Long-term clinical, virological and immunological outcomes following planned treatment interruption in HIV-infected children.

OBJECTIVES: Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial. METHODS: Post-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. RESULTS: In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub-study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post-trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT - PTI) = -0.15; 95% CI: -0.34-0.05), P = 0.14]. The sub-study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells. CONCLUSIONS: Children tolerated PTI with few long-term clinical, virological or immunological consequences.

Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer.

BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).

Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical-pathological features and intratumor heterogeneity over time.

Background: Tumor immune microenvironment (TME) plays a key role in malignant pleural mesothelioma (MPM) pathogenesis and treatment outcome, supporting a role of immune checkpoint inhibitors as anticancer approach. This study retrospectively investigated TME and programmed death ligand 1 (PD-L1) expression in naïve MPM cases and their change under chemotherapy. Patients and methods: Diagnostic biopsies of MPM patients were collected from four Italian and one Slovenian cancer centers. Pathological assessment of necrosis, inflammation, grading, and mitosis was carried out. Ki-67, PD-L1 expression, and tumor infiltrating lymphocytes were detected by immunohistochemistry. When available, the same paired sample after chemotherapy was analyzed. Pathological features and clinical characteristics were correlated to overall survival. Results: TME and PD-L1 expression were assessed in 93 and 65 chemonaive MPM samples, respectively. Twenty-eight samples have not sufficient tumor tissue for PD-L1 expression. Sarcomatoid/biphasic samples were characterized by higher CD8+ T lymphocytes and PD-L1 expression on tumor cells, while epithelioid showed higher peritumoral CD4+ T and CD20+ B lymphocytes. Higher CD8+ T lymphocytes, CD68+ macrophages, and PD-L1 expression were associated with pathological features of aggressiveness (necrosis, grading, Ki-67). MPM cases characterized by higher CD8+ T-infiltrate showed lower response to chemotherapy and worse survival at univariate analysis. Patients stratification according to a combined score including CD8+ T lymphocytes, necrosis, mitosis, and proliferation index showed median overall survival of 11.3 months compared with 16.4 months in cases with high versus low combined score (P < 0.003). Subgroup exploratory analysis of 15 paired samples before and after chemotherapy showed a significant increase in cytotoxic T lymphocytes in MPM samples and PD-L1 expression in immune cells. Conclusions: TME enriched with cytotoxic T lymphocytes is associated with higher levels of macrophages and PD-L1 expression on tumor cells and with aggressive histopathological features, lower response to chemotherapy and shorter survival. The role of chemotherapy as a tumor immunogenicity inducer should be confirmed in a larger validation set.

Bowel function and quality of life after local excision or total mesorectal excision following chemoradiotherapy for rectal cancer.

BACKGROUND: Local excision for rectal cancer is expected to offer a better functional outcome than conventional surgery. The aim of the present study was to compare quality of life and bowel function in patients with rectal cancer who underwent either local excision or conventional surgery after chemoradiotherapy. METHODS: This was a retrospective multicentre study. Patients who underwent local excision were compared with those who had mesorectal excision. Quality of life and bowel function were investigated using validated questionnaires (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29 and Memorial Sloan-Kettering Cancer Center Bowel Function Instrument) at a median follow-up of 49 (range 13-95) months. Further analysis was undertaken of data from patients who underwent local excision alone compared with those requiring subsequent radical surgery. Statistical significance was set at P < 0·010. RESULTS: The mean constipation score was significantly better in the local excision group than in the mesorectal excision group (3·8 (95 per cent c.i. 0·3 to 7·2) versus 19·8 (12·1 to 27·4); P < 0·001). Compared with patients who underwent mesorectal excision, those who had local excision had less sensation of incomplete emptying (mean score 3·7 (3·4 to 4·0) versus 2·8 (2·5 to 3·1); P < 0·001) and second bowel movements within 15 min (mean score 3·6 (3·3 to 3·9) versus 3·0 (2·7 to 3·3); P = 0·006). Patients who underwent local excision alone scored better than those who had mesorectal excision, particularly for bowel function, who, in turn, scored better than patients requiring subsequent radical surgery following local excision. CONCLUSION: Patients who underwent local excision had a better quality of life and bowel function than those who underwent mesorectal excision.

Rectal sparing approach after preoperative radio- and/or chemotherapy (RESARCH) in patients with rectal cancer: a multicentre observational study.

BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. CONCLUSION: This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).

Differences in telomere length between sporadic and familial cutaneous melanoma.

BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesize that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of TL with familial and sporadic melanoma. MATERIALS AND METHODS: TL was measured by multiplex quantitative polymerase chain reaction in leukocytes from 310 patients with melanoma according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres compared with those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumours, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor.

Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide- and dacarbazine- based regimens.

BACKGROUND: This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients. METHODS: A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m(-2) per day; days 1-5) or intravenous dacarbazine (800 mg m(-2); day 1), in combination with intravenous cisplatin (75 mg m(-2); day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI). RESULTS: A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n=74, CDI: n=75). The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P=0.22). In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation. Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm. No difference in toxicity was observed between the two arms. CONCLUSION: The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen. Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies.

Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers.

BACKGROUND: Telomeres, located at chromosome ends, are progressively shortened during each cell cycle by replication-dependent loss of DNA termini. Although maintenance of telomere length is critical for cell-replicative potential and tumourigenesis, the erosion of telomeres can lead to genetic instability, a pivotal mechanism in the neoplastic process. PATIENTS AND METHODS: A total of 118 colorectal cancer (CRC) samples (53 right-colon, 30 left-colon, and 35 rectal tumours) and corresponding adjacent non-cancerous tissues were evaluated for telomere length, p53 mutation, and microsatellite instability (MSI). Telomere length was estimated by real-time PCR. RESULTS: Telomeres were significantly shorter in CRCs than in adjacent tissues, regardless of tumour stage and grade, site, or genetic alterations (P<0.0001). Moreover, in normal tissues, but not in tumours, telomere length inversely correlated with age (r=-0.24, P=0.017). Telomere length in CRCs did not differ with tumour progression or p53 status; however, in CRCs carrying the wild-type p53, telomeres were significantly shorter in tumours with MSI than in those with stable microsatellites (P=0.027). Furthermore, telomere length differed according to tumour location, being longer in rectal cancers (P=0.03). CONCLUSIONS: These findings suggest that telomere shortening is a key initial event in colorectal carcinogenesis. The extent of telomere erosion is related to tumour origin site and may be influenced by the mismatch repair pathway.

Nociceptin/orphanin FQ-induced delay in gastric emptying: role of central corticotropin-releasing factor and glucocorticoid receptors.

When injected intracerebroventricularly (i.c.v.) in rats, nociceptin/orphanin FQ (N/OFQ) delays gastric emptying and increases plasma corticosterone levels. Our aim in this study was to investigate changes in gastric emptying of a phenol red meal, and the plasma corticosterone response to N/OFQ in adrenalectomized (ADX) rats, in ADX rats injected with corticosterone at 1, 24 and 72 h before the gastric emptying assay, and in intact rats i.c.v. pretreated with a glucocorticoid antagonist (RU486) and with a corticotropin-releasing factor receptor antagonist (alpha-helical CRF9-41). In adrenal intact rats, i.c.v. injection of N/OFQ (2.5 nmol rat-1) significantly delayed gastric emptying (by 70%) and increased plasma corticosterone concentrations. Conversely, in ADX rats, N/OFQ left gastric emptying unchanged. In ADX rats, corticosterone injected at 1, 24 and 72 h before the gastric emptying assay almost restored the N/OFQ-induced delay in gastric emptying. Finally, pretreatment with RU486- and alpha-helical CRF9-41 abolished the N/OFQ-induced inhibition of gastric emptying. These findings suggest that central N/OFQ inhibits gastric emptying through an integrated orphaninergic system-CRF interaction in which corticosterone plays a permissive role.

Effects of calcium antagonists on serotonin and noradrenaline venoconstriction in humans.

The activity of some calcium antagonists on 5-hydroxytryptamine (5HT) and noradrenaline-induced venoconstriction has been evaluated in humans. Oral doses of nimodipine, 30 mg, and nifedipine, 10 mg, but not of verapamil, 80 mg, and flunarizine, 10 mg, inhibit 5HT-induced venoconstriction of the dorsal hand vein. Nimodipine, but not verapamil and flunarizine, inhibit noradrenaline-induced venoconstriction as well. Verapamil, locally administered into the hand vein, inhibits 5HT and noradrenaline-induced venoconstriction. These results suggest that only calcium antagonists of the dihydropyridine type have antivenoconstrictive activity in the hand vein at oral clinical doses, whereas verapamil is active only if administered by the intravenous route, which probably produces local plasma concentrations higher than those reached with the oral clinical doses.

Quality of life evaluation in a randomised trial of chemotherapy versus bio-chemotherapy in advanced melanoma patients.

This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.

Endogenous activation of group-II metabotropic glutamate receptors inhibits the hypothalamic-pituitary-adrenocortical axis.

Systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), increased plasma corticosterone in mice to an extent similar to that induced by the despair test. Treatment with the mGlu2/3 receptor agonist, LY379268 (1 mg/kg, i.p.), or the non-competitive mGlu5 receptor antagonist, MPEP (5 mg/kg, i.p.), failed to induce significant changes in corticosterone levels. Searching for a site of action of LY341495, we examined the expression of mGlu receptor subtypes in the various anatomical regions of the mouse hypothalamic-pituitary-adrenal (HPA) axis. Only mGlu5 and -7 receptor mRNAs were detected in the adrenal gland by RT-PCR, whereas mGlu -1, -3, -4, -5, -7 and -8 receptor mRNAs were detected in the anterior pituitary. All transcripts (with the exception of mGlu5 and mGlu6 receptor mRNAs) were detected in the hypothalamus. However, Western blot analysis showed the presence of mGlu2/3 receptor proteins only in the hypothalamus and not in the anterior pituitary. This was consistent with functional data showing that LY341495 (0.1 and 1 microM) failed to affect ACTH secretion from isolated mouse anterior pituitaries. Moving from these observations, we examined whether LY341495 could activate the HPA axis by inhibiting mGlu2/3 receptors at hypothalamic level. We measured the release of corticotropin releasing hormone (CRH) in isolated mouse hypothalami incubated in the presence of subtype-selective mGlu receptor agonists or antagonists. Among all the drugs we have tested, only LY341495 was able to increase CRH secretion. With high concentrations of LY341495 (1 microM) this increase was similar to that induced by 50 mM K(+). The action of LY341495 was prevented by the combined application of the mGlu2/3 receptor agonist, LY379268. We conclude that group-II mGlu receptors tonically regulate the HPA axis by controlling CRH secretion at hypothalamic level.

Relationship between learning, stress and hippocampal brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) expression in the hippocampus is reduced in response to acute, as well as repeated immobilization stress. This effect might be mediated by corticosterone, because corticosterone administration is known to reduce hippocampal BDNF. However, rats subjected to a learning paradigm showed an increased BDNF expression in the hippocampus despite the high corticosterone levels found during the test. To dissect the relative contributions of learning and stress to the overall changes in BDNF levels we set up an experimental model in which two groups of rats received the same amount of stress, but only one group had the possibility to learn how to avoid it. Using this model, we now report that learning and stress exert an opposite modulation on BDNF levels in the hippocampus, and that the increasing effect of learning predominates over the decreasing effect of stress.

Morphine abstinence and serotonin supersensitivity in man: analogies with the mechanism of migraine?

Supersensitivity to serotonin during migraine attack has been previously observed. Since the attack has been attributed to a critical lowering of morphine-like factors, we can expect serotonin supersensitivity during morphine abstinence. Slight signs of morphine abstinence have also been induced in volunteers after mild (10-24 mg/day) and limited (3 days) treatment. To evaluate the sensitivity to serotonin, dopamine, noradrenaline, and tyramine in the smooth muscle of the hand dorsal vein, in vivo, the computerized venotest was applied before, during, and 24 h after withdrawal of morphine. Venous sensitivity to serotonin and dopamine (but not to noradrenaline and tyramine) increased 10- to 20-fold after morphine withdrawal. Venous monoamine supersensitivity in morphine abstinence, similar to that observed during migraine attacks, could be indirect evidence of an analogous mechanism in both conditions.

Somatostatin: peripheral venoconstrictive activity and interaction with monoamines in man.

The mechanism of somatostatin venoconstriction and tachyphylaxis in the human hand vein in vivo has been investigated. No cross-tachyphylaxis was observed between somatostatin and 5-hydroxytryptamine, noradrenaline, adrenaline, dopamine or tyramine-induced venoconstriction. Somatostatin potentiates the venoconstrictive activity of noradrenaline, adrenaline and dopamine, but not that of 5-hydroxytryptamine and tyramine. Phentolamine antagonizes the somatostatin-induced venoconstriction, whereas methysergide, haloperidol and morphine do not. It is suggested that somatostatin could act on specific receptors in the hand vein, but the mechanism of somatostatin venoconstriction and interaction with vasoactive monoamines remains to be defined.

Enkephalinase and angiotensin converting enzyme activities in human venous and arterial plasma.

Circulating opioids, particularly enkephalins, can act on specific receptors located on the neurovascular sympathetic junction. These peptides are quickly metabolized by enkephalinase and angiotensin converting enzyme (ACE). According to the parallel distribution of enkephalinase with opioid receptors in the rat brain, and its location in the vascular bed, putative differences of enkephalinase and ACE activity between arterial and venous plasma of the same subjects was researched. Venous enkephalinase activity was found to be greater than arterial activity. No arterovenous differences were present in ACE activity. The activities of both enzymes presented a positive correlation between venous and arterial plasma in the same subjects. The arterovenous difference in enkephalinase activity supports a release of the enzyme from microvessels.

Naloxone reversal of 5-hydroxytryptamine tachyphylaxis in humans.

The dorsal hand vein, a suitable substrate for testing the effects of spasmogenic amines in vivo, exhibits a rapid tachyphylaxis to 5-hydroxytryptamine (5-HT)-induced vasoconstriction in healthy subjects. In the tachyphylactic vein, naloxone promptly restores and sometimes potentiates the sensitivity to 5-HT. The local opioid system could be excited by the 5-HT-induced release of noradrenaline (NA) into the neuromuscular junction, thereby participating in the 5-HT tachyphylaxis. Naloxone, antagonizing this mechanism, restores the 5-HT spasm. Therefore, the 5-HT tachyphylaxis could be due to an increased opioid modulation and not (or perhaps partially) to a depletion of the NA in the sympathergic neuron.

Peptic ulcer inheritance in patients with elevated serum pepsinogen group A levels and without infection of Helicobacter pylori.

BACKGROUND: Peptic ulcer has multifactorial aetiology, including genetic factors. We have identified a family with pepsinogen Group A levels higher than normal, with a high prevalence of ulcer disease and a low prevalence of Helicobacter pylori infection. AIMS: Performing linkage analysis in the identified family PATIENTS AND METHODS: We examined the segregation of pepsinogens with microsatellite dinucleotide repeat DNA markers along chromosome 11 (D11S480, PYGM) for pepsinogen Group A and along chromosome 6 [D6S105, D6S 1610, TRMI) for pepsinogen Group C. RESULTS: In markers examined along chromosome 11, linkage analysis provided no evidence for significant causal mutation but, controlling for some risk factors we observed that the probability of falling ill, increases. The linkage analysis along chromosome 6 for pepsinogen Group C did not show a uniform genetic profile. CONCLUSIONS: This study evaluates the hypothesis of peptic ulcer inheritance at least in a small group of patients without the common risk factors.