Paul Sherlock

Primary gastrointestinal lymphoma: A 30‐year review

The authors reviewed all cases of non‐Hodgkins lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949–1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes‐Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life‐table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P < 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P < 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affected survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

CELL PROLIFERATION KINETICS IN THE GASTROINTESTINAL TRACT OF MAN. I. CELL RENEWAL IN COLON AND RECTUM

In studies of cell proliferation in the intestine of animals during the past few years, observations have been made that suggest points of interest concerning cell renewal in humans. In rodents, proliferating jejunal and colonic epithelial cells have mean generation times of about 12 to 18 hours, DNA synthesis (S phase) times of 5 to 8 hours, and premitosis (G2) and mitosis (M) times of 1 to 2 hours (1-3). Also, although many epithelial cells undergo a second generation cycle soon after mitosis, some cells appear to remain longer in interphase before dividing again (3). The rate of disappearance of labeled cells from the mucosa has also been shown to vary in different portions of the gastrointestinal tract in a number of species; e.g., more labeled cells are present in the colon and stomach 1 week after injection of H3-thymidine than in the duodenum or jejunum (4). In man, studies of mitotic indexes and radioautographic studies with H3-thymidine have suggested turnover times of intestinal epithelial cells in the order of several days (5-7). In the present study, we have measured the mean generation time and the phases of the proliferative cycle of human colonic and rectal epithelial cells after the administration of H3-thymidine. The results describe cell renewal and give data on the rate of disappearance of labeled cells from the mucosa of the human colon and rectum.

Clinical manifestations of hepatoma: A review of 6 years' experience at a cancer hospital

Abstract During a 6 year period 67 adult patients with histologically documented hepatocellular carcinoma were seen in a hospital specializing in the management of patients with neoplastic disease. More than 70 per cent of these patients came to medical attention because of abdominal pain, right upper quadrant mass and weight loss or ascites. Among the remainder, however, initial presentations were varied and included symptoms suggestive of cholecystitis, deterioration in hepatocellular function, progressive pulmonary tumor, pathologic fracture of metastatic bone lesions, obstructive jaundice with pruritus and repeated bouts of hepatitis. By the time of referral nearly all patients had evidence of single or multiple large intrahepatic masses detectable by physical examination, isotopic liver scan or celiac arteriography. Only three patients had no abnormalities in multiple initial biochemical liver function tests. Alpha-fetoglobulin was present in 36 per cent of the submitted serum samples; hepatitis-associated antigen was not detected in any of the serums tested. In patients who could not be subjected to hepatic lobectomy, survival was brief, with death occurring in over one half of the entire series during the first hospital admission. Sixtynine per cent of the patients with adequate pathologic examination had cirrhosis. Autopsies disclosed extensive metastatic disease, most commonly in the lungs, intraabdominal lymph nodes, adrenal glands, great veins adjacent to the liver, diaphragm and skeleton. Tumor distribution in the liver most commonly involved both right and left lobes, followed by involvement of the right lobe alone; the left lobe was rarely involved by itself. In approximately one eighth of the patients a second malignant neoplasm was documented. Evidence for a variety of paraneoplastic syndromes such as hypercalcemia, hypoglycemia and erythrocytosis was found in a few patients. Modes of death were the usual ones for advanced hepatic parenchymal disease and most frequently included hepatocellular failure, sepsis and massive gastrointestinal bleeding.

Carcinoma complicating Crohn's disease: Report of seven cases and review of the literature

Seven cases of adenocarcinoma complicating Crohns disease are reviewed. In three of the patients, small bowel cancers developed in association with reginal enteritis. In four patients, carcinoma of the colon was superimposed on Crohns colitis. In two of these, the adenocarcinoma infiltrated chronic colocutaneous fistulas. Review of the literature shows an increasing number of reports of carcinoma complicating Crohns disease, with a total of 36 cases of small bowel cancer and 30 cases of colon cancer previously reported. The significane of these and our own cases is discussed. The possibility of carcinoma must be kept in mind by clinicians following patients with Crohns disease. Adenocarcinoma complicating Crohns disease occurs at a younger age, on the average, and in areas similar to the distribution of Crohns disease rather than the usual distribution of the cancer. Preoperative diagnosis is difficult, but changes in the nature of chronic fistulas should be investigated.

Gastrointestinal Manifestations of Malignant Lymphoma

Summary A review was made of 323 patients with lymphoma who came to autopsy at Memorial and James Ewing Hospitals during the 5-year period from 1960 through 1964. Of these 323 cases, 203 had pathological changes in the gastrointestinal tract. The clinical course and the findings at autopsy in this group were evaluated in detail. The cases were divided into reticulum cell sarcoma, lymphosarcoma, and Hodgkins disease on the basis of the final histological diagnosis. Each subgroup was then evaluated with respect to gastrointestinal manifestations, both tumor nontumor, and average survival times, with particular reference to the effect of various complications on survival. Upper gastrointestinal bleeding was most often of nontumor origin particularly when there was no evidence of tumor in the stomach. Perforation was found to be more commonly due to the tumor itself rather than to therapy. Obstructions were found only in patients with reticulum cell sarcoma, and 60% of these were in the jejunum or ileum. Ileocecal intussusception was found in 5 children or young adults. Obstructive jaundice was a complication in 14 cases, a slightly higher incidence than in previous series.

The value of diagnostic aids in detecting pancreas cancer.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a “correct” diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 75Sele‐nomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonog‐raphy gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangio‐pancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (> 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non‐cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se‐methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

Feasibility of fecal occult‐blood testing for detection of colorectal neoplasia. Debits and credits

A screening program for colorectal cancer and adenomas has been applied to 6,579 mostly asymptomatic men and women age 40 years and older utilizing fecal occult‐blood testing followed by investigation of patients with positive slides by air‐contrast barium enema and colonoscopy. A control population of 7,325 patients had sigmoidoscopy only and no occult‐blood testing. Approximately 1% of the patients had positive slides; most patients had only one or two slides positive. Approximately 50% of patients with positive slides had significant neoplastic lesions, including 23 patients with large adenomas and 7 patients with cancers. Pathological staging of cancers was more favorable in the screened asymptomatic group as compared with the control group. Neoplastic lesions seen on sigmoidoscopy in screened patients who had negative fecal occult‐blood tests included 2 cancers and 15 large adenomas. Reasons for false negativity include possible conversion of initially positive slides to negative. Screening for colorectal cancer and adenomas with fecal occult‐blood testing appears to be feasible approach with good patient compliance, and manageable rate of positive slides productive of a high percentage of neoplastic lesions. The number of false‐positives seems to be low. False negativity has been observed and will require further study.

Colonoscopic biopsy and cytology in the diagnosis of colon cancer.

Colonoscopy has revolutionalized the approach to the diagnosis and management of patients with colorectal neoplasia. When malignant‐appearing lesions are visualized by colonoscopy, a variety of diagnostic techniques are currently available for the assessment of the nature of the lesion including biopsy, brush cytology, and lavage cytology. Comparison of results for biopsy alone with biopsy plus either or both cytologic techniques showed a positive yield of 60% for biopsy alone; 76% for biopsy and lavage; 89% for biopsy, brush, and lavage. When the cancers were divided into infiltrative and exophytic lesions the positive yield for biopsy alone was 33% for infiltrative cancer, and 71% for exophytic cancer; for biopsy and lavage cytology, 44% for infiltrative cancer, and 94% for exophytic cancer; for biopsy and brush cytology, 78% for infiltrative, and 94% for exophytic cancer; and for biopsy, brush, and lavage cytology, 83% for infiltrative cancer, and 92% for exophytic cancer. The use of brush cytology improved the yield of tissue diagnosis considerably when added to the biopsy technique. Lavage cytology did not seem to increase significantly the diagnostic yield. The diagnostic yield of the various techniques was related not only to the specific combination of techniques used, but also to the gross tumor pattern. Cancer 42:2849–2853, 1978.

The role of early diagnosis in controlling large bowel cancer. An overview

Since early diagnosis is essential to improve the cure rate for large bowel cancer, we must use all known investigative tools to make a diagnosis in symptomatic patients in addition to periodic selective investigation of high‐risk groups, such as those with familial polyposis, inflammatory bowel disease, previous polyps or cancer. However, our goal must be more ambitious than this. If we wait until patients have symptoms of colorectal cancer, the cure rate will significantly decrease. A mass‐screening approach, therefore, is needed for the asymptomatic patient. One such approach commences with the testing for occult blood in the stool followed by intensive investigation for the source of bleeding. Newer techniques now under investigation, such as determination of CEA in colonic washings, patterns of enzymes in blood and other body fluids, fluorescent cytology and in vitro isotopic surface labeling of colonic cells, may help to identify individuals either harboring an occult neoplasm or at increased risk for the development of colon or rectal cancer. The application of these parameters and the early recognition of precancerous lesions may lead to earlier diagnosis or diagnosis in the incipient stage of disease, which, in turn, should lead to improved survival.

Cytological Examination as an Adjunct to Liver Biopsy in the Diagnosis of Hepatic Metastases

Sixty-seven postmortem cases of cancer had two separate Menghini transthoracic needle liver biopsies performed through the same skin site. Histological and cytological evaluation for cancer was performed on the tissue core and on the aspirated fluid. Twenty-seven of 39 cases (69%) with liver metastases could be diagnosed with these methods, as compared with only 16 of 39 cases (41%) when utilizing only one histological specimen and no cytology, or 21 of 39 cases (54%) using two biopsies. Cytology alone revealed cancer in 6 of 39 cases (15%) when the histological specimens showed no cancer. There were 4 additional cases in whom cancer was diagnosed by cytological examination in an organ through which the needle had passed (pleura, lung, diaphragm, or peritoneum). There were no erroneous cytology reports of cancer. The cytological material which is usually discarded represents no additional risk and significantly increases the diagnostic yield in metastatic liver cancer. A second biopsy through the same skin site also increases the diagnostic yield. The combined use of both the cytology technique and the second liver biopsy through the same skin site is advocated to increase significantly the diagnostic yield in metastatic cancer to the liver.