Multicentre study of perioperative versus adjuvant chemotherapy for resectable colorectal liver metastases.

Background: It is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM. Methods: Consecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS. Results: Some 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16; P = 0·318). For the subgroup of 165 patients who received adjuvant FOLFOX successfully (for at least 3 months), the adjusted effect of neoadjuvant chemotherapy was not significant (HR 1·19, 0·74 to 1·90; P = 0·476). No significant effect of neoadjuvant chemotherapy was observed in multivariable regression analysis. Conclusion: Compared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.

Antecedentes: Se desconoce si la quimioterapia perioperatoria en comparación con la quimioterapia adyuvante sola mejora la supervivencia libre de enfermedad (disease­free survival, DFS) en pacientes con metástasis hepáticas de origen colorrectal (colorectal liver metastases, CLM) resecables de inicio. El objetivo de este estudio fue estimar el impacto de la neoadyuvancia con 5­fluorouracilo, leucovorina y oxaliplatino (FOLFOX) sobre la DFS en pacientes con CLM resecables desde el principio. Métodos: Se incluyeron pacientes consecutivos que presentaban hasta cinco CLM resecables en dos centros japoneses y dos centros franceses entre 2008 a 2015. Ambas instituciones francesas favorecían FOLFOX perioperatorio, mientras que los dos grupos japoneses utilizaban sistemáticamente la cirugía de entrada y quimioterapia adyuvante. Se utilizaron la probabilidad inversa del tratamiento ponderado (Inverse Probability of Treatment Weighting, IPTW) y el modelo multivariable de regresión de Cox para ajustar por factores de confusión. El resultado primario fue la DFS. Resultados: Se incluyeron 300 pacientes (grupo de quimioterapia perioperatoria n = 151 y grupo de cirugía de entrada más quimioterapia adyuvante n = 149). La DFS a los 3 años ponderada fue del 33% después de quimioterapia perioperatoria versus 27% tras cirugía de entrada (cociente de riesgos instantáneos, hazard ratio HR: 0,85; i.c. del 95% (0,62­1,16); P = 0,32). Cuando se consideró el subgrupo de pacientes que (n = 165) de manera efectiva (al menos 3 meses) recibieron FOLFOX adyuvante, el efecto ajustado de la quimioterapia neoadyuvante no fue significativo (HR: 1,19 (0,74­1,90); P = 0,48). No se observó un efecto significativo de la quimioterapia neoadyuvante en el análisis de regresión multivariable. Conclusión: En comparación con la quimioterapia adyuvante, el FOLFOX perioperatorio no mejora la DFS en CLM resecables siempre y cuando la quimioterapia adyuvante se administre de forma efectiva.

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Use of aspirin and bleeding-related complications after hepatic resection.

BACKGROUND: The operative risk of hepatectomy under antiplatelet therapy is unknown. This study sought to assess the outcomes of elective hepatectomy performed with or without aspirin continuation in a well balanced matched cohort. METHODS: Data were retrieved from a multicentre prospective observational study. Aspirin and control groups were compared by non-standardized methods and by propensity score (PS) matching analysis. The main outcome was severe (Dindo-Clavien grade IIIa or more) haemorrhage. Other outcomes analysed were intraoperative transfusion, overall haemorrhage, major morbidity, comprehensive complication index (CCI) score, thromboembolic complications, ischaemic complications and mortality. RESULTS: Before matching, there were 118 patients in the aspirin group and 1685 in the control group. ASA fitness grade, cardiovascular disease, previous history of angina pectoris, angioplasty, diabetes, use of vitamin K antagonists, cirrhosis and type of hepatectomy were significantly different between the groups. After PS matching, 108 patients were included in each group. There were no statistically significant differences between the aspirin and control groups in severe haemorrhage (6·5 versus 5·6 per cent respectively; odds ratio (OR) 1·18, 95 per cent c.i. 0·38 to 3·62), intraoperative transfusion (23·4 versus 23·7 per cent; OR 0·98, 0·51 to 1·87), overall haemorrhage (10·2 versus 12·0 per cent; OR 0·83, 0·35 to 1·94), CCI score (24 versus 28; P = 0·520), major complications (23·1 versus 13·9 per cent; OR 1·82, 0·92 to 3·79) and 90-day mortality (5·6 versus 4·6 per cent; OR 1·21, 0·36 to 4·09). CONCLUSION: This observational study suggested that aspirin continuation is not associated with a higher rate of bleeding-related complications after elective hepatic surgery.

Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Locoregional extension of intrahepatic cholangiocarcinoma (ICC) at the time of diagnosis results in a low resectability rate and poor prognosis. The aim of this retrospective study was to assess the efficacy of neoadjuvant chemotherapy for locally advanced ICC. METHODS: All consecutive patients with ICC between 2000 and 2013 were included prospectively in a single-centre database and analysed retrospectively. Patients with locally advanced ICC considered as initially unresectable received primary chemotherapy, followed by surgery in those with secondary resectability. Results of patients who underwent surgery for locally advanced ICC were compared with those of patients with initially resectable ICC treated by surgery alone. RESULTS: A total of 186 patients were included in the study. Of 74 patients with locally advanced ICC, 39 (53 per cent) underwent secondary resection after a median of six chemotherapy cycles. Patients in this group were younger (P = 0·030) and had more advanced disease than those who had surgery alone, and presented more frequently with lymphadenopathy (P = 0·010) and vascular invasion (P = 0·010). Postoperative morbidity and mortality were no different between the groups. The median survival of patients who had surgery after chemotherapy was 24·1 months, and that of patients who had surgery alone was 25·7 months (P = 0·391). CONCLUSION: Patients with locally advanced ICC treated by surgery following neoadjuvant chemotherapy had similar short- and long-term results to patients with initially resectable ICC who had surgery alone. Neoadjuvant chemotherapy as a first-line treatment for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease.

Organoids as preclinical models to improve intraperitoneal chemotherapy effectiveness for colorectal cancer patients with peritoneal metastases: Preclinical models to improve HIPEC.

BACKGROUND: Peritoneal metastases (PM), corresponding to tumor implants into the peritoneal cavity, are associated with impaired prognosis and low responsiveness to systemic chemotherapy. A new therapeutic approach has dramatically changed the prognosis of patients with PM from colorectal cancer (CRC), consisting in the association of a complete cytoreductive surgery followed by intraperitoneal chemotherapy associated to hyperthermia (HIPEC). Many drugs have been administered intraperitoneally, but no clear consensus has been approved. Therefore, relevant preclinical models are essentials for the efficient translation of treatments option into affected patients. METHOD: Organoids, the last generation of preclinical models, were used to rationalize and improve intraperitoneal chemotherapy. We tested several cytotoxics, combination, effect of hyperthermia, exposure duration and frequency. RESULTS: Organoids were a representative model of response to chemotherapies used for the treatment of PM from CRC; 460mg/m2 of oxaliplatin being the most efficient cytotoxic treatment. Repeated incubations with oxaliplatin; mimicking cycles of intraperitoneal treatment, resulted in an increased efficacy. CONCLUSION & DISCUSSION: Organoids are relevant models to study the chemosensitivity of peritoneal metastases from CRCs. These models could be used for large scale drug screening strategies or personalized medicine, for colorectal carcinoma but also for PM from other origins.

Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases.

BACKGROUND: Despite the gradual diffusion of laparoscopic liver resection, the feasibility and results of laparoscopic two-stage hepatectomy (TSH) for bilobar colorectal liver metastases (CRLM) have not been described frequently. This study aimed to evaluate the feasibility, safety and oncological outcomes of laparoscopic TSH for bilobar CRLM. METHODS: All patients eligible for laparoscopic TSH among those treated for bilobar CRLM from 2000 to 2013 were included. Demographics, tumour characteristics, surgical procedures, and short- and long-term outcomes were analysed. RESULTS: Laparoscopic TSH was planned in 34 patients with bilobar CRLM, representing 17·2 per cent of all 198 patients treated for bilobar CRLM. Thirty patients received preoperative chemotherapy, and 20 had portal vein occlusion to increase the volume of the remnant liver. Laparoscopic resection of the primary colorectal tumour was integrated within the first-stage hepatectomy in 11 patients. After a median interval of 3·1 months, 26 patients subsequently had a successful laparoscopic second-stage hepatectomy, including 18 laparoscopic right or extended right hepatectomies. The mortality rate for both stages was 3 per cent (1 of 34), and the overall morbidity rate for the first and second stages was 50 per cent (17 of 34) and 54 per cent (14 of 26) respectively. Mean length of hospital stay was 6·1 and 9·0 days respectively. With a median follow-up of 37·8 (range 6-129) months, 3- and 5-year overall survival rates in patients who completed TSH were 78 and 41 per cent respectively. The 3- and 5-year disease-free survival rates were 26 and 13 per cent respectively. CONCLUSION: Laparoscopic TSH for bilobar CRLM is safe and does not jeopardize long-term outcomes in selected patients.

Portal biliopathy as a complication of extrahepatic portal hypertension: etiology, presentation and management.

Portal biliopathy (PB) refers to the biliary abnormalities of the biliary ducts observed in patients with extrahepatic portal hypertension. Although majority of patients are asymptomatic, approximately 20% of these patients present with biliary symptoms (pain, pruritus, jaundice, cholangitis). The pathogenesis of PB is uncertain but compression by dilated veins into or around common bile duct may play the main role. CT-scan, MR cholangiopancreatography with MR portography should be the initial investigations in the evaluation of PB. Treatment is limited to symptomatic cases and is dictated by clinical manifestations and complications of the disease. Treatment of PB could be done by endoscopy (sphincterotomy, stone extraction or biliary stenting of the common bile duct) or surgery (definitive decompression by porto-systemic shunt followed by bilioenteric anastomosis, if necessary). This review describes pathogenesis, clinical features, investigation and management of portal biliopathy.

Torque Teno Virus--cause of viral liver disease following liver transplantation: a case report.

Torque Teno Virus (TTV), a nonenveloped human virus of the Circoviridae family, is hepatotropic, causing liver damage, cirrhosis, and, rarely, fulminant hepatitis. It prevails in 10% to 75% of blood donors due to environmental differences, independent of chronic hepatitis B virus (HBV)/HCV hepatitis, cryptogenic cirrhosis, alcoholic cirrhosis, and in fulminant hepatitis non-A-G. Reports about the efficacy of clinical alpha interferon are rare. In July 2007, a 65-year-old man who was serologically negative for A-E viruses presented with acute liver failure due to a ruptured hepatic artery aneurysm and underwent orthotopic liver transplantation (OLT). Immunosuppression was based on cyclosporine and steroids. At postoperative day 20, there was persistent hypertransaminasemia with otherwise normal liver function. A percutaneous hepatic biopsy documented pattern suggestive of a viral etiology. Multiple tests for hepatotropic viruses in the donor and the recipient from the pre- and post-OLT periods remained negative. Only the TTV qualitative test, assessed by polymerase chain reaction (PCR) on patient sera, was positive. Immunosuppressive therapy was not changed; no antiviral therapy was undertaken. At 6 months posttransplantation, transaminase levels spontaneously normalized and the clinical situation was unchanged. No complications were observed; the patient is in good clinical condition. No graft rejection was observed. In histologically proven non-A-E viral hepatitis, it is important to consider TTV as an incidental pathogenic agent. It may be useful to extend virological tests to TTV among transplant recipients and donors and to gain further knowledge about this virus.

Preliminary results of liver transplantation for hepatocellular carcinoma among allocation organ policy strategies, neoadjuvant treatments, and intention-to-treat analysis.

We retrospectively evaluated the impact of our strategy for patients with hepatocellular carcinoma (HCC) according to an intention-to-treat analysis and drop-out probability. We evaluated only patients within the Milan criteria. We analyzed the outcomes of neoadjuvant strategies for HCC, organ allocation policy, and systematic application of strategies to increase the deceased donor pool as the current tendency to expand transplantability criteria for those patients. Kaplan-Meier survival probability rates at 1, 3, and 5 years according to an intention-to-treat analysis were 87.02%, 74.53%, and 65.93% for transplanted patients (n=108), and 50%, 14.29%, and 14.29% for the excluded or waiting list group (n=13), respectively (P< .0001). Drop-out risk at 3, 6, and 12 months was 2.40%, 8.59%, and 16.54%, respectively. During the same period, the mortality probability rates at 3, 6, and 12 months among patients without HCC awaiting orthotopic liver transplantation (OLT) were 3.60%, 9.50%, and 18.34%, respectively. Drop-out rate was lower among patients treated before OLT (P< .0001). On the basis of the neoadjuvant treatment results to reduce drop-out risk, we suggest avoiding the high priority for the HCC cohort, particularly within the first 6 months from entrance on the waiting list, because this approach can reduce the chances of patients with end-stage liver disease (ESLD) alone.

[Calcified pseudotumor of the pleura: description of a case]. / Pseudotumore fibroso calcifico della pleura: descrizione di un caso.

We describe a calcifying fibrous pseudotumour of pleura in a 46-year-old female, smoker. The patient presented with a well-delimited pleural mass, 3-cm across, located at the base of the right lung and attached to the lung with a short pedicle. Seven years after surgical excision of the mass, the patient is alive and well. Microscopically, the lesion was mostly composed of dense collagenous tissue, with sparse benign spindle cells, a rich inflammatory infiltrate and scattered calcifications, sometimes laminated. Immunohistochemically, spindle cells were positive for vimentin and negative for smooth muscle actin, desmin, S100 protein, CD34, CD99 and Bcl2. Calcifying fibrous pseudotumour is rare in the pleura. Pertinent data from the literature and problems in differential diagnosis are briefly discussed.

Ancient schwannoma arising in a lymph node: report of a case and review of the literature.

We report a case of an intranodal schwannoma in a 79-year-old woman. The patient underwent a left colectomy for a colonic adenocarcinoma, with regional lymph node dissection. Macroscopic examination of the specimen revealed a well-circumscribed 4 cm nodule located in the pericolic fat. Macroscopically, it was interpreted as a metastatic lymph node. Microscopically, the nodule was composed of a proliferation of bland spindle cells, was immunohistochemically positive for S100 protein, and negative for smooth muscle actin, desmin, and cytokeratin. The pathological findings led to the diagnosis of a very rare case of primary schwannoma of the lymph node.

Different meaning of CD38 molecule expression on CD4+ and CD8+ cells of children perinatally infected with human immunodeficiency virus type 1 infection surviving longer than five years.

We investigated the relationship between CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell proportions (HLA-DR = major histocompatibility complex class II) (determined by two-color immunofluorescence) and the clinical condition, IL-2 and IL-6 production, viral RNA copy numbers, and the eventual immunologic-virologic course in 25 children perinatally infected with HIV-1 surviving longer than 5 y [median age, 92 (range, 63-136) mo]. Twelve healthy age-matched children were studied as control subjects. HIV-1+ children had lower percentages and absolute numbers of CD4+CD38+, whereas the percentages of CD4+HLA-DR+ and the percentages and absolute numbers of CD8+CD38+ and CD8+HLA-DR+ cells were higher than that of control subjects. The absolute numbers of CD4+ and the percentages of CD4+CD38+, CD8+CD38+, and CD8+HLA-DR+ cells directly correlated, whereas the percentages of CD4+CD38+ and CD4+HLA-DR+ cells, the percentages of CD4+CD38+ and CD8+CD38+ cells, the CD8+ cell absolute numbers, and the percentages of CD8+CD38+ cells did not. Severe manifestations and immunologic deterioration occurred in children with low CD4+CD38+ cell percentages, whereas virologic worsening was associated with low CD8+CD38+ and CD8+HLA-DR+ cell percentages. IL-2 production directly correlated with percentages and absolute numbers of CD4+CD38+ and CD8+CD38+ cells. RNA copy numbers inversely correlated with CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell percentages. This suggests that CD38 molecule expression on both CD4+ and CD8+ cell subsets is a favorable marker in HIV-1+ children. Perhaps CD8+CD38+ subsets are activated cells, whereas CD4+CD38+ subsets are immature cells, possibly the host's attempt at CD4+ cell renewal.

[Monophasic sarcomatoid carcinoma of the ileum. Description of a case and review of the literature]. / Carcinoma sarcomatoide monofasico dell'ileo. Descrizione di un caso e revisione della letteratura.

INTRODUCTION: A case of monophasic sarcomatoid carcinoma of the ileum is described. RESULTS: The patient was a 76 year old woman, presenting with a 5 cm perforated mass of the ileum. The tumor was constituted by epithelioid and spindle atypical cells, arranged in fascicles and in solid sheets; no clear-cut carcinomatous component was evident. Immunohistochemically, the neoplastic cells were positive for cytokeratin and, focally, for vimentin. The patient died of disease 2 months after surgery. DISCUSSION: The literature on small intestine sarcomatoid carcinoma is reviewed and the differential diagnosis is discussed. In the Author's opinion, the term sarcomatoid carcinoma (monophasic or biphasic) should be used in the small intestine for those neoplasms previously described as enteroblastoma, carcinosarcoma or pleomorphic carcinoma.

Postradiation sarcoma of head and neck: report of two cases.

AIMS AND BACKGROUND: Post-irradiation sarcoma (PIS) a rare, late side effect of radiotherapy and, consequently, its natural history is not well known. For this reason, two cases treated between 1975 and 1990 are described. CASE REPORTS: The Authors describe one case of malignant fibrous histiocytoma grown in the larynx 111 months after conservative surgery and postoperative radiotherapy, and one case of soft tissue sarcoma developed in the oral cavity 72 months after radical interstitial low dose rate brachytherapy. Both patients had chronic distress of the soft tissues after the primary treatment. The patients are alive and well respectively at 94 and 18 months from salvage surgery. DISCUSSION: The PIS of the head and neck region is a rare event, usually with a bad prognosis. An improvement in results could be possible with early diagnosis, followed by a timely excision, when anatomically possible. As the chronic suffering of the irradiated tissues may increase the risk of PIS, a longer and more frequent follow-up is advisable in these cases.

Determination of ErbB2 protein in breast cancer tissues by different methods. Relationships with other biological parameters.

Four different methods to measure in parallel the erbB2 protein expression (p185neu) were evaluated in order to: a) compare two enzyme immunoassays with the immunohistochemical assays (IHC) and western blotting (WB) and b) extrapolate eventual relationships between erbB2 and biological parameters. Tissue samples from 248 patients with primary breast cancer were consecutively assayed. We used two different cut-off levels for WB, ELISA, and EIA, defined as follows: 1) the highest level of expression of non malignant tissue was chosen as the discriminant threshold between 'low' and 'elevated' samples: 2) the elevated group was further subdivided into two subgroups: 'intermediate' and 'high', according to their median value. According to the first cut-off, the results were considered 'elevated' in about 52% of cases with the three biochemical methods, while using the second cut-off the percentage lowered to about 26%. Considering this cut-off, the concordance rates between the paired biochemical methods ranged between: 78.4% (WB vs EIA), 93% (ELISA vs EIA), and 82.6% (ELISA vs WB). The comparison between biochemical and immunohistochemical methods gave these concordance rates: 82% (WB vs IHC), 90.5% (ELISA vs IHC), and 85.5% (EIA vs. IHC). According to the first cut off level, 27.5% of tumor samples showed IHC detectable p185 levels, in agreement with other immunohistochemical studies. The relationship between high erbB2 and estrogen and progesterone receptors showed an inverse association. No relationship was found between erbB2 and axillary lymph node positivity or tumor size. In short, the results of the four methods seem generally well correlated; nevertheless, it appears that different methodological approaches of measuring p185neu are not completely equivalent, and there is a need for an authoritative standardization and quality control for clinical applications.

Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component.

The histology, immunohistochemistry and ultrastructure of six gastro-intestinal stromal tumors of the stomach (GSTs) showing a focal to diffuse clear cell component are reported. At light microscopy, all GSTs had typical histopathological features with one case additionally displaying stromal myxoid changes and scattered multinucleated giant cells. Immunohistochemically, 6 of 6 GSTs stained positive for vimentin, 2 of 6 for smooth muscle specific actin and 1 of 6 for desmin. At electron microscopy, GSTs showed microfilaments with focal densities as well as other smooth muscle features, such as subplasmalemmal linear densities and foci of external lamina. Ultrastructural appearances of tumor cells with clear cell features showed these not to be an artifact of fixation, but the expression of an unusual cytophagocytic activity. Inclusions of auto- and heterophagocytic nature were found responsible for the origin of the large, mostly lipidic vacuoles which displaced cell nuclei peripherally in a signet-ring fashion. It is concluded that such previously unrecognized features are ultrastructural aspects of GSTs with smooth muscle differentiation.

Comparison between western blotting, immunohistochemical and ELISA assay for p185neu quantitation in breast cancer specimens.

The protein encoded by erbB2 oncogene was evaluated by three different methodological approaches (Western blotting, ELISA and immunohistochemistry) in 147 breast cancer specimens. A highly significant correlation was found between Western blotting and ELISA results (p < 0.001). The data from ELISA and Western blotting were categorized as negatives (-), low-overexpressing (+) and high-overexpressing (++). Immunohistochemical results were classified as (-) or (+) according to the absence or the presence of specific staining. Overall positive cases (+ and ++) were 42.2% by Western blotting and 51% by ELISA, while (++) cases were 23.8% and 25.2% respectively. Histochemical staining was found in 29.8% of cases. The two by two evaluation of the assays showed a close association (chi2, p < 0.0001). In particular, the comparison between both ELISA and Western blotting with immunohistochemistry showed concordance rates of 78.9% for ELISA and 83.1% for Western blotting considering the + and ++ cases as a single group. When only the ++ cases were considered as positive, the overall agreement rises to 93.3% and 89.1% respectively. From these preliminary data we conclude that p185 values obtained with the three evaluated methods are possibly superimposable. Nevertheless, the biochemical methods seem to identify an intermediate p185 expression group, whose clinical meaning should be investigated.

Lysozyme localization in normal and diseased human gastric and colonic mucosa. A correlative histochemical, immunohistochemical and immunoelectron microscopic investigation.

The distribution of lysozyme in normal and pathological human gastric and colonic mucosa was studied by light and electron microscopic immunocytochemical techniques and compared with histological and histochemical features. Lysozyme was localized in pyloric glandular epithelial cells, mucous neck cells of fundic glands, Paneth cells and some crypt cells of the mature colonic mucosa. In addition, lysozyme was detected in a large spectrum of "immature" or "regenerative" epithelium: neck cells of the gastric regenerative zone, undifferentiated columnar cells of surface and hyperplastic interfoveolar crests of the stomach, regenerative cells in a healed gastric ulcer, some goblet cells in incomplete intestinal metaplasia, cells of the regenerative zone at the bottom of colonic crypts and, finally, fetal intestinal epithelium. Electron microscopically, we localized lysozyme in the central core of mucous granules in the pyloric gastric glandular epithelium and in the dense mucous granules in gastric mucous neck cells. Lysozyme was also detected in some immature mucin-producing cells of the gastric regenerative zone and in the rough endoplasmic reticulum of surface hyperplastic columnar gastric cells. At the electron microscopic level, a peculiar correlation between the immunopattern of lysozyme and the morphology of mucous granules has been postulated. All our data support and extend the view that the presence of lysozyme may be related to cell immaturity as well as to a regenerative state of the cell. Finally, the lysozyme distribution and its relation to mucosubstances in gastric and colonic carcinoma suggest that lysozyme should not be considered an exclusive marker of cells of gastric derivation.