Lymphocytic infiltrate is associated with favorable biomarkers profile in HER2-overexpressing breast cancers and adverse biomarker profile in ER-positive breast cancers.

The value for lymphocytic infiltration (LI) has been increasingly recognized for tumor assessment. In breast cancer, however, the overall significance of LI remains poorly defined, probably due to its heterogeneity. A large cohort of breast cancer was evaluated for the degree of LI and its association with traditional pathologic factors, biomarker expression, and cancer subtypes. The number of CD8 cytotoxic effector and FoxP3 regulatory T cell (Treg) was evaluated in those cases with high LI. High LI was associated with negative ER and PR but positive HER2 and EGFR expression (p < 0.001 for all). In ER-positive cancers, high LI was associated with poor prognostic features including higher grade, the presence of necrosis, and lymphovascular invasion (LVI) (p = 0.007 for LVI and <0.001 for the others). Conversely, LI correlated with smaller tumor size, a good prognostic feature (p = 0.046) in HER2+ ER-cancers. These observations suggested LI may show opposite prognostic values in different breast cancer subgroups. Interestingly, when the phenotype of LI in these subgroups was evaluated, a strong positive association with intratumoral accumulation of Treg was found in ER-positive cancers (p = 0.003, Rs = 0.319), while the opposite was observed in HER2+ ER-cancers (p < 0.001, Rs = -0.427). Also, in ER-positive cancers, positive associations between peri- and intra-tumoral distribution were found with both CD8 and Tregs (CD8: p < 0.001, Rs = 0.547; Treg: p = 0.001, Rs = 0.460). Nonetheless, in HER2+ ER-cancers, such strong association was found with CD8 (p < 0.001, Rs = 0.766) but not Tregs. The results may implicate a differential intratumoral migration of LI in different subtypes of breast cancer. In summary, the clinical value of LI in breast cancers could be subtype-dependent. In ER-positive cancers, high LI correlated with biologic parameters associated with poor prognosis, whereas in HER2 positive cancers, LI correlated with biologic parameters of favorable prognosis.

Androgen receptor expression shows distinctive significance in ER positive and negative breast cancers.

BACKGROUND: Androgen receptor (AR), a nuclear steroid hormone receptor, is differentially expressed in breast cancer subgroups with distinct clinical implications. METHODS: To investigate the clinical significance of AR in breast cancers more precisely, the expression of AR in a large cohort of breast cancer was correlated with clinicopathological features, biomarker expression, and patients' survival according to different molecular groupings in this study. RESULTS: Higher AR expression was found in ER+ (57.8 %) than in ER- (24.7 %) cancers. In the ER+ cancers, AR expression was associated with favorable clinicopathological features, including lower grade (p < .001), lower pT stage (p < .001), and positivity for PR (p < .001). It was an independent prognostic factor for longer disease-free survival, mainly in the HER2+ luminal B cancers (hazard ratio [HR] = 0.251, 95 % CI 0.065-0.972, p = .045). In ER- cancers, AR expression was associated with features distinct from basal-like breast cancer, and such features were found in molecular apocrine (MA) cancers. AR correlated with presence of extensive in situ component (p = .006) and apocrine phenotype (p < .001), HER2 (p = .026), and EGFR (p = .048), but negatively with c-kit (p = .041), CK5/6 (p < .001), CK14 (p = .002), and αB-crystallin (p = .038). However, AR expression was found only in 37.8 % of immunohistochemically defined MA. Of note, AR-MA appeared to have a trend of worse overall survival than AR+MA. CONCLUSIONS: AR expression was different in ER+ and ER- cancers and had different clinical implications. AR alone may not be a good marker for MA subtype. Its expression in MA may have substantial prognostic implication and as such warrants further validation.

A subset of breast cancer predisposes to brain metastasis.

This study evaluated the expression of biological markers of breast cancers with brain metastases. Eighteen paired tumors were assessed, with 42 non-brain-metastasizing breast cancers that were stained with ER, PR, HER2, CK5/6, p63, and Ki67, and were also classified into intrinsic subtypes. The expression patterns between the breast tumors with brain metastases were compared to the brain metastases and the controls. Breast cancers with brain metastases were of higher grade and showed higher incidence of lymph node metastases at initial diagnosis and higher EGFR, p63, and Ki67 expression. In the group of breast cancers with brain metastases, the brain metastases showed higher HER2, CK5/6, and Ki67 expression compared to the breast primaries. There was also a higher incidence of basal subtype and a lower incidence of luminal subtype. When tumors metastasized, changes in hormonal receptor (22%) and HER2 (6%) status were observed. We concluded that breast cancers with higher grade, lymph node involvement at diagnosis, high EGFR, p63, and Ki67 expression, and of basal subtype were at higher risk for brain metastases, and that both hormonal receptors and HER2 status may change in brain metastases.

Predictors of invasion in needle core biopsies of the breast with ductal carcinoma in situ.

A significant proportion of ductal carcinomas in situ (DCISs) of the breast diagnosed on core biopsies had invasion upon excision. An assessment of various invasion predictors in the biopsies yielded conflicting results. A cohort of 157 cases with needle core biopsy diagnosed with DCISs (including 109 histologically proven DCISs, and 48 cases with invasion upon excision) were evaluated for the numbers of positive and total cores, the percentage of positivity, lobular cancerization, tumor nuclear grade, necrosis, calcification, predominate histological pattern, lymphocytic infiltrate and excisional tumor size. The mean positive core percentage and excisional tumor size were 76% and 2.8 cm for invasive and 66% and 1.9 cm for noninvasive groups. In the biopsy of the invasive group, cancerization of lobules was present in 52%, and nuclear grades 1, 2 and 3 were present in 31, 31 and 38%, respectively. Large comedo and small noncomedo necroses were present in 48 and 10%, whereas large and small calcifications were present in 16 and 21%. Solid, cribriform and papillary patterns were observed in 88, 38 and 21%, respectively. Moderate to marked lymphoid infiltrate was present in 31%. In the biopsy of the noninvasive group, cancerization of lobules was present in 69%, and the nuclear grades 1, 2 and 3 were present in 23, 48 and 29%, respectively. Large comedo and small noncomedo necroses were present in 35 and 11%, whereas large and small calcifications were present in 33 and 23%. Solid, cribriform and papillary patterns were observed in 85, 39 and 9%, respectively. Moderate to marked lymphoid infiltrate was present in 36%. Comparing these groups, a higher positive core percentage, papillary pattern and less cancerization of lobules in the cores and larger excisional tumor size were associated with a higher chance of invasion. Calcification, necrosis and nuclear grade were not significant invasion predictors.

Core needle biopsy as an alternative to whole section in IHC4 score assessment for breast cancer prognostication.

AIMS: IHC4 score, based on expression of four routine markers (oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker, Ki67), is a recently developed, cost-effective prognostic tool in breast cancer. Possibly, the score may be useful also in advanced diseases where only core needle biopsy (CNB) is available and neoadjuvant therapy. However, its studies on CNB are scant. This study examined whether IHC4 score assessment on CNB is comparable to that from whole section (WS). METHODS: Immunohistochemical (IHC) analysis was performed for ER, PR, HER2 and Ki67 on 108 paired CNB and WS to evaluate IHC4 score (with follow-up range 1-230 months and 5 relapse/death). Concordance between the two was examined. Factors that affected the concordance were analysed. Additionally, IHC4 score was compared with Nottingham Prognostic Index (NPI). RESULTS: There was moderate concordance between IHC4 score on CNB and WS (all cases: κ=0.699, p<0.001; ER+ cases: κ=0.595, p<0.001). Among the IHC4 components, concordance for HER2 was the poorest (κ=0.178, p<0.001 in all cases; ER+ cases: κ=0.082, p<0.097). Significant factors affecting concordance between CNB and WS included number of cores, total core length and percentage of tumour cells in cores (p≤0.030), indicating the importance of sufficient sampling. Interestingly, the concordance was also affected by patients' age (p=0.039). There was poor agreement between IHC4 score and NPI (κ≤0.160). CONCLUSION: Our results suggested that IHC4 score can be used on adequately sampled CNB. Its poor agreement with NPI highlights the independence of the two factors.

Metachronous bilateral mammary metaplastic and infiltrating duct carcinomas: a molecular study for clonality.

Mammary metaplastic carcinoma is uncommon. In this study, both carcinoma and sarcoma components of a metaplastic carcinoma and a subsequent metachronous contralateral infiltrating ductal carcinoma were analyzed by microsatellite analysis for the loss of heterozygosity (LOH) patterns at multiple sites on chromosome arms 3p, 6q, 8, 9p, 11, 13q, 14q, 16q, and 17p. The LOH patterns between the carcinoma and sarcoma components in the first tumor were similar, indicating clonality. The LOH patterns between the first and second tumors were different at all chromosome arms, indicating different clonality and a second primary. We demonstrated a second primary carcinoma in a patient with previous metaplastic carcinoma rather than a metastasis with carcinoma component only.

Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases.

A retrospective review of 185 mammary phyllodes tumors (105 benign, 51 borderline, 29 malignant) from 4 centers was performed by immunohistochemistry to investigate the expression of vascular endothelial growth factor in the epithelial and stromal cells of mammary phyllodes tumors. The correlation of vascular endothelial growth factor with tumor grade, stromal cell nuclear pleomorphism, cellularity, mitotic rate, margin histomorphology, and the stromal microvessel density was evaluated. Vascular endothelial growth factor expression was found in the epithelium in 29% and in the stromal cells in 31% of cases. There was significant increase of vascular endothelial growth factor expression in the stromal cells with increasing degree of malignancy, but not the epithelium. Microvessel density in the stroma also showed significant correlation with tumor malignancy, and a correlation was shown with the stromal vascular endothelial growth factor expression. Statistical overlap of stromal vascular endothelial growth factor and microvessel density in predicting malignancy suggests that angiogenesis may be an effector mechanism for vascular endothelial growth factor. Assessment of stromal VEGF may be useful as an adjunctive diagnostic criterion in the histologic assessment of malignancy in phyllodes tumors.

Hormonal receptors expression in epithelial cells of mammary phyllodes tumors correlates with pathologic grade of the tumor: a multicenter study of 143 cases.

We used immunohistochemical analysis to detect the presence of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) protein expression in the epithelial and stromal cells of 143 phyllodes tumors (PTs). Expression of epithelial ER and PR proteins was common, occurring in 43% to 84% of PTs. Expression of epithelial AR protein and stromal ER, PR, and AR proteins was low (5% or less) in all tumors. An inverse relationship of epithelial ER and PR protein expression with degree of malignancy in PT was found (P < .05), and ER expression also correlated with mitotic count (P < .05). When considering PT with the expression of ER or PR proteins and the coexpression of both, the inverse relationship with tumor grade also was significant (P < .05). As the hormonal receptor protein expression shows a consistent decrease with increasing malignancy, we infer that the epithelium has a crucial role in the pathogenesis or progression of PT.

Granulomatous mastitis: a clinicopathological review of 26 cases.

AIMS: Twenty-six cases of granulomatous mastitis were examined to determine the common histological and clinical features and the possible association with micro-organisms. METHODS: A retrospective review of the clinical and histological features of these cases was undertaken, including granuloma, inflammatory cell infiltrate, multinucleated giant cells, necrosis and lymphocytic lobulitis, as well as special stains for micro-organisms including Mycobacterium, other bacteria and fungus. PCR for Mycobacterium tuberculosis DNA was also performed in 19 cases. RESULTS: Granulomas were present in all cases (100%) while multinucleated giant cells were seen in 17 cases (65%), background inflammatory cell infiltrate in 23 cases (88%), predominantly lymphocytes in 18 cases (69%), significant lymphocytic lobulitis in 13 of 19 cases (68%) and necrosis in three cases (11%). Special stains and cultures for micro-organisms were all negative. Clinically, four cases (15%) were associated with duct ectasia, eight (31%) with abscess, and there was no such association in 14 cases (54%). Of the 19 cases with PCR for tuberculosis, one case showed Mycobacterium DNA in the sample, raising the possibility of occult tuberculosis infection. CONCLUSIONS: Granulomatous mastitis is a heterogeneous group of diseases with a diverse clinical picture and association. Most idiopathic cases are not associated with specific micro-organisms.

Fine-needle aspiration cytology of pseudoangiomatous stromal hyperplasia of the breast.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon lesion usually found in premenopausal women. Histologically, it is characterized by complex, anatomosing, empty slit-like spaces in a dense collagenous stroma. These pseudoangiomatous spaces are lined by monomorphic spindle cells of myofibroblastic differentiation. Cytological features of PASH are rarely discussed and reported, and may pose diagnostic challenge to surgical pathologists. Two cases of PASH are reported with emphasis on the FNAC features and cytologic differentiation from other benign fibroepithelial lesions.

Keratin expression in breast cancers.

Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.

Granulomatous mastitis: the histological differentials.

BACKGROUND: The management of granulomatous mastitis depends on the causative factor, and accurate diagnosis in distinguishing between idiopathic granulomatous mastitis (IGM) and tuberculous mastitis (TBM) is indispensable. This is particularly problematic in the cases of granulomatous mastitis in which the microbiological studies are negative. In this study, in a large cohort, the histological features for IGM and TBM were compared. METHODS: The histopathology files from the two participating hospitals were searched for cases of granulomatous inflammation of the breast over an 8-year period. The parameters assessed included age of patient, lesional size, systemic and local symptoms, and histological findings of inflammatory cells, granulomas, necrosis, multinucleated giant cells, fibrosis and calcifications. RESULTS: 29 cases of IGM and 33 cases of TBM were included in this study. A significant difference was seen between the two groups with regard to patient age (t=2.52, p<0.05) and lesional size (t=-5.56, p<0.01). TBM occurred in a significantly younger population, and demonstrated larger lesional sizes than IGM. There was no difference between the number of cases showing mass, local and systemic symptoms. Comparing the different histological features, the TBM group showed significantly more fibrosis, eosinophils and necrosis, whereas the IGM group showed significantly more plasma cells. Taking all the cases together as one group to evaluate the relationship between the histological parameters, there was significant positive correlation between eosinophils and fibrosis (r(s)=0.39, p<0.01), and negative correlation between vague and well-formed granulomas (r(s)=-0.38, p<0.01). CONCLUSION: TBM was more likely to occur in younger patients, with a larger clinical mass at presentation. Histologically, TBM tends to show more eosinophils and necrosis, and IGM is associated with more plasma cells. The characteristics of the granulomas and giant cells were not distinguishing features.

Increased p53 protein expression in malignant mammary phyllodes tumors.

The authors reviewed 143 cases (87 benign, 37 borderline, and 19 malignant) of mammary phyllodes tumors (PTs) and used immunohistochemistry to detect p53 protein product semi-quantitatively as negative, weak, moderate and strong (scored 0 to 3). For all PTs, an increasing trend of tumor size and malignancy was detected with increasing age. For p53 staining, 60 cases (42%) were negative, 55 (38%) stained weakly, 28 (13%) stained moderately, and 10 (7%) stained strongly. Of the 87 benign PTs, 41 (47%) were negative, 37 (43%) stained weakly, and 9 (10%) stained moderately. For the 37 borderline PTs, 16 (43%) were negative, 14 (38%) stained weakly, 6 (16%) stained moderately, and 1 (3%) stained strongly. Of the 19 malignant PTs, 3 (16%) were negative, 4 (21%) stained weakly, 3 (16%) stained moderately, and 9 (47%) stained strongly. The mean intensity score for p53 staining increased progressively from benign to borderline to malignant PT, with established statistical significance (P <.0001). This is significantly correlated with mitotic count but not stromal cellularity, pleomorphism, margin, and stromal overgrowth. When considering strong staining alone (score, 3), 47% of malignant, 3% of borderline, and none of the benign PTs were positive. The use of strong positive staining for diagnosing malignant PT gave positive and negative predictive values, specificity, and sensitivity of 90%, 92.5%, 99%, and 47%, respectively. Thus diffuse strong p53 protein staining can be used as a soft sign in assisting the diagnosis of malignant PT. Conversely, negative or weak staining of p53 protein in PT is of little discriminatory value. The role of p53 gene mutation in the malignant transformation of PT is unclear; but this may not be the sole mechanism as many malignant PT were p53 protein negative.

Increased c-kit (CD117) expression in malignant mammary phyllodes tumors.

Mammary phyllodes tumors are uncommon stromal neoplasms, and are divided into benign, borderline and malignant groups basing on histologic criteria. While benign phyllodes tumors may recur, borderline phyllodes tumors show higher propensity to recur locally and rarely metastasize, and malignant phyllodes tumors show even higher chances of local recurrences or distant metastases. c-kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117) and is a marker for gastrointestinal stromal tumors (GIST). With the advent of therapeutic agent targeted at this receptor for GIST, we investigated 179 phyllodes tumors (101 benign, 50 borderline, 28 malignant) for c-kit expression using immunohistochemistry. The staining was compared to the degree of malignancy, and to the degree of stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. The overall positive rate for c-kit was 29% (52/179) and 17% (17/101), 24% (12/50) and 46% (13/28), respectively, for benign, borderline malignant and frank malignant phyllodes and the differences between all categories were significant (chi2=13.844, P=0.001). In mammary phyllodes tumors, there was increasing c-kit expression with increasing degree of malignancy, up to 46% in malignant cases. This provides strong evidence that c-kit receptor mediated tyrosine kinase involvement in the pathogenesis of phyllodes tumors, and the therapeutic agent, STI571, Glivec, may be a potentially useful drug for its management.

Tumour angiogenesis and p53 protein expression in mammary phyllodes tumors.

We examined 186 phyllodes tumors (106 benign, 51 borderline, 29 malignant) for angiogenesis by assessing stromal microvessel density by the hot spot method and assessing p53 protein expression; we correlated these factors with stromal cellularity, margin status, nuclear pleomorphism, mitosis, and stromal overgrowth. Increased degree of malignancy in phyllodes tumors is associated with increased patient age and tumor size. Microvessel density and p53 protein expression also showed a similar increase with malignancy. Using a logistic regression model, microvessel density was shown to be useful in predicting malignancy in phyllodes tumors, independent of key criteria of stromal overgrowth, nuclear pleomorphism, and mitosis. Microvessel density showed correlation with stromal cellularity and margin status, suggesting an interrelationship between these parameters. P53 protein expression showed a positive correlation with microvessel density, suggesting possible overlap in the underlying mechanism of these two factors in the pathogenesis of phyllodes tumors. The numbers of recurrences and metastases are small in our series, and no significant difference was demonstrated in microvessel density and p53 protein expression compared with the primary. We conclude that microvessel density and p53 are useful as independent criteria in evaluating malignancy in phyllodes tumors.

Characterization of lesions of the breast with proton MR spectroscopy: comparison of carcinomas, benign lesions, and phyllodes tumors.

OBJECTIVE: Proton MR spectroscopy is a recently described technique with high sensitivity and specificity for differentiating breast carcinoma from benign lesions. We evaluated the possible relationship between spectroscopy results and the tumor proliferative index, angiogenesis, and HER2/neu oncogene overexpression. SUBJECTS AND METHODS. We prospectively evaluated 19 breast carcinomas, 21 benign breast lesions (including 18 fibroadenomas, one fibrocystic change, one hamartoma, and one papilloma), and six phyllodes tumors (four benign, two of borderline malignancy) using proton MR spectroscopy. All lesions were larger than 1.5 cm. Tumor Ki-67 proliferative index, tumor angiogenesis, and HER2/neu oncogene overexpression were evaluated by immunohistochemistry of the histologic material. RESULTS: Spectroscopy findings were positive in 17 (89%) of 19 carcinomas but negative for all benign lesions and phyllodes tumors (sensitivity, 89%; specificity, 100%). Significantly higher levels were obtained for all biologic parameters in carcinomas compared with benign lesions and phyllodes tumors. HER2/neu oncogene overexpression was present in 37% of carcinomas but not in other lesions. The two false-negative findings of breast carcinoma showed similar Ki-67 proliferative index and microvessel density compared with the remaining carcinomas, but both cases were negative for HER2/neu overexpression. CONCLUSION: Proton MR spectroscopy is useful in the in vivo characterization of breast masses when the lesion exceeds 1.5 cm in maximal dimension. Spectroscopy is unable to reveal benign breast lesions and phyllodes tumors of benign and borderline malignancy. We suggest that a false-negative spectroscopic result may be related to an absence of HER2/neu overexpression in carcinoma of the breast.

Biliary decompression by nasobiliary catheter or biliary stent in acute suppurative cholangitis: a prospective randomized trial.

BACKGROUND: Endoscopic drainage has replaced emergent surgery for biliary decompression in patients with acute cholangitis. The aim of this study was to prospectively compare the efficacy of the nasobiliary catheter and indwelling stent as temporary measures for biliary decompression in acute suppurative cholangitis caused by bile duct stones. METHODS: Over a 60-month period, 79 patients with acute cholangitis who required emergent endoscopic drainage were recruited. Indications for urgent drainage included any one of the following: temperature greater than 39 degrees C, septic shock with systolic blood pressure less than 90 mm Hg, increasing abdominal pain, and impaired level of consciousness. Patients who had previously undergone sphincterotomy or had coexisting intrahepatic duct stones were excluded. After successful bile duct cannulation, patients were randomized to receive either a nasobiliary catheter or indwelling stent without sphincterotomy for biliary decompression. Outcome measures included procedure time, complications, clinical response, and patient discomfort (scored with a 10-cm, unscaled visual analog score). RESULTS: Of the 79 patients, 5 were excluded because of previous sphincterotomy and intrahepatic duct stones, 40 were randomized to receive a nasobiliary catheter (NBC group), and 34 to receive indwelling stent (stent group). Demographic data were similar between the groups. All procedures were successful in the NBC group; there was one failure in the stent group. The mean (SD) procedure time was similar (NBC group 14.0 [9.3] minutes vs. stent group 11.4 [7.2] min). There were 2 ERCP-related complications in the NBC group. Four patients pulled out the nasobiliary catheter and one catheter became kinked. One stent occluded. There was a significantly lower mean (SD) patient discomfort score on day 1 after the procedure in the stent group (stent group 1.8 [2.6] vs. NBC group 3.9 [2.7]; p = 0.02 t test). The overall mortality rate was 6.8% (2.5% NBC group vs. 12% stent group). CONCLUSION: Endoscopic biliary decompression by nasobiliary catheter or indwelling stent was equally effective for patients with acute suppurative cholangitis caused by bile duct stones. The indwelling stent was associated with less postprocedure discomfort and avoided the potential problem of inadvertent removal of the nasobiliary catheter.

Laparoscopic repair for perforated peptic ulcer: a randomized controlled trial.

OBJECTIVE: To compare the results of open versus laparoscopic repair for perforated peptic ulcers. SUMMARY BACKGROUND DATA: Omental patch repair with peritoneal lavage is the mainstay of treatment for perforated peptic ulcers in many institutions. Laparoscopic repair has been used to treat perforated peptic ulcers since 1990, but few randomized studies have been carried out to compare open versus laparoscopic procedures. METHODS: From January 1994 to June 1997, 130 patients with a clinical diagnosis of perforated peptic ulcer were randomly assigned to undergo either open or laparoscopic omental patch repair. Patients were excluded for a history of upper abdominal surgery, concomitant evidence of bleeding from the ulcer, or gastric outlet obstruction. Patients with clinically sealed-off perforations without signs of peritonitis or sepsis were treated without surgery. Laparoscopic repair would be converted to an open procedure for technical difficulties, nonjuxtapyloric gastric ulcers, or perforations larger than 10 mm. A Gastrografin meal was performed 48 to 72 hours after surgery to document sealing of the perforation. The primary end-point was perioperative parenteral analgesic requirement. Secondary endpoints were operative time, postoperative pain score, length of postoperative hospital stay, complications and deaths, and the date of return to normal daily activities. RESULTS: Nine patients with a surgical diagnosis other than perforated peptic ulcer were excluded; 121 patients entered the final analysis. There were 98 male and 23 female patients recruited, ages 16 to 89 years. The two groups were comparable in age, sex, site and size of perforations, and American Society of Anesthesiology classification. There were nine conversions in the laparoscopic group. After surgery, patients in the laparoscopic group required significantly less parenteral analgesics than those who underwent open repair, and the visual analog pain scores in days 1 and 3 after surgery were significantly lower in the laparoscopic group as well. Laparoscopic repair required significantly less time to complete than open repair. The median postoperative stay was 6 days in the laparoscopic group versus 7 days in the open group. There were fewer chest infections in the laparoscopic group. There were two intraabdominal collections in the laparoscopic group. One patient in the laparoscopic group and three patients in the open group died after surgery. CONCLUSIONS: Laparoscopic repair of perforated peptic ulcer is a safe and reliable procedure. It was associated with a shorter operating time, less postoperative pain, reduced chest complications, a shorter postoperative hospital stay, and earlier return to normal daily activities than the conventional open repair.