Hugo V. Villar

Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast

The objective of this study was to determine whether tumor-infiltrating B cells (TIL-B) of infiltrating ductal carcinoma (IDC) of the breast represent a tumor-specific humoral immune response. Immunohistochemical analysis of three Her-2/neu-negative IDC tumors from geriatric patients showed that TIL-B cluster in structures similar to germinal centers containing CD20+ B lymphocyte and CD3+ T lymphocyte zones with interdigitating CD21+ follicular dendritic cells, suggesting an in situ immune response. A total of 29, 31, and 58 IgG1 H chain clones was sequenced from the three IDC tumors, respectively. Intratumoral oligoclonal expansion of TIL-B was demonstrated by a preponderance (45–68%) of clonal B cells. In contrast, only 7% of tumor-draining lymph node and 0% of healthy donor PBL IgG H chains were clonal, consistent with the larger repertoires of node and peripheral populations. Patterns and levels of TIL-B IgG H chain somatic hypermutation suggested affinity maturation in intratumoral germinal centers. To examine the specificity of TIL-B Ig, a phage-displayed Fab library was generated from the TIL-B of one IDC tumor. Panning with an allogeneic breast cancer cell line enriched Fab binding to breast cancer cells, but not nonmalignant cell lines tested. However, panning with autologous tumor tissue lysate increased binding of Fab to both tumor tissue lysate and healthy breast tissue lysate. These data suggest an in situ Ag-driven oligoclonal B cell response to a variety of tumor- and breast-associated Ags.

Cholecystokinin Metabolism in Man and Dogs

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Suppression of gastrin release and gastric secretion by gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP).

Five dogs prepared with Heidenhain pouches received infusions of saline, GIP and VIP before and after a standard meat meal. Blood samples were obtained under basal conditions and at subsequent intervals for measurement of gastrin, insulin, GIP and VIP by radioimmunoassay. GIP and VIP infusions had no effect on basal levels of gastrin. GIP and VIP (in common with secretin and glucagon) were found to suppress food-stimulated release of gastrin and gastrin-stimulated acid secretion from the Heidenhain pouch. Insulin levels were significantly elevated during GIP and VIP infusions. Food released GIP (and perhaps VIP).

Massive cecal dilation: Pseudoobstruction versus cecal volvulus?☆

Seven patients with acute and progressive abdominal distension secondary to massive cecal and right colon ileus are analyzed. Five had pseudoobstruction of the colon and two had cecal volvulus. Two of the patients with pseudoobstruction and one with cecal volvulus died from preexisting diseases. Pseudoobstruction of the colon is not a rare complication of elderly, sick, bedridden patients. Differential diagnoses include cecal and sigmoid volvulus and acute gastric dilation. Initial conservative therapy is warranted if no peritoneal signs are present. If the cecal diameter is more than 12 cm, colonoscopic decompression with a fiberscope should be attempted. If unsuccessful, tube cecostomy will provide curative, life-saving therapy even if taenia splitting is present. Perforation or widely scattered areas of necrosis make resection mandatory.

Lumpectomy and radiation treatment for invasive lobular carcinoma of the breast

BACKGROUND Large studies have shown a similar outcome when comparing mastectomy with lumpectomy and external beam radiation therapy in the treatment of infiltrating ductal carcinoma. However, this has not been studied extensively for invasive lobular carcinoma. We studied the pattern of recurrence and overall survival of patients treated with lumpectomy and radiation for either invasive lobular carcinoma (ILC) or combined invasive lobular carcinoma/invasive ductal carcinoma (ILC/IDC) of the breast. DESIGN A retrospective chart review was performed for 111 patients with ILC or ILC/IDC who were diagnosed and/or treated at the university hospital between 1984 and 1994. RESULTS Of the 111 patients, 93 had stage I or II tumors. Thirty-four patients (37%) were treated with lumpectomy and adjuvant postoperative radiotherapy with one (3%) local recurrence and a mean overall survival of 83.6 months. Fifty-nine patients (63%) were treated by modified radical mastectomy with two local recurrences (3%) and a mean overall survival of 71.7 months. CONCLUSIONS Patients with ILC or ILC/IDC can be effectively treated with lumpectomy and radiation for stage I and II tumors while maintaining a low risk of local recurrence and equivalent overall survival.

Emergency diagnosis of upper gastrointestinal bleeding by fiberoptic endoscopy.

Emergency esophagogastroduodenoscopy has been performed in 192 consecutive patients admitted with massive gastrointestinal bleeding. Accurate endoscopic diagnosis was made in 184 or 96%; 58 patients underwent emergency operations to control bleeding with an overall operative mortality of 26%. Excluding 16 patients who underwent emergency portacaval shunting, the operative mortality was 7%. In 6 patients, the bleeding was controlled by endoscopic electrocoagulation. There were no complications. Emergency endoscopy should be done routinely as the primary diagnostic approach in the diagnosis of upper gastrointestinal bleeding.

The effects on gastrin and gastric secretion of five current operations for duodenal ulcer.

We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P—15 patients), selective proximal vagotomy without drainage (SPV – D—11 patients) and with drainage (SPV + D—19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI—15 patients) or gastrojejunostomy (V + BII—6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV – D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage.

The National Cancer Data Base report on cancer in Hispanics. Relationships between ethnicity, poverty, and the diagnosis of some cancers.

Background. Previous Commission on Cancer studies have examined time trends in stage of disease, treatment patterns, and survival for special populations. Reported herein are the most current National Cancer Data Base data for Hispanics.

Immunophenotyping in the management of gastric lymphoma

Primary gastric lymphoma is a rare tumor in which surgical resection plays a major role in improving the response rate and reducing the incidence of bleeding and perforation after chemotherapy. In 17 consecutive patients, the diagnosis of gastric lymphoma was made by immunophenotyping snap-frozen endoscopic biopsy specimens. All neoplasms were B-cell lymphomas. Pan B surface marker antigens were present in all patients. Levels of Ki-67, a nuclear marker of tumor proliferation, were greater than 45% in two of the four patients who died after progression of their lymphoma. All patients alive had Ki-67 levels of less than 30%. A lower proliferation index, as measured by Ki-67, appears to be associated with better prognosis. Ten of 11 patients treated by resection prior to chemotherapy had no complications. Immunophenotyping is the key in the differential diagnosis when considering malignant lymphoma with gastric carcinoma and benign conditions such as pseudolymphoma.

Jejunoileal bypass: a reversible cause of dementia.

Neurological complications consisting of recent memory loss, visuospatial disorientation, and poor concentration disabled three patients years after a jejunoileal bypass for morbid obesity. The metabolic evaluation and computed tomography gave normal results. The neurological dysfunction cleared completely after reconstitution of normal intestinal anatomy. Neurological recovery was documented by formal neuropsychological testing.