Objective To evaluate the odontogenetic ability of first branchial arch cells of E12.5 rats. Methods First branchial arch cells (mandibular process) of E12.5 SD rats were isolated enzymatically and collected. After combined with gelatin sponge, the cells were transplanted into the renal capsule of a rat. The specimen was taken out and evaluated by histological and immunohistochemical methods in 4 weeks after growth in renal capsule. Results The first branchial arch cells with gelatin sponge developed dentin-pulp complex-like structure. Dentin sialoprotein (DSP) was expressed in the newly formed dentin-like structure. The green mineralized matrix was further identified with Masson’s trichrome staining. Conclusion Cells from first branchial arch of E12.5 rats can partially keep genetic signal of tooth growth and form dentin-pulp complex-like structure in renal capsule.

Objective:To investigate the safety and prognostic value of neoadjuvant chemotherapy and surgery for advanced gastric cancer patients with para-aortic lymph node metastasis.Methods:Clinicopathological data of 25 patients admitted to the Department of Gastrointestinal Surgery, Fujian Cancer Hospital from Jan 2015 to Jun 2017 were retrospectively analyzed. All patients were treated with SOX chemotherapy for 3 cycles. D 2 + paraaortic lymphadenectomy was performed in patients with stable disease (SD) . After operation, SOX regimen was used for 5 cycles of chemotherapy. Results:After 3 cycles of neoadjuvant chemotherapy, there were 2 cases with progressive disease, 6 cases of SD and 17 cases of partial remission. There was no treatment-related death. Twenty-three patients underwent surgery, including 19(76%) patients of R 0 resection. Tirty-four out of 128 para aortic lymph nodes were metastatic. Postoperative complications occurred in 5(22%) patients, with no mortality . The median progression free survival time and median overall survival time were 20 and 29 months respectively. The 1, 3-year overall survival rates were 80% and 48%, and the 1-year and 3-year progression free survival rates were 72% and 38%, respectively. For those with para-aortic lymph node metastasis the 1-year and 3-year OS rate were 70% and 17%, respectively. Multivariate analysis showed that the efficacy of neoadjuvant chemotherapy was an independent prognostic factor. Conclusion:Neoadjuvant chemotherapy is among others an independent prognostic factor affecting the post-op survival of advanced gastric carcinoma with para-aortic lymph node metastasis.

Objective To summarize the clinicopathological characteristics and analyze the prognostic factors of young gastric cancer patients.Methods Data of 1 801 gastric cancer patients (divided into ≤45 years of age group,n =230 cases,and ＞ 45 years old group,n =1 571 cases) undergoing gastrectomy in Department of Gastrointestinal Surgery,Fujian Provincial Cancer Hospital,from June 1999 to November 2015 were retrospectively analyzed.Results Compared with the elderly patients,those ≤45 years old were more female with higher percentage of signet ring cell carcinoma,M1 and non radical resection while less in the upper stomach area (P ＜ 0.05),but there was no statistical difference in tumor size,depth of invasion,lymph node metastasis,Borrmann type,TNM stage,peripheral nerve involvement,cancer embolus,positive margin.Prognostic analysis showed the difference of 5-years survival rate was not statistically significant between young and elderly patients.But the 5-year survival rate in young patients with signet ring cell carcinoma undergoingt radical gastrectomy was better than that of elderly patients (P =0.047,0.038).Multivariate regression analysis showed that M staging and surgical modality were independent prognostic factors for these ≤ 45 years old patients.Conclusion Although there are special clinicopathological features of gastric cancer in young patients,but the postoperative prognosis is relatively the same as those elderly patients.

Objective To investigate the relationship between perineural invasion and clinicopathological factors of gastric cancer or prognosis of patients.Methods The retrospective case-control study was conducted.The clinicopathological data of 1 801 patients with gastric cancer who were admitted to the Affiliated Tumor Hospital of Fujian Medical University between March 1999 and November 2015 were collected.All the patients received surgery in order to the radical resection of gastric cancer,and total gastrectomy or two-thirds and above of gastrectomy and D2 lymph node dissection were performed.Patients with preoperative stage Ⅲ of clinical staging underwent neoadjuvant chemotherapy.Patients with T3-T4 of histopathologic stage,T1-T2 of positive lymph nodes and T2N0 of high risk factors (low differentiated tumor,lymphovascular invasion,perineural invasion and age ＜ 50 years) underwent postoperative chemotherapy.Observation indicators:(1) treatment situations;(2)pathological characteristics;(3) follow-up results;(4) prognostic factors.Follow-up using outpatient examination and telephone interview was performed once within 1 month postoperatively,once every 3 months within 2 years postoperatively and once every 6 months from 3 to 5 years postoperatively up to February 2016.Follow-up included inquiry,physical examination,routine blood test,biochemical test,carcinoembryonic antigen (CEA),CA19-9,color Doppler ultrasound or computed tomography (CT) and endoscopy.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range).Ordinal data was analyzed by the nonparametric test.The univariate analysis and multivariate analysis were done using the COX regression model.The hazard ratio (HR)and 95％ confidence interval (CI) were calculated.The survival curve and survival analysis were respectively drawn and done by the Kaplan-Meier method and Log-rank test.Result (1) Treatment situations:all the 1 801patients underwent traditional open surgery,including 1 570 undergoing radical resection and 231 undergoing palliative surgery.Of 1 801 patients,1 029 received total gastrectomy,540 received distal gastrectomy,201 received extended gastrectomy and 31 received resection of residual stomach.Operation time,volume of intraoperative blood loss,number of lymph node dissected and duration of hospital stay were (173±40) minutes,(224-±91) mL,30± 13 and (15±9) days,respectively.Of 1 801 patients,79 underwent preoperative neoadjuvant chemotherapy and 906 underwent postoperative adjuvant chemotherapy.(2) Pathological characteristics:results of pathological examinations of 1 801 patients showed that 509 had positive perineural invasion and 1 292 had negative perineural invasion.Tumors located in the upper region,middle region and lower region of stomach,whole stomach and stump stomach were respectively detected in 173,189,123,12,12 patients with positive perineural invasion and 395,417,428,29,23 patients with negative perineural invasion.Type Ⅰ,Ⅱ,Ⅲ and Ⅳ of Borrmann type were respectively detected in 13,213,244,39 patients with positive perineural invasion and 92,511,629,60 patients with negative perineural invasion.The good and poor tumor differentiations and tumor diameter ＜5 cm and ≥5 cm were respectively detected in 172,337,244,265 patients with positive perineural invasion and 536,756,833,459 patients with negative perineural invasion.Stage Ⅰ,Ⅱ,Ⅲ,Ⅳv of histopathologic stage,T1,T2,T3,T4 of invasive depth,NO,N1,N2,N3 of lymph node metastasis and positive and negative lymphovascular invasion were respectively detected in 27,54,346,82,17,24,26,442,77,84,109,239,383,126 patients with positive perineural invasion and 263,283,623,123,188,169,289,646,409,219,312,352,437,855 patients with negative perineural invasion,with statistically significant differences in above indexes between positive and negative perineural invasion patients (X2 =14.142,Z =-2.098,X2 =9.061,41.536,Z=-10.389,-13.824,-8.638,X2 =252.624,P＜ 0.05).(3) Follow-up results:1 629patients were followed up for 1.0-99.0 months,with a median time of 37.3 months.The 5-year overall survival rate was 58.5％.(4) Prognostic factors:results of univariate analysis showed that tumor location,Borrmann type,degree of tumor differentiation,tumor diameter,histopathologic stage,invasive depth,lymph node metastasis,lymphovascular invasion and perineural invasion were factors affecting prognosis of patients with gastric cancer (HR=1.209,1.303,1.496,2.303,3.368,2.057,1.812,2.013,1.332,95％ CI:1.123-1.301,1.171-1.449,1.290-1.736,2.001-2.649,3.012-3.767,1.856-2.279,1.694-1.939,1.749-2.317,1.126-1.576,P＜0.05).Resuhs of multivariate analysis showed that tumors located in the upper and middle of stomach,whole stomach and stump stomach,tumor diameter ≥ 5 cm,stage Ⅱ-Ⅳ of histopathologic stage,T2-T4 of invasive depth,N1-N3 of lymph node metastasis,positive lymphovascular invasion and positive perineural invasion were independent risk factors affecting prognosis of patients with gastric cancer (HR =1.087,1.234,2.663,1.174,1.136,1.254,1.272,95％ CI:1.008-1.172,1.063-1.432,2.292-3.095,1.035-1.332,1.044-1.236,1.064-1.501,1.066-1.516,P＜0.05).The 5-year survival rate was 49.1％ in 509 patients with positive perineural invasion and 60.7％ in 1 292 patients with negative perineural invasion,respectively,with a statistically significant difference (X2 =11.270,P＜0.05).The 5-year overall survival rate was 41.1％ in 383patients with positive perineural invasion and lymphovascular invasion,77.1％ in 126 patients with positive perineural invasion and negative lymphovascular invasion,49.1％ in 437 patients with negative perineural invasion and positive lymphovascular invasion and 92.1％ in 855 patients with negative perineural invasion and lymphovascular invasion,respectively,with a statistically significant difference (X2=244.368,P＜0.05).Conclusion Perineural invasion is a high risk factor affecting prognosis of patients with gastric cancer,and it may be useful in evaluating prognosis of patients with gastric cancer.

Objective To compare the therapeutic outcomes between laparoscopic radical Rephrectomy and open radical nephrectomy for renal cancer. Methods A prospective randomized controlled trial was performed in Fujian Provincial Tumor Hospital from January 2006 to July 2009.Sixty-two cases were randomly divided into 2 groups:laparoscopic radical nephrectomy and open radical nephrectomy.Primary outcome(post-operative hospital stay)and second outcome(estimated blood loss,operative time,incision length,post-operative complications,recurrence,metastasis and survival)were compared between 2 groups. Results Post-operative hospital stay was(5.4±1.3)d in laparoscopic group and(8.1±2.2)d in open group(P<0.05).Median estimated blood loss was 100 ml in laparoseopic group and 200 ml in open group(P<0.05).There were no significant difference between teh 2 groups in operative time,post-operative complications,recurrence,metastasis and survival rates(P>0.05). Conclusion Laparoscopic nephrectomy could reduce hospital stay,which provides a minimally invasive approach for renal cancer.

The concept of mesenteric anatomy has been evolving in cognition. With the continuous development of endoscopic techniques, the submicroscopic structures of many mesenteries have been gradually understood, ultimately confirming the ubiquitous presence of mesenteries in the digestive organs. Based on various domestic and foreign mesenteric anatomical theories and combined with years of clinical practice, we have summarized and proposed a new concept and theory-vascular-guided complete mesenteric resection for gastric cancer. The theoretical basis is that, from the perspective of the embryonic development of the digestive tract, the rotation of the digestive tract and its associated mesentery is always centered on blood vessels. Therefore, the supply vessels and digestive tracts and their associated mesentery are naturally connected. The mesentery is a complex structure that encompasses blood vessels, nerves, and lymphatic tissues. The blood vessels serve as the boundary of the mesentery, ensuring that the lymphatic network that drains the tumor is maximally resected. This article focuses on the complete mesenteric resection margins in gastric cancer surgery, that is, the lateral boundary of the mesentery as the vascular-supplied guided resection boundary and its mesentery, and the base boundary as the mesenteric bed. Using precise vascular guidance to define the extent of mesenteric resection will help accurately define the mesenteric margin during radical resection for different stages of gastric cancer.

The concept of mesenteric anatomy has been evolving in cognition. With the continuous development of endoscopic techniques, the submicroscopic structures of many mesenteries have been gradually understood, ultimately confirming the ubiquitous presence of mesenteries in the digestive organs. Based on various domestic and foreign mesenteric anatomical theories and combined with years of clinical practice, we have summarized and proposed a new concept and theory-vascular-guided complete mesenteric resection for gastric cancer. The theoretical basis is that, from the perspective of the embryonic development of the digestive tract, the rotation of the digestive tract and its associated mesentery is always centered on blood vessels. Therefore, the supply vessels and digestive tracts and their associated mesentery are naturally connected. The mesentery is a complex structure that encompasses blood vessels, nerves, and lymphatic tissues. The blood vessels serve as the boundary of the mesentery, ensuring that the lymphatic network that drains the tumor is maximally resected. This article focuses on the complete mesenteric resection margins in gastric cancer surgery, that is, the lateral boundary of the mesentery as the vascular-supplied guided resection boundary and its mesentery, and the base boundary as the mesenteric bed. Using precise vascular guidance to define the extent of mesenteric resection will help accurately define the mesenteric margin during radical resection for different stages of gastric cancer.

OBJECTIVETo evaluate the safty and feasibility of the D2 radical resection of omental bursa and No.12p and No.8p for gastric carcinoma (GC).

METHODSClinical data of 1801 GC patients undergoing D2 radical resection of omental bursa and No.12p and No.8p at Fujian Medical University Cancer Hospital from January 2000 to January 2010 were analyzed retrospectively. Inclusion case criteria: (1)age of 18 to 90 years;(2)pathologically diagnosed as GC and receiving D2 radical resection of omental bursa and No.12p and No.8p;(3)complete clinical, pathological and follow-up data; (4)operation performed by same leading surgeon;(5)exclusion of other gastric malignancies, postoperative relapse of GC, and other simultaneous or heterochronous primary malignancies. Surgical procedure points: (1)The outer part of the peritoneum of duodenum descending was cut; the serosa was migrated to the anterior leaf of the gastrointestinal ligament. (2)The posterior lobe of the gastrocolic ligament and the transverse mesocolon were separated bluntly from left side to reach the omentum attaching to the colon portion; incision was made at the edge of the omentum attaching to the transverse colon behind the gastrocolic ligament; the leaves were turned to the anterior mesenteric anterior leaflets, and the entire anterior leaflet of the transverse mesentery was free.(3)The pancreas was separated, and resection of the posterior wall of the omentum sac continued up so that the entire retinal capsule was free; along the edge of the liver the attachment of the omentum was cut to reach the front of esophagus, and transverse incision was made in abdominal peritoneal layer of the esophagus, and then turned to the spleen on the pole; from the obturator to the esophagus incision was performed behind the peritoneum for the net; the uppermost edge of the resection of the capsule was performed as the posterior peritoneal incision to the right edge of the esophagus and was connected with the posterior parietal lobe of the previous resection; the posterior peritoneum was attached along the right edge of the esophagus and descended to the celiac artery; the posterior wall of the omental sac was removed. In the meantime, the liver duodenum ligament was cut, and the portal vein, hepatic artery trilocular was formed. Then the ligament lymph nodes were cleared.(4)The lymph nodes of celiac artery and its major branches were cleared; the envelope in front of pancreas and the part of the pancreas in posterior abdomen were resected; spleen and part of the pancreas tail were free.

RESULTSA total of 1801 cases were enrolled, including 1292 males and 509 females with a ratio of 2.54 with a mean age of(58.9±11.5)(18 to 89) years. The proportion of cases with T1a, T1b, T2, T3, T4a and T4b was 4.8% (87 cases), 6.6% (118 cases), 10.7% (193 cases), 17.5% (315 cases), 55.7% (1003 cases) and 4.7%(85 cases) respectively. All the patients completed operations successfully. The mean number of harvested lymph node was 28.5±13.7(10 to 85). Lymph node metastasis was found in 1439 cases (79.9%), including 180 cases (10.0%) in No.12p and 232 cases(12.9%) in No.8p respectively. Subgroup analysis showed that in T1a, T1b, T2, T3, T4a and T4b stage, the proportion of No.12p was 0, 1.7% (2/118), 5.2%(10/193), 10.5% (33/315), 12.4% (124/1003) and 12.9%(11/85) respectively, and the proportion of No.8p was 0, 0.8%(1/118), 2.1%(4/193), 4.8%(15/315), 18.9%(190/1003), and 25.9%(22/85) respectively. Postoperative complications were found in 195 patients (10.8%), including 63 cases(3.5%) of peritoneal infection, 52 cases (2.9%) of pulmonary infection, 33 cases(1.8%) of pancreatic leakage, 37 cases (2.1%) of anastomotic fistula, 45 cases (2.5%) of intestinal obstruction and 13 cases(0.7%) of gastroplesia. The 5-year overall survival rate was 53.6%.

CONCLUSIOND2 radical resection of omental bursa and No.12p and No.8p is safe and feasible in the treatment of gastric cancer.

OBJECTIVETo explore the risk factors and prognosis of No.8p lymph node metastasis in cases with advanced gastric cancer.

METHODSClinicopathological and follow-up data of 790 cases with advanced gastric cancer undergoing gastrectomy (including No.8p lymphadenectomy) from October 2003 to October 2013 in Fujian Provincial Tumor Hospital were analyzed retrospectively. Patients receiving neoadjuvant chemotherapy were excluded. Associations of No.8p lymph node metastasis with clinicopathological characteristics and metastasis in other regional lymph node were analyzed. Prognostic difference between positive No.8p group and negative No.8p group was examined.

RESULTSPositive No.8p lymph node was found in 93 cases (11.8%) among 790 cases with advanced gastric cancer. Univariate analysis showed that gender [male 9.8%(56/572) vs. female 17.0%(37/218), P=0.005], preoperative CEA level [<5 μg/L 28.0%(61/218) vs. ≥5 μg/L 5.6%(32/572), P=0.005], tumor size[diameter <5 cm 3.8%(13/346) vs. ≥5 cm 18.0%(80/445), P=0.000], tumor location [gastric fundus and cardiac 10.7% (26/244) vs. gastric body 13.5% (30/222) vs. gastric antrum 10.1% (31/308) vs. total gastric 37.5%(6/16), P=0.007], Borrmann staging [type II( 1.9%(4/211) vs. type III( 11.6% (54/464) vs. type IIII( 30.4%(35/115), P=0.000], tumor differentiation [high 0/8 vs. moderate 6.7%(25/372) vs. low 16.6%(68/410), P=0.000], T staging [T2 2.4%(4/170) vs. T3 13.1%(35/267) vs. T4 15.3%(54/353), P=0.000], N staging [N0 0 (0/227) vs. N1 2.2%(5/223) vs. N2 15.2%(26/171) vs. N3 36.7%(62/169), P=0.000] were closely associated with the No.8p lymph node metastasis. Multivariate analysis that revealed gender (OR=1.762, 95%CI: 1.020-3.043), tumor size (OR=1.107, 95%CI: 1.020-1.203), N staging (OR=4.093, 95%CI: 2.929-5.718), tumor differentiation (OR=1.782, 95%CI:1.042-3.049), and metastasis in No.8a(OR=5.370, 95%CI: 3.425-8.419), No.3(OR=1.127, 95%CI:1.053-1.206), No.6(OR=1.221,95%CI: 1.028-1.450), No.7(OR=2.149, 95%CI: 1.711-2.699), No,11p(OR=2.085, 95%CI: 1.453-2.994), No.14v(OR=2.604, 95%CI: 1.038-6.532) group lymph nodes were the independent risk factors of No.8p lymph node metastasis. One-year, 3-year and 5-year survival rates in positive No.8p group were 85.7%, 47.5% and 22.6%, and those in negative No.8p group were 96.2%, 82.5% and 70.3% respectively, whose differences were significant (χ=109.767, P<0.05).

CONCLUSIONSMetastasis in Np.8p lymph nodes is an important factor affecting the prognosis of patients with advanced gastric cancer. In patients with female gender, tumor diameter ≥5 cm, preoperative late N staging, low tumor differentiation or metastasis in No.8a, No.3, No.6, No.7, No.11p, No.14v group lymph nodes, thorough clean rance of No.8p group lymph node should be considered.

Carcinoembryonic Antigen ; blood ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; methods ; Lymph Nodes ; physiopathology ; surgery ; Lymphatic Metastasis ; diagnosis ; pathology ; physiopathology ; Male ; Multivariate Analysis ; Neoplasm Grading ; statistics & numerical data ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Stomach Neoplasms ; diagnosis ; mortality ; surgery ; Survival Rate

OBJECTIVETo evaluate the clinicopathologic characteristics and prognostic difference of gastric stump cancer between non-anastomotic site and anastomotic site.

METHODSClinicopathologic data of 149 patients with gastric stump cancer undergoing operation (radical resection and palliative resection) in our department from January 1999 to June 2015 were analyzed retrospectively. Gastric stump cancer was defined as a primary carcinoma detected in the remnant stomach more than 5 years after subtotal gastrectomy for a benign disease(87 cases) or over 10 years after radical subtotal gastrectomy for a malignant disease (62 cases). Patients were divided into the anastomotic site group (72 cases) and the non-anastomotic site group (77 cases) according to tumor sites within the remnant stomach. Clinicopathologic characteristics, operative data, lymph node metastasis and prognosis were compared between the two groups.

RESULTSCompared with non-anastomotic site group, the T stage, N stage and TNM stage were later in the anastomotic site group. Number of case of T1, T2, T3, and T4 stage in anastomotic site group was 1(1.4%), 2 (2.8%), 17(23.6%) and 52(72.2%), while such number in non-anastomotic site group was 8(10.4%), 10(13.0%), 27(35.1%) and 32(41.6%) respectively(χ=17.665, P=0.001). Number of case of N0, N1, N2, and N3 in anastomotic site group was 28 (38.9%), 10 (13.9%), 23 (31.9%) and 11 (15.3%), while such number in non-anastomotic site group was 55 (71.4%), 10 (13.0%), 7 (9.1%) and 5 (6.5%) respectively(χ=19.421, P=0.000). Number of case of stage I(, II(, III( and IIII( in anastomotic site group was 3(4.2%), 10(13.9%), 47(65.3%) and 12(16.7%), while such number in non-anastomotic site group was 16(20.8%), 40 (51.9%), 15(19.5%) and 6(7.8%) respectively(χ=45.294, P=0.000). The histology and Borrmann classification were worse in anastomotic site group. Anastomotic site group had 19 cases(26.4%) of good differentiation and 53 cases(73.6%) of bad differentiation, while non-anastomotic site group had 43 cases (55.8%) of well-differentiated and 34 cases (44.2%) of poorly-differentiated tumors respectively(χ=13.287, P=0.000). Anastomotic site group had 3 cases (4.2%) of Borrmann I(, 17 cases (23.6%) of Borrmann II(, 47 cases(65.3%) of Borrmann III( and 5 cases (6.9%) of Borrmann IIII(, while non-anastomotic site group had 18 cases (23.4%) of Borrmann I(, 16 cases (20.8%) of Borrmann II(, 34 cases (50.6%) of Borrmann III( and 4 cases (5.2%) of Borrmann IIII( respectively(χ=11.445, P=0.010). Compared with non-anastomotic site group, anastomotic site group had a lower curative resection rate [63.9% (46/72) vs. 89.6% (69/77), χ=13.977, P=0.000], a higher combined organ resection rate [33.3% (24/72) vs. 16.9% (13/77), χ=5.394, P=0.020] and a more metastatic lymph nodes (4.3±4.9 vs. 1.9±3.6, t=3.478, P=0.000). The lymph node metastasis rates of No.4, No.10 and jejunal mesentery root lymph node in anastomotic site group and non-anastomotic site group were 15.3% (11/72) and 5.2% (4/77)(χ=4.178, P=0.041), 9.7% (7/72) and 1.3% (1/77) (χ=5.196, P=0.023), and 25.0% (18/72) and 3.9% (3/77)(χ=13.687, P=0.000), respectively. Median followed up of all the patients was 37(2 to 154) months and the overall 5-year survival rate was 44.1%. The 5-year survival rate was 33.1% in anastomotic site group and 55.2% in non-anastomotic site group, and the difference was statistically significant between two groups (P=0.015). In the subgroup analysis according to the histology differentiation, the 5-year survival rate of patients with well-differentiation was not significantly different between two groups (43.7% vs. 56.2%, P=0.872), but the 5-year survival rate of patients with bad differentiation in anastomotic site group was significantly lower than that in non-anastomotic site group(29.8% vs. 53.8%, P=0.029).

CONCLUSIONGastric stump cancer locating in anastomotic site indicates worse differentiation histology, higher lymph node metastasis rate, lower curative resection rate and poorer prognosis.

Aged ; Anastomosis, Surgical ; adverse effects ; mortality ; statistics & numerical data ; Carcinoma ; mortality ; pathology ; therapy ; Female ; Gastrectomy ; adverse effects ; Gastric Stump ; pathology ; surgery ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; statistics & numerical data ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; classification ; mortality ; pathology ; therapy ; Survival Rate ; Treatment Outcome