PRIMARY CARCINOMA OF THE GALLBLADDER—Review of 173 Cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females.Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease.All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy.The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred.Gallstones were found in 79.8 per cent of the cases.     

Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers

Background

Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.

Methods

We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.

Results

These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.

Conclusions

Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.     

Retroperitoneal tumors in children; roentgen diagnosis

A study was undertaken to determine whether there are any features of retroperitoneal tumors in children that might be demonstrated on roentgenograms to aid in identifying them preoperatively. Study was limited to Wilms' tumor of the kidney and neuroblastoma. Calcification was found in 57 per cent of the neuroblastomas and in only 12 per cent of Wilms' tumors. Calcifications in neuroblastomas differed from those in Wilms' tumors. Calcification in neuroblastoma was more frequent in older children than in the younger ones. The kidney was frequently displaced by both types of tumor. However, the neuroblastoma always displaced the kidney downward, or downward and slightly outward. In most instances, the Wilms' tumor also displaced the kidney downward and outward, but in some instances upward and medially. This, of course, depended upon the site of origin of the tumor. There was a distortion of the intrarenal structures in 75 per cent of the cases of neuroblastoma and in 71 per cent of the cases of Wilms' tumor.     

RETROPERITONEAL TUMORS IN CHILDREN—Roentgen Diagnosis

A study was undertaken to determine whether there are any features of retroperitoneal tumors in children that might be demonstrated on roentgenograms to aid in identifying them preoperatively. Study was limited to Wilms'' tumor of the kidney and neuroblastoma.Calcification was found in 57 per cent of the neuroblastomas and in only 12 per cent of Wilms'' tumors. Calcifications in neuroblastomas differed from those in Wilms'' tumors. Calcification in neuroblastoma was more frequent in older children than in the younger ones.The kidney was frequently displaced by both types of tumor. However, the neuroblastoma always displaced the kidney downward, or downward and slightly outward.In most instances, the Wilms'' tumor also displaced the kidney downward and outward, but in some instances upward and medially. This, of course, depended upon the site of origin of the tumor.There was a distortion of the intrarenal structures in 75 per cent of the cases of neuroblastoma and in 71 per cent of the cases of Wilms'' tumor.     

The positive pleural effusion. A retrospective study of cytopathologic diagnoses with autopsy confirmation.

We performed an investigation focusing on the distribution of tumor types responsible for positive pleural effusions in 143 patients who died of malignancy and underwent autopsy. The principal malignant tumors were lung carcinoma (41 cases, 51.2%) and pleural mesothelioma (23 cases, 28.7%) in males and breast carcinoma (24 cases, 38.2%) and lung carcinoma (13 cases, 20.6%) in females. Histologically, most of the cases belonged to the adenocarcinoma category. The first morphologic diagnosis was a cytologic one in 86 cases (60.1%), especially regarding lung cancer. In breast cancer a positive pleural effusion always preceded recurrent disease with a rapidly progressive course, even a long time after the initial surgery. The results of this study, based on both cytomorphologic features and postmortem data on the tumor sites, may be a useful working framework for the cytologist dealing with a positive pleural effusion.     

Poikilocytosis in Cancer Patients

The incidence of poikilocytosis in 100 patients with cancer of various organ systems was found to be 12 per cent. Poikilocytosis was more frequently seen in patients with adenocarcinoma of the gastrointestinal tract and with inoperable metastatic carcinoma than in patients with other malignant lesions. Anemia was associated in three cases, but in nine instances the patient was not significantly anemic at admission. Two of these patients may have been dehydrated. Uremia was not a factor in any of the cases.Fifty per cent of the patients exhibiting poikilocytosis died or were in a terminal condition within one month after the observation was made, as compared with 21 per cent of the patients who did not have evidence of poikilocytosis. These findings show that poikilocytosis may occur in cancer patients without anemia or uremia; and they indicate that its presence is an unfavorable prognosis sign.     

Histopathological study on inflammation in cholecystoses

At present, according to the unanimously accepted data, cholecystoses are noninflammatory, nonlithiasic, gallbladder diseases. However the authors' experience has proved that the inflammatory process is much more frequent than it is believed and often associated also with lithiasis, a fact which, in the authors' opinion, would justify a reconsideration of this group of diseases. This study, based on histopathologic examination, was carried out in 1,630 gallbladder specimens, surgically removed. Out of these, 278 (17.05 per cent) were identified as cholecystoses; 156 out of them were cholesteroloses and 122 diverticular diseases of the gallbladder. Inflammation as a well defined morphologic process was found in 104 cases (66.67 per cent) of cholesterolosis and in 119 cases (97.54 per cent) of diverticular disease, therefore 80.21 per cent of the cases of cholecystosis examined were associated with inflammation. As regards lithiasis, it was present in 131 of the cases (46.76 per cent). The inflammatory process presented a chronic aspect with no other particular morphologic characteristics. By correlating the histopathologic data with the clinical evolutive ones, it was observed that the presence of inflammation corresponded with a clinical evolution of the disease of about three years. The authors believed that the group of cholecystoses should be reconsidered bearing in mind that inflammation is present in most of the cases and in almost half of them it is associated with lithiases. Under these conditions the sphere of chronic nonlithiasic, noninflammatory gallbladder diseases becomes considerably reduced today.     

SALIVARY GLAND TUMORS

In a review of a series of 248 salivary gland tumors, seen over a 28-year period, all pathologic material was brought up to date by reclassification according to more recent criteria and nomenclature. In parotid tumors, a probable lowered recurrence rate and a definite decrease in incidence of permanent facial nerve paralysis was found in the more recent cases in which the "Y" incision was used, with identification of the seventh nerve as it leaves the stylomastoid foramen. The five-year recurrence rate for primary mixed tumor was 8.3 per cent, and in recurrent cases it was found to be 18.1 per cent. Of 44 patients with malignant salivary gland tumors in all sites who were observed for five years or more, 32 or 72.7 per cent survived five years.     

CHOLEDOCHOLITHIASIS-Correlation of Preoperative with Operative and Postoperative Data to Enhance Diagnostic Insight

One hundred cases of common bile duct explorations were reviewed in an attempt to obtain information that might give insight into the diagnosis and definitive treatment of choledocholithiasis. Fifty of the hundred patients had common duct stones. Correlations were made between the incidence of choledocholithiasis as proved at operation, and the following factors: Kind and number of choledochal exploratory criteria used, the clinical diagnosis of common duct stones, and the pathologic features of gallbladders removed. The incidence of stones was statistically related to aging. The most frequent choledochal exploratory criteria were common duct dilatation or thickening (63 cases) and history of jaundice (50 cases). The most reliable single criterion in "diagnosing" common duct stones was palpable common or hepatic duct stones, the diagnosis having been correct in 15 of 17 such cases. The most reliable combination of criteria was a history of jaundice, plus palpable stones, with correct diagnosis in all such cases. The clinical diagnosis of choledocholithiasis was correct in only 17 per cent of cases. The correlation of the incidence of common duct stones with the degree of gallbladder disease-that is, acute or chronic-did not provide information that might be helpful in diagnosing choledocholithiasis. The incidence of proven retained common duct stones was 3 per cent, the non-fatal postoperative complication rate was 21 per cent and operative mortality was 1 per cent.     

CIRRHOSIS OF THE LIVER—Clinical Course in 2,377 Patients at San Francisco General Hospital

The records of 2,377 patients with Laennec''s cirrhosis were reviewed for the period 1947-1957. The chief presenting symptom was ascites in 46 per cent, bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both jaundice and ascites in 4 per cent. Nearly half of the patients died during the period under study—one-third from hepatic failure, one-third from gastrointestinal bleeding, and one-third from other causes, most of which were related to alcoholism.Massive gastrointestinal bleeding occurred in 21 per cent of the patients at some time in their clinical course, and in the 10 per cent of these in whom ulcer was demonstrated, one-fifth died as a result of the hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per cent of all those who bled from varices were dead at the end of one year, and 91 per cent were dead at the end of three years.The survival curve of a group of patients who bled once and were good operative risks but had received no operative treatment was compared to the survival curve for entire group who survived the first hemorrhage. The three-year survival in the good risk group was 47 per cent; for the group as a whole it was 30 per cent. The difference in mortality rate was primarily due to an increased number of deaths from hepatic failure in the combined group, whereas 60 per cent of the good risk group died of recurrent gastrointestinal hemorrhage.As 86 per cent of those who were to die of gastrointestinal bleeding did so at the first hemorrhage, it was concluded that any decided improvement in the salvage rate achievable by operation must come from some means of diagnostic forecast of the likelihood of bleeding, with resort to prophylactic operation in such cases.     

SALIVARY GLAND TUMORS

In a review of a series of 248 salivary gland tumors, seen over a 28-year period, all pathologic material was brought up to date by reclassification according to more recent criteria and nomenclature. In parotid tumors, a probable lowered recurrence rate and a definite decrease in incidence of permanent facial nerve paralysis was found in the more recent cases in which the “Y” incision was used, with identification of the seventh nerve as it leaves the stylomastoid foramen. The five-year recurrence rate for primary mixed tumor was 8.3 per cent, and in recurrent cases it was found to be 18.1 per cent.Of 44 patients with malignant salivary gland tumors in all sites who were observed for five years or more, 32 or 72.7 per cent survived five years.     

Selected immunohistochemical markers in stromal neoplasms of the gastrointestinal tract.

We studied immunohistochemical reactions to vimentin, desmin and protein S-100 in 43 cases of stromal tumors of the gastrointestinal tract. The material studied included: 1 esophageal tumor, 18 gastric tumors, 19 small intestinal tumors and 5 colonic tumors, classified in 13 cases as benign and in 30 cases as malignant neoplasms of various degree of malignancy. Mean age of the patients was 58.9 years. A positive reaction to vimentin was found in 37 cases, a negative reaction concerned an esophageal tumor, two benign tumors (gastric and small intestinal) and three malignant tumors (gastric and two small intestinal). A positive reaction to desmin was detected in an esophageal tumor and in nine gastric tumors. Only one benign small intestinal tumor and three benign colonic tumors showed a positive reaction to desmin. Protein S-100 was found in an esophageal tumor and in 7 out of 18 gastric tumors and in 12 out of 24 intestinal tumors. Coexpression of vimentin and desmin was found in 8 gastric tumors, only in one small intestinal tumor and in three colonic tumors. Three gastric tumors showing both these reactions were all benign. Coexpression of desmin and protein S-100 was found in 7 out of 43 tumors of the alimentary tract. In six cases these tumors were benign. Basing on the results we may say that the presence of these antigens reflects the degree of differentiation of gastrointestinal stromal tumors of the gastrointestinal tract, though it does not allow to choose unequivocally conclusions as to their histogenesis.     

Relationship between structural and ionic changes in cardiosclerosis

The parallelism between hypoxic changes in the myocardium revealed by Lie's technique and by fluorescence microscopy and the ionic changes (Na+, K+, Ca2+) was studied in 51 autopsy cases. The Lie technique was positive in 52.6 per cent of the cases of cardiosclerosis with myocardial infarction and in 15 per cent of the cases of cardiosclerosis without infarction, while fluorescent areas were found in all cases of infarction and in 35 per cent of cardiosclerosis cases without infarction. Na+ and K+ were decreased and Ca2+ ions were increased in both ventricles and in both sexes, both in infarctions and in cardiosclerosis cases without infarction. Ionic changes are more probably related to the intensity of cardiosclerosis rather than to age or sex.     

CHOLEDOCHOLITHIASIS—Correlation of Preoperative with Operative and Postoperative Data to Enhance Diagnostic Insight

One hundred cases of common bile duct explorations were reviewed in an attempt to obtain information that might give insight into the diagnosis and definitive treatment of choledocholithiasis. Fifty of the hundred patients had common duct stones. Correlations were made between the incidence of choledocholithiasis as proved at operation, and the following factors: Kind and number of choledochal exploratory criteria used, the clinical diagnosis of common duct stones, and the pathologic features of gallbladders removed.The incidence of stones was statistically related to aging.The most frequent choledochal exploratory criteria were common duct dilatation or thickening (63 cases) and history of jaundice (50 cases).The most reliable single criterion in “diagnosing” common duct stones was palpable common or hepatic duct stones, the diagnosis having been correct in 15 of 17 such cases.The most reliable combination of criteria was a history of jaundice, plus palpable stones, with correct diagnosis in all such cases.The clinical diagnosis of choledocholithiasis was correct in only 17 per cent of cases.The correlation of the incidence of common duct stones with the degree of gallbladder disease—that is, acute or chronic—did not provide information that might be helpful in diagnosing choledocholithiasis.The incidence of proven retained common duct stones was 3 per cent, the non-fatal postoperative complication rate was 21 per cent and operative mortality was 1 per cent.     

Autopsy in California

From information complied from death certificates registered in 1952 and 1962 an examination was made of California''s autopsy performance and the characteristics of deaths in which autopsy was done. The data indicated that California had an overall autopsy rate of 37 per cent of total deaths in 1962, probably higher than any other state. In the decade reviewed, there was a 62 per cent absolute increase in autopsies and a 7 per cent increase relative to total deaths.Substantial increases in the proportion of deaths in which autopsy was done were found for physician-certified deaths in both metropolitan and nonmetropolitan counties and for coroner-certified deaths in nonmetropolitan counties. For all but two of forty-five selected natural causes of death there were increases in the proportion of deaths in which autopsy was done.Seventy per cent of deaths occurred in some type of facility. About one-half of all deaths occurred in general hospitals, and autopsy was done in 42 per cent of such cases.The dual factors of a high autopsy rate and overrepresentation of deaths brought to autopsy in white males, ages 35-64, support the validity of a reported decline in California''s death rate for arteriosclerotic heart disease.     

ACUTE GALLBLADDER DISEASE—Experiences with 103 Consecutive Cases

One hundred and three cases of acute cholecystitis in patients ranging in age from 19 to 88 years were reviewed. Operation was done in all cases. Seventy per cent of the patients were women.Primary cholecystectomy was done in 72.8 per cent of the series. Primary cholecystostomy was performed in the remainder, and one-fourth of these patients had a secondary cholecystectomy. No specific time, with relation to interval after onset of symptoms, was chosen for operation.Jaundice was present in 14.5 per cent of patients at the time of admittance to hospital. Serum amylase was above normal in five of 27 patients on whom this determination was carried out. All five were women.The gallbladder was perforated in 13 cases. Common duct exploration was done in 25 cases and in 12 of them stones were found.The morbidity rate for the series was 11.6 per cent; the mortality rate 9.7 per cent.     

Survey of Salmonellae in mesenteric lymph nodes, gallbladder wall and jejunum from healthy pigs slaughtered in Taiwan

A study made in Taiwan showed that 23.3 per cent of healthy slaughter pigs were infected with salmonellae. Samples of gallbladder wall/liver, mesenteric lymph nodes and jejunum wall were found to yield salmonellae in 16.4, 5.2 and 11.6 per cent of cases respectively. Salmonellae isolated belonged to nine different serotypes, S. london being the serotype most frequently isolated (26.8%) followed by S. anatum, S. panama (16.1% each) and S. typhimurium (12.5%). Of the total number of salmonellae isolated 68.5 per cent were detected simultaneously on brilliant-green phenol-red lactose sucrose agar (BGA) and desoxycholate agar (DCA), whilst 18.5 per cent were detected only on DCA and 13 per cent only on BGA plates.     

Cytopathology of exocrine pancreatic carcinoma in effusions.

The cytomorphologic features were analyzed in 26 fluid samples (18 peritoneal and 8 pleural fluids) obtained in vivo from 20 patients with pancreatic carcinoma. All tumors were ductal adenocarcinomas, as proven histologically on autopsy samples. The basic cytomorphologic pattern in the smears was that of a malignant glandular tumor, consisting of cell groups with various degrees of cohesiveness. The most prominent feature was a linear arrangement (the so-called "Indian file") of tumor cells showing nuclear molding; these aggregates were frequently closely associated with the flat round clusters of cells. Other nonspecific features of adenocarcinoma included eccentric hyperchromatic nuclei, abundant, often well-preserved vacuolated cytoplasm, a variable amount of fibrin and a reactive background. Review of the autopsy specimens also revealed the presence of an "Indian-file" pattern in most cases, especially when a conspicuous desmoplastic reaction was present. These findings suggest that pancreatic carcinoma should be included in the differential diagnosis of positive serous effusions showing these cytomorphologic features.     

The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy.

Male and female offspring of rats given antiandrogens, the steroidal BOMT or the non steroids DIMP or Sch 13521, daily during the last third of pregnancy were studied. Detailed examinations were made of the genital tract of male, and of the nipples of male and female offspring. A) Male offspring. 1) Genital tract of newborn and 31-91 day old males : Modifications of the development of accessory sexual tissues were found in all treatment groups. As indicated by the severity of deviations from normal (morphology and weight of sex accessories), the antiandrogenic effect of the preparations, in the doses given to the mother rats, increased from BOMT (50 or 75 mg/day) via Sch 13521 (30 mg/day) and DIMP (50 or 60 mg/day) to Sch 13521 (60 mg/day). 2) Nipples of 10-60 day old males : Whole mount preparations were made unilaterally of the row of 6 mammary glands with nipples. The number of intact and abnormal nipples, respectively, was recorded. The relation between intact and abnormal nipples served as indicator of the efficiency of the antiandrogenic substances studied. The result showed that the antiandrogenic effect increased from BOMT to Sch 13521, 60 mg, in the same order as that arrived at from studies of the genital tract. The combined results obtained from the male offspring indicated that the tissues of the genital region, the growth and differentiation of which was most readily impaired by antiandrogens, were the same as those known from other work to be stimulated most easily in female rat fetuses by testosterone. B) Female offspring. Nipples of 31-60 day old females were judged from whole mount preparations and recorded as in the males. The nipples of adult virginal females were examined macroscopically. The same procedure was applied to lactating females, but the results were controlled in consecutive lactational periods and at autopsy. The 3 groups of females showed uniformly that 1) offspring of rats given BOMT during pregnancy had many (about 50 per cent) malformed nipples and 2) the treatment of mother rats with DIMP or Sch 13521 did not influence the development of nipples in female offspring. The result was assumed to be due to an androgenic effect of the steroidal antiandrogen, BOMT, on the nipple anlage.     

Urothelial neoplasms of the upper urinary tract. A correlation between cytologic and histologic findings in 43 patients with urothelial neoplasms of the renal pelvis or ureter.

The present study elucidates the possibilities to diagnose and classify urothelial tumors of the upper urinary tract by means of exfoliative cytology on voided urine using a membrane filter method. In a series of 30 patients with renal pelvic tumors and 13 patients with ureteral tumors an overall agreement between cytology and histopathology was obtained in 25 cases (58%). None of the Grade 1 tumors or of the non-invasive Grade 2 tumors were regarded as positive by cytology whilst two out of five invasive Grade 2 tumors had positive cytologic reports. The series included 24 patients with poorly differentiated or anaplastic tumors, 17 of whom had positive cytology (71%). By excluding from the series 13 patients with obstructed urinary passages or radiologically non-functioning kidneys on the tumor side an agreement between cytology and pathology was reached in 83 per cent of the cases, regardless of tumor grade, and in 17 out of 18 patients with Grade 3-4 tumors (94%).