Molecular profile of grade 3 endometrioid endometrial carcinoma: is it a type I or type II endometrial carcinoma?

Two types of endometrial carcinoma (EC) have been delineated on the basis of clinicopathologic studies. Low-grade endometrioid carcinoma (EEC) is the prototype of type I EC and is characterized by microsatellite instability and PTEN, K-ras, and/or β-catenin gene mutations, whereas type II EC is typically represented by serous and clear cell carcinomas (SCs/CCCs), the former frequently showing p53 mutations and c-erb-2 overexpression; however, the molecular profile of grade 3 EEC has not yet been well characterized. The goal of this study was to define the immunohistochemical and molecular profile of grade 3 EEC. We studied 25 patients with grade 3 EEC ranging in age from 35 to 87 (mean 61) years. At the time of initial diagnosis, 16 patients had stage I tumors, whereas 3, 5, and 1 had stages II, III, and IV tumors, respectively. Only 1 patient with stage IV tumor had disease in the peritoneum because of direct extend of tumor through the uterine wall. Two tissue microarrays were constructed from paraffin-embedded blocks and stained for MLH-1, MSH-2, p16, cyclin D1, C-erb-B2, WT-1, and p53. Loss of MLH-1 and MSH-2 was seen in 3 of 25 and 1 of 24 tumors, respectively; none showed loss of both. Diffuse p16 nuclear expression was found in 7 of 23 cases; diffuse and strong nuclear immunostaining for p53, cyclin D1, and Her-2 was seen in 9 of 24 neoplasms, 9 of 25, and 3 of 25 carcinomas, respectively. WT-1 was negative in all 25 tumors. One of the 3 grade 3 EECs with Her-2 overexpression showed gene amplification by fluorescence in situ hybridization analysis. No gene amplification for cyclin D1 was found. Follow-up information was available for all patients. Sixteen had stage I tumors. Of these patients, 11 were alive and well (AW), 3 died of disease (DOD), and 2 died of unrelated causes (DUC), with a mean follow-up time of 56 months (range, 24 to 96 mo); 2 of 3 patients with stage II tumors DOD, and 1 was AW with a mean follow-up time of 81 months (range, 6 to 66 mo); of the 5 patients with stage III tumors, 2 DOD, 1 was AW, 1 was alive with lung metastases, and 1 DUC [mean follow-up of 29 months (range, 12 to 74 mo)]; the only patient who had a stage IV tumor DOD 12 months later. Interestingly, patients with grade 3 EECs showing loss of MLH-1/MSH-2 had stage I tumors, and all were AW (60 to 84 mo). Seventy-seven percent (7 of 9) of patients with tumors showing cyclin D1 overexpression were stage I, and none died of disease, whereas 85% (6 of 7) of patients with p16-positive tumors were high stage (2 stage II, 3 stage III, and 1 stage IV), and 5 DOD. All but one of these patients had tumors that also had p53 overexpression. All 3 patients with Her-2 overexpression DOD (stages I, III, and IV). In conclusion, this study shows that grade 3 EEC shares with low-grade EEC the overexpression but not amplification of cyclin D1 and low frequency of Her-2 overexpression and amplification. Grade 3 EEC shares with SC the relatively common p53 and p16 overexpression and low frequency of loss of mismatch repair genes. However, in contrast to SC ECs, which often show WT-1, cyclin D1 amplification, and Her-2 overexpression and/or amplification, grade 3 EECs rarely overexpressed any of these markers. Moreover, in this study, patients with tumors showing loss of MLH-1/MSH-2 or cyclin D1 overexpression were more likely to have low-stage tumors (stage I), whereas patients with tumors that overexpressed p53, p16, or Her-2 were frequently associated with high-stage tumors.     

Is laparoscopic adrenalectomy feasible for adrenocortical carcinoma or metastasis?

OBJECTIVE: To review our experience with laparoscopic adrenalectomy (LA), to evaluate the effectiveness and safety of this procedure in patients with adrenal malignancy. PATIENTS AND METHODS: The study included patients who underwent LA from 1995 to 2002, with histologically identified adrenocortical cancer (ACC) or metastasis. Indications for LA were adrenal masses with no radiological evidence of involvement of the surrounding structures, or solitary metastasis with well-controlled primary cancer. The variables evaluated were: size of the lesion, operative duration, estimated blood loss, intraoperative complications, local, port-site and intra-abdominal recurrence, distant metastasis, and survival time. RESULTS: Fourteen malignant adrenal lesions in 205 LAs (7%) were confirmed with histological diagnoses that showed a primary ACC in six and metastasis in another seven (in one there was bilateral metastasis). The mean (sd) size of the malignant lesions was 5.9 (2.8) cm. The 12 unilateral procedures required a mean operative duration of 164 (47) min; the bilateral procedure lasted 215 min. There was one conversion to open surgery caused by local infiltration, whereas there were no intraoperative complications. The mean follow-up was 30 months, during which three patients died, one from endoperitoneal and trocar port-site seeding. CONCLUSION: When the malignancy is confined to the adrenal gland, LA seems to be a feasible option if the principles of oncological surgery are respected. Nevertheless, further investigations are required to evaluate the appropriateness of this operation.     

Intraoperative suspicion of gallbladder carcinoma in laparoscopic surgery: what to do?

The frequency of gallbladder cancer in Europe is less than 1% of all gallstone operations. With the introduction of laparoscopic surgery and the higher acceptance of this technique, patients with gallstones have gallbladder removal much earlier in their gallstone history. So the percentage of gallbladder carcinomas will decrease in the future. We report on our surgical procedures in patients with suspicious gallbladders having laparoscopic gallbladder removal, and how to proceed after the diagnosis of gallbladder carcinoma. From June 1990 to December 2001, we have performed 7,130 cholecystectomies in a single department. 47 of these patients (0.66%) were identified as having carcinoma. There were 40 females and 7 males, with a mean age of 70.6 years. In 17 cases (36%) there was a preoperative suspicion of malignancy. Most commonly, in 30 cases (64%), malignancy was suspected intraoperatively or diagnosed postoperatively after pathological examination of the resected gallbladder. We recommend removal with a bag for all gallbladders with a suspected wall or scleroatrophic calcified gallbladder area. In stage Tis or T1 laparoscopy + cholecystectomy is sufficient. For T2 and T3 we perform reoperation with liver bed resection and lymphadenectomy.     

Reflux laryngitis: a feasible indication for laparoscopic antireflux surgery?

Laparoscopic fundoplication is a routine surgical approach in the treatment of moderate or severe gastro-esophageal reflux disease. However, there are still contradictions regarding supraesophageal symptoms as an indication for surgery. The aim of this study was to determine the subjective symptomatic outcome and objective laryngeal findings after antireflux surgery in patients with pH monitoring proven reflux laryngitis. Between 1998 and 2002, 40 patients with reflux laryngitis underwent laparoscopic Nissen fundoplication. Patients were referred to surgery and followed-up by a specialist in otorhinolaryngology. Subjective symptoms were collected by a structured questionnaire at a median follow-up of 42 months. The objective laryngeal findings improved from the preoperative situation; at 12 months after surgery, the otorhinolaryngeal status was improved in 92.3% (n=24) of the patients. However, only 38.5% (n=10) of these patients evaluated an improvement in their voice quality. Of all, 62.5% (n=25) of the patients reported no or only mild cough or voice hoarseness symptoms postoperatively, 22.5% (n=9) had moderate symptoms, and 15.0% (n=6) suffered from difficult supraesophageal symptoms. Ninety-five percent of the patients regarded the result of their surgery excellent, good, or satisfactory. Of all, 82.5% (n=33) of the patients would still choose surgery, 7.5% (n=3) would abstain from surgery, and 10% (n=4) of the patients were hesitant about their choice. For patients suffering from supraesophageal symptoms of gastro-esophageal reflux disease with objective evidence of pharyngeal acid exposure, laparoscopic Nissen fundoplication provides a good and alternative adding to current treatment.     

Vascular calcification in the uremic patient: a cardiovascular risk?

BACKGROUND: Several factors suggest that the presence of vascular calcification (VC) is associated with a high risk of cardiac events in uremic patients. The aim of this study was to analyze the influence of VC on cardiac morbidity and mortality in our hemodialysis (HD) patients. METHODS: We studied 79 patients on HD: 43 males, mean age 48 +/- 15 years old, mean time on HD 83 +/- 63 months. The presence of VC was evaluated by radiologic series. Other cardiovascular risk factors analyzed were arterial hypertension, diabetes mellitus, obesity, cigarette smoking, anemia, and dyslipidemia. All patients underwent M-mode, two-dimensional, Doppler echocardiography. Patients were followed for two years. During this time, clinical information collected included predialysis blood pressure, incidence of ischemic heart disease, episodes of congestive heart failure, and mortality due to cardiovascular event. RESULTS: VC was observed in 55.7% of patients. Left ventricular hypertrophy, diastolic dysfunction, and cardiac valve calcification were significantly associated with VC. Ischemic heart disease (71.4% vs. 28.6%) and episodes of cardiac failure (0.41 vs. 0.18 per year; P < 0.05) appeared more frequently in the patient group with VC. VC was present in 80.6% of patients who developed episodes of heart failure. Eight patients died from cardiac disease; each of them had VC. CONCLUSION: The presence of VC can help to identify those HD patients with a higher cardiovascular risk.     

Cystadenoma and laparoscopic surgery for hepatic cystic disease: a need for laparotomy?

Background This study aimed to evaluate the incidence of cystadenoma diagnosis in a series of laparoscopic treatments for nonparasitic liver cysts, as well as its management. Methods From 1996 to 2004, 26 patients with a nonparasitic cyst of the liver were selected for laparoscopic liver surgery. Solitary nonparasitic liver cysts were, whenever feasible, completely enucleated. Results In four patients, the histopathologic examination showed a cystadenoma. Three patients with 13, 9, and 12-cm cysts, respectively, had undergone complete enucleation of the lesion, with no evidence of recurrence in the follow-up visit. One patient with multicystic liver experienced a recurrence and required an open hepatic resection. Conclusions When a complete laparoscopic enucleation of the cyst can be ensured, a strict follow-up assessment should be considered as the definitive treatment, with surgical intervention demanded only in the case of recurrence or high suspicion for malignancy.     

Vascular emergencies: what's in season?

Seasonality in ischaemic coronary artery disease is well documented with a winter/summer variation the commonest pattern. The influence of seasonal variation on events in other vascular territories is less well documented. The incidence of ruptured abdominal aortic aneurysm and emergency lower-limb ischaemia was analysed on a monthly basis over a 5-year period. A total of 372 ruptured abdominal aortic aneurysms occurred with a peak incidence in spring and autumn; however, no seasonal pattern was seen in the rate of emergency admissions with lower-limb ischaemia (n = 606). The explanation for this seasonal pattern in ruptured aneurysms is unknown. The haemodynamic adjustments to changes in climate require further study.     

Does laparoscopic adrenalectomy jeopardize oncologic outcomes for patients with adrenocortical carcinoma?

Background

For patients with known or suspected adrenocortical carcinoma (ACC), considerable controversy exists over the use of laparoscopic adrenalectomy. The purpose of this study was to assess recurrence and survival patterns in patients with a pathologic diagnosis of ACC treated with laparoscopic versus open adrenalectomy.

Methods

All patients referred to our center with a diagnosis of ACC from April 1, 1993 to May 1, 2012 were reviewed. Three groups of patients were compared: patients referred after laparoscopic resection elsewhere, patients referred after open resection elsewhere, and patients treated primarily at our center (all resected by the open approach). Clinical factors and overall, recurrence-free, and peritoneal recurrence-free survivals were compared between groups.

Results

During the study period, 46 patients presented after laparoscopic resection at an outside institution, 210 patients after open resection at an outside institution, and 46 patients were treated at our institution with open resection. Despite a smaller tumor size, patients treated laparoscopically developed peritoneal carcinomatosis more frequently compared to those treated with an open approach (p = 0.006 for number with peritoneal recurrence). When controlling for tumor stage, open-approach patients experienced superior recurrence-free and overall survival.

Conclusion

Despite typically being performed in patients with smaller tumors, laparoscopic adrenalectomy for ACC is associated with higher rates of recurrence, particularly peritoneal recurrence. For patients with known or suspected ACC, the oncologic benefits of open resection outweigh the short-term benefits of minimally invasive surgery.     

Is it time for a new TNM classification in esophageal carcinoma?

PURPOSE: To investigate the importance of lymph node yield (LNY) and the ratio of afflicted lymph nodes in esophageal carcinoma patients. PATIENTS AND METHODS: Between 1992 and 2004, 368 patients with esophageal carcinoma underwent surgery. Esophagectomy with curative intent was performed in 255 patients. Subtotal esophagectomy was performed either by thoracoabdominal (104 patients, 40.8%) or by transhiatal approach (151 patients, 59.2%). RESULTS: According to the LNY, patients were grouped into 3 groups. Twenty-six patients had < or =5, 96 had 6 to 18, and 113 had > or =19 dissected lymph nodes. In patients with nodal involvement (pN1), no significant overall survival differences were identified when stratifying subgroups according to the LNY. However, LNY had striking prognostic relevance in pN0 patients. The median overall survival was 23 (< or =5 LN), 36 (6-18 LN), and 88 months (> or =19). Even for patients with tripled LNY than the proposed minimum by the International Union Against Cancer (UICC) (18 LN), the rate of patients with detected lymph node metastases was only 46%, compared with 61% for patients with a LNY of > or =19 (P = 0.002). In pN1 patients classified according to the ratio of afflicted lymph nodes, median overall survival was 27 months in patients with a ratio <11%, compared with 15 and 13 months in patients with a ratio of 11% to 33% and >33%, respectively (P < 0.001). Multivariate Cox regression modeling identified ratio as the strongest independent prognostic factor for overall survival in pN1 and the LNY in pN0 patients. CONCLUSIONS: The minimal regional LNY of 6 lymph nodes as recommended by the UICC for esophageal carcinoma is far too low to appropriately stage the disease. The LNY and the ratio should be reflected in the next version of the UICC classification.     

Factors for conversion in laparoscopic cholecystectomy for acute cholecystitis: Is timing important?

Aim: Laparoscopic cholecystectomy is regarded as the gold standard treatment for gallstones. Conversion to open cholecystectomy is still common, and preoperative factors to predict conversion are useful in clinical practice. The aim of this study was to evaluate preoperative factors that could predict conversion in acute cholecystitis. Methods: This is a retrospective review of 83 patients with a diagnosis of acute cholecystitis who had laparoscopic cholecystectomy carried out as an emergency operation. Clinical, biochemical, and operative factors were analyzed for association with conversion. Results: A total of 83 patients were recruited to this study. The overall conversion rate was 33.7% (28/83). A longer duration of symptoms before presentation (P = 0.005) and surgery that was carried out over 48 h after admission (P = 0.022) were associated with a higher conversion rate. Emergency operations that began between 20.00 hours and 08.00 hours were also associated with a higher rate of conversion (P = 0.003). Other factors that were associated with conversion included male sex (P = 0.004), low albumin level upon admission (P = 0.024), prolonged prothrombin time (P = 0.040), and a raised serum total bilirubin level (P = 0.024). ASA scores were found to be similar in both groups (P = 0.509). Multivariate analysis by logistic regression showed that the independent risk factors for conversion in emergency laparoscopic cholecystectomy were surgery >48 h after admission (P = 0.028), emergency operation started between 20.00 hours and 08.00 hours (P = 0.026), and longer duration of symptoms before presentation (P = 0.034). Conclusions: Laparoscopic cholecystectomy should be carried out within 48 h of the patient being admitted for acute cholecystitis. The operation should be carried out during the daytime.