Mario Guerrieri

The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue

Classically, adult humans have been considered not to possess active brown adipose tissue (BAT). However, positron‐emission‐tomography has shown fluorodeoxyglucose uptake that is distributed in such a way (e.g., in the neck) that it would seem to be BAT. Until now this has not been supported by direct evidence that these areas truly represented BAT, that is, the presence of the BAT‐unique uncoupling protein‐1 (UCP1). Samples of adipose tissue from the neck of 35 patients undergoing surgery for thyroid diseases were obtained and analyzed. In 1/3 of the subjects (the younger and leaner), distinct islands composed of UCP1 immunoreactive brown adipocytes could clearly be discerned, accounting for up to 1/3 of all adipocytes. The brown‐adipose islands were richlysympathetically innervated (indicating acute central control); adjacent white adipose areas were not. The capillary density was high, implying a high capacity for oxygen delivery. Cells with features of brown adipocyte precursors were found in pericapillary areas. These data demonstrate that human adults indeed possess BAT and thus imply possibilities of future therapeutic strategies for the treatment of obesity, including maintenance of brown adipocytes and stimulation of the growth of preexisting brown precursors.—Zingaretti, M. C., Crosta, F., Vitali, A., Guerrieri, M., Frontini, A., Cannon, B., Nedergaard, J., Cinti, S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 23, 3113–3120 (2009). www.fasebj.org

Long‐term results in patients with T2–3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery

Local excision after radiotherapy for node‐negative low rectal cancer may be an alternative to radical excision. This study evaluated the results of local excision in patients with small (less than 3 cm in diameter) T2 and T3 distal rectal tumours following neoadjuvant therapy.

Long-term results of laparoscopic versus open resections for rectal cancer for 124 unselected patients

Background: Controversy continues to surround laparoscopic rectal resection for malignancy. A longer follow-up period is required to evaluate the long-term efficacy of the procedure and its impact on survival. Furthermore, no data from ongoing randomized controlled trials are yet available. The aims of this study were to compare long-term outcomes for unselected patients undergoing either laparoscopic or open rectal resection for cancer. Methods: A series of 124 unselected consecutive patients with rectal cancer, who underwent surgery by the same surgical team, have been included in this study. Patients with T1N0 tumors underwent local excision, and emergency cases were excluded from the study. Written consent was submitted by each patient, and inclusion in either group (laparoscopic or open) was left to the patient’s choice. The laparoscopic approach was chosen by 81 patients, and 43 patients chose open surgery. All the patients underwent preoperative radiotherapy (5,040 cGy), performed in selected cases with chemotherapy (for patients younger than 70 years). The following parameters were compared between the two groups: length of the surgical specimen, clearance of the margins of the specimen, number of lymph nodes identified, local recurrence rate, incidence of distant metastases, and survival probability analysis. The mean follow-up period for both groups was 43.8 months (range, l–9 years). Results: We performed 60 laparoscopic and 27 open anterior resections, as well as 21 laparoscopic and 16 open abdomino perineal resections, respectively. No mortality occurred in either group. The mean length of the resected specimens was 24.3 cm in the laparoscopic group and 23.8 cm in the open group (p = 0.47). The mean tumor-free margin was 3.0 cm in the laparoscopic group and 2.8 cm in the open group (p = 0.57), and the mean number of lymph nodes identified was 10.3 in the laparoscopic group and 9.8 in the open group (p = 0.63). Of the 124 patients, 86 (52 laparoscopic and 34 open) were included in out study. We excluded patients who underwent a palliative resection (6 laparoscopic and 6 open patients) or conversion to open surgery (n = 10) and patients who had undergone surgery in the past year (n = 16). One laparoscopic patient was lost to follow-up evaluation, whereas three laparoscopic patients and one open patient died of causes not related to cancer. No wound recurrence was observed. The local recurrence rate after laparoscopic resection was 20.8%, as compared with 16.6% after open resection (p = 0.687). Distant metastases occurred in 18.2% of the patients in the laparoscopic group, as compared with 21.2% in the open group (p = 0.528). Cumulative survival probability was 0.709 after laparoscopic resection after LR and 0.606 after open resection (p = 0.162), whereas for Dukes’ stages A, B, and C in the laparoscopic group versus the open group, it was 0.875 vs 0.889 (p = 0.392), 0.722 vs 0.584 (p = 0.199), and 0.500 vs 0.417 (p = 0.320), respectively. At this writing 20 laparoscopic patients (62.5%) and 20 open patients (60.6%) are disease free (p = 0.623). Conclusions: Oncologic surgical principles were respected. Long-term outcome after laparoscopic resection of rectal cancer was comparable with that after conventional resection. We should wait to draw conclusive scientific statements until the completion of ongoing international radomized controlled trials.

Laparoscopic vs open hemicolectomy for colon cancer

BackgroundThe role of laparoscopic resection in the management of colon cancer is still a subject of debate. In this clinical study, we compared the perioperative results and long-term outcome for two unselected groups of patients undergoing either laparoscopic or open hemicolectomy for colon cancer.MethodsThis prospective nonrandomized study was based on a series of 248 consecutive patients operated on by the same surgical team using the same type of surgical technique for right (RHC) and left (LHC) hemicolectomy, excluding segmental resections; the only difference was the type of access, which was either laparoscopic or open. The choice of type of access was left up to the patient after he or she had read the informed consent form. Operative time, length of stay, complications, and long-term outcome for the two groups were compared. Follow-up time ranged between 12 and 92 months (mean, 42).ResultsBetween March 1992 and January 2000, 140 patients underwent a laparoscopic hemicolectomy (55 RHC and 86 LHC); at the same time, 107 patients (44 RHC and 63 LHC) were treated via an open approach. There were no conversions to open surgery in the laparoscopic RHC group, but six patients (7%) in the laparoscopic LHC group were converted. The mean operative time for laparoscopic surgery was significantly longer than the time for open surgery (190 vs 140 min for RHC, 240 vs 190 min for LHC); however, with increasing experience, this time decreased significantly. The mean hospital stay for the patients who underwent laparoscopic procedures was significantly shorter in both the RHC and the LHC groups (9.2 vs 13.2 days for RHC, 10.0 vs 13.2 days for LHC). No statistically significant difference between the two laparoscopic and open groups was observed for the major complication rate (1.9% vs 2.3% for RHC, 7.5% vs 6.3% for LHC). The patient in the laparoscopic RHC group were lost to follow-up. The local recurrence rate was lower after laparoscopic surgery in both arms (5.4% vs 9% for RHC, 1.5% vs 7.5% for LHC), but the differences were not statistically significant. Two port site recurrences were observed in the laparoscopic groups, one after RHC (2.7%) and one after LHC (1.5%). Metachronous metastases rates were similar for the two groups (16.2% vs 15.1% for RHC, 4.4% vs 5.7% for LHC). Cumulative survival probability at 48 months after laparoscopic RHC was 0.865, as compared to 0.818 after open surgery, and 0.971 after laparoscopic LHC, as compared to 0.887 after open surgery.ConclusionThese results suggest that laparoscopic hemicolectomy for colonic cancer can be performed safely, with morbidity, mortality, and long-term results comparable to those of open surgery.

Long-term Results of Patients with pT2 Rectal Cancer Treated with Radiotherapy and Transanal Endoscopic Microsurgical Excision

AbstractAnterior resection and abdomino-perineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. Local recurrence rates of 10% to 14% are described after these conventional procedures. Preoperative neoadjuvant radiotherapy reduces local failure. Because local excision techniques can be applied to treat early rectal cancer in selected patients, we evaluated the results of preoperative high-dose radiotherapy and transanal endoscopic microsurgical excision (TEM) in patients with T2 rectal cancer. All patients underwent preoperative irradiation with 5,040 cGy, divided over 5 weeks. Fourty days after completion of radiotherapy, the patients underwent complete full-thickness local excision of the rectal lesion including adjacent perirectal fat by TEM. The patients were followed for up to 8 years. Thirty-five patients, with pT2 rectal cancer as determined by pathological examination of the surgical specimen were enrolled in the present study. The tumors were responsive to preoperative radiotherapy in 82.8% of cases. No intraoperative complications and no conversion to open surgery were observed. No major complications and no mortality occurred during the 60-day postoperative period. Minor postoperative complications were observed in 5 patients (14.3%). The median follow-up of the patients was 38 months (range 24 to 96 months). One local recurrence (2.85%) was noted. The probability of surviving at 96 months after completion of treatment was 83%. Local excision by TEM combined with preoperative high-dose radiotherapy can achieve results similar to those observed after conventional surgery in patients with pT2 rectal cancer.

Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial.

BACKGROUND: Transanal local excision has been suggested as an attractive approach for patients with rectal cancer who show a major clinical response after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the impact of transanal local excision on the local recurrence of rectal cancer in patients who had a major clinical response after preoperative chemoradiotherapy. DESIGN: Sequential 2-stage phase II study for early efficacy. SETTING: Multicenter study. PATIENTS: Patients with clinical T3 or low-lying T2 rectal adenocarcinoma that showed a major clinical response after a preoperative chemoradiotherapy. Eligible patients underwent a full-thickness transanal local excision. According to their histopathology, the patients staged as ypT0-1 were observed, while the remaining patients were recommended to undergo a subsequent total mesorectal excision. MAIN OUTCOME MEASURES: A local recurrence rate of ⩽5% was set as a successful rate for stopping the trial early after the first stage. RESULTS: The study group included 63 patients. Before chemoradiotherapy, patients were staged as clinical T3 (n = 42) and T2 (n = 21). After the local excision, 43 patients fulfilled the criteria to be observed with no further treatment. Nine of the remaining 20 patients for whom a subsequent total mesorectal excision was recommended refused surgery. Two of these patients who refused surgery had intraluminal local recurrence; both had a ypT2 tumor and underwent salvage surgery. The estimated cumulative 3-year overall survival, disease-free survival and local disease-free survival were 91.5% (95% CI: 75.9–97.2), 91.0% (95% CI: 77.0–96.6) and 96.9% (95% CI: 80.3–99.5), respectively. LIMITATIONS: The time of follow-up is still short and the sample size is limited. CONCLUSIONS: Our data suggest that local excision is a good option for patients with a major clinical response after chemoradiotherapy. A longer period of follow-up is required to confirm these findings.

Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period.

BackgroundThis study aimed to compare the results and the oncologic outcomes of transanal endoscopic microsurgery (TEM) with neoadjuvant radiochemotherapy and laparoscopic resection (LR), also with neoadjuvant radiochemotherapy, in the treatment of T2–N0 low rectal cancer.MethodsThe study enrolled 40 patients with T2–N0 rectal cancer, randomizing 20 to TEM (arm A) and 20 to LR (arm B).ResultsAfter neoadjuvant radiochemotherapy, tumor downstaging was observed for 13 patients (65%) in arm A (7 pT0 and 6 pT1) and in 11 patients (55%) in arm B (7 pT0 and 4 pT1). More than a 50% reduction of the tumor diameter was observed in four arm A cases and in six arm B cases. At a median follow-up period of 56 months (range, 44–67 months) in both arms, one local failure (5%) occurred after 6 months in arm A and one (5%) after 48 months in arm B. Distant metastases occurred in one arm A patient (5%) after 26 months of follow-up evaluation and in one arm B patient (5%) at 31 months. The probability of local or distant failure was 10% for TEM and 12% for laparoscopic resection, whereas the probability of survival was 95% for TEM and 83% for laparoscopic resection.ConclusionsThe findings show comparative results between the two study arms in terms of probability of failure and survival.

Laparoscopic colorectal resection for endometriosis

BackgroundThe rectosigmoid colon is affected by deep pelvic endometriosis in 3–37% of cases. In the past, treatment of the affected gastrointestinal tract generally required conversion to conventional surgery. We describe our experience with complete laparoscopic management of deep pelvic endometriosis with bowel involvement.MethodsFrom March 1995 to March 2003, 29 consecutive patients with endometriosis requiring laparoscopic intervention were evaluated. In seven patients (24%) colorectal involvement was identified prior to the operation. A low anterior resection was performed in four patients (57%) and a sigmoid resection in three (43%). In all cases, colonoscopy showed a normal mucosa. In all cases, treatment consisted of resection of the bowel involved together with the excision of all other implants. Data analysis included age, previous abdominal operations, previous history of endometriosis, operative time, conversion rate, complications, length of stay, and pain relief.ResultsThere were seven patients with colorectal involvement whose median age was 32.8 years (range, 28–40), with a history of previous abdominal operation in two (28%). Preoperative symptoms were as follow: dysmenorrea in four patients (57%), dyspareunia in four (57%), pelvic pain in seven (100%), rectal bleeding in one (14%), and tenesmus in five (71%). Mean operative time was 190 min (range, 165–230). Length of stay was 8.3 days (range, 7–11). There were no anastomotic leak and no major postoperative complication. One patient had temporary urinary retention. At a median follow-up of 38.7 months (range, 1–84), complete relief of pelvic symptoms was achieved in five patients (71%), and there was improvement in one patient. In one patient complaining of persistent pain, a new colonic implant was diagnosed two years after the surgery requiring reoperation.ConclusionsThe results show that provided that the surgeon is highly skilled in laparoscopy, laparoscopic resection of deep pelvic endometriosis with rectosigmoid involvement is feasible and effective in nearly all patients.

A randomized, controlled, clinical study of laparoscopic vs open tension-free inguinal hernia repair

AbstractBackground: The aim of this prospective, randomized, controlled clinical study was to compare laparoscopic transabdominal preperitoneal (TAPP) hernia repair with a standard tension-free open mesh repair (open). Methods: A total of 108 low-risk patients with unilateral (primary or recurrent) or bilateral hernias were randomized to TAPP (group 1 = 52 cases) or open (group 2 = 56 cases). The outcome measures included operating time, complications, postoperative pain, return to normal activity, operating theater costs, and recurrences. Results: The mean operative time was longer for the TAPP than for the open group only in unilateral primary hernias. At rest, the median Visual Analog Scale (VAS) score was higher for group 1 than group 2 at 48 h postoperatively. Mild to discomforting pain in the inguinal region after 7 days, night pain after 30 days, and inguinal hardening after 3 months were more frequent in group 2 than group 1. No significant differences were observed in return to normal activities between the groups. One hernia recurrence was observed after 1 month in group 1. TAPP was significantly more expensive than open. Conclusions: TAPP was associated with less postoperative pain than open. The increase in operating theater costs, however, was dramatic and was not compensated by shorter time away from work. TAPP should not be adopted routinely unless its costs can be drastically reduced.

Laparoscopic adrenalectomy by the anterior transperitoneal approach: results of 108 operations in unselected cases.

BackgroundThe feasibility, safety, and results of 108 laparoscopic anterior transperitoneal adrenalectomies (six bilateral) were evaluated in a series of 105 patients. Three patients with a preoperative diagnosis of primary adrenal carcinoma were excluded from the study.MethodsA total of 102 patients were included in the study based on exhaustive endocrinological and imaging assessment. Twenty-nine patients with nonsecreting adenoma, 34 with aldosterone-producing adenoma, 27 with cortisol-producing adenoma (five bilateral), 13 with pheochromocytoma (one bilateral), two with androgen-secreting adenoma, and three with metastases were considered eligible for adrenalectomy. Lesion size ranged from 3.5 to 12 cm. Concurrent surgical procedures were performed in 10 patients (9.8%).ResultsOne (0.9%) intraoperative complication, a colon tear in a bilateral adrenalectomy, required conversion. there were two (1.9%) postoperative complications: one patient with thrombocytopenia developed hemoperitoneum and required a second laparoscopic procedure, and an intraabdominal abscess was treated medically. Mean postoperative hospital stay was 2.5 days (range, 1–7 days). Postoperative mortality was 0.9%; the patient with the colon tear died of sepsis 60 days after the operation. At a mean follow-up of 30 months (range, 1–62), normalization or improvement in hormone levels was observed in all patients with secreting adenomas, and significant improvement or cure was achieved in all patients with hypertension.ConclusionPatients with secreting and nonsecreting adrenal lesions can be treated safety and effectively by laparoscopy with the anterior transperitoneal approach.