Lymphadenectomy for gastric cancer at European specialist centres.

BACKGROUND AND AIMS: The aim of this project was to evaluate the current practice of D2 in Europe. MATERIALS AND METHODS: In the first part of the study, 18 European high volume gastric cancer centres completed a questionnaire, designed to evaluate their preferred lymphadenectomy in a series of clinical scenarios. Surgeon compliance with international guidelines for lymphadenectomy was evaluated. In the second part, information on 381 gastrectomies performed for primary gastric cancer by participating surgeons from January to December 2015, was retrospectively collected. RESULTS: Surgical choice in clinical scenarios was affected by tumour stage and to a lesser extent, site and histotype. In particular, in early gastric cancer with diffuse histology D2 was recommended by >70% of surgeons, while this percentage dropped to 44% in intestinal histotypes. When surgeons selected a D2 dissection, the procedure was rarely fully compliant with the Japanese guidelines. In the review of gastrectomy experience an adequate number of nodes (≥15 nodes) was retrieved in 97% after D2. The number of retrieved nodes varied with median values ranging from 17 to 35 (p < 0.001) after D2. D2/D2+ was more frequently performed in mixed (80%) and diffuse (78%) cases than in intestinal cases (69%) (p = 0.016). CONCLUSIONS: Although an adequate lymphadenectomy was achieved in almost all cases in dedicated centres, there is still variation in the number of retrieved nodes. Tumor histology largely affects surgeon's choice as regards the extent of lymphadenectomy; however, the role of histology in planning surgical procedures needs to be verified in prospective trials.

Laparoscopic transhiatal suture and gastric valve as a safe and feasible treatment for Boerhaave's syndrome: an Italian single center case series study.

BACKGROUND: Boerhaave's syndrome (BS) is a rare life-threating condition with poor prognosis. Unfortunately, due to its very low incidence, no clear evidences or definitive guidelines are currently available: in detail, surgical strategy is still a matter of debate. Most of the case series reports thoracic approach as the most widely used; conversely, transhiatal abdominal management is just described in sporadic case reports. In our center, the laparoscopic approach has been adopted for years: in the present study, we aim to show his feasibility by reporting the outcomes of the largest clinical series available to date. METHODS: Clinical records of patients admitted for BS to the General and Upper GI Surgery Division of Verona from February 2014 to December 2019 were retrospectively collected. Clinico-pathological characteristics, preoperative workup, surgical management, and outcomes were analyzed. RESULTS: Seven patients were admitted; epigastric/thoracic pain and vomiting were the most frequent symptoms at diagnosis. Laboratory findings were not specific; conversely, radiological imaging always revealed abnormal findings: particularly, CT had excellent sensitivity in detecting signs of esophageal perforation. All but one case had diagnostic workup and received surgery within 24 h. Every patient had laparoscopic transhiatal direct suture and gastric valve; 2 patients (28.6%) also needed a thoracoscopic toilette. Postoperative complications occurred in 4 patients (57%), but in only two of them (29%), the complication was severe according to Clavien-Dindo classification (both received thoracentesis or thoracic drainage for pleural effusion). Of note, no cases of postoperative esophageal leak were recorded. Postoperative mortality was 14% due to one patient who died for cardiovascular complications. Most of the patients (71.4%) were admitted to ICU after surgery (average length, 8.8 days); mean hospital stay was 14.7 days. No patients had readmissions. CONCLUSIONS: To our knowledge, this is the largest case series reporting laparoscopic management of BS. We show that laparoscopy is a safe and feasible approach associated with a shorter length of hospital stay when compared with clinical series in which thoracic approach had been chosen. Of note, laparoscopic management would be easily adopted by surgical centers treating benign gastro-esophageal junction entailing a proper management more widely.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Perianastomotic drainage in Ivor-Lewis esophagectomy, does habit affect utility? An 11-year single-center experience.

Anastomotic leakage (AL) is a deadly complication after Ivor-Lewis esophagectomy. The use of an anastomotic drainage (AD), to diagnose and to potentially treat the leakage, is still a widespread practice. At present, scientific literature is lacking in this topic and its use is based on each center experience. We performed a retrospective analysis of 239 consecutive patients who underwent an Ivor-Lewis esophagectomy in our Department from 01/01/2006 to 31/12/2017. Until 28/02/2014, a transthoracic anastomotic drainage was routinely placed in 119 patients (anastomotic-drain group). Drainage removal was planned on POD 5 after the resume of oral intake. In the remaining 120 cases, no drainage was placed (no anastomotic-drain group). We compared the two groups to assess whether the anastomotic drainage had an impact on the timing of the anastomotic leakage diagnosis and treatment. In our series, we observed 9 anastomotic leaks in the first group (7.6%) and 3 in the second one (2.5%). In the anastomotic-drain group, median time for leak diagnosis was 10 days, and notably, in seven cases, the anastomotic drainage was already removed. Considering all the patients who experienced an AL, a re-operation was mandatory in one case, while endoscopic treatment was chosen for five cases and conservative treatment was adopted in three cases. The median hospital length of stay in these patients was 31 days. In the no anastomotic-drain group, one patient with anastomotic leakage was treated conservatively and discharged after 34 days. The other two cases were re-operated and an esophageal prosthesis was placed in both cases, and these patients were discharged, respectively, on POD 28 and POD 38. Concluding, the role of the anastomotic drain in Ivor-Lewis esophagectomy is still unclear. There is a shortage of the literature on this topic and our experience shows that the anastomotic drain has a limited sensibility in AL diagnosis and cannot replace the clinical signs and symptoms. Moreover, the drain it is often removed before the leakage becomes visible. In selected patients with a less severe leak, the anastomotic drain can be an effective treatment, but often a percutaneous drainage, it is an effective alternative choice. In severe dehiscence with sepsis, a reoperation remains the mainstay to control the mediastinal contamination and to eventually treat the leakage.

Tailored treatment for signet ring cell gastric cancer.

Gastric cancer with Laurèn diffuse types is increasing in the West. The raising trend is more evident when considering signet ring cells (SRC) histology. However, to control the biologic potential of this GC subtype, some hypotheses of tailored therapeutic strategies for SRC cancers have been made. A review of the literature was performed using the key words "signet ring cells" AND "gastric cancer". Results of literature review were descriptively reported. Endoscopic submucosal dissection (ESD), according to the Japanese extended criteria, could be a therapeutic option for early SRC tumours. However, according to the evidences from more recent studies, indications for ESD to these tumours types should be carefully considered. Concerning the optimal surgical treatment, considering the high lymphotropism and infiltrating behaviour of SRC histotype, the extension of gastric resection should be wider than for intestinal type cancer and laparoscopic surgery should be performed carefully. Moreover, D3 lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The role of surgery in gastric cancer with peritoneal carcinomatosis is still debated and studies on this topic should stratify the good results according to GC histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing randomized trials suggest that multimodal therapy could be the best treatment. Based on the assumption that SRC tumours have specific features, they deserve a specific multimodal treatment. However, a preliminary step to generate strong evidences in this field is the standardization of terminology used to define signet ring cells carcinoma.

Acute bleeding obstruction pancreatitis after Roux-en-Y anastomosis in total gastrectomy: a single center experience.

Anastomotic intraluminal bleeding is a well-known complication after total gastrectomy. Nevertheless, few data are published on acute bleeding obstruction pancreatitis (BOP) due to a bleeding from the jejunojejunostomy (JJ). In this paper we describe our experience. A total of 140 gastrectomies for EGJ cancer were performed in our Institute from January 2012 to January 2017. All reconstructions were performed with a Roux-en-Y anastomosis: a mechanical end-to-side esophago-jejunostomy and a mechanical end-to-side JJ. Three patients suffered from a bleeding at the JJ with a consequent BOP. We analyzed the time of diagnosis, the treatment and the outcomes. The three patients presented anemia at the laboratory findings on postoperative day (POD) 1. In patient I laboratory findings of acute pancreatitis were found in POD 2. CT scan was performed and showed signs of BOP. Endoscopic treatment was tried without success. Therefore, patient underwent surgery: JJ take down, bleeding control and anastomosis rebuild were performed. In spite of this the patient died of MOF in POD 4. Patient II had a persistent anemia treated with blood transfusions until POD 3, when laboratory tests showed increased lipase and bilirubin levels. Patient was successfully treated with endoscopy but several blood transfusions and a prolonged recovery were necessary. Patient III had laboratory findings of acute pancreatitis on POD 1. Immediate surgery was performed and patient was discharged on POD 9 without sequelae. BOP is a rare but deadly complication after Roux-en-Y anastomosis. An early diagnosis and an aggressive treatment seem to improve the outcome.

Validation of two prognostic models for recurrence and survival after radical gastrectomy for gastric cancer.

BACKGROUND: Prognostic models from Korea and Italy have been developed that predict overall survival and cancer recurrence respectively after radical gastrectomy for gastric cancer. The aim of this study was to validate the two models in independent patient cohorts, and to evaluate which factors may explain differences in prognosis between Korean and Italian patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer between January 2000 and December 2004 at Seoul National University Hospital and at eight centres in Italy were included. Discrimination of the models was tested with receiver operating characteristic (ROC) curves and calculation of area under the curve (AUC). Calibration was evaluated by plotting actual survival probability against predicted survival probability for the Korean nomogram, and actual against predicted risk of recurrence for the Italian score. RESULTS: Some 2867 and 940 patients from Korea and Italy respectively were included. The Korean nomogram achieved good discrimination in the Italian cohort (AUC 0·80, 95 per cent c.i. 0·77 to 0·83), and the Italian model performed well in the Korean cohort (AUC 0·87, 0·85 to 0·89). The Korean nomogram also achieved good calibration, but this was not seen for the Italian model. Multivariable analyses confirmed that Italian ethnicity was an independent risk factor for cancer recurrence (odds ratio (OR) 1·72, 1·31 to 2·25; P < 0·001), but not for overall survival (OR 1·20, 0·95 to 1·53; P = 0·130). CONCLUSION: Both prognostic models performed fairly well in independent patient cohorts. Differences in recurrence rates of gastric cancer may be partially explained by ethnicity.

Enhanced recovery after surgery protocol in patients undergoing esophagectomy for cancer: a single center experience.

This article is about an emerging issue in esophageal surgery: enhanced recovery after surgery (ERAS) Few data are published in literature and its safety and feasibility is still debated. The focus of our paper is on the feasibility of an ERAS protocol for esophagectomy (including both the Ivor-Lewis and McKeown procedure) in a high volume center comparing to a standard perioperative protocol. We introduced a novelty item on this type of surgery: resume of oral feeding in the first postoperative day. We analyzed the dropout rate for each item and the postoperative morbidity. We studied 39 patients operated in the Upper GI division of Verona University Hospital between January 2013 and August 2014; 22 patients (ERAS group) were studied in a perspective way while 17 patients (standard group) were studied retrospectively. The enhanced recovery protocol included intraoperative fluid management, time of extubation after surgery, intensive care unit discharge, drains and nasogastric tube management, mobilization of the patient, oral food intake. We compared the results between the two groups in term of hospital stay, postoperative morbidity and mortality. We also calculated the percentage completion of the protocol, evaluating patient drop-out rates for each of the items. Patients showed an improvement in the ERAS group in terms of earlier extubation, earlier intensive care unit discharge (p < 0.01), earlier thoracic drain, urinary catheter (p < 0.01) and nasogastric tube removal (p = 0.02), earlier mobilization (p < 0.01), and resume of oral feeding (p < 0.01). Median length of hospital stays in the ERAS group was 9 days while in the standard group was 10 days (p = 0.23). Postoperative morbidity and mortality were comparable between the two groups. This study shows the feasibility and safety of an ERAS protocol for esophageal surgery in a high-volume center. These data strengthen the literature results on this argument calling for larger sample size studies.

Extended lymphadenectomy in elderly and/or highly co-morbid gastric cancer patients: A retrospective multicenter study.

BACKGROUND: Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity-related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co-morbid patients. METHODS: In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. RESULTS: Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, p < 0.001 and 72.6% vs. 58.1% in D1, p < 0.001, respectively) in all patients. In elderly patients, this benefit was present only in 5-year DSS. D2 nodal dissection induced better 5-year OS and DSS rates in elderly patients with positive nodes (29.7% vs. 21.2% in D1, p = 0.008 and 47.5% vs. 30.6% in D1, p = 0.001, respectively), although it was present only in DSS when highly co-morbid elderly patients were considered. CONCLUSION: Extended lymphadenectomy confirmed better survival rates in gastric cancer patients. Due to high postoperative complication rate and no significant improvement of the OS, D1 lymphadenectomy should be considered in elderly and/or highly co-morbid gastric cancer patients.

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients.

BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor ß activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

Impact of super-extended lymphadenectomy on relapse in advanced gastric cancer.

BACKGROUND: In gastric cancer the incidence of loco-regional recurrences decreases when lymphadenectomy is expanded from D1 to D2. The present study aimed at evaluating whether the pattern of recurrence in advanced gastric cancer (AGC) is further modified when lymphadenectomy is expanded from D2 to D3. METHODS: 568 patients undergoing curative gastrectomy for AGC (274 D2 and 294 D3) were considered; none of them received preoperative chemotherapy. MantelHaenszel test of homogeneity was used to verify whether the relation between extension of lymphadenectomy and recurrence varied as a function of each risk factor considered. The impact of D2 and D3 on relapse was further investigated by multivariable logistic regression model. RESULTS: Cumulative incidence of recurrence did not significantly differ after D2 and after D3 in the whole series (45.3% vs 46.3%; p = 0.866). However, the association between recurrence and extension of lymphadenectomy was significantly affected by histology (Mantel-Haenszel test of homogeneity: p = 0.007). The risk of recurrence was higher after D3 than after D2 (45.1% vs 35.3%) in the intestinal histotype while the pattern was reversed in the mixed/diffuse histotype (48.3% vs 61.5%). This pattern was confirmed in multivariable logistic regression: the interaction between histology and extension of lymphadenectomy was highly significant (p = 0.004). In particular, cumulative incidence of locoregional recurrences was higher in the diffuse histotype after D2, while being higher in the intestinal histotype after D3. CONCLUSIONS: D3 reverses the negative impact of diffuse histotype on relapses, especially on locoregional recurrences. Therefore D3 could be considered a valid therapeutic option in histotype-oriented tailored treatment of AGC.

One stage or two stage treatment of colorectal cancer associated to abdominal aortic aneurysm: morbidity and mortality.

The coexistence of colorectal cancer and abdominal aortic aneurysm has been observed with increasing frequency, raising several questions about therapeutic and surgical strategies for management of both diseases. This study has reviewed 440 cases (359 cases analyzed) of colorectal cancer associated with abdominal aortic aneurysm recovered in the literature from year 1987 to 2010. In 120 cases, patients were treated in one stage; in 239 cases, they were treated in two stages. The treatment in two stages was associated with a morbidity of 26.4%, with a mortality of 5% and prosthetic infection of 0.8%. The treatment in one stage had rates of complications and mortality of 13.3% and 4.2% respectively and no cases of prosthetic infection. Analysis of the literature shows that the treatment in two stages exposes patients to a higher risk of complications and prosthetic infection.

Shape and volume of internal anal sphincter showed by three-dimensional anorectal ultrasonography.

PURPOSE: The aim of this work is to characterize the shape and the volume of the internal anal sphincter (IAS) in normal subjects by three-dimensional anorectal ultrasonography. METHODS: Thirty-nine normal volunteer males (mean age 58.5 ± 18.7) and 25 females (mean age 59.4 ± 14.1) were submitted to anorectal ultrasonography. The tissue is defined by a semiautomatic procedure. Measurements of thickness, length and volume were assessed automatically. The software provides an average number of 57,600 thickness measurements, 360 length measurements for each zone (90 for each quadrant) and seven volume measurements (one for each anatomical area).The mean values of magnitudes were calculated for the entire volume in each quadrant and zone. Age and gender-related variations were analyzed. RESULTS: In assessments of the whole tissue, only thickness was gender-related, with greater thickness for females (male thickness: 1.81 ± 0.47 mm, female thickness 2.16 ± 0.57 mm, P-value<0.01).In the distal zone: thickness, length and volume were all larger in females (for male and female respectively: 1.83 ± 0.49 mm vs 2.34 ± 0.58 mm, P-value<0.01, for the thickness; 10.87 ± 2.10mm vs 12.18 ± 2.21 mm, P-value<0.02 for the length and 1501 ± 605 mm(3) vs 2169 ± 871 mm(3), P-value<0.01 for the volume). In the medial zone, only thickness was gender-related, with greater thickness in females (male thickness: 2.04 ± 0.60mm, female thickness:2.44 ± 0.74 mm, P-value<0.02).The only variation observed in the proximal zone concerned length, larger in males (respectively: 11.27 ± 2.84 mm vs 9.55 ± 2.43 mm, P-value<0.02). The male population was significantly positively correlated with ageing for volume in the whole tissue (ρ = 0.32, P-value<0.05), and for both thickness and volume in the medial zone (ρ = 0.33, P-value<0.05 for thickness; ρ = 0.39, P-value<0.02 for the volume). CONCLUSION: This new method is useful to understand both functional anal disorders and local damage which may affect only part of the muscle tissue.

Species-specific primers for the identification of the ectomycorrhizal fungus Tuber macrosporum Vittad.

Limitations in the use of morphological traits to identify ectomycorrhizae have led to the development of species-specific molecular markers. Herein, we report a PCR-based technique for the reliable molecular identification of the ectomycorrhizal fungus Tuber macrosporum Vittad. Species-specific primers were designed from an alignment of internal transcribed spacer rDNA sequences from Tuber spp. and from the most common ectomycorrhizal contaminants found in the root systems of truffle-infected plants. The primers were tested for selective amplification using both different truffles and different ectomycorrhizae and were found to identify T. macrosporum successfully. The application of the primers in certifying the quality of truffle-inoculated seedlings is discussed.

[Gastric cancer: surgical treatment and prognostic score]. / Il cancro gastrico: trattamento chirurgico ed elaborazione di un nuovo score prognostico.

AIM: Gastric cancer is the fifth most common cause of tumor-related death in Western countries. Surgery is the only effective treatment but only 50-60% of patients can receive a curative treatment because of absent or aspecific symptoms. The aim of this study was to develop a scale for gastric cancer patients that takes into account factors related to the tumor and to the patient. METHODS: Fifty-seven patients with gastric adenocarcinoma admitted to the Department of General, Geriatric Surgery and Diagnostic and Operative Endoscopy of the University ''Federico II'' in Naples, and treated by gastrectomy from January 1998 until December 2002, were included in this retrospective cohort. The prognostic score was created according to the variables identified in Cox analysis as statistically significant (P 0.1). RESULTS: The 5-year mortality rate was 61%. Cox analysis identified these variables with a significant effect on mortality: age ?60 (odds ratio (OR) 4.16; P=0.015), smoking or alcoholism (OR 2.66; P=0.057), pTNM I (OR 0.04; P=0.003), pTNM II (OR 0.18; P=0.029), pTNM III (OR 0.27; P=0.023), pTNM IV (OR 3.28; P=0.012), lymph node ratio (LNR) <20% (OR 0.15; P=0.01), LNR 20% (OR 3.83; P=0.002), Lauren diffuse histotype (OR 2.41; P=0.1) and location of the neoplasm at superior third (OR 6.70; P=0.003), middle third (OR 5.60; P=0.003), or inferior third (OR 0.32; P=0.008). Patients have been randomized into three groups according to their scores (3-40.5; 41-78.5; 79-115.5) and the 5-year mortality rate was 46%, 59%, 90% in group 1, 2 and 3 respectively. CONCLUSION: It is necessary to consider in prognostic stratification of gastric cancer patients not only pTNM staging but also other factors such as age, smoking or alcoholism, Lauren histotype, location and linfonodal involvement. It is possible to design a more effective prognostic score predicting the individual risk and addressing the therapy and the follow-up.

Persistence of anti-HBs in children vaccinated against viral hepatitis B in the first year of life: follow-up at 5 and 10 years.

The persistence of anti-HBs protective levels in groups of children who had been immunized against Hepatitis B 5 and 10 years earlier, in their first year of life, has been studied. The results were analyzed according to the type of vaccine (both plasma-derived and DNA recombinant) and the number of doses administered (three or four doses). In addition, the protective effect of the vaccine in vaccinated subjects was studied in relation to the anti-HBc presence. The serologic results suggest that, in cohorts of children vaccinated 5 years earlier, a higher prevalence of subjects with anti-HBs protective levels was found, when the DNA recombinant vaccines were administered (97.6% for MSD Recombivax and 97.1% for SKF Engerix B); a lower one when the plasma-derived vaccine was used (80.4% Pasteur Merieux, Hevac B). Moreover, in cohorts of children vaccinated with plasma derived vaccine (hevac B) 10 years earlier, a higher prevalence of subjects with anti-HBs protective levels was demonstrated when four doses were administered (76.9%); a lower one when three doses were inoculated (57.5%). The absence of core antibody (anti-HBc) in responders to the vaccination shows the protective efficacy of both the DNA recombinant and plasma derived vaccines. On the other hand the presence of anti-HBc in some anti-HBs negative non-responders subjects shows the susceptibility of these people to infection. In anti-HBs negative vaccinated subjects the appearance of levels of anti-HBs in 95.9% of subjects, 1 week after the administration of a booster dose, demonstrates the presence of a solid immunologic memory.

Effective antibody response in newborn babies living in Maldives to simultaneous vaccination against hepatitis B, poliomyelitis, diphtheria and tetanus.

The antibody responses of Maldivian infants early in their life to simultaneous immunization against hepatitis B virus, poliomyelitis, diphtheria and tetanus were investigated. The vaccines were given at 6, 10 and 14 weeks of age. Among 243 newborn babies from HBsAg-negative mothers, 103 received three doses of oral poliomyelitis (OPV) and diphtheria and tetanus (DTV) vaccines; 105 were similarly immunized but received in addition the recombinant hepatitis B vaccine (HBV); 35 were immunized with the HBV recombinant vaccine alone. The antibody response to all of the vaccines was effective. No significant differences among the groups were observed. Hepatitis B vaccination of infants neither affected nor was affected by the contemporary administration of OPV and DTV vaccines.