Additional endoscopic treatments for patients with positive lateral margins after endoscopic resection of early esophageal squamous cell carcinoma.

There are currently no well-established treatment strategies for early esophageal squamous cell carcinoma (ESCC) for patients with only positive lateral margin (LM+) following endoscopic resection (ER). The present study aimed to find a treatment strategy for patients with early ESCC with non-curative resection (non-CR) and only LM+ following ER. In total, 511 patients with early ESCC treated at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) with ER were retrospectively analyzed, 41 of which (8%) were patients with only LM+ after non-CR. Of these, 28 patients received re-ER and 13 received additional surgical treatment. The clinicopathological characteristics of patients were analyzed and those who underwent additional surgery vs. re-ER were compared. Residual cancer cells were found in 27 patients (27/41, 65.9%) following re-ER or additional surgery. A significant increase in residual cancer cells was observed in patients with poorly differentiated cancer and patients with multiple LM+ (P=0.03 and P=0.015, respectively). Older patients and patients with single LM+ tended to choose re-ER (P=0.023 and P=0.038, respectively). In addition, there were three cases (3/13, 23.1%) of lymph node metastasis in the additional surgery group. However, within the limited follow-up time (mean, 36.1±24.1 months), no recurrence or metastasis was found in the remaining patients. The results showed that re-ER may be a more suitable additional therapy compared with surgery for patients with LM+ following non-CR, at least in the medium-term.

Associated risk factor analysis and the prognostic impact of positive resection margins after endoscopic resection in early esophageal squamous cell carcinoma.

Endoscopic resection for early esophageal cancer has a risk of residual margins. The risk these residual margins pose have not been fully evaluated. The present study aimed to investigate the associated risk factors and prognosis of residual margins following the endoscopic resection of early esophageal squamous cell carcinoma. In total, 369 patients (381 lesions) with early esophageal squamous cell carcinoma treated in the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) with endoscopic resection were retrospectively analyzed. Sex, age, location, tumor diameter, depth of tumor invasion, endoscopic treatment, endoscopic ultrasonography (EUS) before resection, work experience of endoscopists and the degree of tumor differentiation were all evaluated as potential risk factors. In addition, the prognosis of patients with positive margins were analyzed. A total of 73 patients (73/381, 19.2%) had positive margins after endoscopic resection. Amongst the 65 patients who were successfully followed up, five patients succumbed to cardiovascular and cerebrovascular diseases, one patient received radiotherapy, two patients received radiotherapy and chemotherapy whilst one patient received chemotherapy. By contrast, 12 patients received surgery and 20 patients received additional endoscopic mucosal resection or endoscopic submucosal dissection. The other 29 patients were followed up regularly and no recurrence could be found. Univariate analysis revealed that tumor diameter, endoscopic treatment, depth of invasion, EUS before resection, degree of tumor differentiation and direction of invasion were all associated with the positive margin. Multivariate logistic regression analysis then found that EUS before resection, degree of tumor differentiation and depth of tumor invasion are independent risk factors for positive margins after endoscopic resection. These results suggest that poorly differentiated lesions and deeper invasion depth can increase the risk of positive margin after endoscopic resection. As a result, EUS evaluation before resection may reduce the risk of invasion depth. In addition, for poorly differentiated lesions, more aggressive treatment regimens may be recommended for preventing recurrence.

The protocol for the Prospective Urban Rural Epidemiology China Action on Spine and Hip status study.

The Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip status (CASH) study focused on the prevalence of osteoporosis and spinal fracture in China. The aim of the PURE CASH study is to determine the prevalence of osteoporosis and spinal fracture, and explore the potential relationship between spinal fracture and bone mineral density (BMD). This study is a prospective large-scale population study with a community-based sampling and recruitment strategy. The aim is to determine the prevalence of osteoporosis and vertebral fracture in this population, to evaluate the association between vertebral fractures and BMD values, and to assess the prediction power of BMD for incident fractures. Participants in the PURE CASH study are all from the PURE study in China, recruited from 12 centers in 7 Chinese provinces. The inclusion criteria are that participants should be aged more than 40 years and able to give informed consent. Exclusion criteria are pregnant women, individuals with metal implants in the lumbar spine, use of medications or the existence of any disease or condition known to have a major influence on BMD, and inability to give informed consent. A total of 3,457 participants undergo a quantitative computed tomography (QCT) scan of the upper abdomen. The scanning parameters are as follows: 120 kVp at all centers, mAs between 75 and 200, FOV 40 cm×40 cm. The BMD values of L1 to L3 are measured, and the average BMD calculated. The American College of Radiology QCT criteria for the diagnosis of osteoporosis is applied to determine the presence of osteoporosis. The scout view images of T4-L4 vertebrae are reviewed by two experienced radiologists for semi-quantification of vertebral fractures according to Genant's method.

[Effect of erythromycin on electrical activity and gastric emptying of the intrathoracic stomach after esophagectomy for esophageal cancer].

OBJECTIVE: To investigate the effect of erythromycin on electrical activity and emptying of the intrathoracic stomach after esophagectomy for esophageal cancer. METHODS: Thirty patients undergoing esophagectomy for cancer and esophagogastrostomy above the aortic arch were divided into the study group (n=15) and the control group (n=15). Electrogastrography and radionuclide gastric emptying were examined for these patients before and 1, 3, 6, 12 months after surgery. Patients in the study group received erythromycin (0.25 g tid po) for 1 week before examination. RESULTS: The wave amplitude (Uv), dominant frequency (CPM) and percentage of normal slow wave (%) of electrogastrogram decreased after surgery and returned to normal at the first postoperative month in the study group and the 12th postoperative month in the control group (P>0.05). Gastric emptying was significantly delayed after esophagectomy, and returned to normal one year after operation in the study group (P>0.05). However, gastric emptying remained abnormal in the control group (P<0.01). CONCLUSIONS: Erythromycin improves electrical activity and emptying of the stomach after esophagectomy for cancer. Gastric emptying recovery later than the recovery of electrical activity, which may be related to gastric ischemia and edema.

[Impact of techniques for gastrointestinal tract reconstruction following gastrectomy on pancreatic ß-cell function in patients with type 2 diabetes mellitus].

OBJECTIVE: To evaluate the impact of different techniques for gastrointestinal tract reconstruction on postoperative pancreatic ß-cell function in patients with type 2 diabetes mellitus (T2DM). METHODS: Twenty-three patients with gastric cancer and T2DM were studied. Techniques for reconstruction included Billroth I (n=13) and bypass procedures(Billroth II n=4 and Roux-en-Y anastomosis n=6). Pancreatic ß-cell function was evaluated by oral glucose tolerance test (OGTT). Serum insulin was measured by electrochemiluminescence immunoassay and blood glucose by glucose oxidase method. HOMA-IR and HOMA-ß were assessed. RESULTS: T2DM remission rate was 90% (9/10) in the bypass group, and 23% (3/13) in Billroth I group (P<0.01). Glycosylated hemoglobin A1c and glycated hemoglobin HbA1 were improved significantly in patients after bypass procedures(P<0.05), but the difference in Billroth I group was not statistically significant (P>0.05). OGTT showed that fasting and post-glucose load plasma glucose at each time point were significantly lower in the bypass group compared to the Billroth I group. At 30 minutes and 60 minutes after glucose load, insulin levels and insulin release index were significantly higher in the bypass group compared to Billroth I( group, as were levels of HOMA-ß and ΔI30/ΔG30 in the bypass group(P<0.05). CONCLUSION: Gastrointestinal bypass following gastrectomy may induce resolution of T2DM and improve ß-cells function.

[Antireflux anastomosis following resection of esophageal cancer].

OBJECTIVE: To investigate the antireflux effects of a modified Nissen fundoplication following esophagectomy for cancer. METHODS: From March 2006 to March 2007, 70 patients with esophageal cancer were divided into two groups randomly. Esophagogastrostomy with a stapler only was perform in 35 patients as controls (group C), and a modified Nissen fundoplication was added after esophagogastrostomy with stapler in the other 35 patients as observed group (group O). There were 48 male and 22 female, ranging in age from 47 to 77 years (mean 60.1 years). The operative morbidity and mortality were recorded. Fourty-nine patients were followed at 3 months after surgery, and the questionnaire of life quality (EORTC QLQ C-30) was conducted in 24 patients in group C and 25 patients in group O. Thirty patients were examined with esophageal manometry, 24 h pH monitoring and gastroscopy. There were 16 patients in group C and 14 patients in group O. RESULTS: There was no significant difference in postoperative morbidity between the two groups (P > 0.05). However, the scores of heart burn and regurgitation in the group O were less than in group C (P = 0.041 and 0.034 respectively), but there was no difference in scores of dysphagia between the two groups (P = 0.677). The pressure at the anastomotic site was higher than that in the stomach in group O (P = 0.032), but not in group C (P = 0.448). DeMeester score in group O was 53 ± 46, compared to 140 ± 103 in group C (P = 0.043). The score of esophagitis was 0.9 ± 0.8 in group O, which was lower than 1.6 ± 1.0 in group C (P = 0.041). CONCLUSIONS: Addition of modified Nissen fundoplication after esophagectomy and esophagogastrostomy for cancer significantly increases the pressure at the anastomotic site, thus reduces the extent of gastroesophageal reflux, which leads to the reduction of the extent of reflux esophagitis and the improvement of the quality of life.

Radiation therapy in the management of head-and-neck cancer of unknown primary origin: how does the addition of concurrent chemotherapy affect the therapeutic ratio?

PURPOSE: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. METHODS AND MATERIALS: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. RESULTS: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). CONCLUSIONS: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.

Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head-and-neck cancer of unknown primary origin.

PURPOSE: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. METHODS AND MATERIALS: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. RESULTS: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and 84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p>0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p<0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p<0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p<0.001). CONCLUSIONS: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.

Evaluating the role of prophylactic gastrostomy tube placement prior to definitive chemoradiotherapy for head and neck cancer.

PURPOSE: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. METHODS AND MATERIALS: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. RESULTS: Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). CONCLUSIONS: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.

Late esophageal toxicity after radiation therapy for head and neck cancer.

BACKGROUND: The aim of this study was to determine the incidence of esophageal toxicity after radiation therapy for head and neck cancer. METHODS: The records of 211 patients treated by radiation therapy for head and neck cancer were reviewed to identify those with dysphagia lasting more than 90 days after therapy. Late toxicity criteria established by the Radiation Therapy Oncology Group were used to score the symptoms. RESULTS: The incidence of grade 3+ esophageal toxicity at 3 and 6 months was 30% and 19%, respectively. The rate of gastrotomy-tube dependence at 3 and 6 months was 20% and 11%, respectively. Hypopharyngeal and unknown primary site (p = .01, for both), T4 disease (p = .01), and the use of concurrent chemotherapy (p = .001) were associated with grade 3+ esophageal toxicity and stricture formation. CONCLUSION: A significant proportion of patients exhibit symptoms of esophageal toxicity after radiation therapy for head and neck cancer. Therefore, preventive strategies need further investigation.

[Mechanism of relaxation mediated by nitric oxide on human lower esophageal sphincter].

OBJECTIVE: To explore the mechanism of relaxation mediated by nitric oxide on the human lower esophageal sphincter (LES), and compare the difference in relaxation response between clasp fibers and sling fibers. METHODS: 32 LES specimens were obtained from 32 patients with high-positioned carcinoma of the mid-esophagus, 12 males and 16 females, aged 55.9 +/- 9.3, during operation. The clasp fibers and sling fibers were isolated and suspended in perfusion tough. Electric field stimulation (EFS) was applied to the clasp and sling fibers in vitro. Nitric oxide synthase (NOS) inhibitor L-NNA, NOS substrate L-arginine, neurotoxin tetrodotoxin (TTX), and atropine were added respectively to observe their effects on the clasp and sling fibers under EFS. Sodium nitroprusside was added on the two kinds of smooth muscle stripes to observe its influence as well. RESULTS: EFS induced frequency-dependent relaxation to clasp fibers and some of sling fibers, which was inhibited by L-NNA in a concentration-dependent manner and was reversed by L-arginine partially. Maximal relaxation in clasp fibers and sling fibers was observed at 512 Hz and 16 Hz respectively. The higher amplitude relaxation was induced in the sling fibers at lower stimulus frequencies (< 32 Hz). Conversely, the same response was induced in the clasp fibers at higher stimulus frequencies (> 64 Hz). Meanwhile, off-contraction was induced by EFS in some sling fibers and clasp fibers. In some sling fibers, contraction was induced by EFS which was inhibited by atropine. Maximal contraction in these fibers was observed at 128 Hz. TTX abolished the effect of EFS on both clasp and sling fibers, which was considered neurogenic. Sodium nitroprusside elicited the similar response to EFS. CONCLUSIONS: Relaxation of clasp and sling fibers is related to L-NNA, TTX, and sodium nitroprusside, and can be mediated by nitric oxide. Lower stimulus frequencies induce higher amplitude relaxation to sling fibers, and conversely, higher stimulus frequencies induce higher amplitude relaxation to clasp fibers. EFS induces contraction response in some sling fibers.

[Long-term outcome of antireflux surgery for gastroesophageal reflux disease].

OBJECTIVE: To investigate the long-term outcomes of various antireflux procedures for gastroesophageal reflux disease (GERD). METHODS: Between November 1988 and January 2004, 129 patients with GERD underwent antireflux procedures. Six kinds of antireflux procedures were performed including Nissen fundoplication, cardiac oblique invagination (COI) procedure, Belsey Mark IV, Toupet, Thal and Dor procedures. One hundred and sixteen patients were followed up. Esophageal manometry study was carried out in 95 patients preoperatively and 51 postoperatively. 24-hour esophageal pH monitoring were carried out in 56 patients preoperatively and 35 postoperatively. Esophagoscopy were performed in all patients before operation and 48 cases after operation. RESULTS: Clinical symptom scores reduced significantly from 4.1 +/- 0.4 before surgery to 1.1 +/- 1.0 after surgery (t = 27.21, P < 0.01). The outcome of surgery showed excellent in 42 cases (36.2%), good in 60 (51.7%), fair in 7 (6.0%), poor in 7 (6.0%). The long-term follow-up showed excellent or good results in 87.9% of patients. There was no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV. CONCLUSIONS: There are significant differences in symptom score, esophageal manometry, 24-hour esophageal pH monitoring and esophagoscopy pre- and post-operatively. There is no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV.

[Functional study of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer].

OBJECTIVE: To investigate pathophysiological changes of the remnant esophagus and gastric cardia in patients who underwent esophagectomy for cancer, and to provide objective evidences for the improvement of the postoperative quality of life. METHODS: The function of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer were assessed objectively. The methods that we used were gastric scintigraphy, esophageal manometry, 24-hour esophageal pH monitoring, electronic gastroscopy, videofluoroscopy, and DeMeester scoring system for the assessment of heartburn. Findings were recorded and compared with normal controls. RESULTS: After esophagectomy for cancer, the emptying of intrathoracic stomach was delayed (t = 7.105, P < 0.01) and improved over time, but could not reach normal one year after surgery (t = 2.9, P = 0.016). In patients who had undergone esophagectomy for cancer, the contracting pressure of the upper esophageal sphincter and resting pressure of the remnant esophagus were higher than that in normal controls (t = 2.275, P = 0.03; t = 2.16, P = 0.039 respectively). 89.7% of patients who had undergone esophagectomy had gastroesophageal reflux measured with 24-hour pH monitoring. The extent of reflux was less severe when patients were in a semi-reclining position than in a prostration position (t = 3.074, P = 0.005). CONCLUSION: After esophagectomy for cancer, delayed emptying of the intrathoracic stomach is improved gradually over time, but it is inaccessible to normal level. Gastroesophageal reflux extensively exists in patients who underwent esophagectomy for cancer, but it can be lessened by taking semi-reclining position.

[A study on the method of DNA extraction from unbuffered formalin-fixed and paraffin-embedded samples].

BACKGROUND & OBJECTIVE: Unbuffered formalin is widely used to fix resected specimens in China. The DNA in unbuffered formalin-fixed and paraffin-embedded tissues is usually degraded seriously, so the extraction of DNA from these samples is difficult. This study was conducted to seek an optimal method to extract DNA from these samples. METHODS: Fifteen blocks of esophageal carcinoma resected in Fourth Hospital of Hebei Medical University in 2000 were selected. The cells were lyzed by proteinase K digestion or heating under different pH values, then DNA was extracted by phenol:chloroform. After that, four parameters (deparaffined by xylene or histolene; digested for 48 h or 72 h at 37 degrees C or 56 degrees C; extracted by salting-out or phenol:chloroform) were optimized according to the principle of cross design. At last, the quality of obtained DNA was analyzed with electrophoresis and PCR amplification. RESULTS: The quality and quantity of DNA obtained by proteinase K digestion (the average yield is 17.88 microg) were better than that of heating under different pH (7-12)(P< 0.05). The quality and quantity of DNA digested at 56 degrees C were better than that at 37 degrees C, and similarly, digestion for 72 hours was better than that for 48 hours. The methods of deparaffin and extraction had no obvious influence on the quality and quantity of DNA. CONCLUSION: By means of NaCl salting-out after proteinase K digestion, more reliable quality of DNA can be obtained from unbuffered formalin-fixed and paraffin-embedded samples. Furthermore,digestion for three days at 56 degrees C is more likely to obtain DNA with high quality and quantity.

Responses of human clasp and sling fibers to neuromimetics.

BACKGROUND AND AIMS: It has previously been demonstrated that clasp and sling fibers at the human gastroesophageal junction respond differently to acetylcholine (Ach). The present study was undertaken to investigate the differences between the physiological and pharmacological properties of the two types of muscle fiber. METHODS: Recordings were made of the isometric tension of human sling and clasp fibers in response to Ach, dopamine (DA), phenylephrine (Phe), and isoprenaline (Iso). These specimens were obtained from 18 patients who were operated on for esophageal cancer. RESULTS: Both Ach and Phe increased the tension of the two types of muscle; the values in the Ach group being 3-4-fold greater than those in the Phe group, while Iso decreased the tension of both types of muscle strip. The tension of the sling fibers was reduced by DA at lower concentration, and then increased gradually as the concentration was increased. In contrast, the tension of the clasp fibers did not obviously change when the concentration of DA was lower, but a slow elevation of tension was seen with the increase in DA concentration. CONCLUSIONS: The sensitivities and maximum responses to each agent differed between the clasp fibers and sling fibers. This suggests that the two kinds of fiber have different roles in establishing tension in the lower esophageal sphincter, with implications for the medical and surgical treatment of disorders in this region.

Long-term outcome of esophageal myotomy for achalasia.

AIM: Modified Heller's myotomy is still the first choice for achalasia and the assessment of surgical outcomes is usually made based on the subjective sensation of patients. This study was to objectively assess the long-term outcomes of esophageal myotomy for achalasia using esophageal manometry, 24-hour pH monitoring, esophageal scintigraphy and fiberoptic esophagoscopy. METHODS: From February 1979 to October 2000, 176 patients with achalasia underwent modified Heller's myotomy, including esophageal myotomy alone in 146 patients, myotomy in combination with Gallone or Dor antireflux procedure in 22 and 8 patients, respectively. Clinical score, pressure of the lower esophageal sphincter (LES), esophageal clearance rate and gastroesophageal reflux were determined before and 1 to 22 years after surgery. RESULTS: After a median follow-up of 14 years, 84.5% of patients had a good or excellent relief of symptoms, and clinical scores as well as resting pressures of the esophageal body and LES were reduced compared with preoperative values (P<0.001). However, there was no significant difference in DeMeester score between pre- and postoperative patients (P=0.51). Esophageal transit was improved in postoperative patients, but still slower than that in normal controls. The incidence of gastroesophageal reflux in patients who underwent esophageal myotomy alone was 63.6% compared to 27.3% in those who underwent myotomy and antireflux procedure (P=0.087). Three (1.7%) patients were complicated with esophageal cancer after surgery. CONCLUSION: Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent, but further randomized studies should be carried out to demonstrate its efficacy.