Pancreatic head mass: what can be done? Classification: the pathological point of view.
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Adenocarcinoma↗
Biomedical subjects
G Zamboni
Publications and source records attributed to G Zamboni.
Genomic anomalies in pancreatic tumors other than common adenocarcinoma.
In recent years enormous advances have been made in the understanding of the molecular mechanisms governing pancreatic ductal adenocarcinoma. However, little is known about other pancreatic neoplasms, which include intraductal papillary mucinous (IPMT), serous cystic (SCT), mucinous cystic (MCT), solid pseudopapillary (SPT), acinar and islet cell tumors. In addition, the study of tumors grouped under the unfortunate term of periampullary cancers will help distinguish the pathogenetic features of these neoplasms, often confused with pancreatic head neoplasms. The available data suggest that the less common pancreatic tumor types do not generally follow the same molecular pathway as the more common ductal carcinoma. IPMT seems to contain chromosomal anomalies similar to those found in ductal cancers, whereas papilla of Vater and duodenal cancers show genetic anomalies resembling those of gastrointestinal malignancies. The application of genome-wide screening techniques to these less common pancreatic tumors will undoubtedly play a central role in unraveling the complexity behind their pathology.
Adenocarcinoma↗
The FHIT gene is expressed in pancreatic ductular cells and is altered in pancreatic cancers.
We examined 2 normal pancreata, 21 primary pancreatic ductal cancers, and 19 pancreatic cancer cell lines for Fhit expression and FHIT gene status. The normal pancreas expressed Fhit protein in the cytoplasm of ductular cells, whereas interlobular and larger ducts, acini, and insulae of Langerhans were negative. Fhit protein was detected by immunoblot assay in 11 pancreatic cancer cell lines; of the 8 cell lines lacking Fhit protein, 7 lacked FHIT mRNA and 1 showed an abnormally sized transcript. DNA from five of these eight cell lines showed homozygous loss of FHIT exon 5. In 8 of the 21 primary cancers, Fhit expression was detected by immunohistochemistry. Reverse transcription-PCR analysis of 6 of the 13 cases lacking Fhit showed normal-sized FHIT product in 3 cases and a mixture of normal and abnormal products in the other 3. Sequencing showed that abnormal bands were missing variable numbers of exons. Loss of microsatellite DNA markers internal to the FHIT gene was observed in 10 of 13 primary cancers lacking Fhit protein (homozygous in two cases) and in only 1 of the 8 cancers expressing Fhit protein. In nine primary cancers, four expressing and five lacking Fhit protein, it was possible to obtain pure cancer DNA by microdissection. Three of the five microdissected cases lacking Fhit protein exhibited homozygous deletion of FHIT exon 5. In conclusion, the lack of Fhit protein in pancreatic cancers correlated with absence or alteration of FHIT mRNA and was often associated with FHIT gene anomalies.
Acid Anhydride Hydrolases↗
Intermediate results of extended pancreaticoduodenectomy. Verona experience.
BACKGROUND: Extended pancreaticoduodenectomy (EPD) with retroperitoneal lymphatic, neural, and connective clearance has been proposed to improve survival in patients with carcinomas of the head of the pancreas. The open questions are: does EPD allow better staging of the tumor? Does it reduce local recurrences? And does it improve survival? METHOD: We treated 26 patients by EPD between January 1994 and September 1996. Eighteen patients had pancreatic ductal carcinoma, 7, periampullary carcinoma; and 1, intraductal papillary mucinous carcinoma. RESULTS: The pancreatic cancers were International Union against Cancer (UICC) stage I in 3 patients, stage III in 14, and stage IV in 1. Two patients with stage III disease would have been considered as having stage I without EPD. Pancreatic cancer and periampullary carcinoma patients had a 3-year actuarial survival of 32% and 86%, respectively. At a mean follow-up time of 22.5 months (range, 6-39 months), 3 pancreatic cancer patients (16.6%) had loco-regional recurrences, 6 patients (33%) had distant metastases, and 1 (5.5%) had distant and loco-regional recurrences. Only 1 of 7 patients with periampullary carcinoma had distant metastasis 20 months after resection. CONCLUSION: EPD seems to decrease the rate of local recurrences and allows more correct staging. The intermediate survival results are encouraging but a definitive conclusion awaits longer follow-up.
Adenocarcinoma↗
Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors.
The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.
Adenocarcinoma, Mucinous↗
"Non-alcoholic duct destructive chronic pancreatitis" or "primary chronic pancreatitis"?
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Alcoholism↗
Recommendation for the examination of pancreaticoduodenectomy specimens removed from patients with carcinoma of the exocrine pancreas. A proposal for a standardized pathological staging of pancreaticoduodenectomy specimens including a checklist.
The prognosis of ductal adenocarcinoma of the pancreas is poor. Despite many attempts at a more aggressive surgical approach, tumor recurrence rates of around 80% are common. For various reasons, most of the studies on the subject are difficult to compare. Not only do the surgical techniques vary, but, more importantly, the methods used for processing the specimens and for the pathological examination differ. If we are to improve the situation, it would appear imperative to standardize procedures. Standardized pathological staging of pancreaticoduodenectomy specimens should be performed mainly with reference to the guidelines of the WHO and UICC, with optional staging of the lymph nodes according to their anatomical site. Precise definition and accurate examination of the resection margins, especially of that towards the retroperitoneum, is essential for a better comparison of the results of the different therapeutic strategies and approaches to pancreatic carcinoma.
Adenocarcinoma↗
Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.
We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD during GnRHa treatment in girls with precocious puberty is at least completely reversible and preventable if calcium supplementation is associated from the beginning.
Body Height↗
Control of REM sleep: an aspect of the regulation of physiological homeostasis.
Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.
Animals↗
[Colorectal adenoma-carcinoma. Guidelines and minimal diagnostic criteria. Italian Group for Pathology of the Digestive System].
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Adenocarcinoma↗
[24 Hour arterial pressure in insulin-dependent diabetics and non-insulin-dependent diabetics with preserved renal function].
BACKGROUND: The aim of the study was to value the behaviour of systolic (S) and diastolic (D) arterial pressure (AP)/24 hrs in a group of diabetic patients insulin-dependent (IDDM) and non insulin-dependent (NIDDM) with preserved renal function. METHODS: We examined 65 diabetic patients (aged 39.1 +/- 23.3), 33 IDDM (aged 18.2 +/- 7.5; years of diabetes: 5.8 +/- 4.9) and 32 NIDDM (aged 60.7 +/- 11.4; years of diabetes: 7.2 +/- 7.5). In all of them we computed BMI and determined creatinine clearance, glycosylated haemoglobin A, total and HDL-associated cholesterol, triglyceridemia, middle glycemia and microalbuminuria. AP measurement was performed by 24 hrs monitoring (periodicity 15') using a Takeda 2420 measurer. Chronobiological characteristics of AP were analysed by statistical method of cosinor according to Halberg, examining if there was or not a blood pressure circadian rhythm (PCR) (p < 0.05) and its characteristics represented by the mesor, the amplitude and the acrophase. Moreover the patients were subjected to a diet with fixed contents of sodium (130 mEq/day) and afterwards we drew (every 4 hours) renin (R), aldosterone (A1) and atrial natriuretic factor (ANF) which were analysed with cosinor's method. The purpose was not to compare the two populations, not homogeneous between them and not different only for the years of diabetes, but to study their blood pressure behaviour, the rhythm, the order of the indicated hormones for possible pathogenetic connections. RESULTS: NIDDM presented higher blood pressure values (PAS 134.2 +/- 3.5 and PAD 80.9 +/- 2 mmHg) than IDDM (PAS 116.6 +/- 1 and PAD 66.4 +/- 1.7 mmHg), still in limits of substantial normality. The acrophase was in the midday for NIDDM (PAS 11:25', PAD 12:06') and in the early afternoon for IDDM (PAS 14:15', PAD 14:06'). Analysing the trend of the AP in the single cases, PCR was present in 70% and absent in 30% of IDDM while it was persistent in 56% and disappeared in 44% of NIDDM. IDDM without PCR differed from those with it in years of diabetes (p < 0.001), body weight (p < 0.02), BMI (p < 0.01), triglyceridemia (p < 0.05), all more elevated, as well as in higher PAS and PAD (p < 0.001) and in higher concentration of ANF (p < 0.05). The same comparison was done in NIDDM. Patients without PCR were older (p < 0.025), had higher PAS (p < 0.025) and PAD (p < 0.001) and also a more activated ANF (p < 0.001). CONCLUSIONS: This hormonal anomaly may be ascribed to a lower excretion of sodium with consequent expansion of extracellular volume due to antinatriuretic action of insulin often found at high plasmatic levels particularly in NIDDM.
Adolescent↗
The influence of a heavy thermal load on REM sleep in the rat.
This study was carried out in order to further test the hypothesis that the occurrence of REM sleep in the rat in the form of episodes separated by long intervals (single REM sleep episodes) and by short intervals (sequential REM sleep episodes) is differently influenced by changes in both sleep and ambient related processes. Rats were studied during the exposure to Ta -10 degrees C for 24 or 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following either the first or the second 24 h of cold exposure. The exposure to such a low Ta induced an almost complete abolition of REM sleep which was followed, during recovery, by a marked REM sleep rebound. However, in spite of the larger REM sleep deprivation, the REM sleep rebound was weaker following the 48 h-exposure than that following the exposure for 24 h. The increase in the amount of REM sleep during the recovery period was due to an increase in the amount of that occurring in the form of sequential episodes, whilst that in the form of single episodes did not change with respect to control levels. However, the occurrence of REM sleep in the form of sequential episodes was partially impaired during the REM sleep rebound observed in the recovery period following the 48 h-exposure. These results would suggest that the homeostatic regulation of physiological variables may conflict with that of REM sleep occurrence and that the degree of such a contrast is indicated, at low Ta, by the amount of REM sleep in the form of single episodes and, during the following recovery, by the amount of REM sleep in the form of sequential episodes.
Animals↗
Pancreatic endocrine tumours: evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p.
Two molecular pathways leading to cancer are known. Common-type cancers arise from the 'tumour suppressor' pathway, characterized by gross chromosomal changes and allelic losses (LOH) in an average of 25 per cent or more of randomly chosen chromosomal loci. The 'mutator pathway' has been recognized in a subset of cancers, characterized by widespread microsatellite DNA instability and rarity of chromosomal losses. The present study has investigated 20 pancreatic endocrine tumours (PETs) for loss of heterozygosity (LOH) at seven chromosomal loci (3p14, 7q31-32, 11q13, 13q14, 18q21, 17p13, and 17q21); microsatellite instability; and Ki-ras, N-ras, and p53 gene mutations. LOH was found in an average of 24 per cent of the chromosomal loci analysed. No tumour showed microsatellite instability. Ki-ras and p53 mutations were each found in one case. The frequency of losses was higher in malignant (40 per cent) than in benign (17 per cent) tumours (p = 0.009), and the specific chromosome 17p13 LOH was associated with extrapancreatic extension of disease (p = 0.007), high proliferative activity (p = 0.001), and absence of progesterone receptors (p = 0.01). A common deleted region on chromosome 17p13 and the rarity of p53 gene mutations suggest the existence of a novel tumour suppressor gene involved in the pathogenesis of PETs in this chromosomal area.
Adolescent↗
[Growth hormone deficiency. Treatment with growth hormone and body composition].
Increased fat mass, decreased lean mass, muscular mass and bone mineral density are characteristic of the body composition in GH deficiency, GH treatment reverses these abnormalities. Body composition was determined in 20 young adults with GHD diagnosed in childhood, whose GH treatment was stopped 1 year earlier. Reevaluation of GH secretion in these patients showed that 12 remained GH deficient (confirmed GHD) while eight recovered normal GH secretion (transient GHD). One year after stopping the GH treatment, patients with confirmed GHD showed an increased fat mass as compared with value at the end of the treatment; in addition a decreased bone mineral content was observed in the patients with low physical activity. There was no increased fat mass in transient GHD; however, these patients presented with low bone mineral content, as previously reported in adults with history of delayed growth and adolescence.
Adolescent↗
Molecular pathogenesis of sporadic duodenal cancer.
Whether duodenal adenocarcinoma should be considered as a gastrointestinal or as a peripancreatic cancer is a matter of debate, as is the opportunity and type of treatment. We investigated 12 such cancers for the genetic anomalies involved in the pathogenesis of gastrointestinal malignancies, including (a) those occurring in common-type cancers - allelic losses at chromosomes 3p, 5q, 17p and 18q, and Ki-ras and p53 alterations; and (b) those characteristic of mutator-phenotype cancers - microsatellite instability and TGF-betaRII gene mutations. We found Ki-ras and p53 mutations in five (42%) and eight cancers (67%), respectively; chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten (60%), six of nine (67%) and three of ten (30%) informative cancers, respectively. Finally, three cancers (25%) showed widespread microsatellite instability and two of them had a TGF-betaRII gene mutation. Our data suggest that duodenal cancers may arise from either of the two known pathogenetic molecular pathways of gastric and colorectal cancers. The majority of our cases were highly aggressive cancers with frequent chromosomal changes and p53 mutations as observed in the common-type gastrointestinal malignancies, while widespread subtle alterations characteristic of mutator-phenotype cancers occurred in a minority, which also showed a favourable long-term outcome.
Adult↗
Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.
During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium.
Adenoma↗
Ranitidine bismuth citrate with either clarithromycin 1 g/day or 1.5 g/day is equally effective in the eradication of H. pylori and healing of duodenal ulcer.
BACKGROUND: No randomized double-blind studies have been performed to compare clarithromycin 1 g/day with higher doses of the macrolide (1.5 g/day) when combined with ranitidine bismuth citrate (RBC). AIM: To compare H. pylori eradication and ulcer healing rates of RBC 400 mg b.d. for 4 weeks combined for the first 2 weeks either with clarithromycin 500 mg b.d. (Group A) or clarithromycin 500 mg t.d.s. (Group B). METHODS: Two hundred and seventy-three patients with H. pylori-positive active duodenal ulcer were included. H. pylori infection was detected by CLO-test and histology on antral and corpus biopsies before and at least 4 weeks after the end of therapy. Eradication was assumed if both CLO-test and histology results were negative for H. pylori. RESULTS: Eradication/healing rates according to intention-to-treat and per protocol analysis were 76/82% and 87/92% for Group A and 78/85% and 88/95% for Group B, respectively (P = N.S.). Adverse events were reported by 7% and 12% of patients in Groups A and B, respectively, and they were generally mild. CONCLUSIONS: RBC in co-prescription with clarithromycin 500 mg b.d. is as effective as RBC plus clarithromycin 500 t.d.s. in eradicating H. pylori and healing duodenal ulcers.
Adolescent↗
Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence of tuberous sclerosis: a clinicopathologic and genetic study.
We report the clinicopathologic, immunohistochemical, ultrastructural, and genetic features of an unusual renal tumor composed of large, atypical, densely packed, clear/eosinophilic epithelioid cells. Three patients, two men and one woman (ages 31, 36, and 60 years of age, respectively), had abdominal pain. Morphologically, all cases showed aggressive features (largeness, atypical cells, sarcomatoid features, necrosis, and, in one case, invasion of the renal vein). Despite the marked morphologic resemblance of these tumors to high-grade sarcomatoid renal cell carcinoma, their phenotype (HMB45+, CD68+/-, actin+/-, and vimentin and keratin negative) is in contrast to that observed in epithelial tumors and parallels the phenotypic profile of angiomyolipoma. Ultrastructural analysis showed the presence of glycogen, mitochondria, and prominent electron-dense, membrane-bound granules in the neoplastic cells, and the absence of melanosomes or premelanosomes. Genetic study, performed using polymerase chain reaction from paraffin sections, showed a loss of heterozygosity at the TSC2-containing region on 16p in one case, and on 3p in two cases, showing that multiple genetic alterations are taking place in these tumors. Follow-up has shown local recurrence in one case after 6 years, and the patient died 1 year later of cardiorespiratory failure. The other two patients are well after 26 and 10 months. All three patients were evaluated for signs of tuberous sclerosis, and findings were negative. We suggest that these tumors should be considered close relatives of the angiomyolipoma variants, composed purely of perivascular epithelioid cells. More cases and longer follow-up durations are needed to fully evaluate its prognostic implication.
Adult↗