Hans Gerdes

Prevention of Colorectal Cancer by Colonoscopic Polypectomy

BACKGROUND The current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results. METHODS The study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size. RESULTS Ninety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned for one or more of their scheduled colonoscopies. Five asymptomatic early-stage colorectal cancers (malignant polyps) were detected by colonoscopy (three at three years, one at six years, and one at seven years). No symptomatic cancers were detected. The numbers of colorectal cancers expected on the basis of the rates in the three reference groups were 48.3, 43.4, and 20.7, for reductions in the incidence of colorectal cancer of 90, 88, and 76 percent, respectively (P < 0.001). CONCLUSIONS Colonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.

Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial

BACKGROUND Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer. METHODS In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy. RESULTS Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG (p < 0.05). Nine complete tumor responses occurred after PDT and two after Nd:YAG. Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus, in long tumors, and in patients who had prior therapy. More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% (p < 0.05). Termination of laser sessions due to adverse events occurred in 3% with PDT and in 19% with Nd:YAG (p < 0.05). CONCLUSIONS Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy.

Molecular Classification of Gastric Cancer: A New Paradigm

Purpose: Gastric cancer may be subdivided into 3 distinct subtypes—proximal, diffuse, and distal gastric cancer—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design: Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results: Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions: Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. Clin Cancer Res; 17(9); 2693–701. ©2011 AACR.

Management of malignant bowel obstruction.

Malignant bowel obstruction (MBO) is a common and distressing outcome particularly in patients with bowel or gynaecological cancer. Radiological imaging, particularly with CT, is critical in determining the cause of obstruction and possible therapeutic interventions. Although surgery should be the primary treatment for selected patients with MBO, it should not be undertaken routinely in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A number of treatment options are now available for patients unfit for surgery. Nasogastric drainage should generally only be a temporary measure. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical measures such as analgesics according to the W.H.O. guidelines provide adequate pain relief. Vomiting may be controlled using anti-secretory drugs or/and anti-emetics. Somatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions very rapidly and have a particularly important role in patients with high obstruction if hyoscine butylbromide fails. A collaborative approach by surgeons and the oncologist and/or palliative care physician as well as an honest discourse between physicians and patients can offer an individualised and appropriate symptom management plan.

Direct percutaneous endoscopic jejunostomies for enteral feeding

Abstract Background: Enteral feeding through percutaneous endoscopic gastrostomy (PEG) is increasingly utilized in hospitals, homes, and institutions. However, PEGs have two major limitations: (1) risk for aspiration, which occurs in up to 30% of patients, and (2) it does not allow enteral feeding in patients with gastric outlet obstruction, gastroparesis, or gastric resection. Methods: A new endoscopic method for placement of direct percutaneous endoscopic jejunostomy (DPEJ) was attempted in 150 patients with or without a history of major abdominal surgery. Patients were followed-up until tube utilization ceased because of death or resumption of oral feeding. Results: There were 129 (86%) successful procedures and 21 (14%) unsuccessful attempts. Procedure-related complications included nine (6%) incisional infections. Bleeding, abscess, and colonic perforation each occurred in one patient (.6%), and all required surgical intervention. On long-term follow-up (n = 97), tube malfunction occurred in 3 patients (3%) and aspiration in 3 (3%). Duration of tube use in this population was 113 ± 173 days. Conclusions: DPEJs can be performed successfully with a low complication rate. Enteral feeding through DPEJs drastically reduces aspiration, which commonly occurs with PEG feeding. DPEJs allow feeding and hydration of patients with gastric outlet obstruction due to cancer who are not surgical candidates, eliminate the need for intravenous hydration and feeding, and can cut costs of hospitalization and treatment. (Gastrointest Endosc 1996;44:536-40.)

Feasibility and yield of screening in relatives from familial pancreatic cancer families

OBJECTIVES:Pancreatic adenocarcinoma is a lethal disease. Over 80% of patients are found to have metastatic disease at the time of diagnosis. Strategies to improve disease-specific outcome include identification and early detection of precursor lesions or early cancers in high-risk groups. In this study, we investigate whether screening at-risk relatives of familial pancreatic cancer (FPC) patients is safe and has significant yield.METHODS:We enrolled 309 asymptomatic at-risk relatives into our Familial Pancreatic Tumor Registry (FPTR) and offered them screening with magnetic resonance cholangiopancreaticogram (MRCP) followed by endoscopic ultrasound (EUS) with fine needle aspiration if indicated. Relatives with findings were referred for surgical evaluation.RESULTS:As of 1 August 2009, 109 relatives had completed at least one cycle of screening. Abnormal radiographic findings were present on initial screening in 18/109 patients (16.5%), 15 of whom underwent EUS. A significant abnormality was confirmed in 9 of 15 patients, 6 of whom ultimately had surgery for an overall diagnostic yield of 8.3% (9/109). Yield was greatest in relatives >65 years old (35%, 6/17) when compared with relatives 55–65 years (3%, 1/31) and relatives <55 years (3%, 2/61).CONCLUSIONS:Screening at-risk relatives from FPC families has a significant diagnostic yield, particularly in relatives >65 years of age, confirming prior studies. MRCP as initial screening modality is safe and effective.

Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.

PURPOSE AND METHODS We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography (EUS). Neoadjuvant therapy using the fluorouracil, doxorubicin, and metrotrexate (FAMTX) regimen was given for three courses before planned laparotomy with the intention to perform curative resection. Postoperatively, intraperitoneal (IP) cisplatin and fluorouracil (FU) and intravenous (i.v.) FU were administered to patients undergoing resection. RESULTS Fifty-six assessable patients were treated. Preoperative FAMTX therapy was tolerable, with the major toxicity being neutropenic fever. One treatment-related death was seen. Eighty-nine percent of patients underwent surgical exploration and 61% had potentially curative resections. There were two postoperative deaths. Comparison of pathologic tumor (pT) stage with EUS-predicted tumor stage showed apparent downstaging in 51% of patients. Postoperative IP chemotherapy was delivered to 75% of eligible patients. Toxicity was acceptable. There was no increase in operative morbidity or mortality compared with concurrent nonstudy patients undergoing a similar operative procedure and not receiving preoperative therapy. With a median follow-up time of 29 months, the median survival duration was 15.3 months. For patients who underwent potentially curative resections, the median survival duration was 31 months. Peritoneal failure was seen in 16% of patients. CONCLUSION Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer, without an increase in operative morbidity or mortality. IP therapy can be successfully delivered to most resected patients. The intraabdominal failure pattern appears to be decreased compared with expected. This approach is an appropriate investigational arm to pursue in future studies.

Percutaneous endoscopic gastrostomy and jejunostomy for long-term feeding in patients with cancer of the head and neck.

Enteral feeding is often required in patients with cancer of the head and neck. Percutaneous endoscopic gastrostomies (PEGs) and Jejunostomies (PEJs) can facilitate enteral feeding in patients who require this treatment. The endoscopic technique allows for the placement of feeding gastrostomies and Jejunostomies without a surgical procedure and eliminates the need for nasal tubes for long-term enteral feeding. Forty-two patients with head and neck tumors were referred for placement of PEGs because of severe dysphagia induced by tumors, surgery, radiation, or chemotherapy. The procedure was performed in the gastroenterology suite. Patients were sedated with intravenous meperidine and diazepam, and local anesthetic with lidocaine was applied to the area of incision. Average procedure time was approximately 20 minutes. The procedure was successful in 39 patients in whom tubes were placed ranging in diameter from 15F to 22F. PEGs were placed in 36 patients with intact stomachs and PEJs in three patients with previous gastrectomies. The remaining three procedures were unsuccessful because of technical reasons. There were three localized skin infections, and all responded to antibiotic therapy. Neither peritonitis nor any other immediate complication occurred. In 16 nonhospitalized patients, the procedure was performed on an outpatient basis. After a mean followup of 4.5 ± 6 months of enteral feeding in the home, there was only one case of aspiration and subsequent pneumonia, and this case responded to antibiotics. No other long-term complications were noted. Thus feeding gastrostomies and Jejunostomies can be placed safely and easily in patients with cancers of the head and neck by endoscopic methods without abdominal surgery. These tubes can be used for enteral feeding and eliminate the need for nasogastric tubes. They are better tolerated, are of a wider diameter, and have a reduced risk for migration, clogging, and aspiration-related complications.

Endoscopic management of occluded biliary Wallstents: a cancer center experience

BACKGROUND Biliary obstruction caused by unresectable malignancy commonly is treated by placement of a biliary self-expandable metallic stent. The endoscopic and percutaneous techniques for self-expandable metallic stent placement are well established and can be performed with a high success rate. Self-expandable metallic stent placement affords palliation of pruritus and enables treatment of advanced cancer with chemotherapeutic agents metabolized by the liver. Unfortunately, these stents tend to occlude with time. Optimal management of an occluded self-expandable metallic stent remains to be determined. METHODS A retrospective review was undertaken to determine optimal management of the occluded self-expandable metallic stent. Patients with malignant biliary obstruction who had endoscopic management for occluded Wallstents that had been placed percutaneously and endoscopically were studied. All patients underwent ERCP with one of the following interventions: mechanical cleaning, insertion of a plastic stent within the Wallstent, or insertion of a second Wallstent. The effectiveness of the intervention and duration of stent patency thereafter was studied. RESULTS A total of 34 patients with occluded biliary Wallstents underwent the following procedures: mechanical cleaning (6 patients), placement of a second Wallstent (4), or insertion of a plastic stent (24). Mechanical cleaning was effective in only one of 6 patients. For all 4 patients who underwent placement of a second Wallstent, there was resolution of jaundice or cholangitis and no reocclusion. Plastic stent insertion was successful in 22 of 24 patients. Median duration of stent patency after intervention was 192 days (range 81-257 days) after second Wallstent placement, 90 days (11-393 days) after plastic stent insertion, and 21 days (3-263 days) after mechanical cleaning. Duration of stent patency was better when the initial malignant stricture involved the distal vs. the proximal bile duct. CONCLUSIONS Occlusion of a biliary Wallstent is best managed by endoscopic insertion of a second Wallstent or a plastic stent. Mechanical cleaning is less effective. The level of the initial biliary obstruction influences stent patency.

Limitations of Ampullectomy in the Treatment of Nonfamilial Ampullary Neoplasms

BackgroundPancreaticoduodenectomy (PD) is the standard surgical management of invasive ampullary neoplasms. A rational plan to use ampullectomy (AMP) for lesions at this location requires careful analysis of preoperative clinical information (comorbidity, lesion size, and histopathology) and intraoperative data (frozen section pathology and clinical impression) to properly select patients for this treatment.MethodsWe identified 140 consecutive cases of nonfamilial ampullary neoplasms from our prospective institutional database over a 7-year period (1996–2003). Preoperative and intraoperative factors were analyzed and related to outcomes.ResultsAMP was planned for 37 patients with small lesions (median, 1.86 cm [range, 0–3 cm] vs. 2.6 cm [range, 0–8 cm] in PD). AMP was converted to PD because of the extent of disease in three and an intraoperative diagnosis of invasive cancer in five patients. Preoperative biopsy had a diagnostic accuracy of 79% (97 of 123) but missed 23 cancers. Intraoperative frozen section had a diagnostic accuracy of 84%; two cases of high-grade dysplasia and invasive cancer were missed. Patients with invasive cancer treated by AMP had a decreased recurrence-free and disease-specific survival compared with those treated by PD. Lymphatic spread of disease was associated with diminished long-term survival. Although both vascular invasion and tumor stage independently predicted lymphatic metastases, both were limited by their sensitivity.ConclusionsThe reduced morbidity and mortality of AMP makes this the preferred treatment for benign lesions of the ampulla. Conversion to PD should be considered when intraoperative or final pathology identifies invasive adenocarcinoma. Refinement of clinicopathologic factors may reduce the occasional PD for benign disease and AMP for malignancy.