[Show abstract][Hide abstract] ABSTRACT: Treatment of anorectal Buschke-Lowenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid abdomino-perineal resection (APR). Three cases of anorectal BLT with SCC transformation are presented. All patients were HIV positive and treated with antiretroviral drugs. They underwent preoperative endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C in bolus on the first day, plus 5-fluorouracil by continuous infusion in the first and in the sixth week) and subsequent local surgical excision. During the follow-up, patients were subjected to the same preoperative diagnostic investigations and high resolution anoscopy. All patients showed a complete regression of the lesion after CRT and were treated by local surgical excision, thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation therapy with local surgical excision could be considered an effective therapy in the treatment of anorectal BLT with SCC transformation to avoid APR.
Full-text · Article · Sep 2013 · World Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof. Location in article Query / Remark: click on the Q link to go Please insert your reply or correction at the corresponding line in the proof Q1 Please confirm that given names and surnames have been identified correctly. Q2 Please check if the changes made in the Fig. 1 caption are appropriate and amend if necessary. Q3 Please check if the change made here is appropriate and amend if necessary Q4 Highlights should consist of only 85 characters per bullet point, including spaces. However, the Highlights provided for this item exceed the maximum requirement, thus, were not captured. Kindly provide replacement Highlights that conform to the requirement for us to proceed. For more information, please see Guide for Authors. 25 Immunofluorescence 26 Cerebellum 27 An autoimmune hypothesis has been suggested for several disorders in childhood. The aim of the study was 28 to clarify the role of the cerebellum in ADHD and to evaluate the possible association between anti-Yo anti-29 bodies and ADHD. The presence/absence of antibodies was tested by indirect immunofluorescence assay on 30 30 combined subtype ADHD children, on 19 children with other psychiatric disorders (Oppositional-defiant 31 and Conduct Disorders, Dyslexia) and 27 healthy controls. 32 Results showed a significant positive response to the anti-Yo antibody immunoreactivity in the Purkinje cells 33 of the cerebellum of ADHD children, compared with the control group and the psychiatric non-ADHD chil-34 dren. This association points to an immune dysregulation and the involvement of the cerebellum in ADHD.
No preview · Article · Mar 2013 · Journal of Neuroimmunology
[Show abstract][Hide abstract] ABSTRACT: An autoimmune hypothesis has been suggested for several disorders in childhood. The aim of the study was to clarify the role of the cerebellum in ADHD and to evaluate the possible association between anti-Yo antibodies and ADHD. The presence/absence of antibodies was tested by indirect immunofluorescence assay on 30 combined subtype ADHD children, on 19 children with other psychiatric disorders (Oppositional-defiant and Conduct Disorders, Dyslexia) and 27 healthy controls. Results showed a significant positive response to the anti-Yo antibody immunoreactivity in the Purkinje cells of the cerebellum of ADHD children, compared with the control group and the psychiatric non-ADHD children. This association points to an immune dysregulation and the involvement of the cerebellum in ADHD.
No preview · Article · Mar 2013 · Journal of neuroimmunology
[Show abstract][Hide abstract] ABSTRACT: The management of anal fistula is debatable. Although several procedures have been described, none of them is free from complications, such as anal incontinence and anal pain. The purpose of this study was to evaluate the employment of a glue composed of N-butil-2-cyanoacrylate and methacryloxysulfolane (Glubran 2) to treat fistula-in-ano.
Twenty-one patients (14 men and 7 women) with cryptoglandular anal fistula were enrolled in the study and treated as day-cases. Fistulas were assessed both clinically and by trans-rectal endosonography with a rotating 10-MHz 360 degrees endoscopic probe. Assessment of continence was also performed. The fistula tract was identified, curetted and washed-out with normal saline and hydrogen peroxide; then the glue was injected from the syringe nozzle through a catheter previously inserted into the fistula. Additional treatments were performed when the first failed.
Five of seven simple fistulas (71.4%) healed with primary glue treatment; the other two needed second and third injections, and both healed. Ten of 14 (71.4%) complex fistulas healed with primary treatment; of the other four patients, one showed signs of intolerance to cyanoacrylate, which required re-intervention to remove the applied glue. In the second patient, treatment was successful after a second session; in the third case, three glue injections were required; while the fourth patient was lost at follow-up after three unsuccessful sessions. The ratio of cumulative healing with only one treatment was 15/21 (71.4%), and the ratio of overall healing after more than one session was 19/21 (90.2%). There was no sign of recurrence of the disease after 18 months of follow-up.
Cyanoacrylate glue seems to be ideal to treat fistula-in-ano, as it is a safe, cost-effective, repeatable and muscle-sparing technique. The incidence of recurrence is low, and post-procedure complicated fistulas or perianal abscesses were not reported.
Preview · Article · Jan 2007 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: To better understand the role of the number of lymph nodes retrieved on long-term outcome of gastric cancer treatment, 154 patients who had undergone curative resection, with dissection of >15 nodes were retrospectively studied. Dissection of perigastric and extraperigastric lymph nodes, defined as 'extended' (>26 nodes dissected) in 39 cases and 'limited' (< or = 26 nodes dissected) in 115 cases, was performed. A total of 3479 lymph nodes (mean 22.6 per specimen), were dissected and of these 721 showed metastases. A mean of 8.1 lymph node metastases, per metastatic case, was found. Regression analysis showed no independent factor associated with the extent of lymphadenectomy. Depth of wall invasion (p=0.000) and histological growth pattern (p=0.044) were independently associated with the number of lymph nodes involved (pN0, pN1 1-7, pN2 >7). The cumulative 5-year survival rate was 47% in patients without lymph node metastases; 29% in those with 1-7 nodes involved and 17% in those with >8 nodes involved (p=0.002). Receiver operating characteristic (ROC) curve analysis, in 65 nodenegative cancer cases, demonstrated an area under the curve for vital status (alive or dead) of 0.602 (95% CI: 0.473 - 0.721). All node-negative cases with a number equivalent to or exceeding the cutoff point of 23 nodes were alive. ROC analysis showed 11 to be the cutoff number of metastasized lymph nodes in correlation with vital status. Almost all those patients in whom the number of positive nodes was equivalent to, or exceeded the cutoff point had died (area under the ROC curve 0.633; 95% CI: 0.524 - 0.733). ROC analysis showed that the cutoff lymph node ratio, in relation to vital status, was 0.33. The majority of patients at or above this cutoff point had died (area under ROC curve 0.682; 95% CI: 0.574 - 0.776). Multivariate survival analysis showed that lymph node ratio was the only independent prognostic factor (p=0.001). The present findings suggest that, in lymphadenectomy with at least 15 nodes, the number and status of regional nodes dissected, irrespective of the location, provide reliable prognostic information on curatively resected gastric carcinomas.
No preview · Article · Jun 2004 · Journal of experimental & clinical cancer research: CR
[Show abstract][Hide abstract] ABSTRACT: It was suggested that there are no stronger prognostic factors in gastric cancer than nodal involvement or depth of wall invasion. The present paper evaluated the influence of maximum tumor diameter (MTD) value, measured on fixed resected specimens, on the extent of disease progression and the outcome in gastric cancer patients. Clinicopathological data were retrospectively retrieved from records of 122 patients who underwent curative gastrectomy. The patients' MTD values were grouped as follows: MTD1, up to 26 mm; MTD2, between 26 and 50 mm; and MTD3, over 50 mm. The three groups evidenced significant differences with regard to 5 year survival (MTD1: 54%, MTD2: 31%, MTD3: 20%; p = 0.00027), furthermore they were significantly different with respect to the type of gastrectomy (p = 0.021), depth wall invasion (p = 0.000), lymphatic microinvasion (p = 0.014), perineural microinvasion (p = 0.017), stromal reaction (p = 0.025), and stage (p = 0.035). ROC curve analysis individuated a best accurate MTD threshold value for nodal involvement of 32 mm (sensitivity = 56.6%; specificity = 60.9%; positive predictive value = 52.6%; negative predictive value = 64.6%). The logistic regression analysis suggested that the depth of wall invasion was the only independent variable associated with MTD value (p = 0.0005). Multivariate analysis showed that independent prognostic risk factors were sex (p < 0.0025), number of involved nodes (p < 0.001) and MTD (p < 0.001). In conclusion, the maximum tumor diameter value of gastric cancer may be a factor with greater prognostic implications than previously believed.
Full-text · Article · Dec 2003 · Journal of experimental & clinical cancer research: CR
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate patients and polyp variables with statistical relationship and with stronger risk of severe dysplasia. During the period 1987-1997, a total of 853 colorectal polyps were endoscopically removed from 583 patients: 405 patients had a single and 178 multiple polyps. The gender and age of the patients and the indication for colonoscopy as well the size, location, number, morphology and histopathology of the polyps were determined. A total of 499 patients had adenomas and 84 had hyperplastic polyps. Gender had no influence on variables of polyps, while the older patients were more symptomatic (p=0.000), had multiple polyps (p=0.000), their growths were, for the most part, adenomas (p=0.000), with villous component (p=0.001). Multiplicity influenced the size (p=0.001), location (p=0.000) and the occurrence of villous component (p=0.004) and of moderate-severe dysplasia (p=0.003) of the growths. The larger size of adenomas was correlated with increased occurrence of villous component (p=0.000) and of moderate-severe dysplasia (p=0.000).The risk for severe dysplasia was found to be correlated to the size and to the villous component of adenomas.
[Show abstract][Hide abstract] ABSTRACT: The case is presented of extended sigmoid stricture associated with colitis cystica profunda occurring 31 years after radiotherapy for a gynecological cancer. The patient came to our attention with low grade obstructive symptoms and was referred to our department for surgical treatment. Sigmoidoscopy, barium enema and CT scan revealed a rigid, concentric narrowing of the sigmoid colon. Stenosis, 10 cm in length, of the sigmoid loop was recognized at laparotomy and a left colectomy was performed. Histological examination of the resected specimen demonstrated cystic glands deep to the muscularis mucosae, in the submucosa and the muscularis propria. The submucosa appeared diffusely fibrotic. This observation demonstrates that colitis cystica profunda may occur as a late uncommon effect of irradiation.
[Show abstract][Hide abstract] ABSTRACT: In patients operated on for low rectal cancer, the functional results, disease recurrence, and survival have been evaluated with respect to the type of surgery performed. Particular attention was paid to analysis of the pathologic aspects, considered in our opinion, as risk factors for recurrence. The investigation was carried out on 131 patients, of whom 70 received anterior resection, 55 abdominoperineal resection, and 6 local treatment. Abdominoperineal resection was carried out in more advanced disease. Postoperative mortality was 2.1 percent after anterior resection and 0 after abdominoperineal resection or local treatment. Follow-up, carried out in 96 patients (44 anterior resections, 46 abdominoperineal resections, and 6 local treatments), ranged from 12 to 84 (mean, 33.3) months. Recurrence rate was 53.3 percent after abdominoperineal resection and 28.9 percent after anterior resection. Recurrence appears not be related to the treatment performed, but rather depend on certain aspects of the neoplasm such as diameter exceeding 5 cm, extraparietal infiltration, lymphangitis, and tumor indifferentiation. We observed anastomotic recurrence in 28.6 percent of patients with a margin of less than 2 cm. An intensive follow-up scheme enabled us to recognize this type of recurrence early and to reoperate with radical intent. One year after anterior resection functional results were encouraging. No severe incontinence was reported. Local treatment was performed in carefully selected patients (T1, N0) and no cases of mortality or recurrence were observed.
No preview · Article · Mar 1994 · Diseases of the Colon & Rectum
[Show abstract][Hide abstract] ABSTRACT: One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19-9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19-9 showed a sensitivity of 64%, 73% and 60% respectively and a specificity of 67%, 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer. CEA, TPA and Ca 19-9 showed a sensitivity of 73%, 73% and 49% respectively, and a specificity of 77%, 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
No preview · Article · Oct 1991 · Australian and New Zealand Journal of Surgery
[Show abstract][Hide abstract] ABSTRACT: One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorec-tal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcino-embryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19–9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19–9 showed a sensitivity of 64%. 73% and 60% respectively and a specificity of 67%. 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer, CEA, TPA and Ca 19–9 showed a sensitivity of 73%. 73% and 49% respectively, and a specificity of 77%. 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease. In four cases the rises of the three marker levels was the one sign of recurrent disease. In one case, the operation revealed a peritoneal carcinomatosis, and in the other three cases resectable hepatic metastases were found. All these three patients are still living and disease-free. In 46 cases, the rise in the value of CEA (35 cases) and/or TPA (34 cases) and/or Ca 19–9 (28 cases) was the first sign of recurrence. and the diagnosis was established later by clinical methods. In this group. the median time for diagnosis of recurrence, based on increase in initial markers comparison with routine clinical and instrumental follow-up (lead time), was 3 months for liver metastases and 4 months for disseminated metastases.
The results of our study indicate that a follow-up programme based on CEA, TPA and Ca 19–9 assays is related to an early diagnosis and good resectability rate for recurrent gastric disease.
No preview · Article · Aug 1991 · ANZ Journal of Surgery
[Show abstract][Hide abstract] ABSTRACT: Personal experience is reported of 47 consecutive liver resections for metastatic colorectal carcinoma treated in the I Clinica Chirurgica of the University of Rome for the purpose of contributing to treatment and evaluating the clinical factors and possible determinants of prognosis that could be potentially predictive of outcome and length of survival after liver resection: Duke's stage of primary colorectal cancer, synchronous or metachronous disease, number of hepatic lesions. Patients were classified according to the proposed staging system of the "Istituto Nazionale Tumori" in Milan. For Stage I and II patients the median survival time was 15 months, while in Stage III patients survival time was reduced to only 4.5 months. The 3- and 5-year survival rate was 20% and 12% respectively for Stage I patients; no patients at stage II or III survived more than 3 years.
No preview · Article · Jan 1991 · International surgery
[Show abstract][Hide abstract] ABSTRACT: Colonoscopy and air-contrast barium enema performed preoperatively in 389 patients with colorectal cancer revealed synchronous cancer in 4% and polyp in 14%. Nine of the 16 synchronous cancers were located in other surgical segments than the index cancer, and six of the nine were in stage A or B1. Of the 54 synchronous polyps, 28 were located in such other segments. Half of the synchronous cancers and almost half of the synchronous polyps were missed at double-contrast barium enema. All synchronous cancers and three-fourths of the synchronous polyps were detected at colonoscopy. No patient with preoperative colonoscopy presented with metachronous cancer within 3 years from surgery, and only two were subsequently found to have adenocarcinoma arising from an adenomatous polyp. Endoscopic polypectomy was performed in 21 cases during follow-up. Extensive use of preoperative colonoscopy is recommended in the evaluation of colorectal cancer, in order to promote detection of synchronous tumors, reduce the incidence of 'early metachronous' cancer and avoid malignant degeneration of adenomatous polyp.
No preview · Article · Mar 1990 · Acta chirurgica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: Eighty-eight consecutive patients who underwent curative resection for colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential CEA, TPA and CA 19-9 determinations and independent clinical examination in the early diagnosis of resectable recurrences. Twenty nine recurrences were detected between 8 and 38 months after primary surgery. CEA, TPA and CA 19-9 showed a sensitivity of 72%, 62% and 38%, and a specificity of 78%, 86% and 97%, respectively. Of eight recurrences in which CEA was not raised, five induced a rise in TPA and two a rise in CA 19-9. The rise in the serum concentration of one of the three markers was the first sign of relapse in 23 (79%) patients. Two second-look laparotomies based solely on a rise in serum markers were performed. In one case diffuse recurrent disease was found, and in the other a resectable solitary hepatic metastasis was found.
No preview · Article · Jan 1990 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: An early diagnosis in asymptomatic patients and a prompt treatment lead to an improved survival rate in patients with carcinoma of the colon. Patients with a short symptomatic history of colon cancer do not have a better prognosis than patients with a long history. Between 1978 and 1984 a consecutive series of 571 patients with colorectal cancer were admitted to the First Department of Surgery of the University of Rome. All patients were classified into five groups according to the duration of specific intestinal symptoms. In Group 1 (51 cases) asymptomatic patients were included, or patients with no specific symptoms such as asthenia, anemia, occult fecal blood. In Group 2 there were 129 patients with intestinal symptoms of less than 3 months' duration before treatment. In Group 3 there were 192 patients with symptoms of between 4 and 6 months' duration; 151 patients with symptoms of between 6 and 12 months were included in Group 4, and finally 48 patients who presented with symptoms of more than 1 year were included in Group 5. No relationship was noted between tumor site and duration of symptoms. Similarly, no relationship was noted between the duration of intestinal symptoms and stage and tumor differentiation. On the other hand, asymptomatic patients showed a higher incidence of T1N0M0 stage tumor and a lower percentage of undifferentiated neoplasms. The resectability rate was 79% and it was significantly related to the absence of intestinal symptoms. Follow-up data were available in 454 patients (80%). The overall survival rate was 52.4%. In Group 1 through Group 5 the 5-year survival rate was: 83.7%, 50%, 50%, 46.3%, 46.9%. The results of our study indicate that patients admitted in asymptomatic phase presented less-advanced stage tumors and, thus, best survival rate. On the other hand, from our data the duration of intestinal symptoms is not related to the stage and prognosis of tumors.
No preview · Article · Nov 1989 · European Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Between 1976 and 1986, a consecutive series of 195 patients with right colon cancer were admitted at the First Department of Surgery of the University of Rome. Patients were divided into five groups according to the absence of intestinal symptoms (group 1) and the duration of the symptomatic phase (groups 2-5). Analysis of the preoperative investigation showed that colonoscopy was able to identify 33 (26.2%) of tumors misdiagnosed by double contrast X-ray barium enema. We did not notice any correlation among symptom duration and tumor stage, tumor differentiation, operability rate, and survival. Patients admitted in the asymptomatic phase presented tumors of less advanced stage and, thus, had the best survival rate (71.4%). In this group, patients promptly treated had a better survival rate (87.5%) than those treated after 2 months (50%).
Our study suggests that only neoplasms diagnosed in asymptomatic patients and treated promptly are related to a good survival rate. We, therefore, emphasize the importance of education of patients and family physicians about right colon cancer and the necessity to investigate all patients with a suspected right colon cancer by means of colonoscopy.
No preview · Article · Aug 1989 · Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: The incidence of synchronous cancer has been reported to be 1.5% to 7.6%. A retrospective review of all colorectal cancer patients was conducted to determine the incidence of synchronous cancers. 47 synchronous cancers were identified in an operative series of 2586 patients with an incidence of 1.8%. The patients were divided into two groups based on preoperative diagnostic examinations. The first group included 1608 patients examined by double contrast x-ray barium enema (1141) and/or single contrast barium enema (381) and/or rigid sigmoidoscopy (112). The second group included 978 patients examined by double contrast barium enema (459) and/or flexible sigmoidoscopy (631) and/or colonoscopy (389). The incidence of synchronous tumors was 1.6% for patients evaluated only with double contrast roentgenographic study and 4.1% for patients who underwent preoperative colonoscopy. Fifty percent of synchronous cancers detected by colonoscopy were missed at double contrast x-ray barium enema. While twenty two percent of synchronous tumors detected by barium enema were located in different surgical segments and were all "advanced" tumors, when preoperative colonoscopy was performed, 56.2% of synchronous tumors were not located in the same surgical segment, and 66.7% of these were "early" cancers. None of the patients who underwent preoperatively colonoscopy developed a metachronous tumor within 3 years. One percent of patients undergoing flexible sigmoidoscopy or double contrast barium enema developed a second tumor 3 years after surgery. An extended use of preoperative colonoscopy in the diagnosis of colorectal cancers, to increase the detection od synchronous tumors and to decrease the incidence of the so-called "early" metachronous cancers, is stressed.
No preview · Article · Feb 1989 · The Italian journal of surgical sciences / sponsored by Società italiana di chirurgia
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer is rare in patients under 40 years of age. We reviewed all colorectal cancer patients treated at the First Department of Surgery of the University of Rome, to determine the true incidence of large bowel cancer in young patients. During the period 1978-1984 a total of 571 patients were indexed. Out of these 44 were 39 years of age or less. A group of 527 patients 40 years of age or over served as a control. Neoplasms were localized in the right colon in 19 cases and in the left colon in 25 patients, in the young group. In the control group 178 patients presented neoplasms localized in the right colon, while 349 presented tumors localized in the left colon. According to tumor advancement in the young group tumor classification from A stage tumor through D stage was: 4, 6, 14, 5, 9, 6. In the control group 22 patients presented A stage tumors, 106 B1, 139 B2, 50 C1, 118 C2, 92 D tumors. The operability rate was 93.2% in the young group, and 92% in the old one. The operative mortality rate was 0% in the young group, and 2.5% in the old one. Four complications occurred in the young patients, and 57 in the old patients. The five years survival rate was 56.7% and 52.1% in young and old patients respectively. The results of our study indicate that there are no significant differences in prognosis and five years survival in young patients with colorectal cancer.
No preview · Article · Jan 1989 · International surgery