Multimodal treatment for squamous cell esophageal cancer

Preoperative chemotherapy (CTx) and combination radiochemotherapy (RTx/CTx) in patients with squamous cell esophageal carcinoma has recently received increasing attention. Although several prospective randomized trials could not show any benefit of neoadjuvant therapy in patients with potentially resectable tumors, preoperative CTx and combination RTx/CTx appear to increase the resection rate, the rate of complete tumor resection, and survival time in patients with locally advanced tumors. Most available studies show that a survival benefit from multimodal therapy can be expected primarily in patients who have a complete histopathologic response to preoperative treatment (i.e., no viable tumor in the resected specimen). Preoperative RTx/CTx increases the response rate and improves local tumor control compared to preoperative CTx alone, but it is associated with substantial perioperative mortality and morbidity. Distant tumor recurrences are insufficiently controlled with current combined modality protocols. These data indicate that neoadjuvant therapy must be considered investigational in patients with potentially resectable esophageal carcinoma but may soon become standard in patients with locally advanced tumors. Research must focus on modalities that allow pretherapeutic identification of those patients who will respond to neoadjuvant therapy. Furthermore, more effective and less toxic preoperative therapy regimens are required to increase the response rates and combat systemic recurrences. Finally, randomized prospective studies are essential to assess the role, extent, and timing of surgical resection for the combined modality approach to patients with squamous cell esophageal carcinoma.

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Resumen La quimioterapia preoperatoria (CTx) y la combinación radioquimioterapia (RTx/CTx) en los pacientes con carcinoma escamocelular del esófago se constituye en motivo reciente de atención. En tanto que varios ensayos prospectivos y randomizados no han logrado demostrar beneficio de la terapia neoadyuvante en pacientes con tumores potencialmente resecables, la CTx preoperatoria o la combinación RTx/CTx parece aumentar la tasa de resección, la tasa de resección tumoral completa y el tiempo de sobrevida en los pacientes con tumores localmente avanzados. La mayoría de los estudios disponibles demuestra que el beneficio de supervivencia puede esperarse en los pacientes que exhiben respuesta histopatológica completa al tratamiento preoperatorio, o sea aquellos en que no se encuentran células viables en el espécimen de resección. Una combinación de RTx/CTx preoperatoria aumenta las tasas de respuesta y mejora el control tumoral local en comparación con la CTx preoperatoria sola, pero también se asocia con morbilidad y mortalidad perioperatorias considerables. Las recurrencias tumorales a distancia todavía no pueden ser bien controladas mediante los protocolos de terapias combinadas actualmente en boga. Estos datos indican que la terapia neoadyuvante debe ser considerada todavía como de tipo investigativo en los pacientes con carcinoma esofágico potencialmente resecable, pero que tal vez pronto puedan convertirse en tratamiento estandarizado en los pacientes con tumores localmente avanzados. La investigación debe enfocarse sobre las modalidades que permiten la identificación preterapéutica de aquellos pacientes que habrán de responder a la terapia neoadyuvante. Por lo demás, se requieren regímenes terapéuticos preoperatorios más eficaces y menos tóxicos con el objeto de aumentar las tasas de respuesta y de controlar las recurrencias sistémicas. Finalmente, es esencial ejecutar estudios prospectivos randomizados para determinar el rol, la magnitud y el momento de realizar la resección quirúrgica en el aproche multimodal de los pacientes con carcinoma escamocelular del esófago.

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Résumé L'association chimiothérapie et radiochimiothérapie préopératoire a reçu beaucoup d'attention dernièrement. Alors que plusieurs études prospectives randomisées n'ont pu démontrer les bénéfices d'une thérapeutique néoadjuvante chez des patients ayant une tumeur potentiellement résécable, la chimiothérapie seule ou associée à la radiothérapie préopératoires semble augmenter le taux de résécablitié et la survie chez les patients avant des tumeurs locorégionates. La plupart des études disponibles démontrent une amélioration de survie lorsque la thérapeutique est multimodale, lorsque la réponse histologique initiale à la chimiothérapie préoperatoire est positive, c'est à dire, s'il n'y ait aucune tumeur visible dans la pièce opératoire. La radiochimiothérapie préopératoire augmente le taux de réponse et améliore le contrôle local, par rapport à la chimiothérapie seule, mais elle augmente également la mortalité et la morbidité périopératoires. Les métastases à distance ne sont pas bien controlées par la radiochimiothérapeutique associée. Ces donnécs indiquent que la thérapeutique néoadjuvante est encore au stade expérimental chez le patient ayant un cancer de l'oesophage résecable, mais est en voie de devenir la thérapeutique de l'avenir en ce qui concerne les tumeurs locorégionales. La recherche actuelle cherche à identifier les patients qui répondront au mieux à cette thérapeutique néoadjuvante. De plus, des drogues moins toxiques et plus efficaces sont nésessaires pour améliorer le taux de réponse et combattre les récidivcs systémiques. Enfin, des études randomisécs sont essentielles pour évaluer le rôle, l'étendue et le meilleur moment de la résection chirurgicale dans cette optique thérapeutique chez le patient ayant un cancer épithélial de l'oesophage.

     

Operable squamous esophageal cancer: Current results from the East

From 1958 through 1992 a total of 3603 patients underwent surgery for esophageal squamous cell carcinoma in our department. Among these patients 3099 resections were performed, for an overall resectability of 86.0%. Of the resections, 2341 (75.5%) were classified as curative and 758 (24.5%) palliative. The overall morbidity and 30-day mortality rates were 23.4% and 3.8%, respectively. For resected cases the mortality was 4.0%. The more than 5-year follow-up rate of patients with resection was 97%. The actual 5-, 10-, and 15-year survival rates were 30.4%, 23.6%, and 17.9%, respectively. Recurrence or metastasis remained the cause of death in 60.9% and 25.5% of patients who lived longer than 5 years and 15 years, respectively, after operation. The TNM staging, lymph node metastasis, extraesophageal invasion, tumor differentiation, tumor length, and category of operation were major determinants influencing long-term prognosis. The left thoracotomy approach was used exclusively in 2613 cases (84.3% of all resected cases) in which intrathoracic resections and anastomoses were performed. The stomach was used as a substitute for the esophagus in 98.8% of the resected cases compared with 1.2% colon transplants. The former procedure was far safer than the latter. Above-average results presented in this paper support the surgical policy we have pursued thus far: to resect the primary tumor by partial or subtotal esophagectomy and to remove all lymph nodes wherever they were found in all patients with disease earlier than stage III. Early detection and early treatment no doubt are the only ways to materially improve the long-term surgical results.

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Resumen Entre 1958 y 1992, 3.603 pacientes fueron sometidos a cirugía por carcinoma escamocelular del esófago en nuestro departamento; se efectuaron 3.099 resecciones, para una tasa global de resectabilidad de 86%. De las resecciones, 2.341 (75.5%) fueron clasificadas como curativas y 758 (24.5%) como paliatives. Las tasas globales de morbilidad y de mortalidad a 30 días fueron 23.4% y 3.8%, respectivamente.La mortalidad para los casos resecados fue 4.0%. La rata de seguimiento para los pacientes operados más de 5 años atrás fue 97%. Las tasas actuariales de sobrevida a 5, 10 y 15 años fueron 30.4%, 23.6% y 17.9% respectivamente.La recidiva y las metástasis se mantuvieron como causas de muerte en 60.9% y 25.5% respectivamente de los pacientes que sobrevivieron más de 5 años y 15 años luego de la operación.La estadificación TNM, las metástasis ganglionares, la invasión extraesofagiana, el grado de diferenciacíon tumoral, la longitud del tumor y la categoría de la operación fueron los principales factores determinantes de pronóstico a largo plazo.Se utilizó el abordaje por toracotomía izquierda exclusiva en 2.613 casos (84.3% de la totalidad de casos resecados) en los cuales se efectuó resección intratorácica con anastomosis. El estómago fue utilizado como sustituto del esófago en 98.8% de los casos resecados, en contraste con el trasplante de colon que se hizo en 1.2% de los casos. El uso del estómago como sustituto es, por mucho, un procedimiento bastante más seguro.

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Résumé Entre 1958 et 1992, 3603 patients ont été opérés d'un cancer épidermoïde de l'oesophage. Parmi eux, 3099 résections ont pu être effectuées avec un taux de résecabilité de 86%. Parmi ces résections, 2341 (75.5%) ont été considérées comme curatives, et 758 (24.5%) ont été considérées comme palliatives. La morbidité et la mortalité à 30 jours ont été respectivement de 23.4% et de 3.8%. En cas de résection, la mortalité a été de 4%. Quatre-vingt dix-sept pourcent des patients ont été suivis pendant plus de 5 ans. Les taux de survie actuarielle à 5, 10 et 15 ans ont été respectivement de 30.4%, 23.6%, et 17.9%. La récidive ou les métastases ont été la cause principale de décès chez 60.9% et 25.5% des patients ayant vécu plus de 5 et 15 ans après l'opération. Le stade TMN, l'existence de métastases ganglionnaires, l'extension extraoesophagienne, la différentiation tumorale, la longueur de la tumeur et le type de l'intervention ont été des déterminants majeurs du pronostic. Une thoracotomie gauche a été utilisée exclusivement chez 2613 patients (84.3% de toutes les résections en cas de résection et anastomoses intrathoraciques). Une gastroplastie a été utilisée chez 98.8% des cas de résection et un transplant colique seulement dans 1.2% des cas. II n'y avait aucune différence entre les deux en ce qui concerne les complications. Les résultats nettement au-dessus de la moyenne dans cette série sont en faveur de la chirurgie: réséquant la tumeur primitive par une oesophagectomie totale ou subtotale, accompagnée d'un curage lymphatique aussi complet que possible chez les patients stade III ou moins. La détection et le traitement précoces sont sans doute les seules façons d'améliorer les résultats à long terme.

     

Staging of non-small cell lung cancer: clinical value of positron emission tomography and mediastinoscopy

We report about a MEDLINE research from 2000 to 2005 with the key words 'positron emission tomography AND/OR mediastinoscopy'. The search identified 448 potential studies. Out of the published data sensitivity, specificity, positive and negative predictive value, and accuracy for mediastinal lymph node staging by FDG-PET ranged from 58%-94%, 76%-96%, 43%-95%, 56%-98% to 74%-91%, respectively. With corresponding values of 80%-96%, 100%, 100%, 92%-97%, and 94%, respectively, for mediastinoscopy. FDG-PET improved the rate of detection of local and distant metastases in 12% to 62% and changed the management of treatment in 8% to 60% of patients with NSCLC. Our study shows that in the diagnostic strategy of patients with NSCLC, additional FDG-PET can prevent non-therapeutic thoracotomy in a significant number of cases. If FDG-PET imaging and CT scan is negative for mediastinal lymph node involvement routinely mediastinoscopy can be omitted and thoracotomy can immediately be performed. In patients with negative FDG-PET scan, but positive CT scan, histologic verification by invasive methods can individually be considered. Patients with positive FDG-PET scan mediastinoscopy still remain a reliable standard for exact lymph node staging. By incorporating FDG-PET in clinical staging unnecessary exploratory thoracotomies, and mediastinoscopy, can be omitted.     

Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition.     

Staging of prostate cancer. Accuracy of transrectal ultrasound enhanced by prostate-specific antigen.

Transrectal ultrasound (TRUS) has shown some promise in the staging of prostate cancer, while prostate-specific antigen (PSA) alone is insufficient. By combining prospective TRUS evaluation with retrospective PSA analysis, we demonstrated an increased accuracy of this combined staging method over TRUS alone. In 48 men undergoing radical prostatectomy, TRUS was performed and PSA measured pre-operatively. On the basis of TRUS, tumours were classified as contained or uncontained. An "expected" PSA value was then calculated for each patient as follows: K x volume of hypoechoic area +0.07 x prostate volume where K = 2.1 if the combined Gleason score of the initial biopsy was > or = 7, or 4.2 if the score was < or = 6. If a patient's pre-operative PSA value was less than or equal to the expected PSA, his tumour was judged to be contained. Staging by both TRUS and PSA was combined, so that if the tumour was judged uncontained by either parameter, the combined prediction was uncontained. Results of the combined staging were: sensitivity 84%, specificity 82%, positive predictive value 94%, negative predictive value 60%, accuracy 83%. This PSA formula, which takes into account the size and grade of the lesion rather than an arbitrary cut-off value, enhances the local staging of prostate cancer by TRUS.     

Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation

Initial trials of irradiation and chemotherapy followed by operation for squamous carcinoma of the esophagus have produced encouraging results. Over the past three years, with palliative and curative intent, we have treated 27 unselected patients initially with two courses of chemotherapy (fluorouracil and either cisplatin, mitomycin, or cisplatin and vincristine sulfate) given 29 days apart and 3000 rad (30 Gy) of radiation. Ten patients have then undergone esophageal resection and two patients have undergone esophageal bypass. Results are compared with those of 70 unselected historical control patients treated since 1979. Survival at 30 months was significantly improved for multimodality-treated patients (21.4% +/- 10.1%, mean +/- SEM) when compared with historical control patients (4.8% +/- 2.7%). Twenty-four percent of multimodality-treated patients had complete remission of all tumor. These data indicate that overall therapy for carcinoma of the esophagus has been improved in our institutions.     

Preoperative Staging of Rectal Cancer With MRI: Accuracy and Clinical Usefulness

Background: Preoperative staging is essential for planning of optimal therapy for patients with rectal cancer. Recently, magnetic resonance imaging (MRI) is used frequently because of its benefits of clear pelvic image are better than other diagnostic methods. The purpose of this study was to determine accuracy rates and clinical usefulness of MRI in preoperative staging of rectal cancer.Methods: Between February, 1997, and December, 1999, 217 patients with histologically proven rectal cancer were staged preoperatively and had surgical resections performed. MRI criteria for depth of invasion was determined by the degree of disruption of the rectal wall. Metastatic perirectal lymph nodes were considered to be present if they showed heterogenous texture, irregular margin, and enlargement (.10 mm).Results: The accuracy of the MRI for determining depth of invasion was 176/217 (81%) and regional lymph node invasion was 110/217 (63%). In the T stage, accuracy rate of T1 was 3/4 (75%), T2 was 20/37 (54%), T3 was 141/162 (87%), and T4 was 12/14 (86%), respectively. The specificity of lymph node invasion was 45/110 (41%) and the sensitivity was 91/107 (85%). The accuracy rate of regional lymph node involvement was 136/217 (63%). T1 and T2 were overstaged in 1/4 (25%) and 17/37 (46%), respectively, and T3 was understaged in 15/162 (9.2%). The accuracy rate to detect metastatic lateral pelvic lymph node was 4/14 (29%) after lateral pelvic lymph node dissection was done in 14 patients under MRI. The accuracy rate in assessing levator ani muscle tumor involvement was 8/11 (72%).Conclusions: MRI showed a good, comparable accuracy rate for determining depth of tumor invasion, compared with transrectal ultrasonography, which still has a low accuracy rate for detecting metastatic lymph node. MRI with endorectal coil may increase the accuracy rate of T1 and T2 lesions. In addition, clear sagittal and coronal sectional pelvic images can give a lot of information about adjacent organ invasion or any invasion of levator ani muscle. MRI can be useful for choosing an appropriate extent of lymph node dissection and type of surgery.     

Clinical significance and prognostic value of apoptosis related proteins in superficial esophageal squamous cell carcinoma

Background: The purpose of the present study was to examine the expression of cell cycle regulators [p53, p21^WAF1/CIP1 (p21), and Rb] and apoptosis related proteins Bax and Bcl-X_L and to evaluate the relationship between their expressions and clinicopathological findings in patients with superficial squamous cell carcinomas of the esophagus.Methods: We immunohistochemically investigated the expression of p53, p21, Rb, Bax, and Bcl-X_L in 79 patients with superficial esophageal carcinoma.Results: p21 overexpression was found in mucosal carcinoma (P = 0.05) and a high Bcl-X_L score was observed for submucosal carcinoma (P = 0.03). The patients with high Bcl-X_L score had more frequent lymphatic invasion and lymph node metastasis than did those with low Bcl-X_L score (P < 0.05). Univariate analysis revealed significantly shorter survival in patients with high Bcl-X_L expression than in those with low Bcl-X_L expression, but Bcl-X_L expression was not identified as an independent prognostic factor by multivariate analysis.Conclusions: Because Bcl-Xl expression correlated well with depth of tumor invasion, lymphatic invasion, and lymph node metastasis, examination of Bcl-X_L expression will help to estimate the properties in superficial squamous cell carcinoma of the esophagus.     

Staging and management of lung cancer: Sleeve resection

Sleeve lobectomy is a lung-saving procedure usually indicated for central tumors for which the alternative is a pneumonectomy. It preserves normal lung tissue and may enable pulmonary resection to be done in selected patients with inadequate cardiac or pulmonary reserve. One experience extends from January 1972 to December 1991, during which time 142 patients underwent a variety of sleeve resections for bronchogenic neoplasms. The majority of operations were upper-lobe sleeve resections (N=110) and most procedures were considered complete and potentially curative (87%). There were three postoperative deaths (surgical mortality of 2.5%) and prolonged atelectasis was the most common major complication (N=9). Follow-up was complete for the 139 survivors (mean follow-up time of 2,149 days) and overall survival was 46% at 5 years and 33% at 10 years. Five- and 10-year survivals for patients with stage I disease were 63% and 52%, respectively, while only 14% of patients with stage III disease survived 5 years. Local recurrences occurred in 23% of patients but when the resection had been complete, this incidence was 17% (21/124). These results indicate that sleeve resection is an adequate cancer operation for both compromised and uncompromised patients. Operative mortality, survival, and incidence of local recurrence are not different than what is seen after more conventional procedures.

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Resumen La lobectomía con resección en manguito es un procedimiento que preserva tejido pulmonar y que usualmente está indicado para tumores de ubicación central para los cuales la alternativa es la neumonectomía. Al conservar parenquima pulmonar, puede lograrse la resección en pacientes seleccionados con reserva funcional cardiopulmonar inadecuada. Nuestra experiencia se extiende entre enero de 1972 hasta diciembre de 1991, periodo durante el cual 142 pacientes con tumores broncogénicos fueron sometidos a una variedad de resecciones en manguito. La mayoría fueron resecciones en manguito del bronquio del lóbulo superior (N = 110) y casi todos fueron considerados como completas y potencialemte curativas (87%). Se registraron tres muertes postoperatoria (mortalidad quirúrigica de 2.5%); la atelectasis prolongada constituyó la complicación más común (N = 9). El seguimiento fue completo para los 139 sobrevivientes (promedio de seguimiento de 2.149 días) y la tasa global de sobrevida fue de 46% a 5 años y de 33% a 10 años. La sobrevida a 5 y 10 años para los pacientes en estados I fue 63% y 52%, respectivamente, mientras sólo 14% de los pacientes con estado II sobrevivieron 5 años. Se observó recurencia local en 23% de los pacientes, pero cuando la resección fue completa, la tasa fue de 17% (21/124). Estos resultados indican que la resección en manguito es una operación oncológica adecuada tanto para los pacientes en buen estado general como para los que tienen compromiso funcional. La mortalidad operatoria, las tasas de sobrevida y de recurrencia local no son diferentes de las que se observan luego de procedimientos más convencionales.

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Résumé La lobectomie en manchonnage est une méthode de résection indiquée en cas tumeur centrale pour laquelle la seule alternative aurait été une pneumonectomie. Cette intervention conserve du tissu pulmonaire normal et convient aux patients ayant une réserve cardiaque ou pulmonaire limite. Notre expérience s'étend de Janvier 1972 à Décembre 1991, période durant laquelle 142 patients ont eu une résection en manchonnage pour cancers bronchopulmonaires divers. La majorité des interventions étaient des résections du lobe supérieur (n = 110) et la plupart des interventions ont été classées comme curatives ou potentiellement curatives (87%). Il y a eu 3 morts postopératoires (mortalité chirurgicale de 2.5%) et une atélectasie prolongée a été la complication la plus fréquente (n = 9). Le suivi a été complet pour les 139 survivants (suivi moyen de 2149 jours); la survie globale a été de 46% à 5 ans et 33% à 10 ans. La survie à 5 et à 10 ans chez les patients ayant une maladie stade I a été respectivement de 63% et 42% alors que seulement 14% des patients stade III ont survecu 5 ans. Les récidives locales sont survenues chez 23% des patients mais lorsque la résection était complète, cette incidence a été de 17% (21/124). Ces résultats indiquent que la résection en manchonnage est une intervention suffisante pour la plupart des patients. La mortalité opératoire, la survie et l'incidence des récidives locales ne sont pas différentes de celles observées avec des procédés conventionnels.

     

Prognostic value of node skip metastasis on esophageal cancer: A systematic review and meta-analysis

The association between NSM and prognosis of esophageal cancer remains controversial, though several studies have been conducted drawing their own conclusion. Therefore, we firstly carried out this meta-analysis aiming to explore the association. We performed a comprehensive literature search online, including PubMed, Embase and Web of Science. We selected deaths at 5 years and hazard ratio (HR) with 95% (CI) to perform the meta-analysis with Review Manager 5.3, predicting value of clinic-pathological features in NSM also been analyzed. A total of 7 studies were finally enrolled in this study. NSM, defined by either JSED criterion or anatomical compartment criterion, neither showed significant prognostic value on OS of esophageal cancer (P = 0.64), (P = 0.24). Subgroup analysis of JSED criterion, NSM was not a prognostic factor in solitary node metastasis patients (P = 0.39), whereas NSM demonstrated a poor prognostic factor (P = 0.01) for ESCC. Subgroup analysis according to anatomical criterion, NSM was a favorable factor for OS in middle thoracic ESCC (P = 0.003). Pathological N1 status was found to be a risk factor for NSM (P < 0.00001) according to JSED criterion and middle thoracic ESCC was identified as a predictor for NSM (P = 0.0003) according to anatomical compartment criterion. According to JSED criterion, NSM demonstrated poor prognosis on ESCC and N1 status was a risk factor for NSM. Concerning the anatomical compartment criterion, a favorable prognosis of NSM was found in middle thoracic ESCC and NSM was prone to occur in middle thoracic ESCC. CRD42021219333.     

Accuracy of Laparoscopy in the Diagnosis and Staging of Lymphoproliferative Diseases

Laparoscopy seems to be playing an emerging role in the management of lymphoproliferative diseases. The aim of this study was to prospectively analyze personal experience evaluating the role and limits of laparoscopy in the management of lymphomas. From July 1993 to December 2000, 131 consecutive patients were referred to our institution for primary diagnosis (group A, n = 70), suspected relapse (reassessment) (group B, n = 54), or staging/restaging of lymphoproliferative diseases (group C, n = 7). Diagnostic and/or operative laparoscopy was performed in all patients. To assess the accuracy of laparoscopy, the results were analyzed according to the indications for surgery. In all, 128 procedures were completed laparoscopically (95.5%). Conversion was required in 7 cases (5.1%). Causes of the conversions were severe obesity (body mass index 62.5), uncontrolled intraoperative bleeding (HIV+), nondiagnostic tissue sampling (2 cases), perisplenic inflammation and perisplenic abscesses (3 cases). The results of this study highlight the safety of diagnostic and staging laparoscopy and laparoscopic splenectomy in patients with lymphoproliferative diseases (major complications 2.9%, perioperative mortality 0%). In all, 96.4% of patients from group A and 100% of patients from group B were treated on the basis of laparoscopic findings. No false negative diagnosis occurred. Laparoscopy may become the gold standard in the management of lymphoproliferative disease in the following settings: for the differential diagnosis of hepatic and/or splenic focal lesions; when percutaneous needle biopsy fails and/or genetic analysis is needed for therapeutic decision; for the primary diagnosis and abdominal staging of patients with diffuse retroperitoneal lymphadenopathy in the absence of peripheral lymphadenopathy; for cases of abdominal restaging after concurrent chemoradiotherapy and in cases of suspected relapse when percutaneous biopsy is not technically possible; and for patients with lymphoproliferative disease when splenectomy is required. Marked splenomegaly with perisplenic inflammatory reaction and lymphadenopathy in HIV+ patients should be considered possible causes of failure of the laparoscopic approach.