Carlo V. Feo

Effects of Previous Treatment on Results of Laparoscopic Heller Myotomy for Achalasia

Until recently, pneumatic dilatation andintrasphincteric injection of botulinum toxin (Botox)have been used as initial treatments for achalasia, withmyotomy reserved for patients with residual dysphagia. It is unknown, however, whether thesenonsurgical treatments affect the performance of asubsequent myotomy. We compared the results oflaparoscopic Heller myotomy and Dor fundoplication in 44patients with achalasia who had been treated withmedications (group A, 16 patients), pneumatic dilatation(group B, 18 patients), or botulinum toxin (group C, 10patients). The last group was further subdivided according to whether there was (C2, 4 patients)or was not (C1, 6 patients) a response to the treatment.Results for groups A, B, C1, and C2, respectively, were:anatomic planes identified at surgery (% of patients) — 100%, 89%, 100%, and 25%;esophageal perforation (% of patients) — 0%, 5%,0%, and 50%; hospital stay (hrs)-26 ± 8, 38± 25, 26 ± 11, and 72 ± 65; andexcellent/good results (% of patients) — 87%, 95%, 100%, and50%. These results show that: (1) previous pneumaticdilatation did not affect the results of myotomy; (2) inpatients who did not respond to botulinum toxin, the myotomy was technically straightforward and theoutcome was excellent; (3) in patients who responded tobotulinum toxin, the LES muscle had become fibrotic(perforation occurred more often in this setting, and dysphagia was less predictably improved);and (4) myotomy relieved dysphagia in 91% of patientswho had not been treated with botulinum toxin. Thesedata support a strategy of reserving botulinum toxin for patients who are not candidates forpneumatic dilatation or laparoscopic Hellermyotomy.

Elevated Expression of A3 Adenosine Receptors in Human Colorectal Cancer Is Reflected in Peripheral Blood Cells

Purpose: Adenosine is a ubiquitous nucleoside that accumulates at high levels in hypoxic regions of solid tumors, and A3 adenosine receptors have been recently demonstrated to play a pivotal role in the adenosine-mediated inhibition of tumor cell proliferation. In the present work, we addressed the question of the putative relevance of A3 subtypes in colorectal adenocarcinomas. Experimental Design: Seventy-three paired samples of tumor and surrounding peritumoral normal mucosa at a distance of 2 and 10 cm from the tumor and blood samples obtained from a cohort of 30 patients with colorectal cancer were investigated to determine the presence of A3 receptors by means of binding, immunocytochemistry, and real-time reverse transcription-polymerase chain reaction studies. Results: As measured by receptor binding assays, the density of A3 receptor was higher in colon carcinomas as compared with normal mucosa originating from the same individuals (P < 0.05). Overexpression of A3 receptors at the protein level was confirmed by immunohistochemical studies, whereas no changes in A3 mRNA accumulation in tumors as compared with the corresponding normal tissue were revealed. The overexpression of A3 receptors in tumors was reflected in peripheral blood cells, where the density was approximately 3-fold higher compared with healthy subjects (P < 0.01). In a cohort of 10 patients studied longitudinally, expression of A3 receptors in circulating blood cells returned to normal after surgical resection for colorectal cancer. Conclusions: This study provides the first evidence that A3 receptor plays a role in colon tumorigenesis and, more importantly, can potentially be used as a diagnostic marker or a therapeutic target for colon cancer.

Laparoscopic Repair of Paraesophageal Hiatal Hernias

BACKGROUND Regardless of symptoms, paraesophageal hiatal hernias should be repaired in order to prevent complications. This study reports the University of California San Francisco experience with laparoscopic repair of paraesophageal hiatal hernias, emphasizing the technical steps essential for good results. PATIENTS AND METHODS From May 1993 to September 1997, 55 patients, 27 women and 28 men, with a mean age of 67 years (range, 35-102 years) underwent laparoscopic repair of paraesophageal hernias at the University of California San Francisco. Symptoms, which had been present an average of 85 months before surgery, consisted mainly of pain (55%), heartburn (52%), dysphagia (45%), and regurgitation (41%). Of the four patients who presented with acute illness, two had gastric obstruction, one had severe dyspnea, and one had gastric bleeding. Endoscopy demonstrated esophagitis in 25 (69%) of 36 patients, and 24-hour pH-monitoring demonstrated acid reflux in 22 (67%) of 33 patients. Manometry detected severely impaired distal esophageal peristalsis in 17 (52%) of 33 patients. The preferred operation consisted of reduction of the hernia, excision of the sack and the gastric fat pad, closure of the enlarged hiatus without mesh, and construction of a fundoplication anchored by sutures within the abdomen. RESULTS Of the 55 patients, the operations of 49 were completed laparoscopically using the following reconstructions: Guarner (270-degree) fundoplication (30 patients); Nissen fundoplication (10 patients); and gastropexy (9 patients). Five (9%) operations were converted to laparotomies. The average operating time was 219 minutes; the average blood loss was less than 25 mL; resumption of an unrestricted diet, 27 hours; and mean hospital stay, 58 hours. Intraoperative technical complications occurred in five (9%) patients. One patient died during surgery from a sudden pulmonary embolus. Two (4%) patients required a second operation for recurrent paraesophageal hernias. CONCLUSIONS Laparoscopic repair of paraesophageal hiatal hernias is safe and effective, but the operation is difficult and good results hinge on details of the operative technique and the surgeons experience. In this series, the crus could always be closed securely without using mesh. We realized early that a fundoplication should be a routine step, because it corrects reflux and is the best method to secure the gastroesophageal junction in the abdomen.

Adenosine receptors in colon carcinoma tissues and colon tumoral cell lines: Focus on the A3 adenosine subtype

Adenosine may affect several pathophysiological processes, including cellular proliferation, through interaction with A1, A2A, A2B, and A3 receptors. In this study we characterized adenosine receptors in human colon cancer tissues and in colon cancer cell lines Caco2, DLD1, HT29. mRNA of all adenosine subtypes was detected in cancer tissues and cell lines. At a protein levels low amount of A1, A2A, and A2B receptors were detected, whilst the A3 was the most abundant subtype in both cancer tissues and cells, with a pharmacological profile typical of the A3 subtype. All the receptors were coupled to stimulation/inhibition of adenylyl‐cyclase in cancer cells, with the exception of A1 subtype. Adenosine increased cell proliferation with an EC50 of 3–12 µM in cancer cells. This effect was not essentially reduced by adenosine receptor antagonists. However dypiridamol, an adenosine transport inhibitor, increased the stimulatory effect induced by adenosine, suggesting an action at the cell surface. Addition of adenosine deaminase makes the A3 agonist 2‐chloro‐N6‐(3‐iodobenzyl)‐N‐methyl‐5′‐carbamoyladenosine (Cl‐IB‐MECA) able to stimulate cell proliferation with an EC50 of 0.5–0.9 nM in cancer cells, suggesting a tonic proliferative effect induced by endogenous adenosine. This effect was antagonized by 5‐N‐(4‐methoxyphenyl‐carbamoyl)amino‐8‐propyl‐2(2furyl)‐pyrazolo‐[4,3e]‐1,2,4‐triazolo [1,5‐c] pyrimidine (MRE 3008F20) 10 nM. Cl‐IB‐MECA‐stimulated cell proliferation involved extracellular‐signal‐regulated‐kinases (ERK1/2) pathway, as demonstrated by reduction of proliferation with 1,4‐diamino‐2,3‐dicyano‐1,4‐bis‐[2‐amino‐phenylthio]‐butadiene (U0126) and by ERK1/2 phosphorylation. In conclusion this study indicates for the first time that in colon cancer cell lines endogenous adenosine, through the interaction with A3 receptors, mediates a tonic proliferative effect. J. Cell. Physiol. 211: 826–836, 2007.

Comparison of thoracoscopic and laparoscopic Heller myotomy for achalasia.

For more than three decades experts have debated the relative merits of thoracoscopic Heller myotomy (no antireflux procedure) vs. laparoscopic Heller myotomy plus Dor fundoplication for treatment of achalasia. The aim of this study was to compare the results of these two methods with respect to (1) relief of dysphagia, (2) incidence of postoperative gastroesophageal reflux, and (3) hospital course. Sixty patients with esophageal achalasia were operated on between 1991 and 1996. Thirty underwent a thoracoscopic Heller myotomy and 30 had a laparoscopic Heller myotomy with a Dor fundoplication. The two groups were similar with respect to demographic characteristics, clinical findings, and extent of manometric abnormalities. Preoperative pH monitoring showed abnormal reflux in two patients in the laparoscopic group. Average hospital stay was 84 hours for the thoracoscopic group and 42 hours for the laparoscopic group. Excellent (no dysphagia) or good (dysphagia less than once a week) results were obtained in 87% of patients in the thoracoscopic group and in 90% of patients in the laparoscopic group. Postoperative pH monitoring showed abnormal reflux in 6 (60%) of 10 patients in the thoracoscopic group and in 1 (10%) of 10 patients in the laparoscopic group. The two patients in the laparoscopic group who had reflux preoperatively had normal reflux scores postoperatively. Laparoscopic Heller myotomy with Dor fundoplication was found to be superior to thoracoscopic Heller myotomy. Both operations relieved dysphagia, but the laparoscopic approach avoided postoperative reflux and even corrected reflux present preoperatively. In addition, the patients were more comfortable and left the hospital earlier following a laparoscopic myotomy. Whether it is truly possible to perform a Heller myotomy without an antireflux procedure in a way that relieves dysphagia and regularly avoids reflux remains questionable.

Laparoscopic Heller myotomy relieves dysphagia in achalasia when the esophagus is dilated.

AbstractBackground: It has been said that a Heller myotomy cannot improve dysphagia in achalasia when the esophagus is markedly dilated or sigmoid shaped. Those who hold this belief recommend esophagectomy as the primary treatment in such cases. This study aimed to compare the results of laparoscopic Heller myotomy combined with Dor fundoplication in 66 patients with and without esophageal dilatation, all of whom had achalasia. Methods: On the basis of the maximal diameter of the esophageal lumen and the shape of the esophagus, the patients were placed into four groups: group A (esophageal diameter <4.0 cm; 26 patients), group B (diameter 4.0–6.0 cm; 21 patients), group C1 (diameter >6.0 cm and straight esophageal axis; 12 patients), and group C2 (diameter >6.0 cm and sigmoid-shaped esophagus; 7 patients). All patients underwent a laparoscopic Heller myotomy and Dor fundoplication. Results: The duration of the operation and the length of hospital stay were similar among the four groups. Excellent or good results were obtained in 88% of group A, 100% of group B, 83% of group C1, and 100% of group C2. No patient in this consecutive series ultimately required an esophagectomy. Conclusions: In patients with achalasia who have esophageal dilation, a laparoscopic Heller myotomy and Dor fundoplication (a) took no longer and was no more difficult, (b) was associated with no more postoperative complications, and (c) gave just as good relief of dysphagia. We conclude that esophageal dilation by itself should rarely serve as an indication for esophagectomy rather than myotomy as the initial surgical treatment.

Early oral feeding after colorectal resection: a randomized controlled study

Background:  Nasogastric (NG) intubation is widely used following elective abdominal operations although it is associated with morbidity and discomfort. The present study is a randomised controlled trial on the effect of early oral feeding without NG decompression following elective colorectal resection for cancer.

Importance of preoperative and postoperative pH monitoring in patients with esophageal achalasia

Gastroesophageal reflux (GER) can develop in patients with esophageal achalasia either before treatment or following pneumatic dilatation or Heller myotomy. In this study we assessed the value of pre- and postoperative pH monitoring in identifying GER in patients with esophageal achalasia. Ambulatory pH monitoring was performed preoperatively in 40 patients with achalasia (18 untreated patients and 22 patients after pneumatic dilatation), 27 (68%) of whom complained of heartburn in addition to dysphagia (group A), and postoperatively in 18 of 51 patients who underwent a thoracoscopic (n=30) or laparoscopic (n=21) Heller myotomy (group B). The DeMeester reflux score was abnormal in 14 patients in group A, 13 of whom had been treated previously by pneumatic dilatation. Two types of pH tracings were seen: (1) GER in eight patients (7 of whom had undergone dilatation) and (2) pseudo-GER in six patients (all 6 of whom had undergone dilatation). Therefore 7 (32%) of 22 patients had abnormal GER after pneumatic dilatation. Postoperatively (group B) seven patients had abnormal GER (6 after thoracoscopic and 1 after laparoscopic myotomy). Six of the seven patients were asymptomatic. These findings show that (1) approximately one third of patients treated by pneumatic dilatation had GER; (2) symptoms were an unreliable index of the presence of abnormal GER, so pH monitoring must be performed in order to make this diagnosis; and (3) the preoperative detection of GER in patients with achalasia is important because it influences the choice of operation.

Barrett's esophagus: a surgical disease ☆

Barrett’s metaplasia can develop in patients with gastroesophageal reflux disease (GERD), and metaplasia can evolve into dysplasia and adenocarcinoma. The optimal treatment for Barrett’s metaplasia and dysplasia is still being debated. The study reported herein was designed to assess the following: (1) the incidence of Barrett’s metaplasia among patients with GERD; (2) the ability of laparoscopic fundoplication to control symptoms in patients with Barrett’s metaplasia; (3) the results of esophagectomy in patients with high-grade dysplasia; and (4) the character of endoscopic follow-up programs of patients with Barrett’s disease being managed by physicians throughout a large geographic region (northern California). Five-hundred thirty-five patients evaluated between October 1989 and February 1997 at the University of California San Francisco Swallowing Center had a diagnosis of GERD established by upper gastrointestinal series, endoscopy, manometry, and pH monitoring. Thirty-eight symptomatic patients with GERD and Barrett’s metaplasia underwent laparoscopic fundoplication. Eleven other consecutive patients with high-grade dysplasia underwent transhiatal esophagectomies. Barrett’s metaplasia was present in 72 (13 %) of the 53 5 patients with GERD. The following results were achieved in patients who underwent laparoscopic fundoplication (n = 38): Heartburn resolved in 95% of patients, regurgitation in 93% of patients, and cough in 100% of patients. With regard to transhiatal esophagectomy (n = 11), the average duration of the operation was 339 ±89 minutes. The only significant complications were two esophageal anastomotic leaks, both of which resolved without sequelae. Mean hospital stay was 14 ±5 days. There were no deaths. The specimens showed high-grade dysplasia in seven patients and invasive adenocarcinoma (undiagnosed preoperatively) in four (36%). These results can be summarized as follows: (1) Barrett’s metaplasia was present in 13 % of patients with GERD being evaluated at a busy diagnostic center; (2) laparoscopic fundoplication was highly successful in controlling symptoms of GERD in patients with Barrett’s metaplasia; (3) in patients with high-grade dysplasia esophagectomy was performed safely (invasive cancer had eluded preoperative endoscopic biopsies in one third of these patients); and (4) even though periodic endoscopic examination of Barrett’s disease is universally recommended, this was actually done in fewer than two thirds of patients being managed by a large number of independent physicians in this geographic area.

Clinical and Therapeutic Importance of Sentinel Node Biopsy of the Internal Mammary Chain in Patients with Breast Cancer: A Single-Center Study with Long-Term Follow-Up

BackgroundWe evaluated the incidence of sentinel lymph nodes (SLNs) in the internal mammary chain, calculated the lymphoscintigraphy and surgical detection rates, and evaluated the clinical effect on staging and the therapeutic approach in patients with breast cancer.MethodsThe study involved 741 women diagnosed with breast cancer eligible for the SLN technique. Lymphoscintigraphy was performed on the day before the operation by peritumoral injection of 99mTc-labeled nanocolloid. During the operation, a gamma probe was used to detect the SLN, which was then removed.ResultsA total of 719 SLNs were found in the axillary chain and 72 in the internal mammary chain. Preoperative lymphoscintigraphy showed 107 hot spots in the internal mammary chain, but only 72 SLNs in 65 patients were identified by the gamma probe and then removed with no complications. Of these 65 patients, 10 had a positive internal mammary chain SLN on final pathologic examination, whereas 55 patients had ≥1 negative SLNs on final pathologic analysis. Thirty-five (53%) of 65 patients had also an axillary SLN, but only 5 patients (8%) had a positive SLN on pathologic analysis.ConclusionsEvaluation of the SLNs in the internal mammary chain may provide more accurate staging in breast cancer patients. If an internal mammary sampling is not performed, patients may be understaged. This technique may allow better selection of those patients who will be submitted to adjuvant locoregional radiotherapy.