Juan M. Sarmiento

Surgical treatment of neuroendocrine metastases to the liver: : a plea for resection to increase survival

BACKGROUND Hepatic metastases from neuroendocrine tumors have a protracted natural history and are associated with endocrinopathies. Resection is indicated for symptom control. Previous reports have suggested improvement in survival for patients undergoing debulking procedures. STUDY DESIGN The records of all consecutive patients undergoing resection of hepatic metastases from neuroendocrine tumors between 1977 and 1998 were reviewed. Tumors were classified according to histology, endocrine activity, and primary location. Patients lost to followup before 1 year were excluded. Followups were based on outpatient evaluations and were updated by correspondence. The Kaplan-Meier method was used to generate survival and recurrence curves, and the log-rank test was used for comparison. RESULTS A total of 170 patients fulfilled the inclusion criteria, of whom 73 were men. Mean age (+/-SD) was 57 (+/-11.5) years. Carcinoid (n = 120) and nonfunctioning islet cell tumors (n = 18) predominated; the ileum (n = 85) and the pancreas (n = 52) were the most common primary sites. Major hepatectomy (one or more lobes) was performed in 91 patients (54%). The postoperative complication rate was 14%, and two patients died (1.2%). Operation controlled symptoms in 104 of 108 patients, but the recurrence rate at 5 years was 59%. Operation decreased 5-hydroxyindoleacetic acid levels considerably, and no patient experienced carcinoid heart disease postoperatively. Recurrence rate was 84% at 5 years. Overall survival was 61% and 35% at 5 and 10 years, respectively, with no difference between carcinoid and islet cell tumors. CONCLUSIONS Hepatic resection for metastatic neuroendocrine tumors is safe and achieves symptom control in most patients. Debulking extends survival, although recurrence is expected. Hepatic resection is justified by its effects on survival and quality of life.

PERIAMPULLARY CANCERS: Are There Differences?

Our review supports the clinical impression that periampullary cancers vary in outcome after resection. Overall survival after pancreaticoduodenectomy is greatest for patients with ampullary and duodenal cancers, intermediate for patients with bile duct cancer, and least for patients with pancreatic cancer. Moreover, survival for each tumor stage is greater for nonpancreatic periampullary cancers than for pancreatic cancers. Invasion of the pancreas by nonpancreatic periampullary cancers is a major factor adversely affecting survival. Recent data suggest that inherent differences in tumor biology rather than embryologic, anatomic, or histologic factors probably account for these differences in survival. Finally, although pancreaticoduodenectomy remains the procedure of choice for resectable periampullary cancers, further increases in survival will likely evolve through more effective neoadjuvant or adjuvant therapies rather than modifications in the surgical approach.

Paget's disease of the perianal region—An aggressive disease?

Background: Perianal Pagets disease is a rare entity, often associated with internal malignancies and a poor prognosis. METHODS: A chart review of patients with perianal Pagets disease who presented consecutively to Mayo during 25 years (starting in January 1970) was made. Patients included had Pagets disease located in or around the anus (3 cm). Patients were excluded for evidence of spread of vulvaperineal lesions orpagetoidextension of a rectal adenocarcinoma. Histology slides were reviewed, and immunohistochemistry was applied to confirm diagnoses. Follow-up was updated in all patients. Recurrence and survival curves were generated by the Kaplan-Meier method. Survival was compared with an age-matched population by the log-rank test. RESULTS: Thirteen patients, eight females, were diagnosed (age±standard deviation of 68.3±10.6 years). All istologic diagnoses were confirmed with immunohistochemical staining results. Mean follow-up was 6.7 years, 8.8 for living patients. One patient had associated extramammary Pagets disease (scrotum). Lesions were located randomly at the dentate line, anal verge, and/or perianal area. Four patients had associated carcinomas; none of them were visceral. Eleven patients underwent local resection, without adjuvant therapy. Almost all recurrences were treated by wider local excision. The five-year recurrence rate was 61 percent. Overall five-year and ten-year survival was 67 percent, no different from the age-matched population (P=0.546). CONCLUSIONS: These results do not reflect an aggressive nature of perianal Pagets disease, despite a high rate of local recurrence. Both primary lesions and recurrences are susceptible to treatment by wider local resection. Long-term survival is no different from that of the normal age-matched population.

Hepatic Surgery for Metastatic Gastrointestinal Neuroendocrine Tumors

Gastrointestinal neuroendocrine cancers are of significant interest to clinicians and basic scientists. Although there have been marked improvements in the accuracy of diagnosis with improved radioimmune and hormonal assays and in the diagnosis of earlier disease by computed tomography (CT) and magnetic resonance imaging (MRI), many patients still present with hepatic metastases. In contrast to most metastatic gastrointestinal cancers, which have rapid clinical progression with a general decrease in performance status or symptoms related to visceral obstruction and pain, the progression of gastrointestinal neuroendocrine cancers is often slow and associated with clinical endocrinopathies from overproduction of gut hormones. This small subgroup of patients with metastatic neuroendocrine malignancies to the liver has become the focus of intensive multimodality therapy. The aim of this review is to evaluate the role of cytoreductive hepatic surgery in the management of metastatic gastrointestinal malignancies. Over the last two decades, surgical techniques in both pancreatic and hepatic surgery have become reliably safe enough to broadly advocate the aggressive surgical resection of both the primary and metastatic disease whether concomitantly or sequentially. Although clinical reports on cytoreductive surgery for these tumors are sparse, our own experience supports aggressive surgical resection in selected patients with functioning metastatic neuroendocrine malignancies. Although chemotherapy has been employed, low response rates are frequent because of the decreased kinetic activity of these tumors and the high degree of tumor differentiation.

Pancreaticoduodenectomy for islet cell tumors of the head of the pancreas: long-term survival analysis.

Pancreaticoduodenectomy (PD) has been performed infrequently for islet cell tumors of the pancreas because of the perceived perioperative morbidity and the relatively protracted natural history of those tumors. To determine whether the improved safety of PD affects long-term outcome of patients with islet cell tumors, we reviewed our experience. All consecutive patients who underwent PD or total pancreatectomy for islet cell tumors between 1980 and 1995 were analyzed. Diagnoses were based on histologic findings and endocrine (biochemical) manifestations of the tumors. Patients were followed by outpatient clinic visits and mail correspondence. Clinical and pathologic factors were analyzed for prognostic risk. Survival and recurrence curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison (p <0.05 was significant). We identified 29 patients who fulfilled the inclusion criteria with an even distribution by gender (14M:15F). Mean age of patients was 56 years (SD +/- 14 years); mean tumor size was 4.4 cm (SD +/- 2.6 cm). Most tumors were nonfunctioning (n = 20); there were 4 somatostatinomas, 3 insulinomas, and 2 gastrinomas. Operating time was 316 minutes (SD +/- 75 minutes), median transfusion requirement was 0 units (mean 1.5 units). Standard Whipple resection was performed in 20 patients; the pylorus-preserving Whipple procedure, in 7; and total pancreatectomy, in 2. Regional lymph nodes were involved by tumor in 16 patients. The complication rate was 31%, and operative mortality was 10% (n = 3). Length of hospital stay was 17 days (SD +/- 8.8 days). Overall survival was 81% and 70% at 5 and 10 years. Recurrence-free survival was 76% at 5 and 10 years. There was a trend toward greater recurrence-free survival for node-negative patients (88% vs 65% at 5 years, p = 0.13), and overall survival was greater for node-negative patients (100% vs 67% at 5 years, p = 0.04). Mean follow-up was 8.8 years. PD is an appropriate strategy for selected malignant islet cell tumors of the pancreas, which offers extended survival with a low recurrence rate and control of endocrine symptoms.

Perianal Bowen's disease

BACKGROUND: Perianal Bowens disease (BD) is an intraepithelial nonkeratinizing carcinoma, associated historically with internal tumors. METHODS: A review of patients with perianal BD presenting consecutively during a 25-year span was undertaken, excluding Bowenoid papulosis and contiguous genital BD. Histologic slides were resubmitted for review by an experienced pathologist, in a “blind” fashion among other slides. Follow-up was updated in every patient. Survival and recurrence curves were generated by the Kaplan-Meier method and were compared with a normal age-matched population (log-rank test). RESULTS: Nineteen patients were identified; 15 of them were females. Mean age±standard deviation was 49.6±10.6 years. Five patients had a coincidental diagnosis (hemorrhoidectomy or wart excision). No associated carcinomas were found; however, eight patients had isolated BD of the vulva. Eleven patients had a history of anal warts, cervical/vulvar dysplasia, or both. Wide resection, including V-Y flaps, was performed in 18 patients without dysfunction. One-year and five-year recurrence was 16 and 31 percent. Recurrence was treated in all but one case by wider resection. Mean follow-up was 8.4 years. Five-year survival was 75 percent, lower than the matched population (P=0.001); however, only one death was related to BD. CONCLUSIONS: Perianal BD has no association with internal tumors. Despite a high rate of recurrence, perianal BD can be treated by local excision. An increased rate of human papilloma virus-related entities was found, which could suggest a causative role.

Chronic Renal Failure Secondary to Oxalate Nephropathy: A Preventable Complication After Jejunoileal Bypass

Enteric hyperoxaluria is a commonly seen adverse event after the jejunoileal bypass procedure. The increased concentration of urinary oxalate predisposes bypass patients to various renal complications such as nephrolithiasis and oxalate nephropathy. If not diagnosed and appropriately treated, these complications can lead to irreversible renal damage. We describe 3 patients in whom severe renal complications developed with irreversible compromise of renal function after a jejunoileal bypass. Patients who undergo a jejunoileal bypass require lifelong follow-up with close monitoring of their renal function. Marked decline in renal function mandates prompt investigation and aggressive intervention, including reversal of the jejunoileal bypass if necessary. Chronic renal failure secondary to oxalate nephropathy is preventable and treatable but may require conversion of a jejunoileal bypass to a more current form of bypass.

Reconstruction of the hepatic artery using the gastroduodenal artery.

Although injury of the hepatic artery is not common during the performance of biliary and pancreatic resections, the hepatic artery if involved by tumor extension can be injured during its dissection. Several methods for reconstruction of the hepatic artery have been described and although each technique is applicable in a specific situation, autologous tissue conduits are preferable in contaminated operative fields. We report here another transposition technique to reconstruct the proper hepatic artery using the gastroduodenal artery, which may provide a local autologous artery for repair of hepatic artery damage during pancreaticoduodenectomy.

Hepatic resection in the treatment of perihilar cholangiocarcinoma

Proximal bile duct cancer poses a difficult surgical problem in hepatobiliary surgery because of its location, patterns of spread, and required extent of resection for complete excision. This article focuses on the anatomic and pathologic issues that are associated with proximal bile duct cancer and assesses the roles of partial hepatectomy and bile duct resection in the surgical management of this cancer. It is hoped that this article provides clinical evidence that supports hepatic resection as an essential and efficacious component of the surgical management of perihilar cholangiocarcinoma in selected patients.

Physiologic determinants of nocturnal incontinence after ileal pouch—anal anastomosis☆☆☆

The goals of the ileal pouch-anal anastomosis (IPAA) operation are the construction of a fecal reservoir and the preservation of anal function, without compromising continence. Some of the patients are incontinent at night. The aim of our study was to identify the mechanisms responsible for nocturnal incontinence. We analyzed patients undergoing IPAA for ulcerative colitis, who underwent anorectal tests between 1993 and 1995. All patients were subjected to pull-through manometry and pelvic floor function studies, and 33 patients underwent overnight ambulatory manometry. Among 44 patients (27 men and 17 women), 22 had complete continence, whereas 22 had nocturnal incontinence. Mean age was 40±1 years. There were no differences with regard to sex, age, stool consistency, and ability to differentiate gas from stool between groups; only stool frequency was lower in the continent group (median [range] 6 [3 to 10] vs. 8 [5 to 25] stools/24 hours;P=0.011). Resting and squeezing anal canal pressure did not differ (P=0.42 andP=0.73, respectively). Resting, squeezing, and defecating anorectal angle, percentage of pouch evacuation, and perineal descent, all measured scintigraphically, did not differ between groups (allP>0.05). Ambulatory manometry showed that the mean anal canal pressure was higher in continent patients compared to incontinent patients, both during awake (88±11 vs. 62±8;P=0.032) and sleep (81±14 vs. 49±9;P=0.029) periods. The motility index was similar (awake,P=0.88; sleep,P=0.95), as was the number of episodes where the pouch pressure was greater than the anal canal pressure (P=0.28). In otherwise continent patients after IPAA, the combination of high stool frequency and low basal anal canal pressure may be related to nocturanal incontinence. Moreover, standard anorectal physiology tests cannot identify these subtle differences.