0.1 +/- 0.07) but in eight of 24 DMH-EGF-treated mice (mean 0.33 +/- 0.1) (X2 = 4.84; p less than 0.05 for prevalence). Although EGF in this dose has no effect on the frequency of colorectal adenocarcinomas, the frequency of anal squamous cell carcinomas is increased more than three fold.

Thirteen variables were studied for their relative usefulness in predicting recurrent disease in 107 patients with clinical Stage I melanoma of the upper extremity. After a mean follow-up period of 54 months, the only patents who have had recurrent disease to date are those who primary lesions were located either on the hand or posterior upper arm. The five-year disease-free survival role for 44 patients with melanoma at these sites was 68%. None of 63 patients with melanoma located on the forearm of anterior upper arm have had recurrent disease (i.e., the five-year, disease-free survival rate was 100% (p = 0.00004), compared with the hand or posterior arm group). A Cox proportional hazards (multivariate) analysis demonstrated that two primary tumor histologic variable, thickness in millimeters and ulceration, interacted to produce the best prognostic model for those 44 patients with melanoma of the hand or posterior upper arm. Twenty-one patients with primary lesions at these sites had primary tumors less than 2.25 mm in thickness and no evidence of ulceration histologically. Their five-year, disease-free survival role was 95%. For the remaining 23 patients with primary tumors on the hand or posterior upper arm who had either histologic evidence of ulceration or primary tumors greater than or equal to 2.25 mm, the five-year disease-free survival rate was 37% (p = 0.002, compared with group nonulcerated, thin lesions). The excellent survival rate for patients with melanomas on the forearm or anterior upper arm was not completely explained by pathologic stage, by primary tumor thickness, or by histologic ulceration of the primary tumor.

Malignant small-bowel tumors in 171 patients over 64 years included 68 with adenocarcinomas, 41 with primary lymphomas, 50 with carcinoids, and 12 with sarcomas. The distribution of the carcinomas showed approximately 80% preponderance in the duodenum and proximal jejunum. A similar distribution in the upper small bowel in small-bowel carcinomas induced in Fischer and Sprague-Dawley rats by azoxymethane (90-160 mg/kg) suggests defense mechanisms within ileal mucosa. The clinical series from 1958 to 1976 included two Crohn's carcinomas (jejunum, defunctioned ileum), two jejunal cancers (lymphoma, carcinoma) associated with celiac disease, two duodenal carcinomas arising in villous adenomas, and one jejunal lymphoma following exposure to irradiation. Multiple primary malignancies were found in 20 to 25% of enteric cancers. Hemorrhage was more common with carcinoma than lymphoma, but lymphomas predominated considering perforation or a palpable mass. Both carcinoma and lymphoma had 75 to 80% resectability rates and 14 to 15% five-year postoperative survival rates. The prognosis was least poor for carcinoma of the jejunum, one third of patients with "curative" resections surviving five years.

To determine whether the inhibition of intestinal adaptation by total parenteral nutrition (TPN) in young growing animals is reversible, 130 7-week-old rats with 70% resection of the midportion of the small bowel were given an amino acid and glucose TPN solution parenterally or orally or a chow diet for 10 days. After TPN administration, villous height, crypt depth, DNA and RNA content, RNA:DNA ratio, and sucrase activity were decreased. After returning to 4 weeks of chow feeding, rats given TPN achieved similar body weight and 15% greater intestinal length as compared with rats fed chow from the start, although their jejunal villous height, ileal crypt depth, and RNA:DNA were decreased. Therefore, the inhibition by TPN of intestinal adaptation after intestinal resection in young growing rats is largely reversible. Furthermore, oral feeding of a high-calorie, high-protein liquid diet before feeding of a normal diet appears to promote adaptation after intestinal resection in immature, growing rats.

Good palliation from high neoplastic obstruction of the biliary system was achieved by direct anastomosis of the duct draining hepatic segment III to a Roux-en-Y loop of jejunum in six patients. Roentgenologically guided transcutaneous drainage of intrahepatic ducts may be desirable as a preliminary to surgical drainage in severely icteric patients. With improvements in methods of transcutaneous intubation, the selection of proper patients for surgical drainage will be a fine point of judgment.

Four patients with jaundice who had misleading diagnoses as a result of percutaneous transhepatic cholangiography are reported upon. Three of these patients actually had calculous disease and the fourth had pancreatic disease. The levels of obstruction were also roentgenographically inaccurate in three of the four patients. The primary cause of the error appears to be poor mixing of the contrast material with viscid stagnant bile, resulting in blurred definition and failure of the contrast material to traverse the common bile duct.

Because alpha-difluoromethylornithine (DFMO) reduces the incidence of experimental colon cancers, inhibits the growth of human lung cancer cells and human leukemia cells in culture, and in combination with methylglyoxal (bis)guanylhydrazone induces remission in children with leukemia, its effectiveness against a human colon adenocarcinoma cell line (Colo 205) was tested alone and in combination with 5-fluorouracil (5-FU). Both DFMO (2 X 10(-4) M) and 5-FU (10(-6) M) inhibited Colo 205 cell proliferation. Above 5 X 10(-4) M DFMO (p less than 0.001) and at 10(-4) M 5-FU (p less than 0.001), Colo 205 growth was completely inhibited. Although DFMO did not sensitize Colo 205 cells to a noninhibitory concentration of 5-FU, the effectiveness of inhibitory concentrations of 5-FU and DFMO in reducing Colo 205 cell growth was additive. DFMO (2 X 10(-4) M) caused 89 to 93% inhibition of ornithine decarboxylase activity (p less than 0.001) and reduced levels of putrescine (93%; p less than 0.01) and spermidine (57%; p less than 0.02). Growth rate and the intracellular putrescine and spermidine contents were restored by 10(-6) M putrescine. DFMO could be an effective chemotherapeutic agent against human colonic cancer because of its effects at such unusually low concentrations in vitro.

Although a side-to-side portacaval shunt will relieve some patients with Budd-Chiari syndrome, distinction between relief as a result of operation and spontaneous recovery may be inexact. A nonshunting operation relieved one of two patients as much as a side-to-side portacaval shunt did. In these two patients and one additional patient, streptokinase therapy may have been beneficial.

The permanence of the early phases of compensatory renal hypertrophy was tested by interrupting vascular parabiosis between an anephric rat and a normal rat after 48 hours. At the time of interruption, the weights and the ratio of ribonucleic acid (RNA) content to deoxyribonucleic acid (DNA) content of the kidneys were the same as those of the remaining kidney in a single rat subjected to unilateral nephrectomy, previously reported. Within 12 hours after parabiosis was stopped, renal mass and nucleic acid concentrations returned to normal. Compensatory hypertrophy could be produced again by unilateral nephrectomy. Regression of the early phase of compensatory hypertrophy appears to be faster than muscular atrophy produced by disuse or denervation. Compensatory hypertrophy can be activated at least twice.

After the success of shock-wave therapy for fragmentation of renal stones, machines for shock-wave therapy of gallbladder stones were quick to follow. In Munich, gallstones were successfully treated in 174 of 175 patients who were also taking ursodiol to help solubilize the calculous rubble left after treatment. In Boston, of the initial 87 patients accepted, 58 were treated for a single stone (mean diameter 15.7 mm), 16 were treated for 2 stones, and 13 for 3 stones. Although reporting of exact results is not possible before the Food and Drug Administration issues a clearance, it is fair to say that both patients and physicians are generally pleased with the results.

The role of fat-based total parenteral nutrition (TPN) in preventing or ameliorating hepatic dysfunction during TPN was investigated. Adult ACI-N rats were given fat-free carbohydrate-based TPN or isocaloric, isonitrogenous fat-based TPN (50% cal from 20% Intralipid, 50% cal from carbohydrate) for 7 days with Purina Chow-fed and fasting rats as controls. After fat-based TPN as compared with Chow or carbohydrate-based TPN, serum alkaline phosphatase activity and cholesterol levels doubled. Fatty infiltration and periportal inflammation in the liver were more marked. Both the TPN regimens were equally effective in maintaining body weight, positive nitrogen balance, muscle and hepatic protein content. Hepatic dysfunction in rats during TPN was not prevented by using a fat emulsion to provide 50% of the caloric requirement; the optimal proportion of fat as energy substrate in this system is less than 50%.

The influence of adaptive cell proliferation on colonic carcinogenesis was studied in male Fischer rats with a defunctioning transverse colostomy that was closed 4 wk later. Control observations were made in other rats after colonic transection, repeated at 4 wk, after laparotomy alone, or after permanent colostomy. Tumors were induced by 1,2-dimethylhydrazine (total dose, 300 mg/kg) over 11 wk, starting 2 days after the second operation. After creation of the colostomy, amounts of protein, RNA, and DNA in the distal colon halved in 4 wk (p less than 0.001), but returned to normal 7 days after restoration of colonic continuity. This reactive hyperplasia promoted the development of distal colonic carcinomas, as compared with rats having repeated transection of the bowel (incidence 32% vs. 6%; p less than 0.03). Although the amounts of protein and nucleic acid in the proximal colon were unchanged by transverse colostomy, values increased by 18%-59% 4 wk after colostomy closure (p = 0.05-0.002); nonetheless, the yield of tumors in this segment was unaltered. Suture-line cancers were commoner after repeat transection than after colostomy closure (76% vs. 39%; p less than 0.01). These data confirm the promotional effect of increased cell proliferation on intestinal carcinogenesis.

In an analysis of the first 72 cases treated after the formulation of the appendicitis syndrome in 1886 compared with the experience from 1929-1959 and with 307 randomly selected recent cases, the major therapeutic trend has been an emphasis on appendectomy before perforation and abscess formation occur. The rate of infection nonetheless remains approximately 17%. Although the overall mortality rate has declined from 26% overall (40% for surgery) to 0.8%, the current rate of perforation is 28%, with a diagnostic accuracy of 82%. Among 13,848 patients from several reports the perforation rate increases linearly with diagnostic accuracy; therefore, a balance must be sought. Delay awaiting a diagnosis is a major determinant of perforation, but diagnostic aids are of limited help. Clinical acuity and prudent decisiveness are the keys to proper action.